<?xml version="1.0" encoding="UTF-8"?>

<!--XBRL Document Created with the Workiva Platform-->
<!--Copyright 2026 Workiva-->
<!--r:01a01583-bdf5-7c7c-aa6d-7ba69b70f47e,g:977ac8bf-df89-4f00-a090-290b6c2d74d3-->
<link:linkbase xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd">
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain"/>
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member"/>
  <link:roleRef roleURI="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONS" xlink:type="simple" xlink:href="lgnd-20260930.xsd#CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONS"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFOPERATIONS" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_01a01583-bf4e-7857-9f17-0294498c1e1b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_01a01583-bf4e-7fb3-9861-e2959b87f0e3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_01a01583-bf4e-7857-9f17-0294498c1e1b" xlink:to="loc_us-gaap_StatementTable_01a01583-bf4e-7fb3-9861-e2959b87f0e3" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a01583-bf4e-78e0-98b0-89b767bc6aa3" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_01a01583-bf4e-7fb3-9861-e2959b87f0e3" xlink:to="loc_srt_ProductOrServiceAxis_01a01583-bf4e-78e0-98b0-89b767bc6aa3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a01583-bf4e-78e0-98b0-89b767bc6aa3_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a01583-bf4e-78e0-98b0-89b767bc6aa3" xlink:to="loc_srt_ProductsAndServicesDomain_01a01583-bf4e-78e0-98b0-89b767bc6aa3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a01583-bf4e-788d-9b8d-ef667e20cbf6" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a01583-bf4e-78e0-98b0-89b767bc6aa3" xlink:to="loc_srt_ProductsAndServicesDomain_01a01583-bf4e-788d-9b8d-ef667e20cbf6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RoyaltyMember_01a01583-bf4e-74fc-810b-c7072b70eb2e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RoyaltyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bf4e-788d-9b8d-ef667e20cbf6" xlink:to="loc_us-gaap_RoyaltyMember_01a01583-bf4e-74fc-810b-c7072b70eb2e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_IntangibleRoyaltyAssetsMember_01a01583-bf4e-7aaf-851b-a52d8a4d17b3" xlink:href="lgnd-20260930.xsd#lgnd_IntangibleRoyaltyAssetsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RoyaltyMember_01a01583-bf4e-74fc-810b-c7072b70eb2e" xlink:to="loc_lgnd_IntangibleRoyaltyAssetsMember_01a01583-bf4e-7aaf-851b-a52d8a4d17b3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetsMember_01a01583-bf4e-7b77-8bec-e07697b724cc" xlink:href="lgnd-20260930.xsd#lgnd_FinancialRoyaltyAssetsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RoyaltyMember_01a01583-bf4e-74fc-810b-c7072b70eb2e" xlink:to="loc_lgnd_FinancialRoyaltyAssetsMember_01a01583-bf4e-7b77-8bec-e07697b724cc" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MaterialSalesCaptisolMember_01a01583-bf4e-772b-b22f-372b6db71606" xlink:href="lgnd-20260930.xsd#lgnd_MaterialSalesCaptisolMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bf4e-788d-9b8d-ef667e20cbf6" xlink:to="loc_lgnd_MaterialSalesCaptisolMember_01a01583-bf4e-772b-b22f-372b6db71606" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ContractRevenueAndIncomeMember_01a01583-bf4e-77de-9c93-e8f4151860e5" xlink:href="lgnd-20260930.xsd#lgnd_ContractRevenueAndIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bf4e-788d-9b8d-ef667e20cbf6" xlink:to="loc_lgnd_ContractRevenueAndIncomeMember_01a01583-bf4e-77de-9c93-e8f4151860e5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenuesAbstract_01a01583-bf4e-796a-9f8e-8905b831e362" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenuesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a01583-bf4e-7857-9f17-0294498c1e1b" xlink:to="loc_us-gaap_RevenuesAbstract_01a01583-bf4e-796a-9f8e-8905b831e362" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_01a01583-bf4e-71e8-a899-3a646599eab9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RevenuesAbstract_01a01583-bf4e-796a-9f8e-8905b831e362" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_01a01583-bf4e-71e8-a899-3a646599eab9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingCostsAndExpensesAbstract_01a01583-bf4e-7135-a252-5b78d46e6afa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingCostsAndExpensesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a01583-bf4e-7857-9f17-0294498c1e1b" xlink:to="loc_us-gaap_OperatingCostsAndExpensesAbstract_01a01583-bf4e-7135-a252-5b78d46e6afa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostDirectMaterial_01a01583-bf4e-7c06-9281-c21509a2afb9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CostDirectMaterial"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingCostsAndExpensesAbstract_01a01583-bf4e-7135-a252-5b78d46e6afa" xlink:to="loc_us-gaap_CostDirectMaterial_01a01583-bf4e-7c06-9281-c21509a2afb9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSoldAmortization_01a01583-bf4e-7f92-8586-35aaaf3e8ac8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CostOfGoodsAndServicesSoldAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingCostsAndExpensesAbstract_01a01583-bf4e-7135-a252-5b78d46e6afa" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSoldAmortization_01a01583-bf4e-7f92-8586-35aaaf3e8ac8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ResearchAndDevelopmentExpense_01a01583-bf4e-79c4-9253-cb3bf97d4438" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingCostsAndExpensesAbstract_01a01583-bf4e-7135-a252-5b78d46e6afa" xlink:to="loc_us-gaap_ResearchAndDevelopmentExpense_01a01583-bf4e-79c4-9253-cb3bf97d4438" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GeneralAndAdministrativeExpense_01a01583-bf4e-73ff-9355-9a2b4d4fd904" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GeneralAndAdministrativeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingCostsAndExpensesAbstract_01a01583-bf4e-7135-a252-5b78d46e6afa" xlink:to="loc_us-gaap_GeneralAndAdministrativeExpense_01a01583-bf4e-73ff-9355-9a2b4d4fd904" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_01a18e25-7698-74c5-b8a0-f2a7d00a2063" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingCostsAndExpensesAbstract_01a01583-bf4e-7135-a252-5b78d46e6afa" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_01a18e25-7698-74c5-b8a0-f2a7d00a2063" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeGainLossOnDerivativeNet_01a01583-bf4e-70fc-8f2b-5de7962d8b71" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeGainLossOnDerivativeNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingCostsAndExpensesAbstract_01a01583-bf4e-7135-a252-5b78d46e6afa" xlink:to="loc_us-gaap_DerivativeGainLossOnDerivativeNet_01a01583-bf4e-70fc-8f2b-5de7962d8b71" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingCostsAndExpenses_01a01583-bf4e-7607-b296-e63c05785d3b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingCostsAndExpenses"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OperatingCostsAndExpensesAbstract_01a01583-bf4e-7135-a252-5b78d46e6afa" xlink:to="loc_us-gaap_OperatingCostsAndExpenses_01a01583-bf4e-7607-b296-e63c05785d3b" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_01a01583-bf4e-774d-a940-f8230ac2fade" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a01583-bf4e-7857-9f17-0294498c1e1b" xlink:to="loc_us-gaap_OperatingIncomeLoss_01a01583-bf4e-774d-a940-f8230ac2fade" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_01a01583-bf4e-7ab0-8341-4d09cf1a9517" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherNonoperatingIncomeExpenseAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a01583-bf4e-7857-9f17-0294498c1e1b" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_01a01583-bf4e-7ab0-8341-4d09cf1a9517" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GainLossOnInvestments_01a01583-bf4e-7a14-8b0c-1be477d8182a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GainLossOnInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_01a01583-bf4e-7ab0-8341-4d09cf1a9517" xlink:to="loc_us-gaap_GainLossOnInvestments_01a01583-bf4e-7a14-8b0c-1be477d8182a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_GainLossFromChangeInFairValueOfEquityMethodInvestmentsAndOtherInvestments_01a01583-bf4e-71e1-9606-b56c698aa4a8" xlink:href="lgnd-20260930.xsd#lgnd_GainLossFromChangeInFairValueOfEquityMethodInvestmentsAndOtherInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_01a01583-bf4e-7ab0-8341-4d09cf1a9517" xlink:to="loc_lgnd_GainLossFromChangeInFairValueOfEquityMethodInvestmentsAndOtherInvestments_01a01583-bf4e-71e1-9606-b56c698aa4a8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentIncomeInterest_01a01583-bf4e-7d65-ac25-53bf65c839e0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InvestmentIncomeInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_01a01583-bf4e-7ab0-8341-4d09cf1a9517" xlink:to="loc_us-gaap_InvestmentIncomeInterest_01a01583-bf4e-7d65-ac25-53bf65c839e0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_01a01583-bf4e-7ab6-a23c-509545b4ee1a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_01a01583-bf4e-7ab0-8341-4d09cf1a9517" xlink:to="loc_us-gaap_InterestExpenseNonoperating_01a01583-bf4e-7ab6-a23c-509545b4ee1a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherNonoperatingIncomeExpense_01a01583-bf4e-7988-9a30-59fff80a5423" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherNonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_01a01583-bf4e-7ab0-8341-4d09cf1a9517" xlink:to="loc_us-gaap_OtherNonoperatingIncomeExpense_01a01583-bf4e-7988-9a30-59fff80a5423" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NonoperatingIncomeExpense_01a01583-bf4e-7a9c-bc1f-fd7f0e1a14fd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NonoperatingIncomeExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherNonoperatingIncomeExpenseAbstract_01a01583-bf4e-7ab0-8341-4d09cf1a9517" xlink:to="loc_us-gaap_NonoperatingIncomeExpense_01a01583-bf4e-7a9c-bc1f-fd7f0e1a14fd" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_01a01583-bf4e-72d9-b7ed-7cb11c18d38a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a01583-bf4e-7857-9f17-0294498c1e1b" xlink:to="loc_us-gaap_IncomeLossFromContinuingOperationsBeforeIncomeTaxesExtraordinaryItemsNoncontrollingInterest_01a01583-bf4e-72d9-b7ed-7cb11c18d38a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeTaxExpenseBenefit_01a01583-bf4e-7a56-8488-abf84051c22b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeTaxExpenseBenefit"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a01583-bf4e-7857-9f17-0294498c1e1b" xlink:to="loc_us-gaap_IncomeTaxExpenseBenefit_01a01583-bf4e-7a56-8488-abf84051c22b" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_01a01583-bf4e-7d48-978f-4c89690f407d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a01583-bf4e-7857-9f17-0294498c1e1b" xlink:to="loc_us-gaap_NetIncomeLoss_01a01583-bf4e-7d48-978f-4c89690f407d" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareAbstract_01a01583-bf4e-7d9b-a818-3ba86794eff6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EarningsPerShareAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a01583-bf4e-7857-9f17-0294498c1e1b" xlink:to="loc_us-gaap_EarningsPerShareAbstract_01a01583-bf4e-7d9b-a818-3ba86794eff6" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareBasic_01a01583-bf4e-7c95-a4af-758b37c71479" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EarningsPerShareBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareAbstract_01a01583-bf4e-7d9b-a818-3ba86794eff6" xlink:to="loc_us-gaap_EarningsPerShareBasic_01a01583-bf4e-7c95-a4af-758b37c71479" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_01a01583-bf4e-7cda-beb3-f408e3620b2c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareAbstract_01a01583-bf4e-7d9b-a818-3ba86794eff6" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_01a01583-bf4e-7cda-beb3-f408e3620b2c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EarningsPerShareDiluted_01a01583-bf4e-726f-b23f-917c6ad3756b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EarningsPerShareDiluted"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareAbstract_01a01583-bf4e-7d9b-a818-3ba86794eff6" xlink:to="loc_us-gaap_EarningsPerShareDiluted_01a01583-bf4e-726f-b23f-917c6ad3756b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_01a01583-bf4e-7cd9-a4b6-e7c710cd518b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EarningsPerShareAbstract_01a01583-bf4e-7d9b-a818-3ba86794eff6" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_01a01583-bf4e-7cd9-a4b6-e7c710cd518b" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY" xlink:type="simple" xlink:href="lgnd-20260930.xsd#CONDENSEDCONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/CONDENSEDCONSOLIDATEDSTATEMENTSOFSTOCKHOLDERSEQUITY" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementLineItems_01a01583-bf4e-771a-bd08-4043e4823447" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementTable_01a01583-bf4e-73b7-851d-376a4c3c5046" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_StatementLineItems_01a01583-bf4e-771a-bd08-4043e4823447" xlink:to="loc_us-gaap_StatementTable_01a01583-bf4e-73b7-851d-376a4c3c5046" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementEquityComponentsAxis_01a01583-bf4e-76bb-b31a-5f5a37c70775" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementEquityComponentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_01a01583-bf4e-73b7-851d-376a4c3c5046" xlink:to="loc_us-gaap_StatementEquityComponentsAxis_01a01583-bf4e-76bb-b31a-5f5a37c70775" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_01a01583-bf4e-76bb-b31a-5f5a37c70775_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_01a01583-bf4e-76bb-b31a-5f5a37c70775" xlink:to="loc_us-gaap_EquityComponentDomain_01a01583-bf4e-76bb-b31a-5f5a37c70775_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityComponentDomain_01a01583-bf4e-7e16-9662-1bde33b6b54e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityComponentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementEquityComponentsAxis_01a01583-bf4e-76bb-b31a-5f5a37c70775" xlink:to="loc_us-gaap_EquityComponentDomain_01a01583-bf4e-7e16-9662-1bde33b6b54e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_01a01583-bf4e-7800-bd2b-c5ebedb68dff" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_01a01583-bf4e-7e16-9662-1bde33b6b54e" xlink:to="loc_us-gaap_CommonStockMember_01a01583-bf4e-7800-bd2b-c5ebedb68dff" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdditionalPaidInCapitalMember_01a01583-bf4e-7e95-a54b-a750f6353a19" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdditionalPaidInCapitalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_01a01583-bf4e-7e16-9662-1bde33b6b54e" xlink:to="loc_us-gaap_AdditionalPaidInCapitalMember_01a01583-bf4e-7e95-a54b-a750f6353a19" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_01a01583-bf4e-7dd1-9eab-e78574fea718" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_01a01583-bf4e-7e16-9662-1bde33b6b54e" xlink:to="loc_us-gaap_AccumulatedOtherComprehensiveIncomeMember_01a01583-bf4e-7dd1-9eab-e78574fea718" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RetainedEarningsMember_01a01583-bf4e-7a2b-bc1c-a3dd07bcd6c3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RetainedEarningsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EquityComponentDomain_01a01583-bf4e-7e16-9662-1bde33b6b54e" xlink:to="loc_us-gaap_RetainedEarningsMember_01a01583-bf4e-7a2b-bc1c-a3dd07bcd6c3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RestatementAxis_01a01583-bf4e-7b35-a454-0e289c7da8a9" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RestatementAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_01a01583-bf4e-73b7-851d-376a4c3c5046" xlink:to="loc_srt_RestatementAxis_01a01583-bf4e-7b35-a454-0e289c7da8a9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RestatementDomain_01a01583-bf4e-7b35-a454-0e289c7da8a9_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RestatementDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RestatementAxis_01a01583-bf4e-7b35-a454-0e289c7da8a9" xlink:to="loc_srt_RestatementDomain_01a01583-bf4e-7b35-a454-0e289c7da8a9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RestatementDomain_01a01583-bf4e-7bbc-bfee-2f6030112921" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RestatementDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RestatementAxis_01a01583-bf4e-7b35-a454-0e289c7da8a9" xlink:to="loc_srt_RestatementDomain_01a01583-bf4e-7bbc-bfee-2f6030112921" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioPreviouslyReportedMember_01a01583-bf4e-73f0-b0e1-ccbb607636f5" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioPreviouslyReportedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RestatementDomain_01a01583-bf4e-7bbc-bfee-2f6030112921" xlink:to="loc_srt_ScenarioPreviouslyReportedMember_01a01583-bf4e-73f0-b0e1-ccbb607636f5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CumulativeEffectPeriodOfAdoptionAxis_01a01583-bf4e-7eb1-9f68-25954bdddc99" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CumulativeEffectPeriodOfAdoptionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_StatementTable_01a01583-bf4e-73b7-851d-376a4c3c5046" xlink:to="loc_srt_CumulativeEffectPeriodOfAdoptionAxis_01a01583-bf4e-7eb1-9f68-25954bdddc99" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_01a01583-bf4e-7eb1-9f68-25954bdddc99_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CumulativeEffectPeriodOfAdoptionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CumulativeEffectPeriodOfAdoptionAxis_01a01583-bf4e-7eb1-9f68-25954bdddc99" xlink:to="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_01a01583-bf4e-7eb1-9f68-25954bdddc99_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_01a01583-bf4e-763e-8260-7cb893c698aa" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CumulativeEffectPeriodOfAdoptionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CumulativeEffectPeriodOfAdoptionAxis_01a01583-bf4e-7eb1-9f68-25954bdddc99" xlink:to="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_01a01583-bf4e-763e-8260-7cb893c698aa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CumulativeEffectPeriodOfAdoptionAdjustmentMember_01a01583-bf4e-7aa3-bad5-8267baef6e2e" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CumulativeEffectPeriodOfAdoptionAdjustmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_CumulativeEffectPeriodOfAdoptionDomain_01a01583-bf4e-763e-8260-7cb893c698aa" xlink:to="loc_srt_CumulativeEffectPeriodOfAdoptionAdjustmentMember_01a01583-bf4e-7aa3-bad5-8267baef6e2e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncreaseDecreaseInStockholdersEquityRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_StatementLineItems_01a01583-bf4e-771a-bd08-4043e4823447" xlink:to="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_01a01583-bf4e-7ce8-9392-47ef536beb24" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:to="loc_us-gaap_CommonStockSharesOutstanding_01a01583-bf4e-7ce8-9392-47ef536beb24" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_01a01583-bf4e-7c9b-b379-fdd24af72237" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:to="loc_us-gaap_StockholdersEquity_01a01583-bf4e-7c9b-b379-fdd24af72237" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_01a01583-bf4e-7618-ae27-cd476e6ee035" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesShareBasedCompensation_01a01583-bf4e-7618-ae27-cd476e6ee035" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation_01a01583-bf4e-7492-bb4d-d9918f6efde5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:to="loc_us-gaap_StockIssuedDuringPeriodValueShareBasedCompensation_01a01583-bf4e-7492-bb4d-d9918f6efde5" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockRepurchasedDuringPeriodShares_01a01583-bf4e-75ae-9107-df8ecaf0ed05" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockRepurchasedDuringPeriodShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:to="loc_us-gaap_StockRepurchasedDuringPeriodShares_01a01583-bf4e-75ae-9107-df8ecaf0ed05" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ShareRepurchaseInConnectionWithProceedsnFromDebtIssuance_01a01583-bf4e-7da7-9811-ea536b092a34" xlink:href="lgnd-20260930.xsd#lgnd_ShareRepurchaseInConnectionWithProceedsnFromDebtIssuance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:to="loc_lgnd_ShareRepurchaseInConnectionWithProceedsnFromDebtIssuance_01a01583-bf4e-7da7-9811-ea536b092a34" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalEquityComponentOfConvertibleDebt_01a01583-bf4e-7d0a-a207-91240acaf0f3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalEquityComponentOfConvertibleDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalEquityComponentOfConvertibleDebt_01a01583-bf4e-7d0a-a207-91240acaf0f3" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockRepurchasedDuringPeriodValue_01a0aa7b-3b1a-7cae-a6f1-fc1110bd7687" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockRepurchasedDuringPeriodValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:to="loc_us-gaap_StockRepurchasedDuringPeriodValue_01a0aa7b-3b1a-7cae-a6f1-fc1110bd7687" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalConvertibleDebtWithConversionFeature_01a0aa7b-3b1a-744b-8d09-adb449d043f8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalConvertibleDebtWithConversionFeature"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalConvertibleDebtWithConversionFeature_01a0aa7b-3b1a-744b-8d09-adb449d043f8" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_01a01583-bf4e-7987-8f29-33fc69d7db49" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:to="loc_us-gaap_AdjustmentsToAdditionalPaidInCapitalSharebasedCompensationRequisiteServicePeriodRecognitionValue_01a01583-bf4e-7987-8f29-33fc69d7db49" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_01a01583-bf4e-7f4c-b837-0dd5cf24cd19" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:to="loc_us-gaap_OtherComprehensiveIncomeAvailableforsaleSecuritiesAdjustmentNetOfTaxPortionAttributableToParent_01a01583-bf4e-7f4c-b837-0dd5cf24cd19" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent_01a01583-bf4e-739a-91d1-709ceb45c704" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:to="loc_us-gaap_OtherComprehensiveIncomeForeignCurrencyTransactionAndTranslationAdjustmentNetOfTaxPortionAttributableToParent_01a01583-bf4e-739a-91d1-709ceb45c704" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NetIncomeLoss_01a01583-bf4e-709c-99bf-ddc21f84046d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncreaseDecreaseInStockholdersEquityRollForward_01a01583-bf4e-79dd-8f32-173e82e86806" xlink:to="loc_us-gaap_NetIncomeLoss_01a01583-bf4e-709c-99bf-ddc21f84046d" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockSharesOutstanding_01a01583-bf4e-7599-bb62-d9366cd44bbe" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockSharesOutstanding"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockholdersEquity_01a01583-bf4e-71a5-974f-0f835a74b736" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockholdersEquity"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesNarrativeDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PropertyPlantAndEquipmentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_01a01583-bff6-79c4-8648-0e03a2a4ddb3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfPropertyPlantAndEquipmentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_01a01583-bff6-79c4-8648-0e03a2a4ddb3" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a01583-bff6-702f-92fb-82550309e902" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_01a01583-bff6-79c4-8648-0e03a2a4ddb3" xlink:to="loc_srt_ProductOrServiceAxis_01a01583-bff6-702f-92fb-82550309e902" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a01583-bff6-702f-92fb-82550309e902_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a01583-bff6-702f-92fb-82550309e902" xlink:to="loc_srt_ProductsAndServicesDomain_01a01583-bff6-702f-92fb-82550309e902_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a01583-bff6-72cc-9809-64da384676b5" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a01583-bff6-702f-92fb-82550309e902" xlink:to="loc_srt_ProductsAndServicesDomain_01a01583-bff6-72cc-9809-64da384676b5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MaterialSalesCaptisolMember_01a01583-bff6-728b-882a-e0a0cb5dbe66" xlink:href="lgnd-20260930.xsd#lgnd_MaterialSalesCaptisolMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bff6-72cc-9809-64da384676b5" xlink:to="loc_lgnd_MaterialSalesCaptisolMember_01a01583-bff6-728b-882a-e0a0cb5dbe66" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PrimroseBioMember_01a01583-bff6-78a3-84b1-918a14590e11" xlink:href="lgnd-20260930.xsd#lgnd_PrimroseBioMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bff6-72cc-9809-64da384676b5" xlink:to="loc_lgnd_PrimroseBioMember_01a01583-bff6-78a3-84b1-918a14590e11" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_01a01583-bff6-77d3-8b55-f03a80f4c5e6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_01a01583-bff6-79c4-8648-0e03a2a4ddb3" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_01a01583-bff6-77d3-8b55-f03a80f4c5e6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-77d3-8b55-f03a80f4c5e6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_01a01583-bff6-77d3-8b55-f03a80f4c5e6" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-77d3-8b55-f03a80f4c5e6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-7ae4-8ba8-ca73def782e4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_01a01583-bff6-77d3-8b55-f03a80f4c5e6" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-7ae4-8ba8-ca73def782e4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_WarrantsAndOptionMember_01a01583-bff6-7e32-9e80-e803ee842c2f" xlink:href="lgnd-20260930.xsd#lgnd_WarrantsAndOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-7ae4-8ba8-ca73def782e4" xlink:to="loc_lgnd_WarrantsAndOptionMember_01a01583-bff6-7e32-9e80-e803ee842c2f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OrchestraWarrantMember_01a01583-bff6-7965-8cf3-ef76ce2671e7" xlink:href="lgnd-20260930.xsd#lgnd_OrchestraWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-7ae4-8ba8-ca73def782e4" xlink:to="loc_lgnd_OrchestraWarrantMember_01a01583-bff6-7965-8cf3-ef76ce2671e7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LeonaBioWarrantsMember_01a01583-bff6-77fb-96c0-14de0710f1f7" xlink:href="lgnd-20260930.xsd#lgnd_LeonaBioWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-7ae4-8ba8-ca73def782e4" xlink:to="loc_lgnd_LeonaBioWarrantsMember_01a01583-bff6-77fb-96c0-14de0710f1f7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PelthosConversionOptionMember_01a01583-bff6-7cd9-890e-264f90fbda23" xlink:href="lgnd-20260930.xsd#lgnd_PelthosConversionOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-7ae4-8ba8-ca73def782e4" xlink:to="loc_lgnd_PelthosConversionOptionMember_01a01583-bff6-7cd9-890e-264f90fbda23" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_01a01583-bff6-7cf1-92ec-f4b2786cbb1c" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_01a01583-bff6-79c4-8648-0e03a2a4ddb3" xlink:to="loc_srt_CounterpartyNameAxis_01a01583-bff6-7cf1-92ec-f4b2786cbb1c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7cf1-92ec-f4b2786cbb1c_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_01a01583-bff6-7cf1-92ec-f4b2786cbb1c" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7cf1-92ec-f4b2786cbb1c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7535-8a7f-ee93d24b6ddc" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_01a01583-bff6-7cf1-92ec-f4b2786cbb1c" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7535-8a7f-ee93d24b6ddc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AgenusInc.Member_01a01583-bff6-7ad8-9f69-da4f7a2c9969" xlink:href="lgnd-20260930.xsd#lgnd_AgenusInc.Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7535-8a7f-ee93d24b6ddc" xlink:to="loc_lgnd_AgenusInc.Member_01a01583-bff6-7ad8-9f69-da4f7a2c9969" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PrimroseBioMember_01a01583-bff6-7a5d-b05f-c1257d25af03" xlink:href="lgnd-20260930.xsd#lgnd_PrimroseBioMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7535-8a7f-ee93d24b6ddc" xlink:to="loc_lgnd_PrimroseBioMember_01a01583-bff6-7a5d-b05f-c1257d25af03" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightAxis_01a01583-bff6-7b4f-982f-ac1e9a3eb8b4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_01a01583-bff6-79c4-8648-0e03a2a4ddb3" xlink:to="loc_us-gaap_ClassOfWarrantOrRightAxis_01a01583-bff6-7b4f-982f-ac1e9a3eb8b4" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-7b4f-982f-ac1e9a3eb8b4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_01a01583-bff6-7b4f-982f-ac1e9a3eb8b4" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-7b4f-982f-ac1e9a3eb8b4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-7cf4-b0fa-12674bf57083" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_01a01583-bff6-7b4f-982f-ac1e9a3eb8b4" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-7cf4-b0fa-12674bf57083" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AgenusWarrantAndCastleCreekWarrantMember_01a01583-bff6-73ee-bf7a-9dbffe87967f" xlink:href="lgnd-20260930.xsd#lgnd_AgenusWarrantAndCastleCreekWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-7cf4-b0fa-12674bf57083" xlink:to="loc_lgnd_AgenusWarrantAndCastleCreekWarrantMember_01a01583-bff6-73ee-bf7a-9dbffe87967f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-7f3b-8a1c-74fcfdbcd806" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_01a01583-bff6-79c4-8648-0e03a2a4ddb3" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-7f3b-8a1c-74fcfdbcd806" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7f3b-8a1c-74fcfdbcd806_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-7f3b-8a1c-74fcfdbcd806" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7f3b-8a1c-74fcfdbcd806_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75e6-ab8a-dca684eb9ace" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-7f3b-8a1c-74fcfdbcd806" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75e6-ab8a-dca684eb9ace" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RemainCoMember_01a18e3e-8de9-7752-9dbb-b098d0ec1ed1" xlink:href="lgnd-20260930.xsd#lgnd_RemainCoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75e6-ab8a-dca684eb9ace" xlink:to="loc_lgnd_RemainCoMember_01a18e3e-8de9-7752-9dbb-b098d0ec1ed1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PrimroseBioMember_01a01583-bff6-748f-b018-b5a4532bee5c" xlink:href="lgnd-20260930.xsd#lgnd_PrimroseBioMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75e6-ab8a-dca684eb9ace" xlink:to="loc_lgnd_PrimroseBioMember_01a01583-bff6-748f-b018-b5a4532bee5c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AvenCellMember_01a18e58-0f35-7840-91dc-80b61e96cfe5" xlink:href="lgnd-20260930.xsd#lgnd_AvenCellMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75e6-ab8a-dca684eb9ace" xlink:to="loc_lgnd_AvenCellMember_01a18e58-0f35-7840-91dc-80b61e96cfe5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PelthosCommonSharesAndSeriesAConvertiblePreferredSharesMember_01a01583-bff6-7f30-b96a-223efba3cafb" xlink:href="lgnd-20260930.xsd#lgnd_PelthosCommonSharesAndSeriesAConvertiblePreferredSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75e6-ab8a-dca684eb9ace" xlink:to="loc_lgnd_PelthosCommonSharesAndSeriesAConvertiblePreferredSharesMember_01a01583-bff6-7f30-b96a-223efba3cafb" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_01a01583-bff6-7138-b37e-fef5c3905e1e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_01a01583-bff6-79c4-8648-0e03a2a4ddb3" xlink:to="loc_us-gaap_AwardTypeAxis_01a01583-bff6-7138-b37e-fef5c3905e1e" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-bff6-7138-b37e-fef5c3905e1e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_01a01583-bff6-7138-b37e-fef5c3905e1e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-bff6-7138-b37e-fef5c3905e1e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-bff6-78c9-8b3f-7cec8b3970e7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_01a01583-bff6-7138-b37e-fef5c3905e1e" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-bff6-78c9-8b3f-7cec8b3970e7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PerformanceSharesMember_01a01583-bff6-7d2c-a8d6-03f4a38dc2a8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-bff6-78c9-8b3f-7cec8b3970e7" xlink:to="loc_us-gaap_PerformanceSharesMember_01a01583-bff6-7d2c-a8d6-03f4a38dc2a8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_01a01583-bff6-7289-8ef0-f398fbf0cee1" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_01a01583-bff6-79c4-8648-0e03a2a4ddb3" xlink:to="loc_srt_RangeAxis_01a01583-bff6-7289-8ef0-f398fbf0cee1" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a01583-bff6-7289-8ef0-f398fbf0cee1_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_01a01583-bff6-7289-8ef0-f398fbf0cee1" xlink:to="loc_srt_RangeMember_01a01583-bff6-7289-8ef0-f398fbf0cee1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a01583-bff6-7adf-84fc-c8ab04090228" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_01a01583-bff6-7289-8ef0-f398fbf0cee1" xlink:to="loc_srt_RangeMember_01a01583-bff6-7adf-84fc-c8ab04090228" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_01a01583-bff6-7a8e-92ef-34a9f7f96f87" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a01583-bff6-7adf-84fc-c8ab04090228" xlink:to="loc_srt_MinimumMember_01a01583-bff6-7a8e-92ef-34a9f7f96f87" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_01a01583-bff6-7538-8d3e-7deb08c02c8f" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a01583-bff6-7adf-84fc-c8ab04090228" xlink:to="loc_srt_MaximumMember_01a01583-bff6-7538-8d3e-7deb08c02c8f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a18e4a-0e34-7d3f-a1ff-b5a8e98f588a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfPropertyPlantAndEquipmentTable_01a01583-bff6-79c4-8648-0e03a2a4ddb3" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a18e4a-0e34-7d3f-a1ff-b5a8e98f588a" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e4a-0e34-7d3f-a1ff-b5a8e98f588a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e4a-0e34-7d3f-a1ff-b5a8e98f588a" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e4a-0e34-7d3f-a1ff-b5a8e98f588a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e4a-0e34-7029-b41d-da10226c9759" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e4a-0e34-7d3f-a1ff-b5a8e98f588a" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e4a-0e34-7029-b41d-da10226c9759" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MetabasisTherapeuticsMember_01a18e4a-0e34-709c-b746-e124feeb9d8f" xlink:href="lgnd-20260930.xsd#lgnd_MetabasisTherapeuticsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e4a-0e34-7029-b41d-da10226c9759" xlink:to="loc_lgnd_MetabasisTherapeuticsMember_01a18e4a-0e34-709c-b746-e124feeb9d8f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_NonCashChangeInEstimatedFairValueOfContingentValueRights_01a18e32-d389-74e7-984f-05c5388fb1b2" xlink:href="lgnd-20260930.xsd#lgnd_NonCashChangeInEstimatedFairValueOfContingentValueRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_lgnd_NonCashChangeInEstimatedFairValueOfContingentValueRights_01a18e32-d389-74e7-984f-05c5388fb1b2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NumberOfOperatingSegments_01a01583-bff6-7ebf-a1c9-31eb42f5b3ab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NumberOfOperatingSegments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_NumberOfOperatingSegments_01a01583-bff6-7ebf-a1c9-31eb42f5b3ab" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NumberOfReportableSegments_01a01583-bff6-75ec-82d8-c5c5c6136a82" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NumberOfReportableSegments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_NumberOfReportableSegments_01a01583-bff6-75ec-82d8-c5c5c6136a82" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionNumberOfPositions_01a01583-bff6-7605-bfc7-68e95955040e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionNumberOfPositions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionNumberOfPositions_01a01583-bff6-7605-bfc7-68e95955040e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_01a01583-bff6-70fa-9d31-2ac4978bb3f6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleUnrealizedLossPositionAccumulatedLoss_01a01583-bff6-70fa-9d31-2ac4978bb3f6" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLossWriteoff_01a01583-bff6-724c-b04e-012505e47a56" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLossWriteoff"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleAllowanceForCreditLossWriteoff_01a01583-bff6-724c-b04e-012505e47a56" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllowanceForDoubtfulAccountsReceivablePeriodIncreaseDecrease_01a01583-bff6-753d-a70d-123840eb8970" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AllowanceForDoubtfulAccountsReceivablePeriodIncreaseDecrease"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_AllowanceForDoubtfulAccountsReceivablePeriodIncreaseDecrease_01a01583-bff6-753d-a70d-123840eb8970" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryWriteDown_01a01583-bff6-7f7e-8d3e-29ff2c4826ea" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InventoryWriteDown"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_InventoryWriteDown_01a01583-bff6-7f7e-8d3e-29ff2c4826ea" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InventoryNet_01a01583-bff6-7f86-834b-f5b89cfc071f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InventoryNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_InventoryNet_01a01583-bff6-7f86-834b-f5b89cfc071f" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MilestoneCompensationRate_01a01583-bff6-71b2-a2b1-469e3b5923d0" xlink:href="lgnd-20260930.xsd#lgnd_MilestoneCompensationRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_lgnd_MilestoneCompensationRate_01a01583-bff6-71b2-a2b1-469e3b5923d0" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeGainLossOnDerivativeNet_01a01583-bff6-73d1-b83c-63e949ec0171" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeGainLossOnDerivativeNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_DerivativeGainLossOnDerivativeNet_01a01583-bff6-73d1-b83c-63e949ec0171" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_01a01583-bff6-7103-a88a-8f7a8edf2b71" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityMethodInvestmentOwnershipPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_01a01583-bff6-7103-a88a-8f7a8edf2b71" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentOtherThanTemporaryImpairment_01a01583-bff6-78c4-9b83-0b9f41374a90" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityMethodInvestmentOtherThanTemporaryImpairment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_EquityMethodInvestmentOtherThanTemporaryImpairment_01a01583-bff6-78c4-9b83-0b9f41374a90" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestments_01a01583-bff6-71c1-be36-001f7775ff90" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityMethodInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_EquityMethodInvestments_01a01583-bff6-71c1-be36-001f7775ff90" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrealizedGainLossOnInvestments_01a01583-bff6-725a-a648-4f88b6686242" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_UnrealizedGainLossOnInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_UnrealizedGainLossOnInvestments_01a01583-bff6-725a-a648-4f88b6686242" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_NumberOfContingentValueRightsIssued_01a18e4a-0e34-76f5-9334-00c0e1081766" xlink:href="lgnd-20260930.xsd#lgnd_NumberOfContingentValueRightsIssued"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_lgnd_NumberOfContingentValueRightsIssued_01a18e4a-0e34-76f5-9334-00c0e1081766" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_NumberOfContingentValueRightsOutstanding_01a18e4a-0e34-7c61-92fb-72fa2c4ade0b" xlink:href="lgnd-20260930.xsd#lgnd_NumberOfContingentValueRightsOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_lgnd_NumberOfContingentValueRightsOutstanding_01a18e4a-0e34-7c61-92fb-72fa2c4ade0b" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrecognizedTaxBenefits_01a18e4b-21b2-7abd-bf2e-30070b367a44" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_UnrecognizedTaxBenefits"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_UnrecognizedTaxBenefits_01a18e4b-21b2-7abd-bf2e-30070b367a44" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_01a01583-bff6-7eb3-b015-b9507f19c1d5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardAwardRequisiteServicePeriod1_01a01583-bff6-7eb3-b015-b9507f19c1d5" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ShareBasedCompensationAchievementOfPerformanceCriteriaPayoutRangePercent_01a01583-bff6-7e0f-af3e-75848c000d5c" xlink:href="lgnd-20260930.xsd#lgnd_ShareBasedCompensationAchievementOfPerformanceCriteriaPayoutRangePercent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PropertyPlantAndEquipmentLineItems_01a01583-bff6-7f73-91d0-a66d6f5054ba" xlink:to="loc_lgnd_ShareBasedCompensationAchievementOfPerformanceCriteriaPayoutRangePercent_01a01583-bff6-7e0f-af3e-75848c000d5c" xlink:type="arc" order="19"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesSegmentProfitorLossDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesSegmentProfitorLossDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesSegmentProfitorLossDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EntityWideRevenueMajorCustomerLineItems_01a01583-bff6-74f6-8997-461ffe91538e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EntityWideRevenueMajorCustomerLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable_01a01583-bff6-7467-ad9b-809a9260f8c2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_EntityWideRevenueMajorCustomerLineItems_01a01583-bff6-74f6-8997-461ffe91538e" xlink:to="loc_us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable_01a01583-bff6-7467-ad9b-809a9260f8c2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementBusinessSegmentsAxis_01a01583-bff6-7a57-99a3-a5040b0d919f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementBusinessSegmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfEntityWideRevenueByMajorCustomersByReportingSegmentsTable_01a01583-bff6-7467-ad9b-809a9260f8c2" xlink:to="loc_us-gaap_StatementBusinessSegmentsAxis_01a01583-bff6-7a57-99a3-a5040b0d919f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_01a01583-bff6-7a57-99a3-a5040b0d919f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_01a01583-bff6-7a57-99a3-a5040b0d919f" xlink:to="loc_us-gaap_SegmentDomain_01a01583-bff6-7a57-99a3-a5040b0d919f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentDomain_01a01583-bff6-728e-8fad-433ad2e145e2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SegmentDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementBusinessSegmentsAxis_01a01583-bff6-7a57-99a3-a5040b0d919f" xlink:to="loc_us-gaap_SegmentDomain_01a01583-bff6-728e-8fad-433ad2e145e2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_DevelopmentAndLicensingOfBiopharmaceuticalAssetsMember_01a01583-bff6-7fd6-aa6c-8c3cada8690d" xlink:href="lgnd-20260930.xsd#lgnd_DevelopmentAndLicensingOfBiopharmaceuticalAssetsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentDomain_01a01583-bff6-728e-8fad-433ad2e145e2" xlink:to="loc_lgnd_DevelopmentAndLicensingOfBiopharmaceuticalAssetsMember_01a01583-bff6-7fd6-aa6c-8c3cada8690d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_01a01583-bff6-7525-8a80-e4e8edf1f173" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EntityWideRevenueMajorCustomerLineItems_01a01583-bff6-74f6-8997-461ffe91538e" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_01a01583-bff6-7525-8a80-e4e8edf1f173" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpense_01a01583-bff6-7993-96e6-c316c6a36c39" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AllocatedShareBasedCompensationExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EntityWideRevenueMajorCustomerLineItems_01a01583-bff6-74f6-8997-461ffe91538e" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpense_01a01583-bff6-7993-96e6-c316c6a36c39" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingOtherSignificantReconcilingItemConsolidatedAbstract_01a01583-bff6-76d0-9a87-0c1e540871d2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SegmentReportingOtherSignificantReconcilingItemConsolidatedAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EntityWideRevenueMajorCustomerLineItems_01a01583-bff6-74f6-8997-461ffe91538e" xlink:to="loc_us-gaap_SegmentReportingOtherSignificantReconcilingItemConsolidatedAbstract_01a01583-bff6-76d0-9a87-0c1e540871d2" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CostOfGoodsAndServicesSoldAmortization_01a01583-bff6-70d3-bc78-b6fc3181202c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CostOfGoodsAndServicesSoldAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingOtherSignificantReconcilingItemConsolidatedAbstract_01a01583-bff6-76d0-9a87-0c1e540871d2" xlink:to="loc_us-gaap_CostOfGoodsAndServicesSoldAmortization_01a01583-bff6-70d3-bc78-b6fc3181202c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Depreciation_01a01583-bff6-7548-ad4e-56d22d66e251" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Depreciation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingOtherSignificantReconcilingItemConsolidatedAbstract_01a01583-bff6-76d0-9a87-0c1e540871d2" xlink:to="loc_us-gaap_Depreciation_01a01583-bff6-7548-ad4e-56d22d66e251" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestIncomeOperating_01a01583-bff6-7147-9eab-98f8966109dc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestIncomeOperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingOtherSignificantReconcilingItemConsolidatedAbstract_01a01583-bff6-76d0-9a87-0c1e540871d2" xlink:to="loc_us-gaap_InterestIncomeOperating_01a01583-bff6-7147-9eab-98f8966109dc" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseNonoperating_01a01583-bff6-71dd-a3be-1f9b5bbd024b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestExpenseNonoperating"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingOtherSignificantReconcilingItemConsolidatedAbstract_01a01583-bff6-76d0-9a87-0c1e540871d2" xlink:to="loc_us-gaap_InterestExpenseNonoperating_01a01583-bff6-71dd-a3be-1f9b5bbd024b" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SegmentReportingOtherItemAmount_01a01583-bff6-797f-aed8-2de357141ac6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SegmentReportingOtherItemAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SegmentReportingOtherSignificantReconcilingItemConsolidatedAbstract_01a01583-bff6-76d0-9a87-0c1e540871d2" xlink:to="loc_us-gaap_SegmentReportingOtherItemAmount_01a01583-bff6-797f-aed8-2de357141ac6" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OperatingIncomeLoss_01a01583-bff6-7076-8c3e-9f0162fd678e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OperatingIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EntityWideRevenueMajorCustomerLineItems_01a01583-bff6-74f6-8997-461ffe91538e" xlink:to="loc_us-gaap_OperatingIncomeLoss_01a01583-bff6-7076-8c3e-9f0162fd678e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OtherExpenseItemsNet_01a01583-bff6-7cce-93ed-893c5baa0a7b" xlink:href="lgnd-20260930.xsd#lgnd_OtherExpenseItemsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_EntityWideRevenueMajorCustomerLineItems_01a01583-bff6-74f6-8997-461ffe91538e" xlink:to="loc_lgnd_OtherExpenseItemsNet_01a01583-bff6-7cce-93ed-893c5baa0a7b" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesRevenuebySourceDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesRevenuebySourceDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesRevenuebySourceDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueLineItems_01a01583-bff6-7d79-95b7-4f852d641fed" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisaggregationOfRevenueLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DisaggregationOfRevenueTable_01a01583-bff6-7576-bfd5-04165ffd210f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DisaggregationOfRevenueTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_01a01583-bff6-7d79-95b7-4f852d641fed" xlink:to="loc_us-gaap_DisaggregationOfRevenueTable_01a01583-bff6-7576-bfd5-04165ffd210f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a01583-bff6-7111-9c7c-44c6a23ca0d4" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DisaggregationOfRevenueTable_01a01583-bff6-7576-bfd5-04165ffd210f" xlink:to="loc_srt_ProductOrServiceAxis_01a01583-bff6-7111-9c7c-44c6a23ca0d4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a01583-bff6-7111-9c7c-44c6a23ca0d4_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a01583-bff6-7111-9c7c-44c6a23ca0d4" xlink:to="loc_srt_ProductsAndServicesDomain_01a01583-bff6-7111-9c7c-44c6a23ca0d4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a01583-bff6-766a-b861-0bf9954657aa" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a01583-bff6-7111-9c7c-44c6a23ca0d4" xlink:to="loc_srt_ProductsAndServicesDomain_01a01583-bff6-766a-b861-0bf9954657aa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RoyaltyMember_01a01583-bff6-794e-b753-7020d7f29a21" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RoyaltyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bff6-766a-b861-0bf9954657aa" xlink:to="loc_us-gaap_RoyaltyMember_01a01583-bff6-794e-b753-7020d7f29a21" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_IntangibleRoyaltyAssetsMember_01a01583-bff6-792d-8608-e5b097b6bfdf" xlink:href="lgnd-20260930.xsd#lgnd_IntangibleRoyaltyAssetsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RoyaltyMember_01a01583-bff6-794e-b753-7020d7f29a21" xlink:to="loc_lgnd_IntangibleRoyaltyAssetsMember_01a01583-bff6-792d-8608-e5b097b6bfdf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FilspariMember_01a01583-bff6-7745-8079-2e76c3e2a422" xlink:href="lgnd-20260930.xsd#lgnd_FilspariMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_IntangibleRoyaltyAssetsMember_01a01583-bff6-792d-8608-e5b097b6bfdf" xlink:to="loc_lgnd_FilspariMember_01a01583-bff6-7745-8079-2e76c3e2a422" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_KyprolisMember_01a01583-bff6-728a-9703-67e55628288c" xlink:href="lgnd-20260930.xsd#lgnd_KyprolisMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_IntangibleRoyaltyAssetsMember_01a01583-bff6-792d-8608-e5b097b6bfdf" xlink:to="loc_lgnd_KyprolisMember_01a01583-bff6-728a-9703-67e55628288c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_CapvaxiveMember_01a01583-bff6-7887-a629-7b199a909a64" xlink:href="lgnd-20260930.xsd#lgnd_CapvaxiveMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_IntangibleRoyaltyAssetsMember_01a01583-bff6-792d-8608-e5b097b6bfdf" xlink:to="loc_lgnd_CapvaxiveMember_01a01583-bff6-7887-a629-7b199a909a64" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_IntangibleOhtuvayreMember_01a01583-bff6-7efe-b667-f031c6418f79" xlink:href="lgnd-20260930.xsd#lgnd_IntangibleOhtuvayreMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_IntangibleRoyaltyAssetsMember_01a01583-bff6-792d-8608-e5b097b6bfdf" xlink:to="loc_lgnd_IntangibleOhtuvayreMember_01a01583-bff6-7efe-b667-f031c6418f79" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RylazeMember_01a01583-bff6-76ac-bcdc-338fd5c8530c" xlink:href="lgnd-20260930.xsd#lgnd_RylazeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_IntangibleRoyaltyAssetsMember_01a01583-bff6-792d-8608-e5b097b6bfdf" xlink:to="loc_lgnd_RylazeMember_01a01583-bff6-76ac-bcdc-338fd5c8530c" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_TeriparatideInjectionMember_01a01583-bff6-7d3e-965e-bef7813aac90" xlink:href="lgnd-20260930.xsd#lgnd_TeriparatideInjectionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_IntangibleRoyaltyAssetsMember_01a01583-bff6-792d-8608-e5b097b6bfdf" xlink:to="loc_lgnd_TeriparatideInjectionMember_01a01583-bff6-7d3e-965e-bef7813aac90" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VaxneuvanceMember_01a01583-bff6-7e67-9139-653011f03925" xlink:href="lgnd-20260930.xsd#lgnd_VaxneuvanceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_IntangibleRoyaltyAssetsMember_01a01583-bff6-792d-8608-e5b097b6bfdf" xlink:to="loc_lgnd_VaxneuvanceMember_01a01583-bff6-7e67-9139-653011f03925" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RoyaltyIntangibleOtherMember_01a01583-bff6-737b-846b-8b2d93c0de92" xlink:href="lgnd-20260930.xsd#lgnd_RoyaltyIntangibleOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_IntangibleRoyaltyAssetsMember_01a01583-bff6-792d-8608-e5b097b6bfdf" xlink:to="loc_lgnd_RoyaltyIntangibleOtherMember_01a01583-bff6-737b-846b-8b2d93c0de92" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetsMember_01a01583-bff6-73ab-a3b4-592c40889935" xlink:href="lgnd-20260930.xsd#lgnd_FinancialRoyaltyAssetsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RoyaltyMember_01a01583-bff6-794e-b753-7020d7f29a21" xlink:to="loc_lgnd_FinancialRoyaltyAssetsMember_01a01583-bff6-73ab-a3b4-592c40889935" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OjemdaMember_01a143a0-8f4f-7365-a4c1-7a9421a34133" xlink:href="lgnd-20260930.xsd#lgnd_OjemdaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_FinancialRoyaltyAssetsMember_01a01583-bff6-73ab-a3b4-592c40889935" xlink:to="loc_lgnd_OjemdaMember_01a143a0-8f4f-7365-a4c1-7a9421a34133" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_QARZIBAMember_01a01583-bff6-769d-9428-04868d05505e" xlink:href="lgnd-20260930.xsd#lgnd_QARZIBAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_FinancialRoyaltyAssetsMember_01a01583-bff6-73ab-a3b4-592c40889935" xlink:to="loc_lgnd_QARZIBAMember_01a01583-bff6-769d-9428-04868d05505e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VabysmoMember_01a143a1-1289-70b6-8b07-f6713e5eca42" xlink:href="lgnd-20260930.xsd#lgnd_VabysmoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_FinancialRoyaltyAssetsMember_01a01583-bff6-73ab-a3b4-592c40889935" xlink:to="loc_lgnd_VabysmoMember_01a143a1-1289-70b6-8b07-f6713e5eca42" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialOhtuvayreInventorsMember_01a01583-bff6-7e9e-a401-2bc2e7618cde" xlink:href="lgnd-20260930.xsd#lgnd_FinancialOhtuvayreInventorsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_FinancialRoyaltyAssetsMember_01a01583-bff6-73ab-a3b4-592c40889935" xlink:to="loc_lgnd_FinancialOhtuvayreInventorsMember_01a01583-bff6-7e9e-a401-2bc2e7618cde" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MiplyffaMember_01a143a1-58e9-7ebc-9270-5df3eda539b3" xlink:href="lgnd-20260930.xsd#lgnd_MiplyffaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_FinancialRoyaltyAssetsMember_01a01583-bff6-73ab-a3b4-592c40889935" xlink:to="loc_lgnd_MiplyffaMember_01a143a1-58e9-7ebc-9270-5df3eda539b3" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyOtherMember_01a01583-bff6-7f10-9205-412163e7f4d4" xlink:href="lgnd-20260930.xsd#lgnd_FinancialRoyaltyOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_FinancialRoyaltyAssetsMember_01a01583-bff6-73ab-a3b4-592c40889935" xlink:to="loc_lgnd_FinancialRoyaltyOtherMember_01a01583-bff6-7f10-9205-412163e7f4d4" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MaterialSalesCaptisolMember_01a01583-bff6-7e6f-b6f4-ae7446b4516a" xlink:href="lgnd-20260930.xsd#lgnd_MaterialSalesCaptisolMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bff6-766a-b861-0bf9954657aa" xlink:to="loc_lgnd_MaterialSalesCaptisolMember_01a01583-bff6-7e6f-b6f4-ae7446b4516a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_IncomeFromDivestitureTransactionsMember_01a0aab3-5418-7416-9761-59174954997b" xlink:href="lgnd-20260930.xsd#lgnd_IncomeFromDivestitureTransactionsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bff6-766a-b861-0bf9954657aa" xlink:to="loc_lgnd_IncomeFromDivestitureTransactionsMember_01a0aab3-5418-7416-9761-59174954997b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ContractRevenueAndOtherIncomeMember_01a01583-bff6-70fe-b915-a06b92cdea30" xlink:href="lgnd-20260930.xsd#lgnd_ContractRevenueAndOtherIncomeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bff6-766a-b861-0bf9954657aa" xlink:to="loc_lgnd_ContractRevenueAndOtherIncomeMember_01a01583-bff6-70fe-b915-a06b92cdea30" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ContractRevenueMember_01a01583-bff6-7e2f-8b13-58ff46517ded" xlink:href="lgnd-20260930.xsd#lgnd_ContractRevenueMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_ContractRevenueAndOtherIncomeMember_01a01583-bff6-70fe-b915-a06b92cdea30" xlink:to="loc_lgnd_ContractRevenueMember_01a01583-bff6-7e2f-8b13-58ff46517ded" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ContractAndRevenueIncomeOtherMember_01a01583-bff6-7048-899d-2a70aaef08b3" xlink:href="lgnd-20260930.xsd#lgnd_ContractAndRevenueIncomeOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_ContractRevenueAndOtherIncomeMember_01a01583-bff6-70fe-b915-a06b92cdea30" xlink:to="loc_lgnd_ContractAndRevenueIncomeOtherMember_01a01583-bff6-7048-899d-2a70aaef08b3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_01a01583-bff6-7a9c-a3a2-90f9a88bd4c3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DisaggregationOfRevenueLineItems_01a01583-bff6-7d79-95b7-4f852d641fed" xlink:to="loc_us-gaap_RevenueFromContractWithCustomerExcludingAssessedTax_01a01583-bff6-7a9c-a3a2-90f9a88bd4c3" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesScheduleofComponentsOfRestrictedCashDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesScheduleofComponentsOfRestrictedCashDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesScheduleofComponentsOfRestrictedCashDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsItemsLineItems_01a11ae2-40b0-72cf-b753-c727acd8b838" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedCashAndCashEquivalentsItemsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfRestrictedCashAndCashEquivalentsTable_01a11ae2-40b0-7478-b1d9-a5b61304b922" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfRestrictedCashAndCashEquivalentsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsItemsLineItems_01a11ae2-40b0-72cf-b753-c727acd8b838" xlink:to="loc_us-gaap_ScheduleOfRestrictedCashAndCashEquivalentsTable_01a11ae2-40b0-7478-b1d9-a5b61304b922" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_01a11ae2-40b0-7c2a-b1ee-f31fc1eb4f3a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfRestrictedCashAndCashEquivalentsTable_01a11ae2-40b0-7478-b1d9-a5b61304b922" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_01a11ae2-40b0-7c2a-b1ee-f31fc1eb4f3a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_01a11ae2-40b0-7c2a-b1ee-f31fc1eb4f3a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_01a11ae2-40b0-7c2a-b1ee-f31fc1eb4f3a" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_01a11ae2-40b0-7c2a-b1ee-f31fc1eb4f3a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_01a11ae2-40b0-7aff-87f6-c570fac09b10" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsAxis_01a11ae2-40b0-7c2a-b1ee-f31fc1eb4f3a" xlink:to="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_01a11ae2-40b0-7aff-87f6-c570fac09b10" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BostonLeasePaymentsMember_01a11ae2-40b0-7277-98a9-4b3dbd40dc63" xlink:href="lgnd-20260930.xsd#lgnd_BostonLeasePaymentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_01a11ae2-40b0-7aff-87f6-c570fac09b10" xlink:to="loc_lgnd_BostonLeasePaymentsMember_01a11ae2-40b0-7277-98a9-4b3dbd40dc63" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MetabasisCVRPaymentsMember_01a11ae2-40b0-7b8f-b77f-be833be21209" xlink:href="lgnd-20260930.xsd#lgnd_MetabasisCVRPaymentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_01a11ae2-40b0-7aff-87f6-c570fac09b10" xlink:to="loc_lgnd_MetabasisCVRPaymentsMember_01a11ae2-40b0-7b8f-b77f-be833be21209" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LAVACVRPaymentsMember_01a143fa-760c-7a94-9ab8-7b6c1e736cee" xlink:href="lgnd-20260930.xsd#lgnd_LAVACVRPaymentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_01a11ae2-40b0-7aff-87f6-c570fac09b10" xlink:to="loc_lgnd_LAVACVRPaymentsMember_01a143fa-760c-7a94-9ab8-7b6c1e736cee" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BostonLeaseSecurityDepositMember_01a143f9-ed42-73c3-8000-a624c96945db" xlink:href="lgnd-20260930.xsd#lgnd_BostonLeaseSecurityDepositMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsCashAndCashEquivalentsMember_01a11ae2-40b0-7aff-87f6-c570fac09b10" xlink:to="loc_lgnd_BostonLeaseSecurityDepositMember_01a143f9-ed42-73c3-8000-a624c96945db" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashCurrent_01a11ae2-40b0-7725-9d39-d2b68929a951" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedCashCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsItemsLineItems_01a11ae2-40b0-72cf-b753-c727acd8b838" xlink:to="loc_us-gaap_RestrictedCashCurrent_01a11ae2-40b0-7725-9d39-d2b68929a951" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCashNoncurrent_01a11ae2-40b0-7c1b-8678-acbe57d0f3b0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedCashNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsItemsLineItems_01a11ae2-40b0-72cf-b753-c727acd8b838" xlink:to="loc_us-gaap_RestrictedCashNoncurrent_01a11ae2-40b0-7c1b-8678-acbe57d0f3b0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedCash_01a18e37-29b3-7ecc-b092-5973f5a018c2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedCash"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RestrictedCashAndCashEquivalentsItemsLineItems_01a11ae2-40b0-72cf-b753-c727acd8b838" xlink:to="loc_us-gaap_RestrictedCash_01a18e37-29b3-7ecc-b092-5973f5a018c2" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesInvestmentCategoriesDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesInvestmentCategoriesDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesInvestmentCategoriesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a01583-bff6-7c07-ad85-bf1e642aa4dd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_01a01583-bff6-73ab-99bd-fb44afdb6883" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtSecuritiesAvailableForSaleTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a01583-bff6-7c07-ad85-bf1e642aa4dd" xlink:to="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_01a01583-bff6-73ab-99bd-fb44afdb6883" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_01a01583-bff6-7473-aa37-f0aa4636a9c0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtSecuritiesAvailableForSaleTable_01a01583-bff6-73ab-99bd-fb44afdb6883" xlink:to="loc_us-gaap_FinancialInstrumentAxis_01a01583-bff6-7473-aa37-f0aa4636a9c0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-7473-aa37-f0aa4636a9c0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_01a01583-bff6-7473-aa37-f0aa4636a9c0" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-7473-aa37-f0aa4636a9c0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-7ac6-9252-3bfe2463161e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_01a01583-bff6-7473-aa37-f0aa4636a9c0" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-7ac6-9252-3bfe2463161e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_01a01583-bff6-7cfb-8f5a-bc58f41931f4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_USGovernmentAgenciesDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-7ac6-9252-3bfe2463161e" xlink:to="loc_us-gaap_USGovernmentAgenciesDebtSecuritiesMember_01a01583-bff6-7cfb-8f5a-bc58f41931f4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CorporateDebtSecuritiesMember_01a01583-bff6-733c-bddf-b83b861f9c9b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CorporateDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-7ac6-9252-3bfe2463161e" xlink:to="loc_us-gaap_CorporateDebtSecuritiesMember_01a01583-bff6-733c-bddf-b83b861f9c9b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_USTreasurySecuritiesMember_01a01583-bff6-71f7-8248-956a5da7f3ae" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_USTreasurySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-7ac6-9252-3bfe2463161e" xlink:to="loc_us-gaap_USTreasurySecuritiesMember_01a01583-bff6-71f7-8248-956a5da7f3ae" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommercialPaperMember_01a01583-bff6-7650-8866-e3b80cf0e7fa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommercialPaperMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-7ac6-9252-3bfe2463161e" xlink:to="loc_us-gaap_CommercialPaperMember_01a01583-bff6-7650-8866-e3b80cf0e7fa" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesMember_01a01583-bff6-7571-8390-e38b41442451" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquitySecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-7ac6-9252-3bfe2463161e" xlink:to="loc_us-gaap_EquitySecuritiesMember_01a01583-bff6-7571-8390-e38b41442451" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_01a01583-bff6-7546-9a82-d02138d197e2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a01583-bff6-7c07-ad85-bf1e642aa4dd" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis_01a01583-bff6-7546-9a82-d02138d197e2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_01a01583-bff6-7353-aee9-1a324d111b67" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a01583-bff6-7c07-ad85-bf1e642aa4dd" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedGainBeforeTax_01a01583-bff6-7353-aee9-1a324d111b67" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_01a01583-bff6-71b1-85fe-b1d91f3c13a5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a01583-bff6-7c07-ad85-bf1e642aa4dd" xlink:to="loc_us-gaap_AvailableForSaleDebtSecuritiesAccumulatedGrossUnrealizedLossBeforeTax_01a01583-bff6-71b1-85fe-b1d91f3c13a5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_01a01583-bff6-7c3e-90fa-bc40febef9c8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems_01a01583-bff6-7c07-ad85-bf1e642aa4dd" xlink:to="loc_us-gaap_AvailableForSaleSecuritiesDebtSecurities_01a01583-bff6-7c3e-90fa-bc40febef9c8" xlink:type="arc" order="3"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesGoodwillandOtherIdentifiableIntangibleAssetsDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesGoodwillandOtherIdentifiableIntangibleAssetsDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesGoodwillandOtherIdentifiableIntangibleAssetsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a01583-bff6-73ae-91d8-a6c7b5fcfe26" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_01a01583-bff6-7b28-9608-6caf32c2b3a2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a01583-bff6-73ae-91d8-a6c7b5fcfe26" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_01a01583-bff6-7b28-9608-6caf32c2b3a2" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a01583-bff6-7110-8984-4d0d1ddbf5f7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_01a01583-bff6-7b28-9608-6caf32c2b3a2" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a01583-bff6-7110-8984-4d0d1ddbf5f7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a01583-bff6-7110-8984-4d0d1ddbf5f7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a01583-bff6-7110-8984-4d0d1ddbf5f7" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a01583-bff6-7110-8984-4d0d1ddbf5f7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a01583-bff6-7cc1-afff-af2abc0c0fc8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a01583-bff6-7110-8984-4d0d1ddbf5f7" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a01583-bff6-7cc1-afff-af2abc0c0fc8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PatentedTechnologyMember_01a01583-bff6-7793-bc47-51fda4d569e0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PatentedTechnologyMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a01583-bff6-7cc1-afff-af2abc0c0fc8" xlink:to="loc_us-gaap_PatentedTechnologyMember_01a01583-bff6-7793-bc47-51fda4d569e0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TradeNamesMember_01a01583-bff6-7afb-955c-f47cd27689f1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TradeNamesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a01583-bff6-7cc1-afff-af2abc0c0fc8" xlink:to="loc_us-gaap_TradeNamesMember_01a01583-bff6-7afb-955c-f47cd27689f1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CustomerRelationshipsMember_01a01583-bff6-7641-b40c-d0de9f242f3c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CustomerRelationshipsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a01583-bff6-7cc1-afff-af2abc0c0fc8" xlink:to="loc_us-gaap_CustomerRelationshipsMember_01a01583-bff6-7641-b40c-d0de9f242f3c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContractualRightsMember_01a01583-bff6-7cd1-9730-ca8cf24df36f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContractualRightsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a01583-bff6-7cc1-afff-af2abc0c0fc8" xlink:to="loc_us-gaap_ContractualRightsMember_01a01583-bff6-7cd1-9730-ca8cf24df36f" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IntangibleAssetsNetIncludingGoodwillAbstract_01a01583-bff6-7fcc-b3b2-9b1ece49ee48" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IntangibleAssetsNetIncludingGoodwillAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a01583-bff6-73ae-91d8-a6c7b5fcfe26" xlink:to="loc_us-gaap_IntangibleAssetsNetIncludingGoodwillAbstract_01a01583-bff6-7fcc-b3b2-9b1ece49ee48" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_01a01583-bff6-7c01-b7d0-375560c81aa7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Goodwill"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IntangibleAssetsNetIncludingGoodwillAbstract_01a01583-bff6-7fcc-b3b2-9b1ece49ee48" xlink:to="loc_us-gaap_Goodwill_01a01583-bff6-7c01-b7d0-375560c81aa7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsGross_01a01583-bff6-7de6-844f-2cde76104884" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IntangibleAssetsNetIncludingGoodwillAbstract_01a01583-bff6-7fcc-b3b2-9b1ece49ee48" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsGross_01a01583-bff6-7de6-844f-2cde76104884" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_01a01583-bff6-7046-99a1-9b881cadb167" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IntangibleAssetsNetIncludingGoodwillAbstract_01a01583-bff6-7fcc-b3b2-9b1ece49ee48" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization_01a01583-bff6-7046-99a1-9b881cadb167" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsNet_01a01583-bff6-77bf-8f3b-88dd6284194d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IntangibleAssetsNetIncludingGoodwillAbstract_01a01583-bff6-7fcc-b3b2-9b1ece49ee48" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsNet_01a01583-bff6-77bf-8f3b-88dd6284194d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IntangibleAssetsNetIncludingGoodwill_01a01583-bff6-73de-8dd5-74e5cbe07c60" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IntangibleAssetsNetIncludingGoodwill"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IntangibleAssetsNetIncludingGoodwillAbstract_01a01583-bff6-7fcc-b3b2-9b1ece49ee48" xlink:to="loc_us-gaap_IntangibleAssetsNetIncludingGoodwill_01a01583-bff6-73de-8dd5-74e5cbe07c60" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesScheduleofDerivativeAssetsDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesScheduleofDerivativeAssetsDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesScheduleofDerivativeAssetsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLineItems_01a01583-bff6-7956-b2b1-5c6ef735371c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeTable_01a01583-bff6-78a3-a58c-2484c5f3ff1e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DerivativeLineItems_01a01583-bff6-7956-b2b1-5c6ef735371c" xlink:to="loc_us-gaap_DerivativeTable_01a01583-bff6-78a3-a58c-2484c5f3ff1e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeInstrumentRiskAxis_01a01583-bff6-7bce-984d-7b7fae216a8b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeInstrumentRiskAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_01a01583-bff6-78a3-a58c-2484c5f3ff1e" xlink:to="loc_us-gaap_DerivativeInstrumentRiskAxis_01a01583-bff6-7bce-984d-7b7fae216a8b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-7bce-984d-7b7fae216a8b_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_01a01583-bff6-7bce-984d-7b7fae216a8b" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-7bce-984d-7b7fae216a8b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-761d-bb54-27839c16fb56" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeContractTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DerivativeInstrumentRiskAxis_01a01583-bff6-7bce-984d-7b7fae216a8b" xlink:to="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-761d-bb54-27839c16fb56" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AgenusPIPESeriesAWarrantMember_01a143bb-74c8-78d9-832b-544071871835" xlink:href="lgnd-20260930.xsd#lgnd_AgenusPIPESeriesAWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-761d-bb54-27839c16fb56" xlink:to="loc_lgnd_AgenusPIPESeriesAWarrantMember_01a143bb-74c8-78d9-832b-544071871835" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LeonaBioSeriesAWarrantMember_01a01583-bff6-7b9d-9722-f881e9c153a6" xlink:href="lgnd-20260930.xsd#lgnd_LeonaBioSeriesAWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-761d-bb54-27839c16fb56" xlink:to="loc_lgnd_LeonaBioSeriesAWarrantMember_01a01583-bff6-7b9d-9722-f881e9c153a6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OrchestraWarrantMember_01a01583-bff6-71af-a07d-0de2832bd2e8" xlink:href="lgnd-20260930.xsd#lgnd_OrchestraWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-761d-bb54-27839c16fb56" xlink:to="loc_lgnd_OrchestraWarrantMember_01a01583-bff6-71af-a07d-0de2832bd2e8" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantMember_01a01583-bff6-731c-b581-cec4a62ace12" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-761d-bb54-27839c16fb56" xlink:to="loc_us-gaap_WarrantMember_01a01583-bff6-731c-b581-cec4a62ace12" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_CastleCreekWarrantsMember_01a01583-bff6-7f33-aa4f-10242a21de8a" xlink:href="lgnd-20260930.xsd#lgnd_CastleCreekWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-761d-bb54-27839c16fb56" xlink:to="loc_lgnd_CastleCreekWarrantsMember_01a01583-bff6-7f33-aa4f-10242a21de8a" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AvenCellDerivativeAssetMember_01a143b8-2e44-7749-be59-b37ed0638051" xlink:href="lgnd-20260930.xsd#lgnd_AvenCellDerivativeAssetMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-761d-bb54-27839c16fb56" xlink:to="loc_lgnd_AvenCellDerivativeAssetMember_01a143b8-2e44-7749-be59-b37ed0638051" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AgenusPIPESeriesBWarrantMember_01a143ba-c41e-7fa8-8876-52c80b72b907" xlink:href="lgnd-20260930.xsd#lgnd_AgenusPIPESeriesBWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-761d-bb54-27839c16fb56" xlink:to="loc_lgnd_AgenusPIPESeriesBWarrantMember_01a143ba-c41e-7fa8-8876-52c80b72b907" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PelthosConversionOptionMember_01a01583-bff6-7a28-a123-3da5e11732f5" xlink:href="lgnd-20260930.xsd#lgnd_PelthosConversionOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-761d-bb54-27839c16fb56" xlink:to="loc_lgnd_PelthosConversionOptionMember_01a01583-bff6-7a28-a123-3da5e11732f5" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ArecorWarrantMember_01a143ba-55a6-7604-a964-3d158a3a1b56" xlink:href="lgnd-20260930.xsd#lgnd_ArecorWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-761d-bb54-27839c16fb56" xlink:to="loc_lgnd_ArecorWarrantMember_01a143ba-55a6-7604-a964-3d158a3a1b56" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LeonaBioWarrantsMember_01a01583-bff6-7a72-80fb-4a28dac6b391" xlink:href="lgnd-20260930.xsd#lgnd_LeonaBioWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeContractTypeDomain_01a01583-bff6-761d-bb54-27839c16fb56" xlink:to="loc_lgnd_LeonaBioWarrantsMember_01a01583-bff6-7a72-80fb-4a28dac6b391" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_01a01583-bff6-7463-b726-01c609914a5f" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_01a01583-bff6-78a3-a58c-2484c5f3ff1e" xlink:to="loc_srt_CounterpartyNameAxis_01a01583-bff6-7463-b726-01c609914a5f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7463-b726-01c609914a5f_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_01a01583-bff6-7463-b726-01c609914a5f" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7463-b726-01c609914a5f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7ad8-beaa-e88a4a04368b" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_01a01583-bff6-7463-b726-01c609914a5f" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7ad8-beaa-e88a4a04368b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LeonaBioWarrantsMember_01a01583-bff6-72b1-a924-df14190525fc" xlink:href="lgnd-20260930.xsd#lgnd_LeonaBioWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7ad8-beaa-e88a4a04368b" xlink:to="loc_lgnd_LeonaBioWarrantsMember_01a01583-bff6-72b1-a924-df14190525fc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AgenusInc.Member_01a01583-bff6-7e41-9c1b-0f78f3b90482" xlink:href="lgnd-20260930.xsd#lgnd_AgenusInc.Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7ad8-beaa-e88a4a04368b" xlink:to="loc_lgnd_AgenusInc.Member_01a01583-bff6-7e41-9c1b-0f78f3b90482" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeAxis_01a01583-bff6-7e31-abef-bb8279b5143a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DerivativeTable_01a01583-bff6-78a3-a58c-2484c5f3ff1e" xlink:to="loc_us-gaap_MeasurementInputTypeAxis_01a01583-bff6-7e31-abef-bb8279b5143a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7e31-abef-bb8279b5143a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a01583-bff6-7e31-abef-bb8279b5143a" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7e31-abef-bb8279b5143a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7f45-8416-504f4b83876d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a01583-bff6-7e31-abef-bb8279b5143a" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7f45-8416-504f4b83876d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputExpectedTermMember_01a01583-bff6-7cbf-9af3-aaaeecd7b344" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputExpectedTermMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7f45-8416-504f4b83876d" xlink:to="loc_us-gaap_MeasurementInputExpectedTermMember_01a01583-bff6-7cbf-9af3-aaaeecd7b344" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputOptionVolatilityMember_01a01583-bff6-76a9-91f9-953644cf8379" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputOptionVolatilityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7f45-8416-504f4b83876d" xlink:to="loc_us-gaap_MeasurementInputOptionVolatilityMember_01a01583-bff6-76a9-91f9-953644cf8379" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputRiskFreeInterestRateMember_01a01583-bff6-70c9-8e5b-0aabeb21c33a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputRiskFreeInterestRateMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7f45-8416-504f4b83876d" xlink:to="loc_us-gaap_MeasurementInputRiskFreeInterestRateMember_01a01583-bff6-70c9-8e5b-0aabeb21c33a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputSharePriceMember_01a01583-bff6-74f4-8d05-752aaa08f0dc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputSharePriceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7f45-8416-504f4b83876d" xlink:to="loc_us-gaap_MeasurementInputSharePriceMember_01a01583-bff6-74f4-8d05-752aaa08f0dc" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAssetsCurrent_01a01583-bff6-7a22-bbb2-0ff250ad0215" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeAssetsCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_01a01583-bff6-7956-b2b1-5c6ef735371c" xlink:to="loc_us-gaap_DerivativeAssetsCurrent_01a01583-bff6-7a22-bbb2-0ff250ad0215" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAssetsNoncurrent_01a01583-bff6-7b85-83ea-16d65dd1c255" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeAssetsNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_01a01583-bff6-7956-b2b1-5c6ef735371c" xlink:to="loc_us-gaap_DerivativeAssetsNoncurrent_01a01583-bff6-7b85-83ea-16d65dd1c255" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantsAndRightsOutstandingTerm_01a01583-bff6-7063-ad62-260fd331e496" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WarrantsAndRightsOutstandingTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_01a01583-bff6-7956-b2b1-5c6ef735371c" xlink:to="loc_us-gaap_WarrantsAndRightsOutstandingTerm_01a01583-bff6-7063-ad62-260fd331e496" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_01a01583-bff6-7e97-bb0c-037c17aa8a44" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_01a01583-bff6-7956-b2b1-5c6ef735371c" xlink:to="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_01a01583-bff6-7e97-bb0c-037c17aa8a44" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_01a01583-bff6-7c0e-b9a2-bbe62bae6621" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_01a01583-bff6-7956-b2b1-5c6ef735371c" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_01a01583-bff6-7c0e-b9a2-bbe62bae6621" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantsAndRightsOutstandingMeasurementInput_01a01583-bff6-712d-8d0e-eacebed61288" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WarrantsAndRightsOutstandingMeasurementInput"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DerivativeLineItems_01a01583-bff6-7956-b2b1-5c6ef735371c" xlink:to="loc_us-gaap_WarrantsAndRightsOutstandingMeasurementInput_01a01583-bff6-712d-8d0e-eacebed61288" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesOtherInvestmentDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesOtherInvestmentDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesOtherInvestmentDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SummaryOfInvestmentHoldingsLineItems_01a01583-bff6-7390-9d1f-7c543575299e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SummaryOfInvestmentHoldingsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SummaryOfInvestmentHoldingsTable_01a01583-bff6-745c-b219-1de255202da5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SummaryOfInvestmentHoldingsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SummaryOfInvestmentHoldingsLineItems_01a01583-bff6-7390-9d1f-7c543575299e" xlink:to="loc_us-gaap_SummaryOfInvestmentHoldingsTable_01a01583-bff6-745c-b219-1de255202da5" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-773b-afd8-e49eb06e6fc2" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SummaryOfInvestmentHoldingsTable_01a01583-bff6-745c-b219-1de255202da5" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-773b-afd8-e49eb06e6fc2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-773b-afd8-e49eb06e6fc2_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-773b-afd8-e49eb06e6fc2" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-773b-afd8-e49eb06e6fc2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7d49-9721-c9aa12ac9881" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-773b-afd8-e49eb06e6fc2" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7d49-9721-c9aa12ac9881" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PelthosCommonSharesAndSeriesAConvertiblePreferredSharesMember_01a01583-bff6-75f1-99ea-039288577e0e" xlink:href="lgnd-20260930.xsd#lgnd_PelthosCommonSharesAndSeriesAConvertiblePreferredSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7d49-9721-c9aa12ac9881" xlink:to="loc_lgnd_PelthosCommonSharesAndSeriesAConvertiblePreferredSharesMember_01a01583-bff6-75f1-99ea-039288577e0e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PrimroseBioMember_01a01583-bff6-7f69-a9ea-ac8865269497" xlink:href="lgnd-20260930.xsd#lgnd_PrimroseBioMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7d49-9721-c9aa12ac9881" xlink:to="loc_lgnd_PrimroseBioMember_01a01583-bff6-7f69-a9ea-ac8865269497" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_InvIOsMember_01a01583-bff6-755b-8f1a-f79d2f1df57e" xlink:href="lgnd-20260930.xsd#lgnd_InvIOsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7d49-9721-c9aa12ac9881" xlink:to="loc_lgnd_InvIOsMember_01a01583-bff6-755b-8f1a-f79d2f1df57e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PelthosLoanReceivableMember_01a01583-bff6-742f-87c6-ae5ea10741fa" xlink:href="lgnd-20260930.xsd#lgnd_PelthosLoanReceivableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7d49-9721-c9aa12ac9881" xlink:to="loc_lgnd_PelthosLoanReceivableMember_01a01583-bff6-742f-87c6-ae5ea10741fa" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_EquitySecuritiesInZerionMember_01a01583-bff6-7547-9ee6-aeea7edbc4a1" xlink:href="lgnd-20260930.xsd#lgnd_EquitySecuritiesInZerionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7d49-9721-c9aa12ac9881" xlink:to="loc_lgnd_EquitySecuritiesInZerionMember_01a01583-bff6-7547-9ee6-aeea7edbc4a1" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AvenCellSeriesC2WarrantMember_01a143be-37ac-793a-9b47-0f689b01e329" xlink:href="lgnd-20260930.xsd#lgnd_AvenCellSeriesC2WarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7d49-9721-c9aa12ac9881" xlink:to="loc_lgnd_AvenCellSeriesC2WarrantMember_01a143be-37ac-793a-9b47-0f689b01e329" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherInvestments_01a01583-bff6-7fb2-a431-235007108159" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SummaryOfInvestmentHoldingsLineItems_01a01583-bff6-7390-9d1f-7c543575299e" xlink:to="loc_us-gaap_OtherInvestments_01a01583-bff6-7fb2-a431-235007108159" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentTypeExtensibleEnumeration_01a01583-bff6-7b5d-82d1-4d855b684c35" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InvestmentTypeExtensibleEnumeration"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherInvestments_01a01583-bff6-7fb2-a431-235007108159" xlink:to="loc_us-gaap_InvestmentTypeExtensibleEnumeration_01a01583-bff6-7b5d-82d1-4d855b684c35" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesAccountingforShareBasedCompensationDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesAccountingforShareBasedCompensationDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesAccountingforShareBasedCompensationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BasisOfPresentationLineItems_01a01583-bff6-782f-b383-5177cc8e36c5" xlink:href="lgnd-20260930.xsd#lgnd_BasisOfPresentationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BasisOfPresentationTable_01a01583-bff6-7767-af83-51c3b369a283" xlink:href="lgnd-20260930.xsd#lgnd_BasisOfPresentationTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_lgnd_BasisOfPresentationLineItems_01a01583-bff6-782f-b383-5177cc8e36c5" xlink:to="loc_lgnd_BasisOfPresentationTable_01a01583-bff6-7767-af83-51c3b369a283" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a01583-bff6-71ed-b8ab-7f42495e3cdc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementOfIncomeLocationBalanceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_lgnd_BasisOfPresentationTable_01a01583-bff6-7767-af83-51c3b369a283" xlink:to="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a01583-bff6-71ed-b8ab-7f42495e3cdc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LegalEntityAxis_01a18e54-babb-7c10-9c3d-a33794f16477" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_LegalEntityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_lgnd_BasisOfPresentationTable_01a01583-bff6-7767-af83-51c3b369a283" xlink:to="loc_dei_LegalEntityAxis_01a18e54-babb-7c10-9c3d-a33794f16477" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_01a18e54-babb-7c10-9c3d-a33794f16477_default" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_dei_LegalEntityAxis_01a18e54-babb-7c10-9c3d-a33794f16477" xlink:to="loc_dei_EntityDomain_01a18e54-babb-7c10-9c3d-a33794f16477_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_01a18e54-babb-734c-b931-a7f805b57d63" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_dei_LegalEntityAxis_01a18e54-babb-7c10-9c3d-a33794f16477" xlink:to="loc_dei_EntityDomain_01a18e54-babb-734c-b931-a7f805b57d63" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LigandPharmaceuticalsInc.Member_01a18e54-babb-75a9-87bb-f07e36213485" xlink:href="lgnd-20260930.xsd#lgnd_LigandPharmaceuticalsInc.Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_01a18e54-babb-734c-b931-a7f805b57d63" xlink:to="loc_lgnd_LigandPharmaceuticalsInc.Member_01a18e54-babb-75a9-87bb-f07e36213485" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a18e54-babb-712a-8a0d-e8c458ce7310" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_lgnd_BasisOfPresentationTable_01a01583-bff6-7767-af83-51c3b369a283" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a18e54-babb-712a-8a0d-e8c458ce7310" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e54-babb-712a-8a0d-e8c458ce7310_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e54-babb-712a-8a0d-e8c458ce7310" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e54-babb-712a-8a0d-e8c458ce7310_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e54-babb-761c-b309-b383104bc271" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e54-babb-712a-8a0d-e8c458ce7310" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e54-babb-761c-b309-b383104bc271" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMAAcquisitionMember_01a18e54-babb-7f39-a9d4-28486391780a" xlink:href="lgnd-20260930.xsd#lgnd_XOMAAcquisitionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e54-babb-761c-b309-b383104bc271" xlink:to="loc_lgnd_XOMAAcquisitionMember_01a18e54-babb-7f39-a9d4-28486391780a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpenseNetOfTax_01a01583-bff6-70a5-a7f1-9b5f22157be7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AllocatedShareBasedCompensationExpenseNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_BasisOfPresentationLineItems_01a01583-bff6-782f-b383-5177cc8e36c5" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpenseNetOfTax_01a01583-bff6-70a5-a7f1-9b5f22157be7" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesAccountingforShareBasedCompensationDetails_1" xlink:type="simple" xlink:href="lgnd-20260930.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesAccountingforShareBasedCompensationDetails_1"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesAccountingforShareBasedCompensationDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BasisOfPresentationLineItems_01a01583-bff6-782f-b383-5177cc8e36c5" xlink:href="lgnd-20260930.xsd#lgnd_BasisOfPresentationLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BasisOfPresentationTable_01a01583-bff6-7767-af83-51c3b369a283" xlink:href="lgnd-20260930.xsd#lgnd_BasisOfPresentationTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_lgnd_BasisOfPresentationLineItems_01a01583-bff6-782f-b383-5177cc8e36c5" xlink:to="loc_lgnd_BasisOfPresentationTable_01a01583-bff6-7767-af83-51c3b369a283" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LegalEntityAxis_01a18e54-babb-7c10-9c3d-a33794f16477" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_LegalEntityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_lgnd_BasisOfPresentationTable_01a01583-bff6-7767-af83-51c3b369a283" xlink:to="loc_dei_LegalEntityAxis_01a18e54-babb-7c10-9c3d-a33794f16477" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_01a18e54-babb-7c10-9c3d-a33794f16477_default" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_dei_LegalEntityAxis_01a18e54-babb-7c10-9c3d-a33794f16477" xlink:to="loc_dei_EntityDomain_01a18e54-babb-7c10-9c3d-a33794f16477_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_01a18e54-babb-734c-b931-a7f805b57d63" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_dei_LegalEntityAxis_01a18e54-babb-7c10-9c3d-a33794f16477" xlink:to="loc_dei_EntityDomain_01a18e54-babb-734c-b931-a7f805b57d63" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LigandPharmaceuticalsInc.Member_01a18e54-babb-75a9-87bb-f07e36213485" xlink:href="lgnd-20260930.xsd#lgnd_LigandPharmaceuticalsInc.Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_01a18e54-babb-734c-b931-a7f805b57d63" xlink:to="loc_lgnd_LigandPharmaceuticalsInc.Member_01a18e54-babb-75a9-87bb-f07e36213485" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a18e54-babb-712a-8a0d-e8c458ce7310" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_lgnd_BasisOfPresentationTable_01a01583-bff6-7767-af83-51c3b369a283" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a18e54-babb-712a-8a0d-e8c458ce7310" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e54-babb-712a-8a0d-e8c458ce7310_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e54-babb-712a-8a0d-e8c458ce7310" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e54-babb-712a-8a0d-e8c458ce7310_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e54-babb-761c-b309-b383104bc271" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e54-babb-712a-8a0d-e8c458ce7310" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e54-babb-761c-b309-b383104bc271" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMAAcquisitionMember_01a18e54-babb-7f39-a9d4-28486391780a" xlink:href="lgnd-20260930.xsd#lgnd_XOMAAcquisitionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e54-babb-761c-b309-b383104bc271" xlink:to="loc_lgnd_XOMAAcquisitionMember_01a18e54-babb-7f39-a9d4-28486391780a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AllocatedShareBasedCompensationExpenseNetOfTax_01a01583-bff6-70a5-a7f1-9b5f22157be7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AllocatedShareBasedCompensationExpenseNetOfTax"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_BasisOfPresentationLineItems_01a01583-bff6-782f-b383-5177cc8e36c5" xlink:to="loc_us-gaap_AllocatedShareBasedCompensationExpenseNetOfTax_01a01583-bff6-70a5-a7f1-9b5f22157be7" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesNetLossGainPerShareDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#BasisofPresentationandSummaryofSignificantAccountingPoliciesNetLossGainPerShareDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/BasisofPresentationandSummaryofSignificantAccountingPoliciesNetLossGainPerShareDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_01a01583-bff6-754b-a384-b6165903e7f0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_01a01583-bff6-7673-9d54-c76e57fa0b21" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_01a01583-bff6-754b-a384-b6165903e7f0" xlink:to="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_01a01583-bff6-7673-9d54-c76e57fa0b21" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_01a01583-bff6-7d04-a472-b6126d70d826" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_01a01583-bff6-7673-9d54-c76e57fa0b21" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_01a01583-bff6-7d04-a472-b6126d70d826" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a01583-bff6-7d04-a472-b6126d70d826_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_01a01583-bff6-7d04-a472-b6126d70d826" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a01583-bff6-7d04-a472-b6126d70d826_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a01583-bff6-70fc-b626-76589c953973" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis_01a01583-bff6-7d04-a472-b6126d70d826" xlink:to="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a01583-bff6-70fc-b626-76589c953973" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RestrictedStockAndPerformanceSharesMember_01a01583-bff6-74ae-a784-f95aa4db18d0" xlink:href="lgnd-20260930.xsd#lgnd_RestrictedStockAndPerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a01583-bff6-70fc-b626-76589c953973" xlink:to="loc_lgnd_RestrictedStockAndPerformanceSharesMember_01a01583-bff6-74ae-a784-f95aa4db18d0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_01a01583-bff6-7bea-a841-374ef0b97a40" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a01583-bff6-70fc-b626-76589c953973" xlink:to="loc_us-gaap_EmployeeStockOptionMember_01a01583-bff6-7bea-a841-374ef0b97a40" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtSecuritiesMember_01a01583-bff6-7f67-94a3-029957081af3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConvertibleDebtSecuritiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a01583-bff6-70fc-b626-76589c953973" xlink:to="loc_us-gaap_ConvertibleDebtSecuritiesMember_01a01583-bff6-7f67-94a3-029957081af3" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_WarrantRelatedToThe2030NotesMember_01a01583-bff6-7c80-8e2d-b5b7caa828cf" xlink:href="lgnd-20260930.xsd#lgnd_WarrantRelatedToThe2030NotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a01583-bff6-70fc-b626-76589c953973" xlink:to="loc_lgnd_WarrantRelatedToThe2030NotesMember_01a01583-bff6-7c80-8e2d-b5b7caa828cf" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_A2031ConvertibleSeniorNotesMember_01a01583-bff6-718d-b1f5-0e947ae1b037" xlink:href="lgnd-20260930.xsd#lgnd_A2031ConvertibleSeniorNotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a01583-bff6-70fc-b626-76589c953973" xlink:to="loc_lgnd_A2031ConvertibleSeniorNotesMember_01a01583-bff6-718d-b1f5-0e947ae1b037" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_WarrantRelatedToThe2031NotesMember_01a01583-bff6-7fc8-813e-662f66052913" xlink:href="lgnd-20260930.xsd#lgnd_WarrantRelatedToThe2031NotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesNameDomain_01a01583-bff6-70fc-b626-76589c953973" xlink:to="loc_lgnd_WarrantRelatedToThe2031NotesMember_01a01583-bff6-7fc8-813e-662f66052913" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_01a01583-bff6-75bd-93dd-9022365ad31d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable_01a01583-bff6-7673-9d54-c76e57fa0b21" xlink:to="loc_us-gaap_AwardTypeAxis_01a01583-bff6-75bd-93dd-9022365ad31d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-bff6-75bd-93dd-9022365ad31d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_01a01583-bff6-75bd-93dd-9022365ad31d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-bff6-75bd-93dd-9022365ad31d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-bff6-7e7f-a445-c493627d4bab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_01a01583-bff6-75bd-93dd-9022365ad31d" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-bff6-7e7f-a445-c493627d4bab" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RestrictedStockAndPerformanceSharesMember_01a18e5d-0996-7bf9-81a7-626f45e2967b" xlink:href="lgnd-20260930.xsd#lgnd_RestrictedStockAndPerformanceSharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-bff6-7e7f-a445-c493627d4bab" xlink:to="loc_lgnd_RestrictedStockAndPerformanceSharesMember_01a18e5d-0996-7bf9-81a7-626f45e2967b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeStockOptionMember_01a01583-bff6-7632-b4cf-5976d319b0bd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeStockOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-bff6-7e7f-a445-c493627d4bab" xlink:to="loc_us-gaap_EmployeeStockOptionMember_01a01583-bff6-7632-b4cf-5976d319b0bd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_01a01583-bff6-765a-a55d-e5963e920e4b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WeightedAverageNumberOfSharesOutstandingBasic"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_01a01583-bff6-754b-a384-b6165903e7f0" xlink:to="loc_us-gaap_WeightedAverageNumberOfSharesOutstandingBasic_01a01583-bff6-765a-a55d-e5963e920e4b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities_01a18e5d-0996-7b12-99ce-4d3b9e219b5f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_01a01583-bff6-754b-a384-b6165903e7f0" xlink:to="loc_us-gaap_IncrementalCommonSharesAttributableToConversionOfDebtSecurities_01a18e5d-0996-7b12-99ce-4d3b9e219b5f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DilutiveSecuritiesAbstract_01a01583-bff6-7a58-a065-590dfd2decc7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DilutiveSecuritiesAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_01a01583-bff6-754b-a384-b6165903e7f0" xlink:to="loc_us-gaap_DilutiveSecuritiesAbstract_01a01583-bff6-7a58-a065-590dfd2decc7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_01a01583-bff6-79e9-9f15-25bd5ac8e859" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DilutiveSecuritiesAbstract_01a01583-bff6-7a58-a065-590dfd2decc7" xlink:to="loc_us-gaap_IncrementalCommonSharesAttributableToShareBasedPaymentArrangements_01a01583-bff6-79e9-9f15-25bd5ac8e859" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_01a01583-bff6-7773-8319-9c38ad385034" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_01a01583-bff6-754b-a384-b6165903e7f0" xlink:to="loc_us-gaap_WeightedAverageNumberOfDilutedSharesOutstanding_01a01583-bff6-7773-8319-9c38ad385034" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_01a01583-bff6-7bb9-a461-8173d6dfa064" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems_01a01583-bff6-754b-a384-b6165903e7f0" xlink:to="loc_us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount_01a01583-bff6-7bb9-a461-8173d6dfa064" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/XOMAAcquisitionDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#XOMAAcquisitionDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/XOMAAcquisitionDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a11aba-5974-783d-9eee-aa4ff646bdea" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a11aba-5974-783d-9eee-aa4ff646bdea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a11aba-5974-783d-9eee-aa4ff646bdea_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a11aba-5974-783d-9eee-aa4ff646bdea" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a11aba-5974-783d-9eee-aa4ff646bdea_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a11aba-5974-76e8-b465-f5f3c6ef6819" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a11aba-5974-783d-9eee-aa4ff646bdea" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a11aba-5974-76e8-b465-f5f3c6ef6819" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMARoyaltyCorporationMember_01a11aba-5974-73fe-b998-e3da0adb0a04" xlink:href="lgnd-20260930.xsd#lgnd_XOMARoyaltyCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a11aba-5974-76e8-b465-f5f3c6ef6819" xlink:to="loc_lgnd_XOMARoyaltyCorporationMember_01a11aba-5974-73fe-b998-e3da0adb0a04" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_01a18e3e-e73d-7047-81d6-96967f8bd34f" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:to="loc_srt_CounterpartyNameAxis_01a18e3e-e73d-7047-81d6-96967f8bd34f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3e-e73d-7047-81d6-96967f8bd34f_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_01a18e3e-e73d-7047-81d6-96967f8bd34f" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3e-e73d-7047-81d6-96967f8bd34f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3e-e73d-7e77-9b50-91676e743b52" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_01a18e3e-e73d-7047-81d6-96967f8bd34f" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3e-e73d-7e77-9b50-91676e743b52" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_HilleVaxMember_01a18e3f-0d6a-7e5c-8b0b-8dab26de9451" xlink:href="lgnd-20260930.xsd#lgnd_HilleVaxMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3e-e73d-7e77-9b50-91676e743b52" xlink:to="loc_lgnd_HilleVaxMember_01a18e3f-0d6a-7e5c-8b0b-8dab26de9451" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeAxis_01a18e47-6e19-7361-9b30-ba003feea0e3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:to="loc_us-gaap_MeasurementInputTypeAxis_01a18e47-6e19-7361-9b30-ba003feea0e3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a18e47-6e19-7361-9b30-ba003feea0e3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a18e47-6e19-7361-9b30-ba003feea0e3" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a18e47-6e19-7361-9b30-ba003feea0e3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a18e47-6e19-74ee-a173-56001a2dec5c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a18e47-6e19-7361-9b30-ba003feea0e3" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a18e47-6e19-74ee-a173-56001a2dec5c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputDiscountRateMember_01a18e47-9db3-7ae8-ad4a-0f257f4b5aee" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputDiscountRateMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_01a18e47-6e19-74ee-a173-56001a2dec5c" xlink:to="loc_us-gaap_MeasurementInputDiscountRateMember_01a18e47-9db3-7ae8-ad4a-0f257f4b5aee" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_01a18e47-f0ab-7c84-ae93-1b2fe696f12d" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:to="loc_srt_RangeAxis_01a18e47-f0ab-7c84-ae93-1b2fe696f12d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a18e47-f0ab-7c84-ae93-1b2fe696f12d_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_01a18e47-f0ab-7c84-ae93-1b2fe696f12d" xlink:to="loc_srt_RangeMember_01a18e47-f0ab-7c84-ae93-1b2fe696f12d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a18e47-f0ab-70b4-8bcd-63c79587143e" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_01a18e47-f0ab-7c84-ae93-1b2fe696f12d" xlink:to="loc_srt_RangeMember_01a18e47-f0ab-70b4-8bcd-63c79587143e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_01a18e48-22b2-782f-b4cf-be97ae5fce5a" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a18e47-f0ab-70b4-8bcd-63c79587143e" xlink:to="loc_srt_MinimumMember_01a18e48-22b2-782f-b4cf-be97ae5fce5a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_01a18e48-3d29-7e92-b278-9b97d0346d8c" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a18e47-f0ab-70b4-8bcd-63c79587143e" xlink:to="loc_srt_MaximumMember_01a18e48-3d29-7e92-b278-9b97d0346d8c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a18e4e-acb6-7459-bc99-ca9659a9bb46" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a18e4e-acb6-7459-bc99-ca9659a9bb46" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a18e4e-acb6-7459-bc99-ca9659a9bb46_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a18e4e-acb6-7459-bc99-ca9659a9bb46" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a18e4e-acb6-7459-bc99-ca9659a9bb46_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a18e4e-acb6-7473-b24b-e7c370b18747" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a18e4e-acb6-7459-bc99-ca9659a9bb46" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a18e4e-acb6-7473-b24b-e7c370b18747" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RemainCoMember_01a18e4e-acb6-72bb-a027-27bb0d3c760c" xlink:href="lgnd-20260930.xsd#lgnd_RemainCoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a18e4e-acb6-7473-b24b-e7c370b18747" xlink:to="loc_lgnd_RemainCoMember_01a18e4e-acb6-72bb-a027-27bb0d3c760c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LegalEntityAxis_01a18e51-bc75-7d1f-9aee-d1caacb21a1d" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_LegalEntityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:to="loc_dei_LegalEntityAxis_01a18e51-bc75-7d1f-9aee-d1caacb21a1d" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_01a18e51-bc75-7d1f-9aee-d1caacb21a1d_default" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_dei_LegalEntityAxis_01a18e51-bc75-7d1f-9aee-d1caacb21a1d" xlink:to="loc_dei_EntityDomain_01a18e51-bc75-7d1f-9aee-d1caacb21a1d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_01a18e51-bc75-756e-ac35-d90b9f498604" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_dei_LegalEntityAxis_01a18e51-bc75-7d1f-9aee-d1caacb21a1d" xlink:to="loc_dei_EntityDomain_01a18e51-bc75-756e-ac35-d90b9f498604" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FormerXOMARoyaltyStockholdersMember_01a18e51-f3b6-7ee6-8aff-bb2334dd214f" xlink:href="lgnd-20260930.xsd#lgnd_FormerXOMARoyaltyStockholdersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_01a18e51-bc75-756e-ac35-d90b9f498604" xlink:to="loc_lgnd_FormerXOMARoyaltyStockholdersMember_01a18e51-f3b6-7ee6-8aff-bb2334dd214f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMARoyaltyCorporationMember_01a18e53-3779-78cb-8a86-e2b8090eed71" xlink:href="lgnd-20260930.xsd#lgnd_XOMARoyaltyCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_01a18e51-bc75-756e-ac35-d90b9f498604" xlink:to="loc_lgnd_XOMARoyaltyCorporationMember_01a18e53-3779-78cb-8a86-e2b8090eed71" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a18e55-af78-7165-a084-39fd2d46a93f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementOfIncomeLocationBalanceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:to="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a18e55-af78-7165-a084-39fd2d46a93f" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationConsiderationTransferred1_01a11aba-5974-7cd2-ad86-d8e56b8b24ee" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationConsiderationTransferred1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationConsiderationTransferred1_01a11aba-5974-7cd2-ad86-d8e56b8b24ee" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireBusinessesGross_01a11aba-5974-7566-b091-13cbfd567b67" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquireBusinessesGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_PaymentsToAcquireBusinessesGross_01a11aba-5974-7566-b091-13cbfd567b67" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionEquityInterestIssuedOrIssuableValueAssigned_01a18e42-3da3-7a3a-8fb1-9e0dcf3328fa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionEquityInterestIssuedOrIssuableValueAssigned"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessAcquisitionEquityInterestIssuedOrIssuableValueAssigned_01a18e42-3da3-7a3a-8fb1-9e0dcf3328fa" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionSharePrice_01a11aba-5974-7aa7-a281-615ba0cd6392" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionSharePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessAcquisitionSharePrice_01a11aba-5974-7aa7-a281-615ba0cd6392" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfDebt_01a18e44-5c55-7046-a0e7-a59d62cd00d2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RepaymentsOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_RepaymentsOfDebt_01a18e44-5c55-7046-a0e7-a59d62cd00d2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisObligations_01a18e3e-43d8-7ecd-80b2-bf178cd3425a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisObligations_01a18e3e-43d8-7ecd-80b2-bf178cd3425a" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationAcquisitionRelatedCosts_01a18e7b-bcbe-774b-8f60-8c206e16651d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationAcquisitionRelatedCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationAcquisitionRelatedCosts_01a18e7b-bcbe-774b-8f60-8c206e16651d" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationSeparatelyRecognizedTransactionsAdditionalDisclosuresAcquisitionCostExpensed_01a18e44-91c1-7a22-84f9-8cf0d1382a06" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationSeparatelyRecognizedTransactionsAdditionalDisclosuresAcquisitionCostExpensed"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationSeparatelyRecognizedTransactionsAdditionalDisclosuresAcquisitionCostExpensed_01a18e44-91c1-7a22-84f9-8cf0d1382a06" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationShareBasedCompensationPrecombinationServicesValue_01a18e46-4f71-78f2-94f5-400198bb5d0d" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationShareBasedCompensationPrecombinationServicesValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationShareBasedCompensationPrecombinationServicesValue_01a18e46-4f71-78f2-94f5-400198bb5d0d" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationShareBasedCompensationServicesValue_01a18e47-d232-78fa-ab49-892d7c741693" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationShareBasedCompensationServicesValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationShareBasedCompensationServicesValue_01a18e47-d232-78fa-ab49-892d7c741693" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationShareBasedCompensationPostcombinationServicesValue_01a18e49-5bb1-72a5-b7f7-55426c3b7186" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationShareBasedCompensationPostcombinationServicesValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationShareBasedCompensationPostcombinationServicesValue_01a18e49-5bb1-72a5-b7f7-55426c3b7186" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionPercentageOfVotingInterestsAcquired_01a18e4d-d97a-7501-bbcb-3678b817e919" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionPercentageOfVotingInterestsAcquired"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessAcquisitionPercentageOfVotingInterestsAcquired_01a18e4d-d97a-7501-bbcb-3678b817e919" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_IntnagibleAssetFairValueMeasurementInput_01a18e46-c535-793d-9fd6-99dc8b273cd2" xlink:href="lgnd-20260930.xsd#lgnd_IntnagibleAssetFairValueMeasurementInput"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_IntnagibleAssetFairValueMeasurementInput_01a18e46-c535-793d-9fd6-99dc8b273cd2" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OperatingLeaseIncrementalBorrowingRate_01a18e4d-3cd4-7aec-8a6d-ccb81b739c9b" xlink:href="lgnd-20260930.xsd#lgnd_OperatingLeaseIncrementalBorrowingRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_OperatingLeaseIncrementalBorrowingRate_01a18e4d-3cd4-7aec-8a6d-ccb81b739c9b" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_01a18e4e-acb6-7e2e-abc4-6fc09d5c4775" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityMethodInvestmentOwnershipPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_01a18e4e-acb6-7e2e-abc4-6fc09d5c4775" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessAcquisitionCommercialProducts_01a18e4f-75e6-7265-8785-a655b2a615d4" xlink:href="lgnd-20260930.xsd#lgnd_BusinessAcquisitionCommercialProducts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessAcquisitionCommercialProducts_01a18e4f-75e6-7265-8785-a655b2a615d4" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessAcquisitionDevelopmentPrograms_01a18e4f-d009-7e5a-a9ec-c6623fc7f1c7" xlink:href="lgnd-20260930.xsd#lgnd_BusinessAcquisitionDevelopmentPrograms"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessAcquisitionDevelopmentPrograms_01a18e4f-d009-7e5a-a9ec-c6623fc7f1c7" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessAcquisitionAdditionalAssetsInVariousStagesOfDevelopment_01a18e50-5a69-74f1-a51f-37c11146091f" xlink:href="lgnd-20260930.xsd#lgnd_BusinessAcquisitionAdditionalAssetsInVariousStagesOfDevelopment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessAcquisitionAdditionalAssetsInVariousStagesOfDevelopment_01a18e50-5a69-74f1-a51f-37c11146091f" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationProFormaInformationRevenueOfAcquireeSinceAcquisitionDateActual_01a18e57-b2f2-7b00-b82f-0b9b6fe86ff0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationProFormaInformationRevenueOfAcquireeSinceAcquisitionDateActual"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationProFormaInformationRevenueOfAcquireeSinceAcquisitionDateActual_01a18e57-b2f2-7b00-b82f-0b9b6fe86ff0" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationProFormaInformationEarningsOrLossOfAcquireeSinceAcquisitionDateActual_01a18e58-1114-7f99-9a40-d410afa7169b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationProFormaInformationEarningsOrLossOfAcquireeSinceAcquisitionDateActual"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationProFormaInformationEarningsOrLossOfAcquireeSinceAcquisitionDateActual_01a18e58-1114-7f99-9a40-d410afa7169b" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredRestrictedCash_01a18e58-ab29-7605-8694-114b05c420af" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredRestrictedCash"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredRestrictedCash_01a18e58-ab29-7605-8694-114b05c420af" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredReceivableCurrentOther_01a18e58-ab29-726e-91ec-97dbbdba8ed5" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredReceivableCurrentOther"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredReceivableCurrentOther_01a18e58-ab29-726e-91ec-97dbbdba8ed5" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredRightOfUseAsset_01a18e58-ab29-7f04-97ef-0d762c75cefd" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredRightOfUseAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredRightOfUseAsset_01a18e58-ab29-7f04-97ef-0d762c75cefd" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCapitalLeaseObligation_01a18e58-ab29-743e-958b-2a85ce58450d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCapitalLeaseObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCapitalLeaseObligation_01a18e58-ab29-743e-958b-2a85ce58450d" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent_01a18e58-ab29-7ae2-b83a-09402085a989" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent_01a18e58-ab29-7ae2-b83a-09402085a989" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeveranceCosts1_01a18e59-64d9-7433-acec-48144cf8d324" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SeveranceCosts1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_SeveranceCosts1_01a18e59-64d9-7433-acec-48144cf8d324" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife_01a18e5c-b5c7-72fb-abca-643bf994d948" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife_01a18e5c-b5c7-72fb-abca-643bf994d948" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_01a18e60-5da8-7c5e-a6e9-f4de7118ba8b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_01a18e60-5da8-7c5e-a6e9-f4de7118ba8b" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationSeparatelyRecognizedTransactionPaymentToPurchasePreviouslyHeldShares_01a18e7d-d7c0-7f05-bb40-532fb864e665" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationSeparatelyRecognizedTransactionPaymentToPurchasePreviouslyHeldShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationSeparatelyRecognizedTransactionPaymentToPurchasePreviouslyHeldShares_01a18e7d-d7c0-7f05-bb40-532fb864e665" xlink:type="arc" order="28"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/XOMAAcquisitionDetails_1" xlink:type="simple" xlink:href="lgnd-20260930.xsd#XOMAAcquisitionDetails_1"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/XOMAAcquisitionDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a11aba-5974-783d-9eee-aa4ff646bdea" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a11aba-5974-783d-9eee-aa4ff646bdea" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a11aba-5974-783d-9eee-aa4ff646bdea_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a11aba-5974-783d-9eee-aa4ff646bdea" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a11aba-5974-783d-9eee-aa4ff646bdea_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a11aba-5974-76e8-b465-f5f3c6ef6819" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a11aba-5974-783d-9eee-aa4ff646bdea" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a11aba-5974-76e8-b465-f5f3c6ef6819" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMARoyaltyCorporationMember_01a11aba-5974-73fe-b998-e3da0adb0a04" xlink:href="lgnd-20260930.xsd#lgnd_XOMARoyaltyCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a11aba-5974-76e8-b465-f5f3c6ef6819" xlink:to="loc_lgnd_XOMARoyaltyCorporationMember_01a11aba-5974-73fe-b998-e3da0adb0a04" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_01a18e3e-e73d-7047-81d6-96967f8bd34f" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:to="loc_srt_CounterpartyNameAxis_01a18e3e-e73d-7047-81d6-96967f8bd34f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3e-e73d-7047-81d6-96967f8bd34f_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_01a18e3e-e73d-7047-81d6-96967f8bd34f" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3e-e73d-7047-81d6-96967f8bd34f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3e-e73d-7e77-9b50-91676e743b52" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_01a18e3e-e73d-7047-81d6-96967f8bd34f" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3e-e73d-7e77-9b50-91676e743b52" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_HilleVaxMember_01a18e3f-0d6a-7e5c-8b0b-8dab26de9451" xlink:href="lgnd-20260930.xsd#lgnd_HilleVaxMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3e-e73d-7e77-9b50-91676e743b52" xlink:to="loc_lgnd_HilleVaxMember_01a18e3f-0d6a-7e5c-8b0b-8dab26de9451" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeAxis_01a18e47-6e19-7361-9b30-ba003feea0e3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:to="loc_us-gaap_MeasurementInputTypeAxis_01a18e47-6e19-7361-9b30-ba003feea0e3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a18e47-6e19-7361-9b30-ba003feea0e3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a18e47-6e19-7361-9b30-ba003feea0e3" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a18e47-6e19-7361-9b30-ba003feea0e3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a18e47-6e19-74ee-a173-56001a2dec5c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a18e47-6e19-7361-9b30-ba003feea0e3" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a18e47-6e19-74ee-a173-56001a2dec5c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputDiscountRateMember_01a18e47-9db3-7ae8-ad4a-0f257f4b5aee" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputDiscountRateMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_01a18e47-6e19-74ee-a173-56001a2dec5c" xlink:to="loc_us-gaap_MeasurementInputDiscountRateMember_01a18e47-9db3-7ae8-ad4a-0f257f4b5aee" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_01a18e47-f0ab-7c84-ae93-1b2fe696f12d" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:to="loc_srt_RangeAxis_01a18e47-f0ab-7c84-ae93-1b2fe696f12d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a18e47-f0ab-7c84-ae93-1b2fe696f12d_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_01a18e47-f0ab-7c84-ae93-1b2fe696f12d" xlink:to="loc_srt_RangeMember_01a18e47-f0ab-7c84-ae93-1b2fe696f12d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a18e47-f0ab-70b4-8bcd-63c79587143e" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_01a18e47-f0ab-7c84-ae93-1b2fe696f12d" xlink:to="loc_srt_RangeMember_01a18e47-f0ab-70b4-8bcd-63c79587143e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_01a18e48-22b2-782f-b4cf-be97ae5fce5a" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a18e47-f0ab-70b4-8bcd-63c79587143e" xlink:to="loc_srt_MinimumMember_01a18e48-22b2-782f-b4cf-be97ae5fce5a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_01a18e48-3d29-7e92-b278-9b97d0346d8c" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a18e47-f0ab-70b4-8bcd-63c79587143e" xlink:to="loc_srt_MaximumMember_01a18e48-3d29-7e92-b278-9b97d0346d8c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a18e4e-acb6-7459-bc99-ca9659a9bb46" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a18e4e-acb6-7459-bc99-ca9659a9bb46" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a18e4e-acb6-7459-bc99-ca9659a9bb46_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a18e4e-acb6-7459-bc99-ca9659a9bb46" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a18e4e-acb6-7459-bc99-ca9659a9bb46_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a18e4e-acb6-7473-b24b-e7c370b18747" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a18e4e-acb6-7459-bc99-ca9659a9bb46" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a18e4e-acb6-7473-b24b-e7c370b18747" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RemainCoMember_01a18e4e-acb6-72bb-a027-27bb0d3c760c" xlink:href="lgnd-20260930.xsd#lgnd_RemainCoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a18e4e-acb6-7473-b24b-e7c370b18747" xlink:to="loc_lgnd_RemainCoMember_01a18e4e-acb6-72bb-a027-27bb0d3c760c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LegalEntityAxis_01a18e51-bc75-7d1f-9aee-d1caacb21a1d" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_LegalEntityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a11aba-5974-7cda-b401-5e3e24165026" xlink:to="loc_dei_LegalEntityAxis_01a18e51-bc75-7d1f-9aee-d1caacb21a1d" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_01a18e51-bc75-7d1f-9aee-d1caacb21a1d_default" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_dei_LegalEntityAxis_01a18e51-bc75-7d1f-9aee-d1caacb21a1d" xlink:to="loc_dei_EntityDomain_01a18e51-bc75-7d1f-9aee-d1caacb21a1d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_01a18e51-bc75-756e-ac35-d90b9f498604" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_dei_LegalEntityAxis_01a18e51-bc75-7d1f-9aee-d1caacb21a1d" xlink:to="loc_dei_EntityDomain_01a18e51-bc75-756e-ac35-d90b9f498604" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FormerXOMARoyaltyStockholdersMember_01a18e51-f3b6-7ee6-8aff-bb2334dd214f" xlink:href="lgnd-20260930.xsd#lgnd_FormerXOMARoyaltyStockholdersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_01a18e51-bc75-756e-ac35-d90b9f498604" xlink:to="loc_lgnd_FormerXOMARoyaltyStockholdersMember_01a18e51-f3b6-7ee6-8aff-bb2334dd214f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMARoyaltyCorporationMember_01a18e53-3779-78cb-8a86-e2b8090eed71" xlink:href="lgnd-20260930.xsd#lgnd_XOMARoyaltyCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_01a18e51-bc75-756e-ac35-d90b9f498604" xlink:to="loc_lgnd_XOMARoyaltyCorporationMember_01a18e53-3779-78cb-8a86-e2b8090eed71" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationConsiderationTransferred1_01a11aba-5974-7cd2-ad86-d8e56b8b24ee" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationConsiderationTransferred1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationConsiderationTransferred1_01a11aba-5974-7cd2-ad86-d8e56b8b24ee" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireBusinessesGross_01a11aba-5974-7566-b091-13cbfd567b67" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquireBusinessesGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_PaymentsToAcquireBusinessesGross_01a11aba-5974-7566-b091-13cbfd567b67" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionEquityInterestIssuedOrIssuableValueAssigned_01a18e42-3da3-7a3a-8fb1-9e0dcf3328fa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionEquityInterestIssuedOrIssuableValueAssigned"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessAcquisitionEquityInterestIssuedOrIssuableValueAssigned_01a18e42-3da3-7a3a-8fb1-9e0dcf3328fa" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionSharePrice_01a11aba-5974-7aa7-a281-615ba0cd6392" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionSharePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessAcquisitionSharePrice_01a11aba-5974-7aa7-a281-615ba0cd6392" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfDebt_01a18e44-5c55-7046-a0e7-a59d62cd00d2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RepaymentsOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_RepaymentsOfDebt_01a18e44-5c55-7046-a0e7-a59d62cd00d2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisObligations_01a18e3e-43d8-7ecd-80b2-bf178cd3425a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisObligations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisObligations_01a18e3e-43d8-7ecd-80b2-bf178cd3425a" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationAcquisitionRelatedCosts_01a18e7b-bcbe-774b-8f60-8c206e16651d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationAcquisitionRelatedCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationAcquisitionRelatedCosts_01a18e7b-bcbe-774b-8f60-8c206e16651d" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationSeparatelyRecognizedTransactionsAdditionalDisclosuresAcquisitionCostExpensed_01a18e44-91c1-7a22-84f9-8cf0d1382a06" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationSeparatelyRecognizedTransactionsAdditionalDisclosuresAcquisitionCostExpensed"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationSeparatelyRecognizedTransactionsAdditionalDisclosuresAcquisitionCostExpensed_01a18e44-91c1-7a22-84f9-8cf0d1382a06" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationShareBasedCompensationPrecombinationServicesValue_01a18e46-4f71-78f2-94f5-400198bb5d0d" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationShareBasedCompensationPrecombinationServicesValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationShareBasedCompensationPrecombinationServicesValue_01a18e46-4f71-78f2-94f5-400198bb5d0d" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationShareBasedCompensationServicesValue_01a18e47-d232-78fa-ab49-892d7c741693" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationShareBasedCompensationServicesValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationShareBasedCompensationServicesValue_01a18e47-d232-78fa-ab49-892d7c741693" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationShareBasedCompensationPostcombinationServicesValue_01a18e49-5bb1-72a5-b7f7-55426c3b7186" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationShareBasedCompensationPostcombinationServicesValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationShareBasedCompensationPostcombinationServicesValue_01a18e49-5bb1-72a5-b7f7-55426c3b7186" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionPercentageOfVotingInterestsAcquired_01a18e4d-d97a-7501-bbcb-3678b817e919" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionPercentageOfVotingInterestsAcquired"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessAcquisitionPercentageOfVotingInterestsAcquired_01a18e4d-d97a-7501-bbcb-3678b817e919" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_IntnagibleAssetFairValueMeasurementInput_01a18e46-c535-793d-9fd6-99dc8b273cd2" xlink:href="lgnd-20260930.xsd#lgnd_IntnagibleAssetFairValueMeasurementInput"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_IntnagibleAssetFairValueMeasurementInput_01a18e46-c535-793d-9fd6-99dc8b273cd2" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OperatingLeaseIncrementalBorrowingRate_01a18e4d-3cd4-7aec-8a6d-ccb81b739c9b" xlink:href="lgnd-20260930.xsd#lgnd_OperatingLeaseIncrementalBorrowingRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_OperatingLeaseIncrementalBorrowingRate_01a18e4d-3cd4-7aec-8a6d-ccb81b739c9b" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_01a18e4e-acb6-7e2e-abc4-6fc09d5c4775" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityMethodInvestmentOwnershipPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_01a18e4e-acb6-7e2e-abc4-6fc09d5c4775" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessAcquisitionCommercialProducts_01a18e4f-75e6-7265-8785-a655b2a615d4" xlink:href="lgnd-20260930.xsd#lgnd_BusinessAcquisitionCommercialProducts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessAcquisitionCommercialProducts_01a18e4f-75e6-7265-8785-a655b2a615d4" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessAcquisitionDevelopmentPrograms_01a18e4f-d009-7e5a-a9ec-c6623fc7f1c7" xlink:href="lgnd-20260930.xsd#lgnd_BusinessAcquisitionDevelopmentPrograms"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessAcquisitionDevelopmentPrograms_01a18e4f-d009-7e5a-a9ec-c6623fc7f1c7" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessAcquisitionAdditionalAssetsInVariousStagesOfDevelopment_01a18e50-5a69-74f1-a51f-37c11146091f" xlink:href="lgnd-20260930.xsd#lgnd_BusinessAcquisitionAdditionalAssetsInVariousStagesOfDevelopment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessAcquisitionAdditionalAssetsInVariousStagesOfDevelopment_01a18e50-5a69-74f1-a51f-37c11146091f" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationProFormaInformationRevenueOfAcquireeSinceAcquisitionDateActual_01a18e57-b2f2-7b00-b82f-0b9b6fe86ff0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationProFormaInformationRevenueOfAcquireeSinceAcquisitionDateActual"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationProFormaInformationRevenueOfAcquireeSinceAcquisitionDateActual_01a18e57-b2f2-7b00-b82f-0b9b6fe86ff0" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationProFormaInformationEarningsOrLossOfAcquireeSinceAcquisitionDateActual_01a18e58-1114-7f99-9a40-d410afa7169b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationProFormaInformationEarningsOrLossOfAcquireeSinceAcquisitionDateActual"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationProFormaInformationEarningsOrLossOfAcquireeSinceAcquisitionDateActual_01a18e58-1114-7f99-9a40-d410afa7169b" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredRestrictedCash_01a18e58-ab29-7605-8694-114b05c420af" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredRestrictedCash"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredRestrictedCash_01a18e58-ab29-7605-8694-114b05c420af" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredReceivableCurrentOther_01a18e58-ab29-726e-91ec-97dbbdba8ed5" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredReceivableCurrentOther"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredReceivableCurrentOther_01a18e58-ab29-726e-91ec-97dbbdba8ed5" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredRightOfUseAsset_01a18e58-ab29-7f04-97ef-0d762c75cefd" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredRightOfUseAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredRightOfUseAsset_01a18e58-ab29-7f04-97ef-0d762c75cefd" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCapitalLeaseObligation_01a18e58-ab29-743e-958b-2a85ce58450d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCapitalLeaseObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCapitalLeaseObligation_01a18e58-ab29-743e-958b-2a85ce58450d" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent_01a18e58-ab29-7ae2-b83a-09402085a989" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent_01a18e58-ab29-7ae2-b83a-09402085a989" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeveranceCosts1_01a18e59-64d9-7433-acec-48144cf8d324" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SeveranceCosts1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_SeveranceCosts1_01a18e59-64d9-7433-acec-48144cf8d324" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife_01a18e5c-b5c7-72fb-abca-643bf994d948" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife_01a18e5c-b5c7-72fb-abca-643bf994d948" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_01a18e60-5da8-7c5e-a6e9-f4de7118ba8b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_01a18e60-5da8-7c5e-a6e9-f4de7118ba8b" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationSeparatelyRecognizedTransactionPaymentToPurchasePreviouslyHeldShares_01a18e7d-d7c0-7f05-bb40-532fb864e665" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationSeparatelyRecognizedTransactionPaymentToPurchasePreviouslyHeldShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a11aba-5974-779b-91b0-e0882d56df32" xlink:to="loc_lgnd_BusinessCombinationSeparatelyRecognizedTransactionPaymentToPurchasePreviouslyHeldShares_01a18e7d-d7c0-7f05-bb40-532fb864e665" xlink:type="arc" order="28"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/XOMAAcquisitionConsiderationDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#XOMAAcquisitionConsiderationDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/XOMAAcquisitionConsiderationDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionLineItems_01a18e41-0ece-75b6-9f36-189e53ff4c9b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e41-0ece-7e51-8023-5273cbe1fdba" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e41-0ece-75b6-9f36-189e53ff4c9b" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e41-0ece-7e51-8023-5273cbe1fdba" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a18e41-0ece-7528-8ad4-7c7bd80ef29c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e41-0ece-7e51-8023-5273cbe1fdba" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a18e41-0ece-7528-8ad4-7c7bd80ef29c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e41-0ece-7528-8ad4-7c7bd80ef29c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e41-0ece-7528-8ad4-7c7bd80ef29c" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e41-0ece-7528-8ad4-7c7bd80ef29c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e41-0ece-74d3-a3ea-78e642b73238" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e41-0ece-7528-8ad4-7c7bd80ef29c" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e41-0ece-74d3-a3ea-78e642b73238" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMARoyaltyCorporationMember_01a18e41-0ece-74f9-85d6-7571a4e2cbe7" xlink:href="lgnd-20260930.xsd#lgnd_XOMARoyaltyCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e41-0ece-74d3-a3ea-78e642b73238" xlink:to="loc_lgnd_XOMARoyaltyCorporationMember_01a18e41-0ece-74f9-85d6-7571a4e2cbe7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionEquityInterestIssuedOrIssuableValueAssigned_01a18e4c-972d-7d70-9297-572ae1fb7fab" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionEquityInterestIssuedOrIssuableValueAssigned"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e41-0ece-75b6-9f36-189e53ff4c9b" xlink:to="loc_us-gaap_BusinessAcquisitionEquityInterestIssuedOrIssuableValueAssigned_01a18e4c-972d-7d70-9297-572ae1fb7fab" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfDebt_01a18e4c-972d-77a1-9efe-9c56f1c25658" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RepaymentsOfDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e41-0ece-75b6-9f36-189e53ff4c9b" xlink:to="loc_us-gaap_RepaymentsOfDebt_01a18e4c-972d-77a1-9efe-9c56f1c25658" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationShareBasedCompensationPrecombinationServicesValue_01a18e4c-972d-7a3f-9fb1-3372c46746ce" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationShareBasedCompensationPrecombinationServicesValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e41-0ece-75b6-9f36-189e53ff4c9b" xlink:to="loc_lgnd_BusinessCombinationShareBasedCompensationPrecombinationServicesValue_01a18e4c-972d-7a3f-9fb1-3372c46746ce" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationSeparatelyRecognizedTransactionsAdditionalDisclosuresAcquisitionCostExpensed_01a18e43-9a8b-70cc-88c0-c35b107fce10" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationSeparatelyRecognizedTransactionsAdditionalDisclosuresAcquisitionCostExpensed"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e41-0ece-75b6-9f36-189e53ff4c9b" xlink:to="loc_us-gaap_BusinessCombinationSeparatelyRecognizedTransactionsAdditionalDisclosuresAcquisitionCostExpensed_01a18e43-9a8b-70cc-88c0-c35b107fce10" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationConsiderationTransferred1_01a18e41-0ece-7236-a8c6-5f4f9cfdf821" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationConsiderationTransferred1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e41-0ece-75b6-9f36-189e53ff4c9b" xlink:to="loc_us-gaap_BusinessCombinationConsiderationTransferred1_01a18e41-0ece-7236-a8c6-5f4f9cfdf821" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionSharePrice_01a18e4d-24bd-7f4f-8f2f-22005686137a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionSharePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e41-0ece-75b6-9f36-189e53ff4c9b" xlink:to="loc_us-gaap_BusinessAcquisitionSharePrice_01a18e4d-24bd-7f4f-8f2f-22005686137a" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/XOMAAcquisitionScheduleofAssetsAcquiredNetDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#XOMAAcquisitionScheduleofAssetsAcquiredNetDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/XOMAAcquisitionScheduleofAssetsAcquiredNetDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e22-25a4-75fe-be7c-54936a41aabb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e22-25a4-75fe-be7c-54936a41aabb" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a18e22-25a4-7a1a-9860-835ffbdbe581" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e22-25a4-75fe-be7c-54936a41aabb" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a18e22-25a4-7a1a-9860-835ffbdbe581" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e22-25a4-7a1a-9860-835ffbdbe581_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e22-25a4-7a1a-9860-835ffbdbe581" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e22-25a4-7a1a-9860-835ffbdbe581_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e22-25a4-7253-b0b8-99e46fa8fdbe" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e22-25a4-7a1a-9860-835ffbdbe581" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e22-25a4-7253-b0b8-99e46fa8fdbe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMARoyaltyCorporationMember_01a18e2f-4a78-7d38-ad0d-af248f785f6a" xlink:href="lgnd-20260930.xsd#lgnd_XOMARoyaltyCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e22-25a4-7253-b0b8-99e46fa8fdbe" xlink:to="loc_lgnd_XOMARoyaltyCorporationMember_01a18e2f-4a78-7d38-ad0d-af248f785f6a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCashAndEquivalents_01a18e22-25a4-72a5-8a2c-e456f60c9f30" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCashAndEquivalents"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCashAndEquivalents_01a18e22-25a4-72a5-8a2c-e456f60c9f30" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredRestrictedCash_01a18e23-b96c-7060-be4d-2fc9f9b6f10c" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredRestrictedCash"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredRestrictedCash_01a18e23-b96c-7060-be4d-2fc9f9b6f10c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredInvestment_01a18e25-88d9-7d53-b83e-e9fde681974b" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredInvestment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredInvestment_01a18e25-88d9-7d53-b83e-e9fde681974b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentAssetsReceivables_01a18e26-421d-78d6-9c27-6f53f9cd0ef8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentAssetsReceivables"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentAssetsReceivables_01a18e26-421d-78d6-9c27-6f53f9cd0ef8" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredReceivableCurrentOther_01a18e29-4b19-7526-b611-152ea087c3c5" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredReceivableCurrentOther"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredReceivableCurrentOther_01a18e29-4b19-7526-b611-152ea087c3c5" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredDerivativeAssetCurrent_01a18e2a-5c39-7101-881e-36c29202f991" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredDerivativeAssetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredDerivativeAssetCurrent_01a18e2a-5c39-7101-881e-36c29202f991" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent_01a18e2b-15f8-7c3a-b258-efe5b13e8604" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent_01a18e2b-15f8-7c3a-b258-efe5b13e8604" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetNonCurrent_01a18e2b-9c76-71dd-845a-a1d8746b3aa5" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetNonCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetNonCurrent_01a18e2b-9c76-71dd-845a-a1d8746b3aa5" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsOtherThanGoodwill_01a18e2b-ef6f-7e41-8d65-3e5e95c5a178" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsOtherThanGoodwill"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIntangibleAssetsOtherThanGoodwill_01a18e2b-ef6f-7e41-8d65-3e5e95c5a178" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredEquityMethodInvestment_01a18e2c-c0a5-7000-8d83-b6c341fd983f" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredEquityMethodInvestment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredEquityMethodInvestment_01a18e2c-c0a5-7000-8d83-b6c341fd983f" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredRightOfUseAsset_01a18e2d-a769-7a90-b76d-32c3e8203a70" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredRightOfUseAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredRightOfUseAsset_01a18e2d-a769-7a90-b76d-32c3e8203a70" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxAssets_01a18e2d-e741-7680-82e4-84be21f7a097" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxAssets_01a18e2d-e741-7680-82e4-84be21f7a097" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherNoncurrentAssets_01a18e2e-55e3-791b-9b9e-cdc211eea483" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherNoncurrentAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherNoncurrentAssets_01a18e2e-55e3-791b-9b9e-cdc211eea483" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets_01a18e2e-b2ea-74e4-9469-942b00647332" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedAssets_01a18e2e-b2ea-74e4-9469-942b00647332" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesAccountsPayable_01a18e30-bfb4-73c0-b587-71e66a54ac93" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesAccountsPayable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCurrentLiabilitiesAccountsPayable_01a18e30-bfb4-73c0-b587-71e66a54ac93" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCapitalLeaseObligation_01a18e31-0983-750f-901d-28eb9f74cba1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCapitalLeaseObligation"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCapitalLeaseObligation_01a18e31-0983-750f-901d-28eb9f74cba1" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContingentLiability_01a18e31-4e96-788c-9ff9-8a39334739d8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContingentLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContingentLiability_01a18e31-4e96-788c-9ff9-8a39334739d8" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities_01a18e32-73c8-745d-bd9b-aaa837e6e41f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities_01a18e32-73c8-745d-bd9b-aaa837e6e41f" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities_01a18e32-b9d5-7ad1-a4a2-28c3ca9dd86c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedLiabilities_01a18e32-b9d5-7ad1-a4a2-28c3ca9dd86c" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedNet_01a18e33-2d45-732e-897c-42f54de9cc2e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedNet_01a18e33-2d45-732e-897c-42f54de9cc2e" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Goodwill_01a18e33-7512-75cf-9e8f-608f0ebb359d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Goodwill"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_Goodwill_01a18e33-7512-75cf-9e8f-608f0ebb359d" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet_01a18e33-b3fb-74e5-8cbd-ed0e7bdc8f4c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e22-25a4-7965-9ebe-3feb24fb869a" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet_01a18e33-b3fb-74e5-8cbd-ed0e7bdc8f4c" xlink:type="arc" order="21"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/XOMAAcquisitionRoyaltyAssetsAcquiredDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#XOMAAcquisitionRoyaltyAssetsAcquiredDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/XOMAAcquisitionRoyaltyAssetsAcquiredDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionLineItems_01a18e38-767b-73f5-9425-75ec402105de" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e38-767b-73f5-9425-75ec402105de" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a18e38-767b-7db8-a625-1b1a4f4f8319" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a18e38-767b-7db8-a625-1b1a4f4f8319" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e38-767b-7db8-a625-1b1a4f4f8319_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e38-767b-7db8-a625-1b1a4f4f8319" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e38-767b-7db8-a625-1b1a4f4f8319_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e38-767b-7f69-9c5b-97ccc5bd589a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e38-767b-7db8-a625-1b1a4f4f8319" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e38-767b-7f69-9c5b-97ccc5bd589a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMARoyaltyCorporationMember_01a18e38-767b-75c0-8b14-a01fb14802f3" xlink:href="lgnd-20260930.xsd#lgnd_XOMARoyaltyCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e38-767b-7f69-9c5b-97ccc5bd589a" xlink:to="loc_lgnd_XOMARoyaltyCorporationMember_01a18e38-767b-75c0-8b14-a01fb14802f3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a18e38-767b-7703-a98d-1af794803fd6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementOfIncomeLocationBalanceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_us-gaap_StatementOfIncomeLocationBalanceAxis_01a18e38-767b-7703-a98d-1af794803fd6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_OwnershipAxis_01a18e38-767b-7e77-949a-75a799dc770a" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_OwnershipAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_srt_OwnershipAxis_01a18e38-767b-7e77-949a-75a799dc770a" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_OwnershipDomain_01a18e38-767b-7e77-949a-75a799dc770a_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_OwnershipDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_OwnershipAxis_01a18e38-767b-7e77-949a-75a799dc770a" xlink:to="loc_srt_OwnershipDomain_01a18e38-767b-7e77-949a-75a799dc770a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_OwnershipDomain_01a18e38-767b-7fba-9c03-b9aae0aa94f4" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_OwnershipDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_OwnershipAxis_01a18e38-767b-7e77-949a-75a799dc770a" xlink:to="loc_srt_OwnershipDomain_01a18e38-767b-7fba-9c03-b9aae0aa94f4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_01a18e38-767b-7b80-a7fb-c4161e03bd32" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_us-gaap_StatementClassOfStockAxis_01a18e38-767b-7b80-a7fb-c4161e03bd32" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a18e38-767b-7b80-a7fb-c4161e03bd32_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a18e38-767b-7b80-a7fb-c4161e03bd32" xlink:to="loc_us-gaap_ClassOfStockDomain_01a18e38-767b-7b80-a7fb-c4161e03bd32_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a18e38-767b-7802-8a76-66e31a54329a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a18e38-767b-7b80-a7fb-c4161e03bd32" xlink:to="loc_us-gaap_ClassOfStockDomain_01a18e38-767b-7802-8a76-66e31a54329a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationTechniqueAxis_01a18e38-767b-7644-9e75-6f55619ee4f2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ValuationTechniqueAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_us-gaap_ValuationTechniqueAxis_01a18e38-767b-7644-9e75-6f55619ee4f2" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationTechniqueDomain_01a18e38-767b-7644-9e75-6f55619ee4f2_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ValuationTechniqueDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ValuationTechniqueAxis_01a18e38-767b-7644-9e75-6f55619ee4f2" xlink:to="loc_us-gaap_ValuationTechniqueDomain_01a18e38-767b-7644-9e75-6f55619ee4f2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationTechniqueDomain_01a18e38-767b-76c5-9c2c-f42fc9aa04a5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ValuationTechniqueDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ValuationTechniqueAxis_01a18e38-767b-7644-9e75-6f55619ee4f2" xlink:to="loc_us-gaap_ValuationTechniqueDomain_01a18e38-767b-76c5-9c2c-f42fc9aa04a5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_01a18e38-767b-7bf4-b170-e19c562f0238" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_srt_RangeAxis_01a18e38-767b-7bf4-b170-e19c562f0238" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a18e38-767b-7bf4-b170-e19c562f0238_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_01a18e38-767b-7bf4-b170-e19c562f0238" xlink:to="loc_srt_RangeMember_01a18e38-767b-7bf4-b170-e19c562f0238_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a18e38-767b-75e5-ba0f-87a60d47bae9" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_01a18e38-767b-7bf4-b170-e19c562f0238" xlink:to="loc_srt_RangeMember_01a18e38-767b-75e5-ba0f-87a60d47bae9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeAxis_01a18e38-767b-7d8f-96fe-67fd98918d95" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_us-gaap_MeasurementInputTypeAxis_01a18e38-767b-7d8f-96fe-67fd98918d95" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a18e38-767b-7d8f-96fe-67fd98918d95_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a18e38-767b-7d8f-96fe-67fd98918d95" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a18e38-767b-7d8f-96fe-67fd98918d95_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a18e38-767b-7dfe-b895-456d5b6308ef" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a18e38-767b-7d8f-96fe-67fd98918d95" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a18e38-767b-7dfe-b895-456d5b6308ef" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a18e3b-73f1-78e3-8d2d-aecf3bddc588" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_srt_ProductOrServiceAxis_01a18e3b-73f1-78e3-8d2d-aecf3bddc588" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-78e3-8d2d-aecf3bddc588_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a18e3b-73f1-78e3-8d2d-aecf3bddc588" xlink:to="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-78e3-8d2d-aecf3bddc588_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a18e3b-73f1-78e3-8d2d-aecf3bddc588" xlink:to="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OjemdaMember_01a18e3c-c393-7207-bece-a6afc19431c2" xlink:href="lgnd-20260930.xsd#lgnd_OjemdaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_OjemdaMember_01a18e3c-c393-7207-bece-a6afc19431c2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VabysmoMember_01a18e3c-c393-7c67-94f5-f96b39f30ea9" xlink:href="lgnd-20260930.xsd#lgnd_VabysmoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_VabysmoMember_01a18e3c-c393-7c67-94f5-f96b39f30ea9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MiplyffaMember_01a18e3c-c393-7576-b6e2-8b6c6ddc9277" xlink:href="lgnd-20260930.xsd#lgnd_MiplyffaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_MiplyffaMember_01a18e3c-c393-7576-b6e2-8b6c6ddc9277" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_IxinityMember_01a18e3c-c393-7947-9502-43b8cc168789" xlink:href="lgnd-20260930.xsd#lgnd_IxinityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_IxinityMember_01a18e3c-c393-7947-9502-43b8cc168789" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VolixibatMember_01a18e3c-c393-7622-b94b-af5ca7d714eb" xlink:href="lgnd-20260930.xsd#lgnd_VolixibatMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_VolixibatMember_01a18e3c-c393-7622-b94b-af5ca7d714eb" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OsavampatorMember_01a18e3c-c393-7baf-8cb8-f2ac3f7cef72" xlink:href="lgnd-20260930.xsd#lgnd_OsavampatorMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_OsavampatorMember_01a18e3c-c393-7baf-8cb8-f2ac3f7cef72" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_REC4881Member_01a18e3c-c393-7aed-9854-23be1e9a4b23" xlink:href="lgnd-20260930.xsd#lgnd_REC4881Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_REC4881Member_01a18e3c-c393-7aed-9854-23be1e9a4b23" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_TwistProgramsMember_01a18e3c-c393-7466-9d99-d6b69e4914bd" xlink:href="lgnd-20260930.xsd#lgnd_TwistProgramsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_TwistProgramsMember_01a18e3c-c393-7466-9d99-d6b69e4914bd" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OtherMember_01a18e3c-c393-73da-92f0-07374613df2b" xlink:href="lgnd-20260930.xsd#lgnd_OtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_OtherMember_01a18e3c-c393-73da-92f0-07374613df2b" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RoyaltyMethodAxis_01a18e3d-a4b7-7246-91df-e6245e44b9ec" xlink:href="lgnd-20260930.xsd#lgnd_RoyaltyMethodAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_lgnd_RoyaltyMethodAxis_01a18e3d-a4b7-7246-91df-e6245e44b9ec" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RoyaltyMethodDomain_01a18e3d-a4b7-7246-91df-e6245e44b9ec_default" xlink:href="lgnd-20260930.xsd#lgnd_RoyaltyMethodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_lgnd_RoyaltyMethodAxis_01a18e3d-a4b7-7246-91df-e6245e44b9ec" xlink:to="loc_lgnd_RoyaltyMethodDomain_01a18e3d-a4b7-7246-91df-e6245e44b9ec_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RoyaltyMethodDomain_01a18e3d-a4b7-73b4-96e6-0b9a0f9ce2c6" xlink:href="lgnd-20260930.xsd#lgnd_RoyaltyMethodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_lgnd_RoyaltyMethodAxis_01a18e3d-a4b7-7246-91df-e6245e44b9ec" xlink:to="loc_lgnd_RoyaltyMethodDomain_01a18e3d-a4b7-73b4-96e6-0b9a0f9ce2c6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_EffectiveInterestMember_01a18e3d-f2f9-7e64-8c3d-cb983bdd88b2" xlink:href="lgnd-20260930.xsd#lgnd_EffectiveInterestMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_RoyaltyMethodDomain_01a18e3d-a4b7-73b4-96e6-0b9a0f9ce2c6" xlink:to="loc_lgnd_EffectiveInterestMember_01a18e3d-f2f9-7e64-8c3d-cb983bdd88b2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_NonAccuralMethodMember_01a18e3f-1bc2-7e00-a059-79becc709e74" xlink:href="lgnd-20260930.xsd#lgnd_NonAccuralMethodMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_RoyaltyMethodDomain_01a18e3d-a4b7-73b4-96e6-0b9a0f9ce2c6" xlink:to="loc_lgnd_NonAccuralMethodMember_01a18e3f-1bc2-7e00-a059-79becc709e74" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetNonCurrent_01a18e38-767b-7b37-90bc-187f3dc67bf2" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetNonCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e38-767b-73f5-9425-75ec402105de" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetNonCurrent_01a18e38-767b-7b37-90bc-187f3dc67bf2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAsset_01a18e3a-398f-72d1-9826-b6722e4a9290" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e38-767b-73f5-9425-75ec402105de" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAsset_01a18e3a-398f-72d1-9826-b6722e4a9290" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent_01a18e3a-7a3e-7acb-bd14-362384f54740" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e38-767b-73f5-9425-75ec402105de" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent_01a18e3a-7a3e-7acb-bd14-362384f54740" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/XOMAAcquisitionRoyaltyAssetsAcquiredDetails_1" xlink:type="simple" xlink:href="lgnd-20260930.xsd#XOMAAcquisitionRoyaltyAssetsAcquiredDetails_1"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/XOMAAcquisitionRoyaltyAssetsAcquiredDetails_1" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionLineItems_01a18e38-767b-73f5-9425-75ec402105de" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e38-767b-73f5-9425-75ec402105de" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a18e38-767b-7db8-a625-1b1a4f4f8319" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a18e38-767b-7db8-a625-1b1a4f4f8319" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e38-767b-7db8-a625-1b1a4f4f8319_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e38-767b-7db8-a625-1b1a4f4f8319" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e38-767b-7db8-a625-1b1a4f4f8319_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e38-767b-7f69-9c5b-97ccc5bd589a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e38-767b-7db8-a625-1b1a4f4f8319" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e38-767b-7f69-9c5b-97ccc5bd589a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMARoyaltyCorporationMember_01a18e38-767b-75c0-8b14-a01fb14802f3" xlink:href="lgnd-20260930.xsd#lgnd_XOMARoyaltyCorporationMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e38-767b-7f69-9c5b-97ccc5bd589a" xlink:to="loc_lgnd_XOMARoyaltyCorporationMember_01a18e38-767b-75c0-8b14-a01fb14802f3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_OwnershipAxis_01a18e38-767b-7e77-949a-75a799dc770a" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_OwnershipAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_srt_OwnershipAxis_01a18e38-767b-7e77-949a-75a799dc770a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_OwnershipDomain_01a18e38-767b-7e77-949a-75a799dc770a_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_OwnershipDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_OwnershipAxis_01a18e38-767b-7e77-949a-75a799dc770a" xlink:to="loc_srt_OwnershipDomain_01a18e38-767b-7e77-949a-75a799dc770a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_OwnershipDomain_01a18e38-767b-7fba-9c03-b9aae0aa94f4" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_OwnershipDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_OwnershipAxis_01a18e38-767b-7e77-949a-75a799dc770a" xlink:to="loc_srt_OwnershipDomain_01a18e38-767b-7fba-9c03-b9aae0aa94f4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_01a18e38-767b-7b80-a7fb-c4161e03bd32" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_us-gaap_StatementClassOfStockAxis_01a18e38-767b-7b80-a7fb-c4161e03bd32" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a18e38-767b-7b80-a7fb-c4161e03bd32_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a18e38-767b-7b80-a7fb-c4161e03bd32" xlink:to="loc_us-gaap_ClassOfStockDomain_01a18e38-767b-7b80-a7fb-c4161e03bd32_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a18e38-767b-7802-8a76-66e31a54329a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a18e38-767b-7b80-a7fb-c4161e03bd32" xlink:to="loc_us-gaap_ClassOfStockDomain_01a18e38-767b-7802-8a76-66e31a54329a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationTechniqueAxis_01a18e38-767b-7644-9e75-6f55619ee4f2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ValuationTechniqueAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_us-gaap_ValuationTechniqueAxis_01a18e38-767b-7644-9e75-6f55619ee4f2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationTechniqueDomain_01a18e38-767b-7644-9e75-6f55619ee4f2_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ValuationTechniqueDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ValuationTechniqueAxis_01a18e38-767b-7644-9e75-6f55619ee4f2" xlink:to="loc_us-gaap_ValuationTechniqueDomain_01a18e38-767b-7644-9e75-6f55619ee4f2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationTechniqueDomain_01a18e38-767b-76c5-9c2c-f42fc9aa04a5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ValuationTechniqueDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ValuationTechniqueAxis_01a18e38-767b-7644-9e75-6f55619ee4f2" xlink:to="loc_us-gaap_ValuationTechniqueDomain_01a18e38-767b-76c5-9c2c-f42fc9aa04a5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_01a18e38-767b-7bf4-b170-e19c562f0238" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_srt_RangeAxis_01a18e38-767b-7bf4-b170-e19c562f0238" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a18e38-767b-7bf4-b170-e19c562f0238_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_01a18e38-767b-7bf4-b170-e19c562f0238" xlink:to="loc_srt_RangeMember_01a18e38-767b-7bf4-b170-e19c562f0238_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a18e38-767b-75e5-ba0f-87a60d47bae9" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_01a18e38-767b-7bf4-b170-e19c562f0238" xlink:to="loc_srt_RangeMember_01a18e38-767b-75e5-ba0f-87a60d47bae9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeAxis_01a18e38-767b-7d8f-96fe-67fd98918d95" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_us-gaap_MeasurementInputTypeAxis_01a18e38-767b-7d8f-96fe-67fd98918d95" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a18e38-767b-7d8f-96fe-67fd98918d95_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a18e38-767b-7d8f-96fe-67fd98918d95" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a18e38-767b-7d8f-96fe-67fd98918d95_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a18e38-767b-7dfe-b895-456d5b6308ef" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a18e38-767b-7d8f-96fe-67fd98918d95" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a18e38-767b-7dfe-b895-456d5b6308ef" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a18e3b-73f1-78e3-8d2d-aecf3bddc588" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_srt_ProductOrServiceAxis_01a18e3b-73f1-78e3-8d2d-aecf3bddc588" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-78e3-8d2d-aecf3bddc588_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a18e3b-73f1-78e3-8d2d-aecf3bddc588" xlink:to="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-78e3-8d2d-aecf3bddc588_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a18e3b-73f1-78e3-8d2d-aecf3bddc588" xlink:to="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OjemdaMember_01a18e3c-c393-7207-bece-a6afc19431c2" xlink:href="lgnd-20260930.xsd#lgnd_OjemdaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_OjemdaMember_01a18e3c-c393-7207-bece-a6afc19431c2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VabysmoMember_01a18e3c-c393-7c67-94f5-f96b39f30ea9" xlink:href="lgnd-20260930.xsd#lgnd_VabysmoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_VabysmoMember_01a18e3c-c393-7c67-94f5-f96b39f30ea9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MiplyffaMember_01a18e3c-c393-7576-b6e2-8b6c6ddc9277" xlink:href="lgnd-20260930.xsd#lgnd_MiplyffaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_MiplyffaMember_01a18e3c-c393-7576-b6e2-8b6c6ddc9277" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_IxinityMember_01a18e3c-c393-7947-9502-43b8cc168789" xlink:href="lgnd-20260930.xsd#lgnd_IxinityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_IxinityMember_01a18e3c-c393-7947-9502-43b8cc168789" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VolixibatMember_01a18e3c-c393-7622-b94b-af5ca7d714eb" xlink:href="lgnd-20260930.xsd#lgnd_VolixibatMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_VolixibatMember_01a18e3c-c393-7622-b94b-af5ca7d714eb" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OsavampatorMember_01a18e3c-c393-7baf-8cb8-f2ac3f7cef72" xlink:href="lgnd-20260930.xsd#lgnd_OsavampatorMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_OsavampatorMember_01a18e3c-c393-7baf-8cb8-f2ac3f7cef72" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_REC4881Member_01a18e3c-c393-7aed-9854-23be1e9a4b23" xlink:href="lgnd-20260930.xsd#lgnd_REC4881Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_REC4881Member_01a18e3c-c393-7aed-9854-23be1e9a4b23" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_TwistProgramsMember_01a18e3c-c393-7466-9d99-d6b69e4914bd" xlink:href="lgnd-20260930.xsd#lgnd_TwistProgramsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_TwistProgramsMember_01a18e3c-c393-7466-9d99-d6b69e4914bd" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OtherMember_01a18e3c-c393-73da-92f0-07374613df2b" xlink:href="lgnd-20260930.xsd#lgnd_OtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a18e3b-73f1-7ccd-ab21-61c451a09d4c" xlink:to="loc_lgnd_OtherMember_01a18e3c-c393-73da-92f0-07374613df2b" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RoyaltyMethodAxis_01a18e3d-a4b7-7246-91df-e6245e44b9ec" xlink:href="lgnd-20260930.xsd#lgnd_RoyaltyMethodAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e38-767b-7852-8c27-b263fafae2f8" xlink:to="loc_lgnd_RoyaltyMethodAxis_01a18e3d-a4b7-7246-91df-e6245e44b9ec" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RoyaltyMethodDomain_01a18e3d-a4b7-7246-91df-e6245e44b9ec_default" xlink:href="lgnd-20260930.xsd#lgnd_RoyaltyMethodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_lgnd_RoyaltyMethodAxis_01a18e3d-a4b7-7246-91df-e6245e44b9ec" xlink:to="loc_lgnd_RoyaltyMethodDomain_01a18e3d-a4b7-7246-91df-e6245e44b9ec_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RoyaltyMethodDomain_01a18e3d-a4b7-73b4-96e6-0b9a0f9ce2c6" xlink:href="lgnd-20260930.xsd#lgnd_RoyaltyMethodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_lgnd_RoyaltyMethodAxis_01a18e3d-a4b7-7246-91df-e6245e44b9ec" xlink:to="loc_lgnd_RoyaltyMethodDomain_01a18e3d-a4b7-73b4-96e6-0b9a0f9ce2c6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_EffectiveInterestMember_01a18e3d-f2f9-7e64-8c3d-cb983bdd88b2" xlink:href="lgnd-20260930.xsd#lgnd_EffectiveInterestMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_RoyaltyMethodDomain_01a18e3d-a4b7-73b4-96e6-0b9a0f9ce2c6" xlink:to="loc_lgnd_EffectiveInterestMember_01a18e3d-f2f9-7e64-8c3d-cb983bdd88b2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_NonAccuralMethodMember_01a18e3f-1bc2-7e00-a059-79becc709e74" xlink:href="lgnd-20260930.xsd#lgnd_NonAccuralMethodMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_RoyaltyMethodDomain_01a18e3d-a4b7-73b4-96e6-0b9a0f9ce2c6" xlink:to="loc_lgnd_NonAccuralMethodMember_01a18e3f-1bc2-7e00-a059-79becc709e74" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetNonCurrent_01a18e38-767b-7b37-90bc-187f3dc67bf2" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetNonCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e38-767b-73f5-9425-75ec402105de" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetNonCurrent_01a18e38-767b-7b37-90bc-187f3dc67bf2" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAsset_01a18e3a-398f-72d1-9826-b6722e4a9290" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e38-767b-73f5-9425-75ec402105de" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAsset_01a18e3a-398f-72d1-9826-b6722e4a9290" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent_01a18e3a-7a3e-7acb-bd14-362384f54740" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e38-767b-73f5-9425-75ec402105de" xlink:to="loc_lgnd_BusinessCombinationRecognizedAssetAcquiredFinancialRoyaltyAssetCurrent_01a18e3a-7a3e-7acb-bd14-362384f54740" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/XOMAAcquisitionIntangibleAssetsAcquiredDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#XOMAAcquisitionIntangibleAssetsAcquiredDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/XOMAAcquisitionIntangibleAssetsAcquiredDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionLineItems_01a18e39-017d-744b-ad1a-bb2e73f53188" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e39-017c-7002-b9b8-6ec2cdea2da9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e39-017d-744b-ad1a-bb2e73f53188" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e39-017c-7002-b9b8-6ec2cdea2da9" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a18e39-017c-740c-b7c9-8e4185863a7e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e39-017c-7002-b9b8-6ec2cdea2da9" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a18e39-017c-740c-b7c9-8e4185863a7e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e39-017c-740c-b7c9-8e4185863a7e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e39-017c-740c-b7c9-8e4185863a7e" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e39-017c-740c-b7c9-8e4185863a7e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e39-017c-7046-a506-b80c3d1d2699" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e39-017c-740c-b7c9-8e4185863a7e" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e39-017c-7046-a506-b80c3d1d2699" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMAAcquisitionMember_01a18e39-f250-770b-927d-fd35c666e98f" xlink:href="lgnd-20260930.xsd#lgnd_XOMAAcquisitionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e39-017c-7046-a506-b80c3d1d2699" xlink:to="loc_lgnd_XOMAAcquisitionMember_01a18e39-f250-770b-927d-fd35c666e98f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a18e3a-1087-74e1-b303-7560f8093bd4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e39-017c-7002-b9b8-6ec2cdea2da9" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a18e3a-1087-74e1-b303-7560f8093bd4" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a18e3a-1087-74e1-b303-7560f8093bd4_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a18e3a-1087-74e1-b303-7560f8093bd4" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a18e3a-1087-74e1-b303-7560f8093bd4_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a18e3a-1087-767c-a540-cad52f0d0665" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis_01a18e3a-1087-74e1-b303-7560f8093bd4" xlink:to="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a18e3a-1087-767c-a540-cad52f0d0665" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MezagitamabMember_01a18e59-9d57-72dc-ac57-4762268098cd" xlink:href="lgnd-20260930.xsd#lgnd_MezagitamabMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a18e3a-1087-767c-a540-cad52f0d0665" xlink:to="loc_lgnd_MezagitamabMember_01a18e59-9d57-72dc-ac57-4762268098cd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ErsodetugMember_01a18e59-9d57-7e96-a37b-58825d14c30d" xlink:href="lgnd-20260930.xsd#lgnd_ErsodetugMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a18e3a-1087-767c-a540-cad52f0d0665" xlink:to="loc_lgnd_ErsodetugMember_01a18e59-9d57-7e96-a37b-58825d14c30d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AntiTL1AMember_01a18e59-9d57-7dd1-94fd-64412604cc7f" xlink:href="lgnd-20260930.xsd#lgnd_AntiTL1AMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a18e3a-1087-767c-a540-cad52f0d0665" xlink:to="loc_lgnd_AntiTL1AMember_01a18e59-9d57-7dd1-94fd-64412604cc7f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_KinnateProgramsMember_01a18e59-9d57-7acd-a5b7-88cd0c5994aa" xlink:href="lgnd-20260930.xsd#lgnd_KinnateProgramsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a18e3a-1087-767c-a540-cad52f0d0665" xlink:to="loc_lgnd_KinnateProgramsMember_01a18e59-9d57-7acd-a5b7-88cd0c5994aa" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FiclatuzumabMember_01a18e59-9d57-72b8-b585-44cc7e5f95aa" xlink:href="lgnd-20260930.xsd#lgnd_FiclatuzumabMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a18e3a-1087-767c-a540-cad52f0d0665" xlink:to="loc_lgnd_FiclatuzumabMember_01a18e59-9d57-72b8-b585-44cc7e5f95aa" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RilvegostomigMember_01a18e59-9d57-7168-b11b-b51f9e22163c" xlink:href="lgnd-20260930.xsd#lgnd_RilvegostomigMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a18e3a-1087-767c-a540-cad52f0d0665" xlink:to="loc_lgnd_RilvegostomigMember_01a18e59-9d57-7168-b11b-b51f9e22163c" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_CetrelimabMember_01a18e59-9d57-7178-bb30-00af4a3e2ecf" xlink:href="lgnd-20260930.xsd#lgnd_CetrelimabMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a18e3a-1087-767c-a540-cad52f0d0665" xlink:to="loc_lgnd_CetrelimabMember_01a18e59-9d57-7178-bb30-00af4a3e2ecf" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PhageDisplayLibraryMember_01a18e59-9d57-7aa4-a3bb-3e21ea81af04" xlink:href="lgnd-20260930.xsd#lgnd_PhageDisplayLibraryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_01a18e3a-1087-767c-a540-cad52f0d0665" xlink:to="loc_lgnd_PhageDisplayLibraryMember_01a18e59-9d57-7aa4-a3bb-3e21ea81af04" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinitelivedIntangibleAssetsAcquired1_01a18e39-017d-7fd4-86e4-c091bff62f5c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinitelivedIntangibleAssetsAcquired1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e39-017d-744b-ad1a-bb2e73f53188" xlink:to="loc_us-gaap_FinitelivedIntangibleAssetsAcquired1_01a18e39-017d-7fd4-86e4-c091bff62f5c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife_01a18e39-aedc-73e5-8f0f-25cc074c0cad" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e39-017d-744b-ad1a-bb2e73f53188" xlink:to="loc_us-gaap_AcquiredFiniteLivedIntangibleAssetsWeightedAverageUsefulLife_01a18e39-aedc-73e5-8f0f-25cc074c0cad" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/XOMAAcquisitionContingentLiabilitiesDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#XOMAAcquisitionContingentLiabilitiesDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/XOMAAcquisitionContingentLiabilitiesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionLineItems_01a18e33-1aeb-7e9d-b2a6-bd44e1c38f82" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e33-1aeb-77a1-8e59-0b1849235406" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e33-1aeb-7e9d-b2a6-bd44e1c38f82" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e33-1aeb-77a1-8e59-0b1849235406" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a18e33-1aeb-7766-9773-4dc184eed020" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e33-1aeb-77a1-8e59-0b1849235406" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a18e33-1aeb-7766-9773-4dc184eed020" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e33-1aeb-7766-9773-4dc184eed020_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e33-1aeb-7766-9773-4dc184eed020" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e33-1aeb-7766-9773-4dc184eed020_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e33-1aeb-7428-b9b5-86ccf4c629fe" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e33-1aeb-7766-9773-4dc184eed020" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e33-1aeb-7428-b9b5-86ccf4c629fe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMAAcquisitionMember_01a18e36-34fe-7eb0-bf0a-567717242ec7" xlink:href="lgnd-20260930.xsd#lgnd_XOMAAcquisitionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e33-1aeb-7428-b9b5-86ccf4c629fe" xlink:to="loc_lgnd_XOMAAcquisitionMember_01a18e36-34fe-7eb0-bf0a-567717242ec7" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ContingentLiabilityTypeAxis_01a18e36-8802-7285-a1c9-104d05d51398" xlink:href="lgnd-20260930.xsd#lgnd_ContingentLiabilityTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e33-1aeb-77a1-8e59-0b1849235406" xlink:to="loc_lgnd_ContingentLiabilityTypeAxis_01a18e36-8802-7285-a1c9-104d05d51398" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ContingentLiabilityTypeDomain_01a18e36-8802-7285-a1c9-104d05d51398_default" xlink:href="lgnd-20260930.xsd#lgnd_ContingentLiabilityTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_lgnd_ContingentLiabilityTypeAxis_01a18e36-8802-7285-a1c9-104d05d51398" xlink:to="loc_lgnd_ContingentLiabilityTypeDomain_01a18e36-8802-7285-a1c9-104d05d51398_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ContingentLiabilityTypeDomain_01a18e36-8802-7a32-8984-33e71364ae63" xlink:href="lgnd-20260930.xsd#lgnd_ContingentLiabilityTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_lgnd_ContingentLiabilityTypeAxis_01a18e36-8802-7285-a1c9-104d05d51398" xlink:to="loc_lgnd_ContingentLiabilityTypeDomain_01a18e36-8802-7a32-8984-33e71364ae63" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ProgramRelatedObligationsMember_01a18e38-761e-750f-a7bf-8da38ecad5f1" xlink:href="lgnd-20260930.xsd#lgnd_ProgramRelatedObligationsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_ContingentLiabilityTypeDomain_01a18e36-8802-7a32-8984-33e71364ae63" xlink:to="loc_lgnd_ProgramRelatedObligationsMember_01a18e38-761e-750f-a7bf-8da38ecad5f1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_HilleVaxCVRMember_01a18e37-3530-71dc-bd2c-3771cd722c66" xlink:href="lgnd-20260930.xsd#lgnd_HilleVaxCVRMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_ProgramRelatedObligationsMember_01a18e38-761e-750f-a7bf-8da38ecad5f1" xlink:to="loc_lgnd_HilleVaxCVRMember_01a18e37-3530-71dc-bd2c-3771cd722c66" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LAVACVRMember_01a18e37-5a42-77d7-944a-633eb3ef91cb" xlink:href="lgnd-20260930.xsd#lgnd_LAVACVRMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_ProgramRelatedObligationsMember_01a18e38-761e-750f-a7bf-8da38ecad5f1" xlink:to="loc_lgnd_LAVACVRMember_01a18e37-5a42-77d7-944a-633eb3ef91cb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BioInventMember_01a18e37-899d-74b5-9c7d-93ebb8f1b326" xlink:href="lgnd-20260930.xsd#lgnd_BioInventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_ProgramRelatedObligationsMember_01a18e38-761e-750f-a7bf-8da38ecad5f1" xlink:to="loc_lgnd_BioInventMember_01a18e37-899d-74b5-9c7d-93ebb8f1b326" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_KinnateCVRKinnateProgramsMember_01a18e37-c7e7-76c6-9e7a-4febaf7f36c0" xlink:href="lgnd-20260930.xsd#lgnd_KinnateCVRKinnateProgramsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_ProgramRelatedObligationsMember_01a18e38-761e-750f-a7bf-8da38ecad5f1" xlink:to="loc_lgnd_KinnateCVRKinnateProgramsMember_01a18e37-c7e7-76c6-9e7a-4febaf7f36c0" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_KinnateCVRExarafenibMember_01a18e37-edfd-73c6-8547-69695d8ed2d4" xlink:href="lgnd-20260930.xsd#lgnd_KinnateCVRExarafenibMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_ProgramRelatedObligationsMember_01a18e38-761e-750f-a7bf-8da38ecad5f1" xlink:to="loc_lgnd_KinnateCVRExarafenibMember_01a18e37-edfd-73c6-8547-69695d8ed2d4" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ObligationOtherMember_01a18e38-181e-7cf3-8165-0d686ef713fb" xlink:href="lgnd-20260930.xsd#lgnd_ObligationOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_ProgramRelatedObligationsMember_01a18e38-761e-750f-a7bf-8da38ecad5f1" xlink:to="loc_lgnd_ObligationOtherMember_01a18e38-181e-7cf3-8165-0d686ef713fb" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_01a18e3b-349c-722c-a85d-9f380ec8e87d" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e33-1aeb-77a1-8e59-0b1849235406" xlink:to="loc_srt_CounterpartyNameAxis_01a18e3b-349c-722c-a85d-9f380ec8e87d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3b-349c-722c-a85d-9f380ec8e87d_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_01a18e3b-349c-722c-a85d-9f380ec8e87d" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3b-349c-722c-a85d-9f380ec8e87d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3b-349c-7a2a-a5fd-d954b61ef707" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_01a18e3b-349c-722c-a85d-9f380ec8e87d" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3b-349c-7a2a-a5fd-d954b61ef707" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BioInventMember_01a18e3b-57b1-78f6-af2c-9803a36d21e3" xlink:href="lgnd-20260930.xsd#lgnd_BioInventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e3b-349c-7a2a-a5fd-d954b61ef707" xlink:to="loc_lgnd_BioInventMember_01a18e3b-57b1-78f6-af2c-9803a36d21e3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_01a18e33-1aeb-79c1-b13c-796f0c29777c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e33-1aeb-7e9d-b2a6-bd44e1c38f82" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_01a18e33-1aeb-79c1-b13c-796f0c29777c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MilestonePayable_01a18e3a-cc5a-7adf-8d4c-efc463ef3378" xlink:href="lgnd-20260930.xsd#lgnd_MilestonePayable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e33-1aeb-7e9d-b2a6-bd44e1c38f82" xlink:to="loc_lgnd_MilestonePayable_01a18e3a-cc5a-7adf-8d4c-efc463ef3378" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PayablesRateToHolders_01a18e63-979a-7271-842d-514b351d1abf" xlink:href="lgnd-20260930.xsd#lgnd_PayablesRateToHolders"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e33-1aeb-7e9d-b2a6-bd44e1c38f82" xlink:to="loc_lgnd_PayablesRateToHolders_01a18e63-979a-7271-842d-514b351d1abf" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/XOMAAcquisitionProformaDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#XOMAAcquisitionProformaDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/XOMAAcquisitionProformaDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionLineItems_01a18e32-ec1a-72bb-a4cb-cc9b2cc72382" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e32-ec1a-7856-936e-c446be9fb3df" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e32-ec1a-72bb-a4cb-cc9b2cc72382" xlink:to="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e32-ec1a-7856-936e-c446be9fb3df" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a18e32-ec1a-7d16-ab7a-c709339d0439" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable_01a18e32-ec1a-7856-936e-c446be9fb3df" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a18e32-ec1a-7d16-ab7a-c709339d0439" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e32-ec1a-7d16-ab7a-c709339d0439_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e32-ec1a-7d16-ab7a-c709339d0439" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e32-ec1a-7d16-ab7a-c709339d0439_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e32-ec1a-7d51-8bd6-c8a7c56bb299" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e32-ec1a-7d16-ab7a-c709339d0439" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e32-ec1a-7d51-8bd6-c8a7c56bb299" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMAAcquisitionMember_01a18e33-6196-717e-b83e-b5a64379e016" xlink:href="lgnd-20260930.xsd#lgnd_XOMAAcquisitionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e32-ec1a-7d51-8bd6-c8a7c56bb299" xlink:to="loc_lgnd_XOMAAcquisitionMember_01a18e33-6196-717e-b83e-b5a64379e016" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionsProFormaRevenue_01a18e32-ec1a-7262-8d82-f75634e23972" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionsProFormaRevenue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e32-ec1a-72bb-a4cb-cc9b2cc72382" xlink:to="loc_us-gaap_BusinessAcquisitionsProFormaRevenue_01a18e32-ec1a-7262-8d82-f75634e23972" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionsProFormaNetIncomeLoss_01a18e32-ec1a-71f4-8cdb-87f1315e5067" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionsProFormaNetIncomeLoss"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionLineItems_01a18e32-ec1a-72bb-a4cb-cc9b2cc72382" xlink:to="loc_us-gaap_BusinessAcquisitionsProFormaNetIncomeLoss_01a18e32-ec1a-71f4-8cdb-87f1315e5067" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/PelthosTransactionNarrativeDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#PelthosTransactionNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/PelthosTransactionNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems_01a01583-bff6-7ab0-858a-68a494b07390" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable_01a01583-bff6-75e6-89f4-4b641eb99864" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems_01a01583-bff6-7ab0-858a-68a494b07390" xlink:to="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable_01a01583-bff6-75e6-89f4-4b641eb99864" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_01a01583-bff6-7166-bf97-58fa72c5e3c3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RelatedPartyTransactionsByRelatedPartyAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable_01a01583-bff6-75e6-89f4-4b641eb99864" xlink:to="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_01a01583-bff6-7166-bf97-58fa72c5e3c3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_01a01583-bff6-7166-bf97-58fa72c5e3c3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_01a01583-bff6-7166-bf97-58fa72c5e3c3" xlink:to="loc_us-gaap_RelatedPartyDomain_01a01583-bff6-7166-bf97-58fa72c5e3c3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RelatedPartyDomain_01a01583-bff6-7d94-9d2d-a5021e461d3e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RelatedPartyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_RelatedPartyTransactionsByRelatedPartyAxis_01a01583-bff6-7166-bf97-58fa72c5e3c3" xlink:to="loc_us-gaap_RelatedPartyDomain_01a01583-bff6-7d94-9d2d-a5021e461d3e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CoVenturerMember_01a01583-bff6-72a6-b021-b86af360002d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CoVenturerMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_RelatedPartyDomain_01a01583-bff6-7d94-9d2d-a5021e461d3e" xlink:to="loc_us-gaap_CoVenturerMember_01a01583-bff6-72a6-b021-b86af360002d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_01a01583-bff6-7a20-bf00-138364eade13" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable_01a01583-bff6-75e6-89f4-4b641eb99864" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_01a01583-bff6-7a20-bf00-138364eade13" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_01a01583-bff6-7a20-bf00-138364eade13_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_01a01583-bff6-7a20-bf00-138364eade13" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_01a01583-bff6-7a20-bf00-138364eade13_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_01a01583-bff6-7eb8-a324-e7496682edc8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_01a01583-bff6-7a20-bf00-138364eade13" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_01a01583-bff6-7eb8-a324-e7496682edc8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PrivatePlacementMember_01a01583-bff6-769e-8845-db93f6043c1e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PrivatePlacementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_01a01583-bff6-7eb8-a324-e7496682edc8" xlink:to="loc_us-gaap_PrivatePlacementMember_01a01583-bff6-769e-8845-db93f6043c1e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LegalEntityAxis_01a01583-bff6-7180-b865-3f393f7adca6" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_LegalEntityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable_01a01583-bff6-75e6-89f4-4b641eb99864" xlink:to="loc_dei_LegalEntityAxis_01a01583-bff6-7180-b865-3f393f7adca6" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_01a01583-bff6-7180-b865-3f393f7adca6_default" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_dei_LegalEntityAxis_01a01583-bff6-7180-b865-3f393f7adca6" xlink:to="loc_dei_EntityDomain_01a01583-bff6-7180-b865-3f393f7adca6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_01a01583-bff6-75fd-bf79-b987dd3f93cd" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_dei_LegalEntityAxis_01a01583-bff6-7180-b865-3f393f7adca6" xlink:to="loc_dei_EntityDomain_01a01583-bff6-75fd-bf79-b987dd3f93cd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_InvestorGroupMember_01a01583-bff6-7666-8b7a-b8d6913dc265" xlink:href="lgnd-20260930.xsd#lgnd_InvestorGroupMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_01a01583-bff6-75fd-bf79-b987dd3f93cd" xlink:to="loc_lgnd_InvestorGroupMember_01a01583-bff6-7666-8b7a-b8d6913dc265" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-7a98-9bf6-4be66999dfc9" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable_01a01583-bff6-75e6-89f4-4b641eb99864" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-7a98-9bf6-4be66999dfc9" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7a98-9bf6-4be66999dfc9_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-7a98-9bf6-4be66999dfc9" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7a98-9bf6-4be66999dfc9_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7143-9412-7129d7644b73" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-7a98-9bf6-4be66999dfc9" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7143-9412-7129d7644b73" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PelthosTechnologiesMember_01a01583-bff6-72b1-81a5-965b6a5d8c95" xlink:href="lgnd-20260930.xsd#lgnd_PelthosTechnologiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7143-9412-7129d7644b73" xlink:to="loc_lgnd_PelthosTechnologiesMember_01a01583-bff6-72b1-81a5-965b6a5d8c95" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_01a01583-bff6-7545-811f-a3a37d712eb3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable_01a01583-bff6-75e6-89f4-4b641eb99864" xlink:to="loc_us-gaap_StatementClassOfStockAxis_01a01583-bff6-7545-811f-a3a37d712eb3" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-7545-811f-a3a37d712eb3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a01583-bff6-7545-811f-a3a37d712eb3" xlink:to="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-7545-811f-a3a37d712eb3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-7b7f-be24-a4aee892ea4e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a01583-bff6-7545-811f-a3a37d712eb3" xlink:to="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-7b7f-be24-a4aee892ea4e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_01a01583-bff6-73c4-ba53-2316295de9bc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-7b7f-be24-a4aee892ea4e" xlink:to="loc_us-gaap_CommonStockMember_01a01583-bff6-73c4-ba53-2316295de9bc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_SeriesAConvertiblePreferredStockMember_01a01583-bff6-740b-94f7-984a6dd19aa4" xlink:href="lgnd-20260930.xsd#lgnd_SeriesAConvertiblePreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-7b7f-be24-a4aee892ea4e" xlink:to="loc_lgnd_SeriesAConvertiblePreferredStockMember_01a01583-bff6-740b-94f7-984a6dd19aa4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a01583-bff6-761b-9c2a-3b5b03abb091" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable_01a01583-bff6-75e6-89f4-4b641eb99864" xlink:to="loc_srt_ProductOrServiceAxis_01a01583-bff6-761b-9c2a-3b5b03abb091" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a01583-bff6-761b-9c2a-3b5b03abb091_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a01583-bff6-761b-9c2a-3b5b03abb091" xlink:to="loc_srt_ProductsAndServicesDomain_01a01583-bff6-761b-9c2a-3b5b03abb091_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a01583-bff6-73b1-b363-923d262e85cf" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a01583-bff6-761b-9c2a-3b5b03abb091" xlink:to="loc_srt_ProductsAndServicesDomain_01a01583-bff6-73b1-b363-923d262e85cf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ZelsuvmiMember_01a01583-bff6-7541-a148-1b5f17ef099a" xlink:href="lgnd-20260930.xsd#lgnd_ZelsuvmiMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bff6-73b1-b363-923d262e85cf" xlink:to="loc_lgnd_ZelsuvmiMember_01a01583-bff6-7541-a148-1b5f17ef099a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_01a01583-bff6-73aa-aa98-4a3f72f38425" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SaleOfStockConsiderationReceivedOnTransaction"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems_01a01583-bff6-7ab0-858a-68a494b07390" xlink:to="loc_us-gaap_SaleOfStockConsiderationReceivedOnTransaction_01a01583-bff6-73aa-aa98-4a3f72f38425" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestments_01a01583-bff6-77c7-a9cd-255e82390e77" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityMethodInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems_01a01583-bff6-7ab0-858a-68a494b07390" xlink:to="loc_us-gaap_EquityMethodInvestments_01a01583-bff6-77c7-a9cd-255e82390e77" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfRelatedPartyDebt_01a01583-bff6-7ec6-a06b-906cc2abb6c1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RepaymentsOfRelatedPartyDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems_01a01583-bff6-7ab0-858a-68a494b07390" xlink:to="loc_us-gaap_RepaymentsOfRelatedPartyDebt_01a01583-bff6-7ec6-a06b-906cc2abb6c1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_01a01583-bff6-71f8-abe3-cbb733f48d9d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityMethodInvestmentOwnershipPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems_01a01583-bff6-7ab0-858a-68a494b07390" xlink:to="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_01a01583-bff6-71f8-abe3-cbb733f48d9d" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_EquityMethodInvestmentMaximumOwnershipPercentage_01a01583-bff6-78ac-a75e-bae6b05d7900" xlink:href="lgnd-20260930.xsd#lgnd_EquityMethodInvestmentMaximumOwnershipPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems_01a01583-bff6-7ab0-858a-68a494b07390" xlink:to="loc_lgnd_EquityMethodInvestmentMaximumOwnershipPercentage_01a01583-bff6-78ac-a75e-bae6b05d7900" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ProductRoyaltyRate_01a01583-bff6-7058-8745-6fc40aa1d2dd" xlink:href="lgnd-20260930.xsd#lgnd_ProductRoyaltyRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems_01a01583-bff6-7ab0-858a-68a494b07390" xlink:to="loc_lgnd_ProductRoyaltyRate_01a01583-bff6-7058-8745-6fc40aa1d2dd" xlink:type="arc" order="5"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/PelthosTransactionScheduleofInvestmentsDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#PelthosTransactionScheduleofInvestmentsDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/PelthosTransactionScheduleofInvestmentsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems_01a01583-bff6-7edc-b444-fc8d6de907c8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable_01a01583-bff6-7b3e-acb2-06ed994ba6c3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems_01a01583-bff6-7edc-b444-fc8d6de907c8" xlink:to="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable_01a01583-bff6-7b3e-acb2-06ed994ba6c3" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_01a01583-bff6-73b0-aa6e-8b00e0a3cf76" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable_01a01583-bff6-7b3e-acb2-06ed994ba6c3" xlink:to="loc_us-gaap_StatementClassOfStockAxis_01a01583-bff6-73b0-aa6e-8b00e0a3cf76" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-73b0-aa6e-8b00e0a3cf76_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a01583-bff6-73b0-aa6e-8b00e0a3cf76" xlink:to="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-73b0-aa6e-8b00e0a3cf76_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-7b96-a31b-e687cbe1abae" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a01583-bff6-73b0-aa6e-8b00e0a3cf76" xlink:to="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-7b96-a31b-e687cbe1abae" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredClassAMember_01a01583-bff6-71da-8861-9fc6ae852909" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PreferredClassAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-7b96-a31b-e687cbe1abae" xlink:to="loc_us-gaap_PreferredClassAMember_01a01583-bff6-71da-8861-9fc6ae852909" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_01a01583-bff6-72b8-a0c8-4002d674d9b5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-7b96-a31b-e687cbe1abae" xlink:to="loc_us-gaap_CommonStockMember_01a01583-bff6-72b8-a0c8-4002d674d9b5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-739a-b297-3693261e0372" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable_01a01583-bff6-7b3e-acb2-06ed994ba6c3" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-739a-b297-3693261e0372" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-739a-b297-3693261e0372_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-739a-b297-3693261e0372" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-739a-b297-3693261e0372_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-797e-95c8-8436d93b2147" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-739a-b297-3693261e0372" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-797e-95c8-8436d93b2147" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PelthosTechnologiesMember_01a01583-bff6-7330-9a87-304c35552f57" xlink:href="lgnd-20260930.xsd#lgnd_PelthosTechnologiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-797e-95c8-8436d93b2147" xlink:to="loc_lgnd_PelthosTechnologiesMember_01a01583-bff6-7330-9a87-304c35552f57" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_01a01583-bff6-75bb-bd5d-959beb9f7d5c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsTable_01a01583-bff6-7b3e-acb2-06ed994ba6c3" xlink:to="loc_us-gaap_FinancialInstrumentAxis_01a01583-bff6-75bb-bd5d-959beb9f7d5c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-75bb-bd5d-959beb9f7d5c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_01a01583-bff6-75bb-bd5d-959beb9f7d5c" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-75bb-bd5d-959beb9f7d5c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-717d-b641-ca466338e3df" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_01a01583-bff6-75bb-bd5d-959beb9f7d5c" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-717d-b641-ca466338e3df" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueOptionOtherEligibleItemsMember_01a01583-bff6-77c3-8952-429d34059c5a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueOptionOtherEligibleItemsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-bff6-717d-b641-ca466338e3df" xlink:to="loc_us-gaap_FairValueOptionOtherEligibleItemsMember_01a01583-bff6-77c3-8952-429d34059c5a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_InvestmentsRollForward_01a01583-bff6-79dd-b737-27986946adb3" xlink:href="lgnd-20260930.xsd#lgnd_InvestmentsRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementBalanceSheetAndAdditionalDisclosuresByDisposalGroupsIncludingDiscontinuedOperationsLineItems_01a01583-bff6-7edc-b444-fc8d6de907c8" xlink:to="loc_lgnd_InvestmentsRollForward_01a01583-bff6-79dd-b737-27986946adb3" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherInvestments_01a01583-bff6-7a27-8f33-0a019bf1cf6d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_InvestmentsRollForward_01a01583-bff6-79dd-b737-27986946adb3" xlink:to="loc_us-gaap_OtherInvestments_01a01583-bff6-7a27-8f33-0a019bf1cf6d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestments_01a01583-bff6-71b8-861a-aa36e24eeec5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityMethodInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_InvestmentsRollForward_01a01583-bff6-79dd-b737-27986946adb3" xlink:to="loc_us-gaap_EquityMethodInvestments_01a01583-bff6-71b8-861a-aa36e24eeec5" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Investments_01a01583-bff6-7f6b-85b6-2c475a6810cf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Investments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_InvestmentsRollForward_01a01583-bff6-79dd-b737-27986946adb3" xlink:to="loc_us-gaap_Investments_01a01583-bff6-7f6b-85b6-2c475a6810cf" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueOptionChangesInFairValueGainLoss1_01a01583-bff6-7e95-8657-3f475f74eae0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueOptionChangesInFairValueGainLoss1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_InvestmentsRollForward_01a01583-bff6-79dd-b737-27986946adb3" xlink:to="loc_us-gaap_FairValueOptionChangesInFairValueGainLoss1_01a01583-bff6-7e95-8657-3f475f74eae0" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherInvestments_01a01583-bff6-72a0-988b-b121954b03b8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherInvestments"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestments_01a01583-bff6-7832-95a7-2b466335e1e1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityMethodInvestments"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_Investments_01a01583-bff6-7758-8d55-ec13176513d5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_Investments"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/InvestmentTransactionsDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#InvestmentTransactionsDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/InvestmentTransactionsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsAxis_01a01583-bff6-776a-a35e-8fba3a08bb4c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_us-gaap_OtherCommitmentsAxis_01a01583-bff6-776a-a35e-8fba3a08bb4c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsDomain_01a01583-bff6-776a-a35e-8fba3a08bb4c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_OtherCommitmentsAxis_01a01583-bff6-776a-a35e-8fba3a08bb4c" xlink:to="loc_us-gaap_OtherCommitmentsDomain_01a01583-bff6-776a-a35e-8fba3a08bb4c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_OtherCommitmentsDomain_01a01583-bff6-70c6-bd42-1f57322f9ae2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_OtherCommitmentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_OtherCommitmentsAxis_01a01583-bff6-776a-a35e-8fba3a08bb4c" xlink:to="loc_us-gaap_OtherCommitmentsDomain_01a01583-bff6-70c6-bd42-1f57322f9ae2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OrchestraBioMedMember_01a01583-bff6-7b8f-b2d2-1947af2356af" xlink:href="lgnd-20260930.xsd#lgnd_OrchestraBioMedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_OtherCommitmentsDomain_01a01583-bff6-70c6-bd42-1f57322f9ae2" xlink:to="loc_lgnd_OrchestraBioMedMember_01a01583-bff6-7b8f-b2d2-1947af2356af" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-7b48-815a-6ed1f2d28fd6" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-7b48-815a-6ed1f2d28fd6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7b48-815a-6ed1f2d28fd6_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-7b48-815a-6ed1f2d28fd6" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-7b48-815a-6ed1f2d28fd6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75c6-b8a5-c3b4e5baf98a" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a01583-bff6-7b48-815a-6ed1f2d28fd6" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75c6-b8a5-c3b4e5baf98a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_SyndexisMember_01a18e52-5417-7fab-86d4-9798738f9105" xlink:href="lgnd-20260930.xsd#lgnd_SyndexisMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75c6-b8a5-c3b4e5baf98a" xlink:to="loc_lgnd_SyndexisMember_01a18e52-5417-7fab-86d4-9798738f9105" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AvenCellMember_01a18e27-15c5-7c14-bced-c8a31a5d9097" xlink:href="lgnd-20260930.xsd#lgnd_AvenCellMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75c6-b8a5-c3b4e5baf98a" xlink:to="loc_lgnd_AvenCellMember_01a18e27-15c5-7c14-bced-c8a31a5d9097" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PrimroseBioMember_01a18e2f-0398-7593-b76e-9423d03cd222" xlink:href="lgnd-20260930.xsd#lgnd_PrimroseBioMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75c6-b8a5-c3b4e5baf98a" xlink:to="loc_lgnd_PrimroseBioMember_01a18e2f-0398-7593-b76e-9423d03cd222" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OrchestraBioMedMember_01a01583-bff6-7847-ac54-513b29df3807" xlink:href="lgnd-20260930.xsd#lgnd_OrchestraBioMedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75c6-b8a5-c3b4e5baf98a" xlink:to="loc_lgnd_OrchestraBioMedMember_01a01583-bff6-7847-ac54-513b29df3807" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OrchestraWarrantMember_01a01583-bff6-7e3a-9fc5-856e608a47ef" xlink:href="lgnd-20260930.xsd#lgnd_OrchestraWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75c6-b8a5-c3b4e5baf98a" xlink:to="loc_lgnd_OrchestraWarrantMember_01a01583-bff6-7e3a-9fc5-856e608a47ef" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ZerionPharmaMember_01a01583-bff6-7f09-90aa-267823e8bc4e" xlink:href="lgnd-20260930.xsd#lgnd_ZerionPharmaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75c6-b8a5-c3b4e5baf98a" xlink:to="loc_lgnd_ZerionPharmaMember_01a01583-bff6-7f09-90aa-267823e8bc4e" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LeonaBioMember_01a01583-bff6-7fba-b01c-e7b67c72cbe8" xlink:href="lgnd-20260930.xsd#lgnd_LeonaBioMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75c6-b8a5-c3b4e5baf98a" xlink:to="loc_lgnd_LeonaBioMember_01a01583-bff6-7fba-b01c-e7b67c72cbe8" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PelthosConvertibleNotesMember_01a01583-bff6-7bdc-b421-4dd3083e283b" xlink:href="lgnd-20260930.xsd#lgnd_PelthosConvertibleNotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75c6-b8a5-c3b4e5baf98a" xlink:to="loc_lgnd_PelthosConvertibleNotesMember_01a01583-bff6-7bdc-b421-4dd3083e283b" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PelthosTechnologiesMember_01a01583-bff6-7091-854f-cb9e3d2d3614" xlink:href="lgnd-20260930.xsd#lgnd_PelthosTechnologiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75c6-b8a5-c3b4e5baf98a" xlink:to="loc_lgnd_PelthosTechnologiesMember_01a01583-bff6-7091-854f-cb9e3d2d3614" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_CastleCreekInvestmentMember_01a01583-bff6-77e5-8578-1284adc3e05b" xlink:href="lgnd-20260930.xsd#lgnd_CastleCreekInvestmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a01583-bff6-75c6-b8a5-c3b4e5baf98a" xlink:to="loc_lgnd_CastleCreekInvestmentMember_01a01583-bff6-77e5-8578-1284adc3e05b" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_HurdleAxis_01a01583-bff6-7dbe-bc8d-a7bf51ad0294" xlink:href="lgnd-20260930.xsd#lgnd_HurdleAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_lgnd_HurdleAxis_01a01583-bff6-7dbe-bc8d-a7bf51ad0294" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_HurdleDomain_01a01583-bff6-7dbe-bc8d-a7bf51ad0294_default" xlink:href="lgnd-20260930.xsd#lgnd_HurdleDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_lgnd_HurdleAxis_01a01583-bff6-7dbe-bc8d-a7bf51ad0294" xlink:to="loc_lgnd_HurdleDomain_01a01583-bff6-7dbe-bc8d-a7bf51ad0294_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_HurdleDomain_01a01583-bff6-7635-90db-39a2d4508cb0" xlink:href="lgnd-20260930.xsd#lgnd_HurdleDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_lgnd_HurdleAxis_01a01583-bff6-7dbe-bc8d-a7bf51ad0294" xlink:to="loc_lgnd_HurdleDomain_01a01583-bff6-7635-90db-39a2d4508cb0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_HurdleOneMember_01a01583-bff6-7e4d-acbb-8cfd97387e58" xlink:href="lgnd-20260930.xsd#lgnd_HurdleOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_HurdleDomain_01a01583-bff6-7635-90db-39a2d4508cb0" xlink:to="loc_lgnd_HurdleOneMember_01a01583-bff6-7e4d-acbb-8cfd97387e58" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FundingAllocationAxis_01a01583-bff6-7a07-90e0-7d161614151c" xlink:href="lgnd-20260930.xsd#lgnd_FundingAllocationAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_lgnd_FundingAllocationAxis_01a01583-bff6-7a07-90e0-7d161614151c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FundingAllocationDomain_01a01583-bff6-7a07-90e0-7d161614151c_default" xlink:href="lgnd-20260930.xsd#lgnd_FundingAllocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_lgnd_FundingAllocationAxis_01a01583-bff6-7a07-90e0-7d161614151c" xlink:to="loc_lgnd_FundingAllocationDomain_01a01583-bff6-7a07-90e0-7d161614151c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FundingAllocationDomain_01a01583-bff6-7350-98c4-b4cd5ceb2b2c" xlink:href="lgnd-20260930.xsd#lgnd_FundingAllocationDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_lgnd_FundingAllocationAxis_01a01583-bff6-7a07-90e0-7d161614151c" xlink:to="loc_lgnd_FundingAllocationDomain_01a01583-bff6-7350-98c4-b4cd5ceb2b2c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OrchestraWarrantMember_01a01583-bff6-784a-a074-3fc63cd8490a" xlink:href="lgnd-20260930.xsd#lgnd_OrchestraWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_FundingAllocationDomain_01a01583-bff6-7350-98c4-b4cd5ceb2b2c" xlink:to="loc_lgnd_OrchestraWarrantMember_01a01583-bff6-784a-a074-3fc63cd8490a" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ResearchAndDevelopmentFundingMember_01a01583-bff6-78f6-8b23-34068ecd5813" xlink:href="lgnd-20260930.xsd#lgnd_ResearchAndDevelopmentFundingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_FundingAllocationDomain_01a01583-bff6-7350-98c4-b4cd5ceb2b2c" xlink:to="loc_lgnd_ResearchAndDevelopmentFundingMember_01a01583-bff6-78f6-8b23-34068ecd5813" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RoyaltyRightsMember_01a01583-bff6-77ed-9adf-d027f048b84a" xlink:href="lgnd-20260930.xsd#lgnd_RoyaltyRightsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_FundingAllocationDomain_01a01583-bff6-7350-98c4-b4cd5ceb2b2c" xlink:to="loc_lgnd_RoyaltyRightsMember_01a01583-bff6-77ed-9adf-d027f048b84a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OrdinarySharesMember_01a01583-bff6-7903-a6ed-12cb272ab76c" xlink:href="lgnd-20260930.xsd#lgnd_OrdinarySharesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_FundingAllocationDomain_01a01583-bff6-7350-98c4-b4cd5ceb2b2c" xlink:to="loc_lgnd_OrdinarySharesMember_01a01583-bff6-7903-a6ed-12cb272ab76c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightAxis_01a01583-bff6-7f21-821e-987f8f74d07c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_us-gaap_ClassOfWarrantOrRightAxis_01a01583-bff6-7f21-821e-987f8f74d07c" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-7f21-821e-987f8f74d07c_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_01a01583-bff6-7f21-821e-987f8f74d07c" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-7f21-821e-987f8f74d07c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-724a-8317-00ce4b4fcce0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_01a01583-bff6-7f21-821e-987f8f74d07c" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-724a-8317-00ce4b4fcce0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OrchestraWarrantMember_01a01583-bff6-7a44-87f1-5c2c256ff9e1" xlink:href="lgnd-20260930.xsd#lgnd_OrchestraWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-724a-8317-00ce4b4fcce0" xlink:to="loc_lgnd_OrchestraWarrantMember_01a01583-bff6-7a44-87f1-5c2c256ff9e1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_SeriesAWarrantsMember_01a01583-bff6-7113-bb15-6d0d0cc4b837" xlink:href="lgnd-20260930.xsd#lgnd_SeriesAWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-724a-8317-00ce4b4fcce0" xlink:to="loc_lgnd_SeriesAWarrantsMember_01a01583-bff6-7113-bb15-6d0d0cc4b837" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LeaonaBioSeriesBWarrantsMember_01a01583-bff6-773f-871f-f260dc823b64" xlink:href="lgnd-20260930.xsd#lgnd_LeaonaBioSeriesBWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-724a-8317-00ce4b4fcce0" xlink:to="loc_lgnd_LeaonaBioSeriesBWarrantsMember_01a01583-bff6-773f-871f-f260dc823b64" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AcecorWarrantsMember_01a01583-bff6-714a-a9ec-81dee2e34fb5" xlink:href="lgnd-20260930.xsd#lgnd_AcecorWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-724a-8317-00ce4b4fcce0" xlink:to="loc_lgnd_AcecorWarrantsMember_01a01583-bff6-714a-a9ec-81dee2e34fb5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_CastleCreekWarrantsMember_01a01583-bff6-78d4-b19c-bc7b28b6734f" xlink:href="lgnd-20260930.xsd#lgnd_CastleCreekWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_01a01583-bff6-724a-8317-00ce4b4fcce0" xlink:to="loc_lgnd_CastleCreekWarrantsMember_01a01583-bff6-78d4-b19c-bc7b28b6734f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeAxis_01a01583-bff6-753d-906b-e9caf665f07e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_us-gaap_MeasurementInputTypeAxis_01a01583-bff6-753d-906b-e9caf665f07e" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-753d-906b-e9caf665f07e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a01583-bff6-753d-906b-e9caf665f07e" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-753d-906b-e9caf665f07e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7d59-8c2b-e37cd23d4bf6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a01583-bff6-753d-906b-e9caf665f07e" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7d59-8c2b-e37cd23d4bf6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputOptionVolatilityMember_01a01583-bff6-7a0d-b4dc-c1d92a5cda3e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputOptionVolatilityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7d59-8c2b-e37cd23d4bf6" xlink:to="loc_us-gaap_MeasurementInputOptionVolatilityMember_01a01583-bff6-7a0d-b4dc-c1d92a5cda3e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputRiskFreeInterestRateMember_01a01583-bff6-7181-ba33-84d137451bca" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputRiskFreeInterestRateMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7d59-8c2b-e37cd23d4bf6" xlink:to="loc_us-gaap_MeasurementInputRiskFreeInterestRateMember_01a01583-bff6-7181-ba33-84d137451bca" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputSharePriceMember_01a01583-bff6-7249-9048-898b8fe5bc16" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputSharePriceMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7d59-8c2b-e37cd23d4bf6" xlink:to="loc_us-gaap_MeasurementInputSharePriceMember_01a01583-bff6-7249-9048-898b8fe5bc16" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputExpectedTermMember_01a01583-bff6-7488-a19f-c04df3e1762c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputExpectedTermMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_01a01583-bff6-7d59-8c2b-e37cd23d4bf6" xlink:to="loc_us-gaap_MeasurementInputExpectedTermMember_01a01583-bff6-7488-a19f-c04df3e1762c" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_01a01583-bff6-77b7-aa77-34ff06615068" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_us-gaap_StatementClassOfStockAxis_01a01583-bff6-77b7-aa77-34ff06615068" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-77b7-aa77-34ff06615068_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a01583-bff6-77b7-aa77-34ff06615068" xlink:to="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-77b7-aa77-34ff06615068_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-726a-b907-df0af0f32f91" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a01583-bff6-77b7-aa77-34ff06615068" xlink:to="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-726a-b907-df0af0f32f91" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_01a01583-bff6-722e-844d-22a166bd637d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_01a01583-bff6-726a-b907-df0af0f32f91" xlink:to="loc_us-gaap_CommonStockMember_01a01583-bff6-722e-844d-22a166bd637d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_LegalEntityAxis_01a01583-bff6-75b3-8599-2614e271dd91" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_LegalEntityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_dei_LegalEntityAxis_01a01583-bff6-75b3-8599-2614e271dd91" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_01a01583-bff6-75b3-8599-2614e271dd91_default" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_dei_LegalEntityAxis_01a01583-bff6-75b3-8599-2614e271dd91" xlink:to="loc_dei_EntityDomain_01a01583-bff6-75b3-8599-2614e271dd91_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_dei_EntityDomain_01a01583-bff6-7b6f-86b9-accf5af148f7" xlink:href="https://xbrl.sec.gov/dei/2026/dei-2026.xsd#dei_EntityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_dei_LegalEntityAxis_01a01583-bff6-75b3-8599-2614e271dd91" xlink:to="loc_dei_EntityDomain_01a01583-bff6-7b6f-86b9-accf5af148f7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PurchasersMember_01a01583-bff6-778a-8c30-7ce8827de800" xlink:href="lgnd-20260930.xsd#lgnd_PurchasersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_01a01583-bff6-7b6f-86b9-accf5af148f7" xlink:to="loc_lgnd_PurchasersMember_01a01583-bff6-778a-8c30-7ce8827de800" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PelthosTechnologiesMember_01a01583-bff6-7c6d-8b58-a5059216f1ec" xlink:href="lgnd-20260930.xsd#lgnd_PelthosTechnologiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_01a01583-bff6-7b6f-86b9-accf5af148f7" xlink:to="loc_lgnd_PelthosTechnologiesMember_01a01583-bff6-7c6d-8b58-a5059216f1ec" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OtherPurchasersMember_01a01583-bff6-71e1-990c-de5d2c045138" xlink:href="lgnd-20260930.xsd#lgnd_OtherPurchasersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_dei_EntityDomain_01a01583-bff6-7b6f-86b9-accf5af148f7" xlink:to="loc_lgnd_OtherPurchasersMember_01a01583-bff6-71e1-990c-de5d2c045138" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a01583-bff6-7a90-8ad2-050d0fc067ec" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_srt_ProductOrServiceAxis_01a01583-bff6-7a90-8ad2-050d0fc067ec" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a01583-bff6-7a90-8ad2-050d0fc067ec_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a01583-bff6-7a90-8ad2-050d0fc067ec" xlink:to="loc_srt_ProductsAndServicesDomain_01a01583-bff6-7a90-8ad2-050d0fc067ec_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a01583-bff6-7670-b2fe-d06da0b606dd" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a01583-bff6-7a90-8ad2-050d0fc067ec" xlink:to="loc_srt_ProductsAndServicesDomain_01a01583-bff6-7670-b2fe-d06da0b606dd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XepiMember_01a01583-bff6-784d-978d-611fe7d84703" xlink:href="lgnd-20260930.xsd#lgnd_XepiMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bff6-7670-b2fe-d06da0b606dd" xlink:to="loc_lgnd_XepiMember_01a01583-bff6-784d-978d-611fe7d84703" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_SatoMember_01a01583-bff6-7ff9-b163-d77fc9c194bb" xlink:href="lgnd-20260930.xsd#lgnd_SatoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bff6-7670-b2fe-d06da0b606dd" xlink:to="loc_lgnd_SatoMember_01a01583-bff6-7ff9-b163-d77fc9c194bb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AT220ProgramMember_01a01583-bff6-7b09-92d0-cd174ee629a7" xlink:href="lgnd-20260930.xsd#lgnd_AT220ProgramMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bff6-7670-b2fe-d06da0b606dd" xlink:to="loc_lgnd_AT220ProgramMember_01a01583-bff6-7b09-92d0-cd174ee629a7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AT292ProgramMember_01a01583-bff6-7cd9-b01e-6c850d5d7337" xlink:href="lgnd-20260930.xsd#lgnd_AT292ProgramMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bff6-7670-b2fe-d06da0b606dd" xlink:to="loc_lgnd_AT292ProgramMember_01a01583-bff6-7cd9-b01e-6c850d5d7337" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PeliCRM197Member_01a18e35-f59f-7776-af6f-867e8ad03092" xlink:href="lgnd-20260930.xsd#lgnd_PeliCRM197Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-bff6-7670-b2fe-d06da0b606dd" xlink:to="loc_lgnd_PeliCRM197Member_01a18e35-f59f-7776-af6f-867e8ad03092" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_01a01583-bff6-7deb-a1b9-c9b815953b46" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_srt_CounterpartyNameAxis_01a01583-bff6-7deb-a1b9-c9b815953b46" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7deb-a1b9-c9b815953b46_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_01a01583-bff6-7deb-a1b9-c9b815953b46" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7deb-a1b9-c9b815953b46_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7b30-b532-148349135fc3" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_01a01583-bff6-7deb-a1b9-c9b815953b46" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7b30-b532-148349135fc3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PrimroseBioMember_01a18e35-9ae8-7a70-8c82-73eb603afd04" xlink:href="lgnd-20260930.xsd#lgnd_PrimroseBioMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7b30-b532-148349135fc3" xlink:to="loc_lgnd_PrimroseBioMember_01a18e35-9ae8-7a70-8c82-73eb603afd04" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PelthosTechnologiesMember_01a01583-bff6-72cc-bbde-e695cc3a4ea2" xlink:href="lgnd-20260930.xsd#lgnd_PelthosTechnologiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-bff6-7b30-b532-148349135fc3" xlink:to="loc_lgnd_PelthosTechnologiesMember_01a01583-bff6-72cc-bbde-e695cc3a4ea2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AccountsNotesLoansAndFinancingReceivableByReceivableTypeAxis_01a01583-bff6-773e-b2b5-fd42c370857e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AccountsNotesLoansAndFinancingReceivableByReceivableTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_us-gaap_AccountsNotesLoansAndFinancingReceivableByReceivableTypeAxis_01a01583-bff6-773e-b2b5-fd42c370857e" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReceivableTypeDomain_01a01583-bff6-773e-b2b5-fd42c370857e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ReceivableTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AccountsNotesLoansAndFinancingReceivableByReceivableTypeAxis_01a01583-bff6-773e-b2b5-fd42c370857e" xlink:to="loc_us-gaap_ReceivableTypeDomain_01a01583-bff6-773e-b2b5-fd42c370857e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReceivableTypeDomain_01a01583-bff6-7171-9c3c-25c3f59fd337" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ReceivableTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AccountsNotesLoansAndFinancingReceivableByReceivableTypeAxis_01a01583-bff6-773e-b2b5-fd42c370857e" xlink:to="loc_us-gaap_ReceivableTypeDomain_01a01583-bff6-7171-9c3c-25c3f59fd337" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NotesReceivableMember_01a01583-bff6-7c8d-88bd-6e072578a54c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NotesReceivableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ReceivableTypeDomain_01a01583-bff6-7171-9c3c-25c3f59fd337" xlink:to="loc_us-gaap_NotesReceivableMember_01a01583-bff6-7c8d-88bd-6e072578a54c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionAxis_01a01583-bff6-75be-aa73-bfa43948ed41" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_us-gaap_AssetAcquisitionAxis_01a01583-bff6-75be-aa73-bfa43948ed41" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_01a01583-bff6-75be-aa73-bfa43948ed41_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AssetAcquisitionAxis_01a01583-bff6-75be-aa73-bfa43948ed41" xlink:to="loc_us-gaap_AssetAcquisitionDomain_01a01583-bff6-75be-aa73-bfa43948ed41_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionDomain_01a01583-bff6-7dac-9fd5-b81a1b9dec81" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AssetAcquisitionAxis_01a01583-bff6-75be-aa73-bfa43948ed41" xlink:to="loc_us-gaap_AssetAcquisitionDomain_01a01583-bff6-7dac-9fd5-b81a1b9dec81" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AvenCellMember_01a18e4a-cbe1-7a4e-bc04-8132f40a7f56" xlink:href="lgnd-20260930.xsd#lgnd_AvenCellMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionDomain_01a01583-bff6-7dac-9fd5-b81a1b9dec81" xlink:to="loc_lgnd_AvenCellMember_01a18e4a-cbe1-7a4e-bc04-8132f40a7f56" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AvenCellSeriesC1PreferredStockMember_01a18e42-4249-7b92-bf0f-cea012a0e558" xlink:href="lgnd-20260930.xsd#lgnd_AvenCellSeriesC1PreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_AvenCellMember_01a18e4a-cbe1-7a4e-bc04-8132f40a7f56" xlink:to="loc_lgnd_AvenCellSeriesC1PreferredStockMember_01a18e42-4249-7b92-bf0f-cea012a0e558" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AvenCellPurchaseAndSaleAgreementMember_01a18e45-3c3a-7d62-8e23-9d3b14265d59" xlink:href="lgnd-20260930.xsd#lgnd_AvenCellPurchaseAndSaleAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_AvenCellMember_01a18e4a-cbe1-7a4e-bc04-8132f40a7f56" xlink:to="loc_lgnd_AvenCellPurchaseAndSaleAgreementMember_01a18e45-3c3a-7d62-8e23-9d3b14265d59" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ArecorLimitedMember_01a01583-bff6-7383-9c1c-8ce66872c8a5" xlink:href="lgnd-20260930.xsd#lgnd_ArecorLimitedMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionDomain_01a01583-bff6-7dac-9fd5-b81a1b9dec81" xlink:to="loc_lgnd_ArecorLimitedMember_01a01583-bff6-7383-9c1c-8ce66872c8a5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidatedEntitiesAxis_01a18e26-b281-7881-8b33-4e35c8d438aa" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ConsolidatedEntitiesAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_srt_ConsolidatedEntitiesAxis_01a18e26-b281-7881-8b33-4e35c8d438aa" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidatedEntitiesDomain_01a18e26-b281-7881-8b33-4e35c8d438aa_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ConsolidatedEntitiesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ConsolidatedEntitiesAxis_01a18e26-b281-7881-8b33-4e35c8d438aa" xlink:to="loc_srt_ConsolidatedEntitiesDomain_01a18e26-b281-7881-8b33-4e35c8d438aa_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ConsolidatedEntitiesDomain_01a18e26-b281-7216-96e6-67b63c902851" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ConsolidatedEntitiesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ConsolidatedEntitiesAxis_01a18e26-b281-7881-8b33-4e35c8d438aa" xlink:to="loc_srt_ConsolidatedEntitiesDomain_01a18e26-b281-7216-96e6-67b63c902851" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableInterestEntityNotPrimaryBeneficiaryMember_01a18e26-d0c9-7900-8575-2f9b596f86b6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_VariableInterestEntityNotPrimaryBeneficiaryMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ConsolidatedEntitiesDomain_01a18e26-b281-7216-96e6-67b63c902851" xlink:to="loc_us-gaap_VariableInterestEntityNotPrimaryBeneficiaryMember_01a18e26-d0c9-7900-8575-2f9b596f86b6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MilestoneAxis_01a18e37-fb83-7a32-814c-5d3883661f0f" xlink:href="lgnd-20260930.xsd#lgnd_MilestoneAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_AssetAcquisitionTable_01a01583-bff6-7bc6-9f49-feeb1f160d61" xlink:to="loc_lgnd_MilestoneAxis_01a18e37-fb83-7a32-814c-5d3883661f0f" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MilestoneDomain_01a18e37-fb83-7a32-814c-5d3883661f0f_default" xlink:href="lgnd-20260930.xsd#lgnd_MilestoneDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_lgnd_MilestoneAxis_01a18e37-fb83-7a32-814c-5d3883661f0f" xlink:to="loc_lgnd_MilestoneDomain_01a18e37-fb83-7a32-814c-5d3883661f0f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MilestoneDomain_01a18e37-fb83-723c-a888-6b7292e6f4b4" xlink:href="lgnd-20260930.xsd#lgnd_MilestoneDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_lgnd_MilestoneAxis_01a18e37-fb83-7a32-814c-5d3883661f0f" xlink:to="loc_lgnd_MilestoneDomain_01a18e37-fb83-723c-a888-6b7292e6f4b4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BelowMilestoneMember_01a18e38-2129-7fc7-b8f0-31c4ff404415" xlink:href="lgnd-20260930.xsd#lgnd_BelowMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_MilestoneDomain_01a18e37-fb83-723c-a888-6b7292e6f4b4" xlink:to="loc_lgnd_BelowMilestoneMember_01a18e38-2129-7fc7-b8f0-31c4ff404415" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AboveMilestoneMember_01a18e38-7b30-7e64-ac49-6c4d060ea1d2" xlink:href="lgnd-20260930.xsd#lgnd_AboveMilestoneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_MilestoneDomain_01a18e37-fb83-723c-a888-6b7292e6f4b4" xlink:to="loc_lgnd_AboveMilestoneMember_01a18e38-7b30-7e64-ac49-6c4d060ea1d2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetsInterestAcquiredPercentage_01a18e53-97e4-7149-a6a5-8b37751f3d38" xlink:href="lgnd-20260930.xsd#lgnd_FinancialRoyaltyAssetsInterestAcquiredPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_FinancialRoyaltyAssetsInterestAcquiredPercentage_01a18e53-97e4-7149-a6a5-8b37751f3d38" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PaymentsToAcquireFinancialRoyaltyAssets_01a18e51-eacc-7605-a08e-93b8094bb341" xlink:href="lgnd-20260930.xsd#lgnd_PaymentsToAcquireFinancialRoyaltyAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_PaymentsToAcquireFinancialRoyaltyAssets_01a18e51-eacc-7605-a08e-93b8094bb341" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetAcquisitionConsiderationTransferred_01a01583-bff6-7383-ba06-988bef34f96a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetAcquisitionConsiderationTransferred"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_AssetAcquisitionConsiderationTransferred_01a01583-bff6-7383-ba06-988bef34f96a" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AssetAcquisitionDeferredConsiderationPayable_01a01583-bff6-7910-82e7-a72740141af5" xlink:href="lgnd-20260930.xsd#lgnd_AssetAcquisitionDeferredConsiderationPayable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_AssetAcquisitionDeferredConsiderationPayable_01a01583-bff6-7910-82e7-a72740141af5" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PaymentsForAssetAcquisitions_01a18e43-825a-7ef5-beef-940ba38d3b9f" xlink:href="lgnd-20260930.xsd#lgnd_PaymentsForAssetAcquisitions"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_PaymentsForAssetAcquisitions_01a18e43-825a-7ef5-beef-940ba38d3b9f" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AssetAcquisitionOptionToAcquireIncrementalRoyaltyRightsMaximumAmount_01a18e48-98f0-7060-b5a5-0ffda8e4edc0" xlink:href="lgnd-20260930.xsd#lgnd_AssetAcquisitionOptionToAcquireIncrementalRoyaltyRightsMaximumAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_AssetAcquisitionOptionToAcquireIncrementalRoyaltyRightsMaximumAmount_01a18e48-98f0-7060-b5a5-0ffda8e4edc0" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AssetAcquisitionConsiderationTransferredCapitalizedTransactionCosts_01a18e4d-047a-77cb-8b79-61469c26c197" xlink:href="lgnd-20260930.xsd#lgnd_AssetAcquisitionConsiderationTransferredCapitalizedTransactionCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_AssetAcquisitionConsiderationTransferredCapitalizedTransactionCosts_01a18e4d-047a-77cb-8b79-61469c26c197" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AssetAcquisitionConsiderationTransferredIncludingCapitalizedTransactionCosts_01a18e4b-a634-7aa7-bb46-b8777324230f" xlink:href="lgnd-20260930.xsd#lgnd_AssetAcquisitionConsiderationTransferredIncludingCapitalizedTransactionCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_AssetAcquisitionConsiderationTransferredIncludingCapitalizedTransactionCosts_01a18e4b-a634-7aa7-bb46-b8777324230f" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AssetAcquisitionRoyaltyRights_01a18e4e-ded0-75a7-877e-b839ca227aca" xlink:href="lgnd-20260930.xsd#lgnd_AssetAcquisitionRoyaltyRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_AssetAcquisitionRoyaltyRights_01a18e4e-ded0-75a7-877e-b839ca227aca" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AssetAcquisitionEmbeddedDerivative_01a18e4f-bd60-77cb-96dc-0a4235e3f7d9" xlink:href="lgnd-20260930.xsd#lgnd_AssetAcquisitionEmbeddedDerivative"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_AssetAcquisitionEmbeddedDerivative_01a18e4f-bd60-77cb-96dc-0a4235e3f7d9" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AssetAcquisitionWarrant_01a18e50-4a3a-76e9-b50e-d3f81911761e" xlink:href="lgnd-20260930.xsd#lgnd_AssetAcquisitionWarrant"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_AssetAcquisitionWarrant_01a18e50-4a3a-76e9-b50e-d3f81911761e" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_01a18e22-2d8f-7c0b-8419-9291ecdfa48e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityMethodInvestmentOwnershipPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_EquityMethodInvestmentOwnershipPercentage_01a18e22-2d8f-7c0b-8419-9291ecdfa48e" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestments_01a18e23-3032-7097-be3a-35659bf51ea5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityMethodInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_EquityMethodInvestments_01a18e23-3032-7097-be3a-35659bf51ea5" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_VariableInterestEntityEntityMaximumLossExposureAmount_01a18e24-c24c-72eb-8050-5c4bac447e81" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_VariableInterestEntityEntityMaximumLossExposureAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_VariableInterestEntityEntityMaximumLossExposureAmount_01a18e24-c24c-72eb-8050-5c4bac447e81" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VariableInterestEntityReportingEntityInvolvementMaximumLossExposureAmountAggregateCarryingAmountOfInterests_01a18e28-3222-720c-b3e4-12a86b6b2e62" xlink:href="lgnd-20260930.xsd#lgnd_VariableInterestEntityReportingEntityInvolvementMaximumLossExposureAmountAggregateCarryingAmountOfInterests"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_VariableInterestEntityReportingEntityInvolvementMaximumLossExposureAmountAggregateCarryingAmountOfInterests_01a18e28-3222-720c-b3e4-12a86b6b2e62" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VariableInterestEntityReportingEntityInvolvementMaximumLossExposureAmountPotentialAdditionalPayment_01a18e2a-3b1c-7669-afd3-21e121f2f79d" xlink:href="lgnd-20260930.xsd#lgnd_VariableInterestEntityReportingEntityInvolvementMaximumLossExposureAmountPotentialAdditionalPayment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_VariableInterestEntityReportingEntityInvolvementMaximumLossExposureAmountPotentialAdditionalPayment_01a18e2a-3b1c-7669-afd3-21e121f2f79d" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VariableInterestEntityReportingEntityInvolvementMaximumLossExposureAmountAdditionalCommittedEquityFunding_01a18e2b-5011-7b97-81f5-8ff1bedfc65a" xlink:href="lgnd-20260930.xsd#lgnd_VariableInterestEntityReportingEntityInvolvementMaximumLossExposureAmountAdditionalCommittedEquityFunding"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_VariableInterestEntityReportingEntityInvolvementMaximumLossExposureAmountAdditionalCommittedEquityFunding_01a18e2b-5011-7b97-81f5-8ff1bedfc65a" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_SalesContractInterestInSalesRevenue_01a18e32-ffe1-7282-bffb-b6ccefc0e0da" xlink:href="lgnd-20260930.xsd#lgnd_SalesContractInterestInSalesRevenue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_SalesContractInterestInSalesRevenue_01a18e32-ffe1-7282-bffb-b6ccefc0e0da" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_SalesRevenueMilestoneThreshold_01a18e36-6820-7d73-81e4-41e3b2a3c307" xlink:href="lgnd-20260930.xsd#lgnd_SalesRevenueMilestoneThreshold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_SalesRevenueMilestoneThreshold_01a18e36-6820-7d73-81e4-41e3b2a3c307" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_InterestInPotentialDevelopmentMilestone_01a18e39-b982-7220-ba2f-9ce3e080ebd5" xlink:href="lgnd-20260930.xsd#lgnd_InterestInPotentialDevelopmentMilestone"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_InterestInPotentialDevelopmentMilestone_01a18e39-b982-7220-ba2f-9ce3e080ebd5" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireEquitySecuritiesFvNi_01a01583-bff6-7e8b-a20b-16a08c5fa85e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquireEquitySecuritiesFvNi"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_PaymentsToAcquireEquitySecuritiesFvNi_01a01583-bff6-7e8b-a20b-16a08c5fa85e" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ConsiderationPaidForAnInterestInPotentialDevelopmentMilestone_01a18e3c-5450-7f65-9a92-dba540517317" xlink:href="lgnd-20260930.xsd#lgnd_ConsiderationPaidForAnInterestInPotentialDevelopmentMilestone"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_ConsiderationPaidForAnInterestInPotentialDevelopmentMilestone_01a18e3c-5450-7f65-9a92-dba540517317" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesFvNiCurrentAndNoncurrent_01a18e2e-10ab-7c7e-b634-8b80e6c96449" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquitySecuritiesFvNiCurrentAndNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_EquitySecuritiesFvNiCurrentAndNoncurrent_01a18e2e-10ab-7c7e-b634-8b80e6c96449" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OtherCommitmentInvestmentAmountMaximum_01a01583-bff6-7e30-bb4a-b2b208cc9b28" xlink:href="lgnd-20260930.xsd#lgnd_OtherCommitmentInvestmentAmountMaximum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_OtherCommitmentInvestmentAmountMaximum_01a01583-bff6-7e30-bb4a-b2b208cc9b28" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OtherCommitmentInvestmentAmountCurrent_01a01583-bff6-782d-b7eb-973c151c1361" xlink:href="lgnd-20260930.xsd#lgnd_OtherCommitmentInvestmentAmountCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_OtherCommitmentInvestmentAmountCurrent_01a01583-bff6-782d-b7eb-973c151c1361" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockPricePerShare_01a01583-bff6-702b-b6b7-b413aae83211" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SaleOfStockPricePerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_SaleOfStockPricePerShare_01a01583-bff6-702b-b6b7-b413aae83211" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinanceAgreementContractedRoyaltyRevenue_01a01583-bff6-71f9-9802-9cd173883f15" xlink:href="lgnd-20260930.xsd#lgnd_FinanceAgreementContractedRoyaltyRevenue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_FinanceAgreementContractedRoyaltyRevenue_01a01583-bff6-71f9-9802-9cd173883f15" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfWarrants_01a01583-bff6-7be9-b7c1-b25901fe118b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsForRepurchaseOfWarrants"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfWarrants_01a01583-bff6-7be9-b7c1-b25901fe118b" xlink:type="arc" order="27"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PaymentsToAcquireFinancialRoyaltyAssetsAndRecognizedResearchAndDevelopmentExpense_01a01583-bff6-723f-ab46-6db4377255fe" xlink:href="lgnd-20260930.xsd#lgnd_PaymentsToAcquireFinancialRoyaltyAssetsAndRecognizedResearchAndDevelopmentExpense"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_PaymentsToAcquireFinancialRoyaltyAssetsAndRecognizedResearchAndDevelopmentExpense_01a01583-bff6-723f-ab46-6db4377255fe" xlink:type="arc" order="28"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantsAndRightsOutstandingTerm_01a01583-bff6-7c91-865d-5bb16e5715fb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WarrantsAndRightsOutstandingTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_WarrantsAndRightsOutstandingTerm_01a01583-bff6-7c91-865d-5bb16e5715fb" xlink:type="arc" order="29"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_WarrantsAndRightsOutstandingMeasurementInput_01a01583-bff6-7648-9d72-426cb9b5b117" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_WarrantsAndRightsOutstandingMeasurementInput"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_WarrantsAndRightsOutstandingMeasurementInput_01a01583-bff6-7648-9d72-426cb9b5b117" xlink:type="arc" order="30"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireInvestments_01a01583-bff6-7c6f-8100-a339db0bdab1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquireInvestments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_PaymentsToAcquireInvestments_01a01583-bff6-7c6f-8100-a339db0bdab1" xlink:type="arc" order="31"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_NoncashOrPartNoncashAcquisitionNoncashFinancialOrEquityInstrumentConsiderationSharesIssued1_01a01583-bff6-767b-83e8-c30d9c018178" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_NoncashOrPartNoncashAcquisitionNoncashFinancialOrEquityInstrumentConsiderationSharesIssued1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_NoncashOrPartNoncashAcquisitionNoncashFinancialOrEquityInstrumentConsiderationSharesIssued1_01a01583-bff6-767b-83e8-c30d9c018178" xlink:type="arc" order="32"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RoyaltyIncomeRateBaseTier_01a01583-bff6-7515-ba63-187d15ea1c39" xlink:href="lgnd-20260930.xsd#lgnd_RoyaltyIncomeRateBaseTier"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_RoyaltyIncomeRateBaseTier_01a01583-bff6-7515-ba63-187d15ea1c39" xlink:type="arc" order="33"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RoyaltyIncomeRevenueThreshold_01a01583-bff6-777a-84ae-28f54a5a5eb3" xlink:href="lgnd-20260930.xsd#lgnd_RoyaltyIncomeRevenueThreshold"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_RoyaltyIncomeRevenueThreshold_01a01583-bff6-777a-84ae-28f54a5a5eb3" xlink:type="arc" order="34"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RoyaltyIncomeRateUpperTier_01a01583-bff6-7fb6-bf63-277c3c79ec23" xlink:href="lgnd-20260930.xsd#lgnd_RoyaltyIncomeRateUpperTier"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_RoyaltyIncomeRateUpperTier_01a01583-bff6-7fb6-bf63-277c3c79ec23" xlink:type="arc" order="35"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AnnualRoyaltyFee_01a01583-bff6-798a-b75c-6bce2258c638" xlink:href="lgnd-20260930.xsd#lgnd_AnnualRoyaltyFee"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_AnnualRoyaltyFee_01a01583-bff6-798a-b75c-6bce2258c638" xlink:type="arc" order="36"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PaymentsToAcquireCommonStockAndWarrants_01a01583-bff6-7bad-9467-fc840bac689d" xlink:href="lgnd-20260930.xsd#lgnd_PaymentsToAcquireCommonStockAndWarrants"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_PaymentsToAcquireCommonStockAndWarrants_01a01583-bff6-7bad-9467-fc840bac689d" xlink:type="arc" order="37"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_EquityIssuanceCost_01a01583-bff6-74a4-8e6f-475ddd2337e4" xlink:href="lgnd-20260930.xsd#lgnd_EquityIssuanceCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_EquityIssuanceCost_01a01583-bff6-74a4-8e6f-475ddd2337e4" xlink:type="arc" order="38"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireLoansReceivable_01a01583-bff6-7cca-9bbe-ca61a0addc0b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquireLoansReceivable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_PaymentsToAcquireLoansReceivable_01a01583-bff6-7cca-9bbe-ca61a0addc0b" xlink:type="arc" order="39"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReceivableWithImputedInterestEffectiveYieldInterestRate_01a01583-bff6-7558-83d0-b999494f6ba6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ReceivableWithImputedInterestEffectiveYieldInterestRate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_ReceivableWithImputedInterestEffectiveYieldInterestRate_01a01583-bff6-7558-83d0-b999494f6ba6" xlink:type="arc" order="40"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LoanReceivableConversionPrice_01a01583-bff6-73ba-8186-0a7bec328044" xlink:href="lgnd-20260930.xsd#lgnd_LoanReceivableConversionPrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_LoanReceivableConversionPrice_01a01583-bff6-73ba-8186-0a7bec328044" xlink:type="arc" order="41"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_EquityMethodInvestmentMaximumOwnershipPercentage_01a01583-bff6-7d68-9cfb-b5ff168d7ace" xlink:href="lgnd-20260930.xsd#lgnd_EquityMethodInvestmentMaximumOwnershipPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_EquityMethodInvestmentMaximumOwnershipPercentage_01a01583-bff6-7d68-9cfb-b5ff168d7ace" xlink:type="arc" order="42"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AccountsReceivableIssuanceCost_01a01583-bff6-73d8-aa20-77279f223c8a" xlink:href="lgnd-20260930.xsd#lgnd_AccountsReceivableIssuanceCost"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_AccountsReceivableIssuanceCost_01a01583-bff6-73d8-aa20-77279f223c8a" xlink:type="arc" order="43"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ConvertibleReceivableEmbeddedConversionValue_01a01583-bff6-73d6-8546-f7b1a1cbb872" xlink:href="lgnd-20260930.xsd#lgnd_ConvertibleReceivableEmbeddedConversionValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_ConvertibleReceivableEmbeddedConversionValue_01a01583-bff6-73d6-8546-f7b1a1cbb872" xlink:type="arc" order="44"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ConvertibleReceivableReceivableValue_01a01583-bff6-75f1-b66b-cb015690b2a6" xlink:href="lgnd-20260930.xsd#lgnd_ConvertibleReceivableReceivableValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_ConvertibleReceivableReceivableValue_01a01583-bff6-75f1-b66b-cb015690b2a6" xlink:type="arc" order="45"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLiabilityMeasurementInput_01a01583-bff6-7025-ac23-a2cfa14f3dfd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeLiabilityMeasurementInput"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_DerivativeLiabilityMeasurementInput_01a01583-bff6-7025-ac23-a2cfa14f3dfd" xlink:type="arc" order="46"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_UnrealizedGainLossOnHybridInstrumentNet_01a01583-bff6-7c39-8e50-d52d8fb9f3a1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_UnrealizedGainLossOnHybridInstrumentNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_UnrealizedGainLossOnHybridInstrumentNet_01a01583-bff6-7c39-8e50-d52d8fb9f3a1" xlink:type="arc" order="47"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentIncomeInterest_01a01583-bff6-79de-a02d-cca127de9465" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InvestmentIncomeInterest"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_InvestmentIncomeInterest_01a01583-bff6-79de-a02d-cca127de9465" xlink:type="arc" order="48"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfDebtDiscountPremium_01a01583-bff6-7962-937c-ee5c2020514a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AmortizationOfDebtDiscountPremium"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_AmortizationOfDebtDiscountPremium_01a01583-bff6-7962-937c-ee5c2020514a" xlink:type="arc" order="49"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AssetAcquisitionDeferredConsiderationNumberOfInstallments_01a01583-bff6-7b47-819e-cdcd60e1543e" xlink:href="lgnd-20260930.xsd#lgnd_AssetAcquisitionDeferredConsiderationNumberOfInstallments"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_AssetAcquisitionDeferredConsiderationNumberOfInstallments_01a01583-bff6-7b47-819e-cdcd60e1543e" xlink:type="arc" order="50"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_01a01583-bff6-72dd-ae68-5d1ebf43715e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_01a01583-bff6-72dd-ae68-5d1ebf43715e" xlink:type="arc" order="51"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AssetAcquisitionRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContractAssets_01a01583-bff6-7dc2-afe0-d62a57522594" xlink:href="lgnd-20260930.xsd#lgnd_AssetAcquisitionRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContractAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_lgnd_AssetAcquisitionRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContractAssets_01a01583-bff6-7dc2-afe0-d62a57522594" xlink:type="arc" order="52"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentForContingentConsiderationLiabilityInvestingActivities_01a01583-bff6-7adb-8a79-76e584ffe9e1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentForContingentConsiderationLiabilityInvestingActivities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_PaymentForContingentConsiderationLiabilityInvestingActivities_01a01583-bff6-7adb-8a79-76e584ffe9e1" xlink:type="arc" order="53"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireProductiveAssets_01a01583-bff6-78a0-a9f5-c62df05e28ce" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquireProductiveAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_PaymentsToAcquireProductiveAssets_01a01583-bff6-78a0-a9f5-c62df05e28ce" xlink:type="arc" order="54"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ReceivableWithImputedInterestFaceAmount_01a01583-bff6-7eeb-b1b4-9ea7f72c91c9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ReceivableWithImputedInterestFaceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_ReceivableWithImputedInterestFaceAmount_01a01583-bff6-7eeb-b1b4-9ea7f72c91c9" xlink:type="arc" order="55"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireNotesReceivable_01a01583-bff6-7060-962f-90b5c95464d1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquireNotesReceivable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetAcquisitionLineItems_01a01583-bff6-7d5d-8ede-d66224f2d32b" xlink:to="loc_us-gaap_PaymentsToAcquireNotesReceivable_01a01583-bff6-7060-962f-90b5c95464d1" xlink:type="arc" order="56"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/FinancialRoyaltyAssetsnetScheduleofFinancialRoyaltyAssetsDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#FinancialRoyaltyAssetsnetScheduleofFinancialRoyaltyAssetsDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/FinancialRoyaltyAssetsnetScheduleofFinancialRoyaltyAssetsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a143c8-a0f0-7954-b846-d69f05677a41" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_01a143c8-a0f0-7845-9ce0-9cc6f536d04e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a143c8-a0f0-7954-b846-d69f05677a41" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_01a143c8-a0f0-7845-9ce0-9cc6f536d04e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a143c8-a0f0-7611-9004-bcc0fb7b30fc" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_01a143c8-a0f0-7845-9ce0-9cc6f536d04e" xlink:to="loc_srt_ProductOrServiceAxis_01a143c8-a0f0-7611-9004-bcc0fb7b30fc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7611-9004-bcc0fb7b30fc_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a143c8-a0f0-7611-9004-bcc0fb7b30fc" xlink:to="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7611-9004-bcc0fb7b30fc_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a143c8-a0f0-7611-9004-bcc0fb7b30fc" xlink:to="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OjemdaMember_01a143c8-a0f0-776f-aa52-992127a72c11" xlink:href="lgnd-20260930.xsd#lgnd_OjemdaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_OjemdaMember_01a143c8-a0f0-776f-aa52-992127a72c11" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VabysmoMember_01a143c8-a0f0-7c2d-bf5f-898f6e3b2339" xlink:href="lgnd-20260930.xsd#lgnd_VabysmoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_VabysmoMember_01a143c8-a0f0-7c2d-bf5f-898f6e3b2339" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_QarzibaMember_01a143c8-a0f0-76db-919c-8a6eae26a17f" xlink:href="lgnd-20260930.xsd#lgnd_QarzibaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_QarzibaMember_01a143c8-a0f0-76db-919c-8a6eae26a17f" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AgenusBotBalMember_01a143c8-a0f0-79e3-9d0f-6e09c8a53303" xlink:href="lgnd-20260930.xsd#lgnd_AgenusBotBalMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_AgenusBotBalMember_01a143c8-a0f0-79e3-9d0f-6e09c8a53303" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MiplyffaMember_01a143c8-a0f0-7550-b0e6-b04991a27456" xlink:href="lgnd-20260930.xsd#lgnd_MiplyffaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_MiplyffaMember_01a143c8-a0f0-7550-b0e6-b04991a27456" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VolixibatMember_01a143c8-a0f0-7904-b171-8f52321229d7" xlink:href="lgnd-20260930.xsd#lgnd_VolixibatMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_VolixibatMember_01a143c8-a0f0-7904-b171-8f52321229d7" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OsavampatorMember_01a143c8-a0f0-728f-9a53-bc0b5066a1a6" xlink:href="lgnd-20260930.xsd#lgnd_OsavampatorMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_OsavampatorMember_01a143c8-a0f0-728f-9a53-bc0b5066a1a6" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_REC4881Member_01a143c8-a0f0-7fd9-8049-30dabbf7c5ae" xlink:href="lgnd-20260930.xsd#lgnd_REC4881Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_REC4881Member_01a143c8-a0f0-7fd9-8049-30dabbf7c5ae" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ToleranceTherapeuticsTzieldMember_01a143c8-a0f0-746a-b009-b6cd43ad2099" xlink:href="lgnd-20260930.xsd#lgnd_ToleranceTherapeuticsTzieldMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_ToleranceTherapeuticsTzieldMember_01a143c8-a0f0-746a-b009-b6cd43ad2099" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RyjuneaMember_01a143c8-a0f0-7e48-ab59-df1ef9319e05" xlink:href="lgnd-20260930.xsd#lgnd_RyjuneaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_RyjuneaMember_01a143c8-a0f0-7e48-ab59-df1ef9319e05" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OhtuvayreInventorsMember_01a143c8-a0f0-75cd-9911-3ef90b294962" xlink:href="lgnd-20260930.xsd#lgnd_OhtuvayreInventorsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_OhtuvayreInventorsMember_01a143c8-a0f0-75cd-9911-3ef90b294962" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_TwistProgramsMember_01a143c8-a0f0-718b-8e94-7fb0b2c7c323" xlink:href="lgnd-20260930.xsd#lgnd_TwistProgramsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_TwistProgramsMember_01a143c8-a0f0-718b-8e94-7fb0b2c7c323" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OakHillProgramsMember_01a143c8-a0f0-755f-9b86-c382e9d969b5" xlink:href="lgnd-20260930.xsd#lgnd_OakHillProgramsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_OakHillProgramsMember_01a143c8-a0f0-755f-9b86-c382e9d969b5" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PrimroseMRNAMember_01a143c8-a0f0-7aaa-a4e5-96db50998eea" xlink:href="lgnd-20260930.xsd#lgnd_PrimroseMRNAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_PrimroseMRNAMember_01a143c8-a0f0-7aaa-a4e5-96db50998eea" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VidutolimodMember_01a143c8-a0f0-7816-88ad-43e107d0d4dc" xlink:href="lgnd-20260930.xsd#lgnd_VidutolimodMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_VidutolimodMember_01a143c8-a0f0-7816-88ad-43e107d0d4dc" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_DFiMember_01a143c8-a0f0-7dce-a161-8e81c92849c0" xlink:href="lgnd-20260930.xsd#lgnd_DFiMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_DFiMember_01a143c8-a0f0-7dce-a161-8e81c92849c0" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_IxinityMember_01a143c8-a0f0-73d0-b216-ca5d481d2ebb" xlink:href="lgnd-20260930.xsd#lgnd_IxinityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_IxinityMember_01a143c8-a0f0-73d0-b216-ca5d481d2ebb" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AT220Member_01a143c8-a0f0-73e5-9ee3-a4fdb7a1faf5" xlink:href="lgnd-20260930.xsd#lgnd_AT220Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_AT220Member_01a143c8-a0f0-73e5-9ee3-a4fdb7a1faf5" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ElutiaCorMatrixMember_01a143c8-a0f0-7a38-97b7-302bb75430be" xlink:href="lgnd-20260930.xsd#lgnd_ElutiaCorMatrixMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_ElutiaCorMatrixMember_01a143c8-a0f0-7a38-97b7-302bb75430be" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OthersMember_01a143c8-a0f0-713e-a14f-41bc0f31bdb5" xlink:href="lgnd-20260930.xsd#lgnd_OthersMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a143c8-a0f0-7c0f-b3f8-b00b5b5fe67d" xlink:to="loc_lgnd_OthersMember_01a143c8-a0f0-713e-a14f-41bc0f31bdb5" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetsGross_01a143c8-a0f0-7e27-a651-62e27c165932" xlink:href="lgnd-20260930.xsd#lgnd_FinancialRoyaltyAssetsGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a143c8-a0f0-7954-b846-d69f05677a41" xlink:to="loc_lgnd_FinancialRoyaltyAssetsGross_01a143c8-a0f0-7e27-a651-62e27c165932" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetsAllowance_01a143c8-a0f0-70e2-b49e-89b8524707ee" xlink:href="lgnd-20260930.xsd#lgnd_FinancialRoyaltyAssetsAllowance"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a143c8-a0f0-7954-b846-d69f05677a41" xlink:to="loc_lgnd_FinancialRoyaltyAssetsAllowance_01a143c8-a0f0-70e2-b49e-89b8524707ee" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetsNet_01a143c8-a0f0-7da3-b9fd-f85bb2130f2c" xlink:href="lgnd-20260930.xsd#lgnd_FinancialRoyaltyAssetsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a143c8-a0f0-7954-b846-d69f05677a41" xlink:to="loc_lgnd_FinancialRoyaltyAssetsNet_01a143c8-a0f0-7da3-b9fd-f85bb2130f2c" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/FinancialRoyaltyAssetsnetNarrativeDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#FinancialRoyaltyAssetsnetNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/FinancialRoyaltyAssetsnetNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a01583-c0a6-71d0-a9af-7c47cbc6d5f2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FiniteLivedIntangibleAssetsLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_01a01583-c0a6-7da0-8639-c093326f815f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a01583-c0a6-71d0-a9af-7c47cbc6d5f2" xlink:to="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_01a01583-c0a6-7da0-8639-c093326f815f" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductOrServiceAxis_01a01583-c0a6-7fc0-aa71-973af558fab1" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductOrServiceAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_01a01583-c0a6-7da0-8639-c093326f815f" xlink:to="loc_srt_ProductOrServiceAxis_01a01583-c0a6-7fc0-aa71-973af558fab1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a01583-c0a6-7fc0-aa71-973af558fab1_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ProductOrServiceAxis_01a01583-c0a6-7fc0-aa71-973af558fab1" xlink:to="loc_srt_ProductsAndServicesDomain_01a01583-c0a6-7fc0-aa71-973af558fab1_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ProductsAndServicesDomain_01a01583-c0a6-70ec-b0e6-299b113c96be" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ProductsAndServicesDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ProductOrServiceAxis_01a01583-c0a6-7fc0-aa71-973af558fab1" xlink:to="loc_srt_ProductsAndServicesDomain_01a01583-c0a6-70ec-b0e6-299b113c96be" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_QARZIBAMember_01a01583-c0a6-73ed-a801-210de0523d2b" xlink:href="lgnd-20260930.xsd#lgnd_QARZIBAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-c0a6-70ec-b0e6-299b113c96be" xlink:to="loc_lgnd_QARZIBAMember_01a01583-c0a6-73ed-a801-210de0523d2b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_InvIOsMember_01a01583-c0a6-7bea-83ab-816732e134e6" xlink:href="lgnd-20260930.xsd#lgnd_InvIOsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ProductsAndServicesDomain_01a01583-c0a6-70ec-b0e6-299b113c96be" xlink:to="loc_lgnd_InvIOsMember_01a01583-c0a6-7bea-83ab-816732e134e6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a01583-c0a6-7ada-b4bf-f61c72d098d6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_01a01583-c0a6-7da0-8639-c093326f815f" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a01583-c0a6-7ada-b4bf-f61c72d098d6" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-7ada-b4bf-f61c72d098d6_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a01583-c0a6-7ada-b4bf-f61c72d098d6" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-7ada-b4bf-f61c72d098d6_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-702d-96e2-c2a7d42a280f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a01583-c0a6-7ada-b4bf-f61c72d098d6" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-702d-96e2-c2a7d42a280f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_APEIRONMember_01a01583-c0a6-74d9-97f7-652a072d05ab" xlink:href="lgnd-20260930.xsd#lgnd_APEIRONMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-702d-96e2-c2a7d42a280f" xlink:to="loc_lgnd_APEIRONMember_01a01583-c0a6-74d9-97f7-652a072d05ab" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ToleranceTherapeuticsMember_01a01583-c0a6-7e5e-b440-777231ca8d66" xlink:href="lgnd-20260930.xsd#lgnd_ToleranceTherapeuticsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-702d-96e2-c2a7d42a280f" xlink:to="loc_lgnd_ToleranceTherapeuticsMember_01a01583-c0a6-7e5e-b440-777231ca8d66" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OjemdaMember_01a17d07-2737-7cbd-bb93-2ae581ab0fbf" xlink:href="lgnd-20260930.xsd#lgnd_OjemdaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-702d-96e2-c2a7d42a280f" xlink:to="loc_lgnd_OjemdaMember_01a17d07-2737-7cbd-bb93-2ae581ab0fbf" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VabysmoMember_01a17d07-f811-7993-94f5-8d2f902dbb59" xlink:href="lgnd-20260930.xsd#lgnd_VabysmoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-702d-96e2-c2a7d42a280f" xlink:to="loc_lgnd_VabysmoMember_01a17d07-f811-7993-94f5-8d2f902dbb59" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MiplyffaMember_01a17d09-2a29-734f-9a54-7462d845b9b2" xlink:href="lgnd-20260930.xsd#lgnd_MiplyffaMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-702d-96e2-c2a7d42a280f" xlink:to="loc_lgnd_MiplyffaMember_01a17d09-2a29-734f-9a54-7462d845b9b2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_VolixibatMember_01a17d09-8214-7c8a-849b-3e9d88bcd212" xlink:href="lgnd-20260930.xsd#lgnd_VolixibatMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-702d-96e2-c2a7d42a280f" xlink:to="loc_lgnd_VolixibatMember_01a17d09-8214-7c8a-849b-3e9d88bcd212" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OsavampatorMember_01a17d09-d132-794e-8b64-47f52b0498d2" xlink:href="lgnd-20260930.xsd#lgnd_OsavampatorMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-702d-96e2-c2a7d42a280f" xlink:to="loc_lgnd_OsavampatorMember_01a17d09-d132-794e-8b64-47f52b0498d2" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_REC4881Member_01a17d0a-5547-7746-a917-8c83e2a1ecac" xlink:href="lgnd-20260930.xsd#lgnd_REC4881Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-702d-96e2-c2a7d42a280f" xlink:to="loc_lgnd_REC4881Member_01a17d0a-5547-7746-a917-8c83e2a1ecac" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_01a01583-c0a6-7655-8526-8c83356221e0" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfFiniteLivedIntangibleAssetsTable_01a01583-c0a6-7da0-8639-c093326f815f" xlink:to="loc_srt_CounterpartyNameAxis_01a01583-c0a6-7655-8526-8c83356221e0" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-c0a6-7655-8526-8c83356221e0_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_01a01583-c0a6-7655-8526-8c83356221e0" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-c0a6-7655-8526-8c83356221e0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-c0a6-77dc-96c6-712143453a9e" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_01a01583-c0a6-7655-8526-8c83356221e0" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-c0a6-77dc-96c6-712143453a9e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_OhtuvayreInventorsMember_01a01583-c0a6-7cda-98d6-bfa3e49f4dd6" xlink:href="lgnd-20260930.xsd#lgnd_OhtuvayreInventorsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a01583-c0a6-77dc-96c6-712143453a9e" xlink:to="loc_lgnd_OhtuvayreInventorsMember_01a01583-c0a6-7cda-98d6-bfa3e49f4dd6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ImpairmentLossOnFinancialRoyaltyAssets_01a01583-c0a6-7884-80a8-fbaa2f626d65" xlink:href="lgnd-20260930.xsd#lgnd_ImpairmentLossOnFinancialRoyaltyAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a01583-c0a6-71d0-a9af-7c47cbc6d5f2" xlink:to="loc_lgnd_ImpairmentLossOnFinancialRoyaltyAssets_01a01583-c0a6-7884-80a8-fbaa2f626d65" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_01a17d06-aad3-7016-b6eb-cf1351c18b24" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a01583-c0a6-71d0-a9af-7c47cbc6d5f2" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_01a17d06-aad3-7016-b6eb-cf1351c18b24" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_IncomeRecognizedFinancialRoyaltyAsset_01a17d0f-2a22-7057-a77d-1ff6327decb1" xlink:href="lgnd-20260930.xsd#lgnd_IncomeRecognizedFinancialRoyaltyAsset"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a01583-c0a6-71d0-a9af-7c47cbc6d5f2" xlink:to="loc_lgnd_IncomeRecognizedFinancialRoyaltyAsset_01a17d0f-2a22-7057-a77d-1ff6327decb1" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContractAssets_01a01583-c0a6-756f-881b-78cc85208557" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContractAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a01583-c0a6-71d0-a9af-7c47cbc6d5f2" xlink:to="loc_lgnd_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedContractAssets_01a01583-c0a6-756f-881b-78cc85208557" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsToAcquireBusinessesGross_01a01583-c0a6-77cf-a7af-61035c7311ba" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsToAcquireBusinessesGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a01583-c0a6-71d0-a9af-7c47cbc6d5f2" xlink:to="loc_us-gaap_PaymentsToAcquireBusinessesGross_01a01583-c0a6-77cf-a7af-61035c7311ba" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ProductRoyaltyPercentage_01a01583-c0a6-7fa2-ad2c-332ed498b499" xlink:href="lgnd-20260930.xsd#lgnd_ProductRoyaltyPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a01583-c0a6-71d0-a9af-7c47cbc6d5f2" xlink:to="loc_lgnd_ProductRoyaltyPercentage_01a01583-c0a6-7fa2-ad2c-332ed498b499" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities_01a01583-c0a6-7a0c-9983-924f985111f0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a01583-c0a6-71d0-a9af-7c47cbc6d5f2" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities_01a01583-c0a6-7a0c-9983-924f985111f0" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetsGross_01a01583-c0a6-7147-ac48-86e14e1fba18" xlink:href="lgnd-20260930.xsd#lgnd_FinancialRoyaltyAssetsGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FiniteLivedIntangibleAssetsLineItems_01a01583-c0a6-71d0-a9af-7c47cbc6d5f2" xlink:to="loc_lgnd_FinancialRoyaltyAssetsGross_01a01583-c0a6-7147-ac48-86e14e1fba18" xlink:type="arc" order="7"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/FairValueMeasurementsAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#FairValueMeasurementsAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/FairValueMeasurementsAssetsandLiabilitiesMeasuredatFairValueonRecurringBasisDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a01583-c0a6-7c7e-83f8-039f6e79640f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a01583-c0a6-7368-9e5f-ed681f5fed93" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a01583-c0a6-7c7e-83f8-039f6e79640f" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a01583-c0a6-7368-9e5f-ed681f5fed93" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_01a01583-c0a6-7f21-b392-12538e3dd3a8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a01583-c0a6-7368-9e5f-ed681f5fed93" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_01a01583-c0a6-7f21-b392-12538e3dd3a8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a01583-c0a6-7f21-b392-12538e3dd3a8_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_01a01583-c0a6-7f21-b392-12538e3dd3a8" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a01583-c0a6-7f21-b392-12538e3dd3a8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a01583-c0a6-7bdc-8414-f6a841e3dffa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_01a01583-c0a6-7f21-b392-12538e3dd3a8" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a01583-c0a6-7bdc-8414-f6a841e3dffa" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel1Member_01a01583-c0a6-7acf-9a40-e2ca4a02c1f1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel1Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a01583-c0a6-7bdc-8414-f6a841e3dffa" xlink:to="loc_us-gaap_FairValueInputsLevel1Member_01a01583-c0a6-7acf-9a40-e2ca4a02c1f1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel2Member_01a01583-c0a6-7fe1-bab0-8c84ae3856eb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel2Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a01583-c0a6-7bdc-8414-f6a841e3dffa" xlink:to="loc_us-gaap_FairValueInputsLevel2Member_01a01583-c0a6-7fe1-bab0-8c84ae3856eb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_01a01583-c0a6-7d11-8ea6-aec761d8f56d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a01583-c0a6-7bdc-8414-f6a841e3dffa" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_01a01583-c0a6-7d11-8ea6-aec761d8f56d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FinancialInstrumentAxis_01a01583-c0a6-74e1-98c4-dff6e420a3bb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FinancialInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a01583-c0a6-7368-9e5f-ed681f5fed93" xlink:to="loc_us-gaap_FinancialInstrumentAxis_01a01583-c0a6-74e1-98c4-dff6e420a3bb" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-c0a6-74e1-98c4-dff6e420a3bb_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FinancialInstrumentAxis_01a01583-c0a6-74e1-98c4-dff6e420a3bb" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-c0a6-74e1-98c4-dff6e420a3bb_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-c0a6-713c-9de0-e9c8f8ed01d6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FinancialInstrumentAxis_01a01583-c0a6-74e1-98c4-dff6e420a3bb" xlink:to="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-c0a6-713c-9de0-e9c8f8ed01d6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShortTermInvestmentsMember_01a01583-c0a6-7dda-9f6d-7bb5c875683c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShortTermInvestmentsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-c0a6-713c-9de0-e9c8f8ed01d6" xlink:to="loc_us-gaap_ShortTermInvestmentsMember_01a01583-c0a6-7dda-9f6d-7bb5c875683c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PreferredStockMember_01a01583-c0a6-7b1a-b916-ce5a2e0069f5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-c0a6-713c-9de0-e9c8f8ed01d6" xlink:to="loc_us-gaap_PreferredStockMember_01a01583-c0a6-7b1a-b916-ce5a2e0069f5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ContingentLiabilitiesMember_01a01583-c0a6-7ccc-bb1c-c77fe3fdb20d" xlink:href="lgnd-20260930.xsd#lgnd_ContingentLiabilitiesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_TransfersAndServicingOfFinancialInstrumentsTypesOfFinancialInstrumentsDomain_01a01583-c0a6-713c-9de0-e9c8f8ed01d6" xlink:to="loc_lgnd_ContingentLiabilitiesMember_01a01583-c0a6-7ccc-bb1c-c77fe3fdb20d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a01583-c0a6-74ae-aa19-cfe28f42ad90" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a01583-c0a6-7368-9e5f-ed681f5fed93" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a01583-c0a6-74ae-aa19-cfe28f42ad90" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-74ae-aa19-cfe28f42ad90_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a01583-c0a6-74ae-aa19-cfe28f42ad90" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-74ae-aa19-cfe28f42ad90_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-73ed-9438-ed8a573bb3fd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a01583-c0a6-74ae-aa19-cfe28f42ad90" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-73ed-9438-ed8a573bb3fd" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_CyDexMember_01a01583-c0a6-7d11-8f24-366169dbc46d" xlink:href="lgnd-20260930.xsd#lgnd_CyDexMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-73ed-9438-ed8a573bb3fd" xlink:to="loc_lgnd_CyDexMember_01a01583-c0a6-7d11-8f24-366169dbc46d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MetabasisMember_01a01583-c0a6-754d-845a-494c2be88095" xlink:href="lgnd-20260930.xsd#lgnd_MetabasisMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-73ed-9438-ed8a573bb3fd" xlink:to="loc_lgnd_MetabasisMember_01a01583-c0a6-754d-845a-494c2be88095" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_HilleVaxMember_01a143cc-5493-7c9d-a632-090bc7325646" xlink:href="lgnd-20260930.xsd#lgnd_HilleVaxMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-73ed-9438-ed8a573bb3fd" xlink:to="loc_lgnd_HilleVaxMember_01a143cc-5493-7c9d-a632-090bc7325646" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LAVAMember_01a143cc-a29a-7d14-bfc0-af1df48666de" xlink:href="lgnd-20260930.xsd#lgnd_LAVAMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-73ed-9438-ed8a573bb3fd" xlink:to="loc_lgnd_LAVAMember_01a143cc-a29a-7d14-bfc0-af1df48666de" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BioInventMember_01a143cc-e0ae-7b6e-b687-e73001b65f9e" xlink:href="lgnd-20260930.xsd#lgnd_BioInventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-73ed-9438-ed8a573bb3fd" xlink:to="loc_lgnd_BioInventMember_01a143cc-e0ae-7b6e-b687-e73001b65f9e" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PulmokineMember_01a143cd-1a6d-7e01-94bd-6eea42ac4e82" xlink:href="lgnd-20260930.xsd#lgnd_PulmokineMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-73ed-9438-ed8a573bb3fd" xlink:to="loc_lgnd_PulmokineMember_01a143cd-1a6d-7e01-94bd-6eea42ac4e82" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_KinnateMember_01a143cd-54c8-7b30-aa32-b5d16fd56c6b" xlink:href="lgnd-20260930.xsd#lgnd_KinnateMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-73ed-9438-ed8a573bb3fd" xlink:to="loc_lgnd_KinnateMember_01a143cd-54c8-7b30-aa32-b5d16fd56c6b" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ExarafenibMember_01a143cd-896a-7778-bd24-69c285259e4f" xlink:href="lgnd-20260930.xsd#lgnd_ExarafenibMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-73ed-9438-ed8a573bb3fd" xlink:to="loc_lgnd_ExarafenibMember_01a143cd-896a-7778-bd24-69c285259e4f" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ContingentLiabilitiesOtherMember_01a143cd-c71e-7562-b0b8-f1b09c7a2365" xlink:href="lgnd-20260930.xsd#lgnd_ContingentLiabilitiesOtherMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a01583-c0a6-73ed-9438-ed8a573bb3fd" xlink:to="loc_lgnd_ContingentLiabilitiesOtherMember_01a143cd-c71e-7562-b0b8-f1b09c7a2365" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_01a01583-c0a6-7852-84cf-dc8989a6dd44" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a01583-c0a6-7368-9e5f-ed681f5fed93" xlink:to="loc_srt_RangeAxis_01a01583-c0a6-7852-84cf-dc8989a6dd44" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a01583-c0a6-7852-84cf-dc8989a6dd44_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_01a01583-c0a6-7852-84cf-dc8989a6dd44" xlink:to="loc_srt_RangeMember_01a01583-c0a6-7852-84cf-dc8989a6dd44_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a01583-c0a6-7ea7-81e1-e409eddd4130" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_01a01583-c0a6-7852-84cf-dc8989a6dd44" xlink:to="loc_srt_RangeMember_01a01583-c0a6-7ea7-81e1-e409eddd4130" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_01a01583-c0a6-732f-9ecd-a3ee9facc21e" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a01583-c0a6-7ea7-81e1-e409eddd4130" xlink:to="loc_srt_MaximumMember_01a01583-c0a6-732f-9ecd-a3ee9facc21e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_01a18e68-f1e0-78a7-9655-0d57f665615e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a01583-c0a6-7368-9e5f-ed681f5fed93" xlink:to="loc_us-gaap_StatementClassOfStockAxis_01a18e68-f1e0-78a7-9655-0d57f665615e" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a18e68-f1e0-78a7-9655-0d57f665615e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a18e68-f1e0-78a7-9655-0d57f665615e" xlink:to="loc_us-gaap_ClassOfStockDomain_01a18e68-f1e0-78a7-9655-0d57f665615e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a18e68-f1e0-737b-ad77-5ee58f915cc9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a18e68-f1e0-78a7-9655-0d57f665615e" xlink:to="loc_us-gaap_ClassOfStockDomain_01a18e68-f1e0-737b-ad77-5ee58f915cc9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_01a18e69-160a-7ff9-928c-10c25bb458ed" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_01a18e68-f1e0-737b-ad77-5ee58f915cc9" xlink:to="loc_us-gaap_CommonStockMember_01a18e69-160a-7ff9-928c-10c25bb458ed" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a18e69-0685-74ba-9cf5-61da759eca0c" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a01583-c0a6-7368-9e5f-ed681f5fed93" xlink:to="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a18e69-0685-74ba-9cf5-61da759eca0c" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a18e69-0685-74ba-9cf5-61da759eca0c_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a18e69-0685-74ba-9cf5-61da759eca0c" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a18e69-0685-74ba-9cf5-61da759eca0c_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_EquityMethodInvesteeNameDomain_01a18e69-0685-7194-8d65-a589d04212f5" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_EquityMethodInvesteeNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ScheduleOfEquityMethodInvestmentEquityMethodInvesteeNameAxis_01a18e69-0685-74ba-9cf5-61da759eca0c" xlink:to="loc_srt_EquityMethodInvesteeNameDomain_01a18e69-0685-7194-8d65-a589d04212f5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_RemainCoMember_01a18e69-4741-77ca-99ee-f8edde8f75f0" xlink:href="lgnd-20260930.xsd#lgnd_RemainCoMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_EquityMethodInvesteeNameDomain_01a18e69-0685-7194-8d65-a589d04212f5" xlink:to="loc_lgnd_RemainCoMember_01a18e69-4741-77ca-99ee-f8edde8f75f0" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosureAbstract_01a01583-c0a6-74b0-8be5-d2be403b62b4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a01583-c0a6-7c7e-83f8-039f6e79640f" xlink:to="loc_us-gaap_AssetsFairValueDisclosureAbstract_01a01583-c0a6-74b0-8be5-d2be403b62b4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InvestmentsFairValueDisclosure_01a01583-c0a6-79a6-8468-6b868f760e8c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InvestmentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_01a01583-c0a6-74b0-8be5-d2be403b62b4" xlink:to="loc_us-gaap_InvestmentsFairValueDisclosure_01a01583-c0a6-79a6-8468-6b868f760e8c" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquitySecuritiesFvNiCurrentAndNoncurrent_01a01583-c0a6-730b-be1f-0da17993df34" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquitySecuritiesFvNiCurrentAndNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_01a01583-c0a6-74b0-8be5-d2be403b62b4" xlink:to="loc_us-gaap_EquitySecuritiesFvNiCurrentAndNoncurrent_01a01583-c0a6-730b-be1f-0da17993df34" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EquityMethodInvestmentsFairValueDisclosure_01a18e69-f69b-75db-a49a-9477fa2ec8b8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EquityMethodInvestmentsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_01a01583-c0a6-74b0-8be5-d2be403b62b4" xlink:to="loc_us-gaap_EquityMethodInvestmentsFairValueDisclosure_01a18e69-f69b-75db-a49a-9477fa2ec8b8" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeAssets_01a01583-c0a6-7250-883e-3791bbacbf55" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_01a01583-c0a6-74b0-8be5-d2be403b62b4" xlink:to="loc_us-gaap_DerivativeAssets_01a01583-c0a6-7250-883e-3791bbacbf55" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AssetsFairValueDisclosure_01a01583-c0a6-73ee-bbff-b2849c17e892" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_01a01583-c0a6-74b0-8be5-d2be403b62b4" xlink:to="loc_us-gaap_AssetsFairValueDisclosure_01a01583-c0a6-73ee-bbff-b2849c17e892" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_DerivativeAssetStatementOfFinancialPositionExtensibleEnumerationNotDisclosedFlag_01a01583-c0a6-764f-955f-a29eff38619d" xlink:href="lgnd-20260930.xsd#lgnd_DerivativeAssetStatementOfFinancialPositionExtensibleEnumerationNotDisclosedFlag"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_AssetsFairValueDisclosureAbstract_01a01583-c0a6-74b0-8be5-d2be403b62b4" xlink:to="loc_lgnd_DerivativeAssetStatementOfFinancialPositionExtensibleEnumerationNotDisclosedFlag_01a01583-c0a6-764f-955f-a29eff38619d" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_01a01583-c0a6-76d7-a48a-b0d3f5e832e0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LiabilitiesFairValueDisclosureAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a01583-c0a6-7c7e-83f8-039f6e79640f" xlink:to="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_01a01583-c0a6-76d7-a48a-b0d3f5e832e0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationContingentConsiderationLiabilityFairValueDisclosure_01a01583-c0a6-75ec-969f-bd388c95cf7a" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationContingentConsiderationLiabilityFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_01a01583-c0a6-76d7-a48a-b0d3f5e832e0" xlink:to="loc_lgnd_BusinessCombinationContingentConsiderationLiabilityFairValueDisclosure_01a01583-c0a6-75ec-969f-bd388c95cf7a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DerivativeLiabilities_01a01583-c0a6-7f40-888d-72c5b832fc26" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DerivativeLiabilities"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_01a01583-c0a6-76d7-a48a-b0d3f5e832e0" xlink:to="loc_us-gaap_DerivativeLiabilities_01a01583-c0a6-7f40-888d-72c5b832fc26" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueDisclosure_01a01583-c0a6-7fb7-98be-5df003070871" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LiabilitiesFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LiabilitiesFairValueDisclosureAbstract_01a01583-c0a6-76d7-a48a-b0d3f5e832e0" xlink:to="loc_us-gaap_LiabilitiesFairValueDisclosure_01a01583-c0a6-7fb7-98be-5df003070871" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueAdjustment_01a01583-c0a6-70ac-a214-489ca5c9727a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LiabilitiesFairValueAdjustment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a01583-c0a6-7c7e-83f8-039f6e79640f" xlink:to="loc_us-gaap_LiabilitiesFairValueAdjustment_01a01583-c0a6-70ac-a214-489ca5c9727a" xlink:type="arc" order="2"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/FairValueMeasurementsNarrativeDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#FairValueMeasurementsNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/FairValueMeasurementsNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a17cea-75c4-7e1b-ba7f-3595c57ec535" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a17cea-75c4-7e1b-ba7f-3595c57ec535" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a17cea-75c4-7dec-acdd-6512135cc3bf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a17cea-75c4-7e1b-ba7f-3595c57ec535" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a17cea-75c4-7dec-acdd-6512135cc3bf" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a17cea-75c4-7dec-acdd-6512135cc3bf_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a17cea-75c4-7dec-acdd-6512135cc3bf" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a17cea-75c4-7dec-acdd-6512135cc3bf_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a17cea-75c4-7e48-b6ef-13b81b12c1e2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a17cea-75c4-7dec-acdd-6512135cc3bf" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a17cea-75c4-7e48-b6ef-13b81b12c1e2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_MetabasisMember_01a17cea-75c4-79ea-8037-45701a37e273" xlink:href="lgnd-20260930.xsd#lgnd_MetabasisMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a17cea-75c4-7e48-b6ef-13b81b12c1e2" xlink:to="loc_lgnd_MetabasisMember_01a17cea-75c4-79ea-8037-45701a37e273" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_HilleVaxCVRMember_01a17cea-75c4-74ed-811f-3ca57f1facfe" xlink:href="lgnd-20260930.xsd#lgnd_HilleVaxCVRMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a17cea-75c4-7e48-b6ef-13b81b12c1e2" xlink:to="loc_lgnd_HilleVaxCVRMember_01a17cea-75c4-74ed-811f-3ca57f1facfe" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LAVACVRMember_01a18e61-ac5b-77eb-ba20-0a907893ffac" xlink:href="lgnd-20260930.xsd#lgnd_LAVACVRMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a17cea-75c4-7e48-b6ef-13b81b12c1e2" xlink:to="loc_lgnd_LAVACVRMember_01a18e61-ac5b-77eb-ba20-0a907893ffac" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMAAcquisitionMember_01a17cea-9533-7abf-ac30-5addc29a7168" xlink:href="lgnd-20260930.xsd#lgnd_XOMAAcquisitionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a17cea-75c4-7e48-b6ef-13b81b12c1e2" xlink:to="loc_lgnd_XOMAAcquisitionMember_01a17cea-9533-7abf-ac30-5addc29a7168" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_01a17cea-75c4-7df4-96de-e635fc69285d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a17cea-75c4-7e1b-ba7f-3595c57ec535" xlink:to="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_01a17cea-75c4-7df4-96de-e635fc69285d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a17cea-75c4-7df4-96de-e635fc69285d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_01a17cea-75c4-7df4-96de-e635fc69285d" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a17cea-75c4-7df4-96de-e635fc69285d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a17cea-75c4-77f0-a094-ccdca99de9a9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByFairValueHierarchyLevelAxis_01a17cea-75c4-7df4-96de-e635fc69285d" xlink:to="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a17cea-75c4-77f0-a094-ccdca99de9a9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueInputsLevel3Member_01a17cea-75c4-785c-b05e-8a4b747195fc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueInputsLevel3Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueMeasurementsFairValueHierarchyDomain_01a17cea-75c4-77f0-a094-ccdca99de9a9" xlink:to="loc_us-gaap_FairValueInputsLevel3Member_01a17cea-75c4-785c-b05e-8a4b747195fc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_01a17cea-9533-7410-8c9c-b67a28a249a8" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a17cea-75c4-7e1b-ba7f-3595c57ec535" xlink:to="loc_srt_RangeAxis_01a17cea-9533-7410-8c9c-b67a28a249a8" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a17cea-9533-7410-8c9c-b67a28a249a8_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_01a17cea-9533-7410-8c9c-b67a28a249a8" xlink:to="loc_srt_RangeMember_01a17cea-9533-7410-8c9c-b67a28a249a8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a17cea-9533-7eec-8f8c-eaac239383b5" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_01a17cea-9533-7410-8c9c-b67a28a249a8" xlink:to="loc_srt_RangeMember_01a17cea-9533-7eec-8f8c-eaac239383b5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MinimumMember_01a17cea-9533-7c99-a2f5-a4b6a8cd2427" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MinimumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a17cea-9533-7eec-8f8c-eaac239383b5" xlink:to="loc_srt_MinimumMember_01a17cea-9533-7c99-a2f5-a4b6a8cd2427" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_01a17cea-9533-732b-a47e-1fc8262a4533" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a17cea-9533-7eec-8f8c-eaac239383b5" xlink:to="loc_srt_MaximumMember_01a17cea-9533-732b-a47e-1fc8262a4533" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_WeightedAverageMember_01a17cea-b555-77db-8904-dbb9f9fafd88" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_WeightedAverageMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a17cea-9533-7eec-8f8c-eaac239383b5" xlink:to="loc_srt_WeightedAverageMember_01a17cea-b555-77db-8904-dbb9f9fafd88" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeAxis_01a17cea-9533-71ce-afc7-ca38ec86cce3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a17cea-75c4-7e1b-ba7f-3595c57ec535" xlink:to="loc_us-gaap_MeasurementInputTypeAxis_01a17cea-9533-71ce-afc7-ca38ec86cce3" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a17cea-9533-71ce-afc7-ca38ec86cce3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a17cea-9533-71ce-afc7-ca38ec86cce3" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a17cea-9533-71ce-afc7-ca38ec86cce3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputTypeDomain_01a17cea-9533-7143-81a2-0dcf5be07033" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_MeasurementInputTypeAxis_01a17cea-9533-71ce-afc7-ca38ec86cce3" xlink:to="loc_us-gaap_MeasurementInputTypeDomain_01a17cea-9533-7143-81a2-0dcf5be07033" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_MeasurementInputDiscountRateMember_01a17cea-9533-70d6-8123-54c7890b0468" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_MeasurementInputDiscountRateMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_MeasurementInputTypeDomain_01a17cea-9533-7143-81a2-0dcf5be07033" xlink:to="loc_us-gaap_MeasurementInputDiscountRateMember_01a17cea-9533-70d6-8123-54c7890b0468" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContingentConsiderationByTypeAxis_01a17cea-9533-7121-99e8-2b495516d95a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContingentConsiderationByTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a17cea-75c4-7e1b-ba7f-3595c57ec535" xlink:to="loc_us-gaap_ContingentConsiderationByTypeAxis_01a17cea-9533-7121-99e8-2b495516d95a" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContingentConsiderationTypeDomain_01a17cea-9533-7121-99e8-2b495516d95a_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContingentConsiderationTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ContingentConsiderationByTypeAxis_01a17cea-9533-7121-99e8-2b495516d95a" xlink:to="loc_us-gaap_ContingentConsiderationTypeDomain_01a17cea-9533-7121-99e8-2b495516d95a_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ContingentConsiderationTypeDomain_01a17cea-9533-704e-b918-a17543ecec67" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ContingentConsiderationTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ContingentConsiderationByTypeAxis_01a17cea-9533-7121-99e8-2b495516d95a" xlink:to="loc_us-gaap_ContingentConsiderationTypeDomain_01a17cea-9533-704e-b918-a17543ecec67" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FundedByPartnerRoyaltyAndMilestoneReceiptsMember_01a17cea-9533-70f9-8d34-c89e0d0316ae" xlink:href="lgnd-20260930.xsd#lgnd_FundedByPartnerRoyaltyAndMilestoneReceiptsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ContingentConsiderationTypeDomain_01a17cea-9533-704e-b918-a17543ecec67" xlink:to="loc_lgnd_FundedByPartnerRoyaltyAndMilestoneReceiptsMember_01a17cea-9533-70f9-8d34-c89e0d0316ae" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueByMeasurementBasisAxis_01a17cea-b555-713f-b6b9-ad30b907ec5f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueByMeasurementBasisAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable_01a17cea-75c4-7e1b-ba7f-3595c57ec535" xlink:to="loc_us-gaap_FairValueByMeasurementBasisAxis_01a17cea-b555-713f-b6b9-ad30b907ec5f" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PortionAtFairValueFairValueDisclosureMember_01a17cea-b555-713f-b6b9-ad30b907ec5f_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PortionAtFairValueFairValueDisclosureMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_FairValueByMeasurementBasisAxis_01a17cea-b555-713f-b6b9-ad30b907ec5f" xlink:to="loc_us-gaap_PortionAtFairValueFairValueDisclosureMember_01a17cea-b555-713f-b6b9-ad30b907ec5f_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueDisclosureItemAmountsDomain_01a18e66-b32a-7e8b-96b3-38118faa020e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueDisclosureItemAmountsDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_FairValueByMeasurementBasisAxis_01a17cea-b555-713f-b6b9-ad30b907ec5f" xlink:to="loc_us-gaap_FairValueDisclosureItemAmountsDomain_01a18e66-b32a-7e8b-96b3-38118faa020e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PortionAtFairValueFairValueDisclosureMember_01a17cea-b555-7414-9a90-fd3fcb96f1e6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PortionAtFairValueFairValueDisclosureMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueDisclosureItemAmountsDomain_01a18e66-b32a-7e8b-96b3-38118faa020e" xlink:to="loc_us-gaap_PortionAtFairValueFairValueDisclosureMember_01a17cea-b555-7414-9a90-fd3fcb96f1e6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EstimateOfFairValueFairValueDisclosureMember_01a17cea-b555-73a0-badb-66cfe4665277" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EstimateOfFairValueFairValueDisclosureMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PortionAtFairValueFairValueDisclosureMember_01a17cea-b555-7414-9a90-fd3fcb96f1e6" xlink:to="loc_us-gaap_EstimateOfFairValueFairValueDisclosureMember_01a17cea-b555-73a0-badb-66cfe4665277" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CarryingReportedAmountFairValueDisclosureMember_01a17cea-b555-7704-9097-91af8f9c314c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CarryingReportedAmountFairValueDisclosureMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PortionAtFairValueFairValueDisclosureMember_01a17cea-b555-7414-9a90-fd3fcb96f1e6" xlink:to="loc_us-gaap_CarryingReportedAmountFairValueDisclosureMember_01a17cea-b555-7704-9097-91af8f9c314c" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LiabilitiesFairValueAdjustment_01a17cea-75c4-7c10-94e7-d6a9da661738" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LiabilitiesFairValueAdjustment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_us-gaap_LiabilitiesFairValueAdjustment_01a17cea-75c4-7c10-94e7-d6a9da661738" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_01a17cea-75c4-742a-bf95-191011566108" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationLiability"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiability_01a17cea-75c4-742a-bf95-191011566108" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_01a17cea-75c4-78f1-b632-9a4f73353171" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1_01a17cea-75c4-78f1-b632-9a4f73353171" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAcquiredFromAcquisition_01a18e67-49eb-7980-95b6-60f02a2b3062" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashAcquiredFromAcquisition"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_us-gaap_CashAcquiredFromAcquisition_01a18e67-49eb-7980-95b6-60f02a2b3062" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CashAcquiredInExcessOfPaymentsToAcquireBusiness_01a18e67-49eb-74b0-a015-3356127224de" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CashAcquiredInExcessOfPaymentsToAcquireBusiness"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_us-gaap_CashAcquiredInExcessOfPaymentsToAcquireBusiness_01a18e67-49eb-74b0-a015-3356127224de" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationLiabilityMeasurementInput_01a17cea-9533-7b0b-bc63-dcfbe6874884" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationLiabilityMeasurementInput"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationLiabilityMeasurementInput_01a17cea-9533-7b0b-bc63-dcfbe6874884" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh_01a17cea-9533-70ea-bdf0-7620a677bedb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh_01a17cea-9533-70ea-bdf0-7620a677bedb" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueLow_01a17cea-9533-7bc5-8aaf-a863d4904881" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueLow"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueLow_01a17cea-9533-7bc5-8aaf-a863d4904881" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_BusinessCombinationContingentConsiderationLiabilityFairValueDisclosure_01a17cea-9533-77f3-881e-c8cbb67aaf80" xlink:href="lgnd-20260930.xsd#lgnd_BusinessCombinationContingentConsiderationLiabilityFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_lgnd_BusinessCombinationContingentConsiderationLiabilityFairValueDisclosure_01a17cea-9533-77f3-881e-c8cbb67aaf80" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossIncludedInEarnings_01a17cea-9533-7e5d-97cb-c5db50851b32" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossIncludedInEarnings"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisLiabilityGainLossIncludedInEarnings_01a17cea-9533-7e5d-97cb-c5db50851b32" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TangibleAssetImpairmentCharges_01a17cea-b555-75f0-8115-ceb0a50a6622" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TangibleAssetImpairmentCharges"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_us-gaap_TangibleAssetImpairmentCharges_01a17cea-b555-75f0-8115-ceb0a50a6622" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a17cea-b555-73a0-98fc-0135f30bdcb5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_GoodwillAndIntangibleAssetImpairment"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_us-gaap_GoodwillAndIntangibleAssetImpairment_01a17cea-b555-73a0-98fc-0135f30bdcb5" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetsFairValueDisclosure_01a17cea-b555-77a3-9553-b4868103f4fe" xlink:href="lgnd-20260930.xsd#lgnd_FinancialRoyaltyAssetsFairValueDisclosure"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_lgnd_FinancialRoyaltyAssetsFairValueDisclosure_01a17cea-b555-77a3-9553-b4868103f4fe" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_FinancialRoyaltyAssetMeasurementInput_01a17cea-b555-73fe-b743-8ac81ed53852" xlink:href="lgnd-20260930.xsd#lgnd_FinancialRoyaltyAssetMeasurementInput"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems_01a17cea-75c4-76e9-a8be-6c768c5aa02a" xlink:to="loc_lgnd_FinancialRoyaltyAssetMeasurementInput_01a17cea-b555-73fe-b743-8ac81ed53852" xlink:type="arc" order="13"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/DebtNarrativeDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#DebtNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/DebtNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LineOfCreditFacilityLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityTable_01a0edc2-de88-7fd9-abb5-37017bf29bc1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LineOfCreditFacilityTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_LineOfCreditFacilityTable_01a0edc2-de88-7fd9-abb5-37017bf29bc1" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_01a0edc2-de88-73e9-8e15-c7ffa54b2844" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LineOfCreditFacilityTable_01a0edc2-de88-7fd9-abb5-37017bf29bc1" xlink:to="loc_us-gaap_DebtInstrumentAxis_01a0edc2-de88-73e9-8e15-c7ffa54b2844" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a0edc2-de88-73e9-8e15-c7ffa54b2844_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a0edc2-de88-73e9-8e15-c7ffa54b2844" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a0edc2-de88-73e9-8e15-c7ffa54b2844_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a0edc2-de88-772e-a935-c33af6e920e5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a0edc2-de88-73e9-8e15-c7ffa54b2844" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a0edc2-de88-772e-a935-c33af6e920e5" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ConvertibleSeniorNotesDue2031Member_01a0edc2-de88-763c-9ff4-3ee151d9042f" xlink:href="lgnd-20260930.xsd#lgnd_ConvertibleSeniorNotesDue2031Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a0edc2-de88-772e-a935-c33af6e920e5" xlink:to="loc_lgnd_ConvertibleSeniorNotesDue2031Member_01a0edc2-de88-763c-9ff4-3ee151d9042f" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ConvertibleSeniorNotesDue2031InitialPurchaseOptionMember_01a0edc2-de88-7aba-a933-31f053a96a60" xlink:href="lgnd-20260930.xsd#lgnd_ConvertibleSeniorNotesDue2031InitialPurchaseOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a0edc2-de88-772e-a935-c33af6e920e5" xlink:to="loc_lgnd_ConvertibleSeniorNotesDue2031InitialPurchaseOptionMember_01a0edc2-de88-7aba-a933-31f053a96a60" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ConvertibleSeniorNotesDue2030Member_01a0edc3-50ac-78ae-aa46-42b77d765575" xlink:href="lgnd-20260930.xsd#lgnd_ConvertibleSeniorNotesDue2030Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a0edc2-de88-772e-a935-c33af6e920e5" xlink:to="loc_lgnd_ConvertibleSeniorNotesDue2030Member_01a0edc3-50ac-78ae-aa46-42b77d765575" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ConvertibleSeniorNotesDue2030InitialPurchaseOptionMember_01a0edc3-50ac-77fd-83a3-c42441d6343e" xlink:href="lgnd-20260930.xsd#lgnd_ConvertibleSeniorNotesDue2030InitialPurchaseOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a0edc2-de88-772e-a935-c33af6e920e5" xlink:to="loc_lgnd_ConvertibleSeniorNotesDue2030InitialPurchaseOptionMember_01a0edc3-50ac-77fd-83a3-c42441d6343e" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AmendedCreditAgreementMember_01a143ec-e175-7f45-af4b-a4e27805889d" xlink:href="lgnd-20260930.xsd#lgnd_AmendedCreditAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a0edc2-de88-772e-a935-c33af6e920e5" xlink:to="loc_lgnd_AmendedCreditAgreementMember_01a143ec-e175-7f45-af4b-a4e27805889d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_01a0edc2-de88-7652-8bea-3520df5be1e0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LineOfCreditFacilityTable_01a0edc2-de88-7fd9-abb5-37017bf29bc1" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_01a0edc2-de88-7652-8bea-3520df5be1e0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_01a0edc2-de88-7652-8bea-3520df5be1e0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_01a0edc2-de88-7652-8bea-3520df5be1e0" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_01a0edc2-de88-7652-8bea-3520df5be1e0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_01a0edc2-de88-757b-b88f-78d6f5fef733" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_01a0edc2-de88-7652-8bea-3520df5be1e0" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_01a0edc2-de88-757b-b88f-78d6f5fef733" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleNotesPayableMember_01a0edc2-de88-7ffc-9d34-c2335130926e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConvertibleNotesPayableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_01a0edc2-de88-757b-b88f-78d6f5fef733" xlink:to="loc_us-gaap_ConvertibleNotesPayableMember_01a0edc2-de88-7ffc-9d34-c2335130926e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditMember_01a0edc3-9942-7af2-ba58-5c42179487d2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LineOfCreditMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_01a0edc2-de88-757b-b88f-78d6f5fef733" xlink:to="loc_us-gaap_LineOfCreditMember_01a0edc3-9942-7af2-ba58-5c42179487d2" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeAxis_01a0edc3-0216-76c2-9501-dc56ec4102ad" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LineOfCreditFacilityTable_01a0edc2-de88-7fd9-abb5-37017bf29bc1" xlink:to="loc_srt_RangeAxis_01a0edc3-0216-76c2-9501-dc56ec4102ad" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a0edc3-0216-76c2-9501-dc56ec4102ad_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_RangeAxis_01a0edc3-0216-76c2-9501-dc56ec4102ad" xlink:to="loc_srt_RangeMember_01a0edc3-0216-76c2-9501-dc56ec4102ad_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RangeMember_01a0edc3-0216-7f24-8046-4c068f985679" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RangeMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_RangeAxis_01a0edc3-0216-76c2-9501-dc56ec4102ad" xlink:to="loc_srt_RangeMember_01a0edc3-0216-7f24-8046-4c068f985679" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_MaximumMember_01a0edc3-0216-781e-9dfb-9e9a929ceaaf" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_MaximumMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RangeMember_01a0edc3-0216-7f24-8046-4c068f985679" xlink:to="loc_srt_MaximumMember_01a0edc3-0216-781e-9dfb-9e9a929ceaaf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_01a0edc3-0216-7fea-84e9-336105b152c2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentRedemptionPeriodAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LineOfCreditFacilityTable_01a0edc2-de88-7fd9-abb5-37017bf29bc1" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_01a0edc3-0216-7fea-84e9-336105b152c2" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_01a0edc3-0216-7fea-84e9-336105b152c2_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentRedemptionPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_01a0edc3-0216-7fea-84e9-336105b152c2" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_01a0edc3-0216-7fea-84e9-336105b152c2_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_01a0edc3-0216-7147-a790-c57eeea282c8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentRedemptionPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodAxis_01a0edc3-0216-7fea-84e9-336105b152c2" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_01a0edc3-0216-7147-a790-c57eeea282c8" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPeriodOneMember_01a0edc3-0216-746e-8272-3ea6e7732729" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentRedemptionPeriodOneMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentRedemptionPeriodDomain_01a0edc3-0216-7147-a790-c57eeea282c8" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPeriodOneMember_01a0edc3-0216-746e-8272-3ea6e7732729" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightAxis_01a0edc3-2cad-7c9c-80e9-cba596527308" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LineOfCreditFacilityTable_01a0edc2-de88-7fd9-abb5-37017bf29bc1" xlink:to="loc_us-gaap_ClassOfWarrantOrRightAxis_01a0edc3-2cad-7c9c-80e9-cba596527308" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_01a0edc3-2cad-7c9c-80e9-cba596527308_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_01a0edc3-2cad-7c9c-80e9-cba596527308" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_01a0edc3-2cad-7c9c-80e9-cba596527308_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightDomain_01a0edc3-2cad-7762-92b9-dbd61cfa4458" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_ClassOfWarrantOrRightAxis_01a0edc3-2cad-7c9c-80e9-cba596527308" xlink:to="loc_us-gaap_ClassOfWarrantOrRightDomain_01a0edc3-2cad-7762-92b9-dbd61cfa4458" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ConvertibleNoteHedgeAndWarrantMember_01a0edc3-2cad-7df5-9198-37c37dd5f977" xlink:href="lgnd-20260930.xsd#lgnd_ConvertibleNoteHedgeAndWarrantMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_01a0edc3-2cad-7762-92b9-dbd61cfa4458" xlink:to="loc_lgnd_ConvertibleNoteHedgeAndWarrantMember_01a0edc3-2cad-7df5-9198-37c37dd5f977" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_A2031NotesOptionMember_01a0edc3-2cad-7883-99ed-c7e5b18848b6" xlink:href="lgnd-20260930.xsd#lgnd_A2031NotesOptionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_01a0edc3-2cad-7762-92b9-dbd61cfa4458" xlink:to="loc_lgnd_A2031NotesOptionMember_01a0edc3-2cad-7883-99ed-c7e5b18848b6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_InitialPurchaserWarrantsMember_01a0edc3-82e6-7daf-b543-85c3a26c49ae" xlink:href="lgnd-20260930.xsd#lgnd_InitialPurchaserWarrantsMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfWarrantOrRightDomain_01a0edc3-2cad-7762-92b9-dbd61cfa4458" xlink:to="loc_lgnd_InitialPurchaserWarrantsMember_01a0edc3-82e6-7daf-b543-85c3a26c49ae" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityAxis_01a0edc3-9942-7411-abad-ce97c4100116" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CreditFacilityAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LineOfCreditFacilityTable_01a0edc2-de88-7fd9-abb5-37017bf29bc1" xlink:to="loc_us-gaap_CreditFacilityAxis_01a0edc3-9942-7411-abad-ce97c4100116" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_01a0edc3-9942-7411-abad-ce97c4100116_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_CreditFacilityAxis_01a0edc3-9942-7411-abad-ce97c4100116" xlink:to="loc_us-gaap_CreditFacilityDomain_01a0edc3-9942-7411-abad-ce97c4100116_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CreditFacilityDomain_01a0edc3-9942-7b18-b326-843b2f0295a6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CreditFacilityDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_CreditFacilityAxis_01a0edc3-9942-7411-abad-ce97c4100116" xlink:to="loc_us-gaap_CreditFacilityDomain_01a0edc3-9942-7b18-b326-843b2f0295a6" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RevolvingCreditFacilityMember_01a0edc3-9942-72ad-bd95-bb6e75c0c84c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RevolvingCreditFacilityMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_CreditFacilityDomain_01a0edc3-9942-7b18-b326-843b2f0295a6" xlink:to="loc_us-gaap_RevolvingCreditFacilityMember_01a0edc3-9942-72ad-bd95-bb6e75c0c84c" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_DebtCovenantPeriodAxis_01a143ed-761e-7cc5-8c12-c6f7e218fbe8" xlink:href="lgnd-20260930.xsd#lgnd_DebtCovenantPeriodAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LineOfCreditFacilityTable_01a0edc2-de88-7fd9-abb5-37017bf29bc1" xlink:to="loc_lgnd_DebtCovenantPeriodAxis_01a143ed-761e-7cc5-8c12-c6f7e218fbe8" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_DebtCovenantPeriodDomain_01a143ed-761e-7cc5-8c12-c6f7e218fbe8_default" xlink:href="lgnd-20260930.xsd#lgnd_DebtCovenantPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_lgnd_DebtCovenantPeriodAxis_01a143ed-761e-7cc5-8c12-c6f7e218fbe8" xlink:to="loc_lgnd_DebtCovenantPeriodDomain_01a143ed-761e-7cc5-8c12-c6f7e218fbe8_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_DebtCovenantPeriodDomain_01a143ed-761e-78f9-ae4b-a99398047f9e" xlink:href="lgnd-20260930.xsd#lgnd_DebtCovenantPeriodDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_lgnd_DebtCovenantPeriodAxis_01a143ed-761e-7cc5-8c12-c6f7e218fbe8" xlink:to="loc_lgnd_DebtCovenantPeriodDomain_01a143ed-761e-78f9-ae4b-a99398047f9e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_DebtCovenantInitialPeriodMember_01a143ed-761e-7437-abd1-274c28c1feb6" xlink:href="lgnd-20260930.xsd#lgnd_DebtCovenantInitialPeriodMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_DebtCovenantPeriodDomain_01a143ed-761e-78f9-ae4b-a99398047f9e" xlink:to="loc_lgnd_DebtCovenantInitialPeriodMember_01a143ed-761e-7437-abd1-274c28c1feb6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_DebtCovenantSubsequentPeriodMember_01a143ed-761e-7549-ac29-229ae95983a4" xlink:href="lgnd-20260930.xsd#lgnd_DebtCovenantSubsequentPeriodMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_DebtCovenantPeriodDomain_01a143ed-761e-78f9-ae4b-a99398047f9e" xlink:to="loc_lgnd_DebtCovenantSubsequentPeriodMember_01a143ed-761e-7549-ac29-229ae95983a4" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StatementScenarioAxis_01a18e76-8064-74f3-8191-1896ed42ff40" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_StatementScenarioAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LineOfCreditFacilityTable_01a0edc2-de88-7fd9-abb5-37017bf29bc1" xlink:to="loc_srt_StatementScenarioAxis_01a18e76-8064-74f3-8191-1896ed42ff40" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_01a18e76-8064-74f3-8191-1896ed42ff40_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_StatementScenarioAxis_01a18e76-8064-74f3-8191-1896ed42ff40" xlink:to="loc_srt_ScenarioUnspecifiedDomain_01a18e76-8064-74f3-8191-1896ed42ff40_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ScenarioUnspecifiedDomain_01a18e76-8064-7c48-8220-27a32239eb87" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ScenarioUnspecifiedDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_StatementScenarioAxis_01a18e76-8064-74f3-8191-1896ed42ff40" xlink:to="loc_srt_ScenarioUnspecifiedDomain_01a18e76-8064-7c48-8220-27a32239eb87" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScenarioAdjustmentMember_01a18e76-be37-7420-9b6a-7c60f92c7083" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScenarioAdjustmentMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ScenarioUnspecifiedDomain_01a18e76-8064-7c48-8220-27a32239eb87" xlink:to="loc_us-gaap_ScenarioAdjustmentMember_01a18e76-be37-7420-9b6a-7c60f92c7083" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_01a0edc2-de88-78e6-847f-01c902ba6bda" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_01a0edc2-de88-78e6-847f-01c902ba6bda" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFaceAmount_01a0edc2-de88-74bb-a1ce-613142051839" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentFaceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_DebtInstrumentFaceAmount_01a0edc2-de88-74bb-a1ce-613142051839" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleConversionRatio1_01a0edc6-6153-7801-8944-c97d1e71b245" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentConvertibleConversionRatio1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_DebtInstrumentConvertibleConversionRatio1_01a0edc6-6153-7801-8944-c97d1e71b245" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_01a0edc2-de88-7353-a625-e042bcf61883" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProceedsFromDebtNetOfIssuanceCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_ProceedsFromDebtNetOfIssuanceCosts_01a0edc2-de88-7353-a625-e042bcf61883" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleConversionPrice1_01a0edc3-0216-7d74-892c-bf0218f5decc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentConvertibleConversionPrice1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_DebtInstrumentConvertibleConversionPrice1_01a0edc3-0216-7d74-892c-bf0218f5decc" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger_01a0edc3-0216-7212-bbb6-b9c1f18095f4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdPercentageOfStockPriceTrigger_01a0edc3-0216-7212-bbb6-b9c1f18095f4" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdTradingDays_01a0edc3-0216-7b6d-81a8-059128f4488e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentConvertibleThresholdTradingDays"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdTradingDays_01a0edc3-0216-7b6d-81a8-059128f4488e" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1_01a0edc3-0216-7ffd-8343-be02ad99838c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_DebtInstrumentConvertibleThresholdConsecutiveTradingDays1_01a0edc3-0216-7ffd-8343-be02ad99838c" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentRedemptionPricePercentage_01a0edc3-0216-7c9d-aaca-602fc460b036" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentRedemptionPricePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_DebtInstrumentRedemptionPricePercentage_01a0edc3-0216-7c9d-aaca-602fc460b036" xlink:type="arc" order="8"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DeferredFinanceCostsNet_01a0edc3-0216-738f-9f30-f37a81cfedfc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DeferredFinanceCostsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_DeferredFinanceCostsNet_01a0edc3-0216-738f-9f30-f37a81cfedfc" xlink:type="arc" order="9"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateEffectivePercentage_01a0edc3-0216-78ee-834f-6876064d556b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentInterestRateEffectivePercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_DebtInstrumentInterestRateEffectivePercentage_01a0edc3-0216-78ee-834f-6876064d556b" xlink:type="arc" order="10"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AmortizationOfFinancingCosts_01a0edc3-0216-789f-9194-c01e9417de5f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AmortizationOfFinancingCosts"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_AmortizationOfFinancingCosts_01a0edc3-0216-789f-9194-c01e9417de5f" xlink:type="arc" order="11"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_01a0edc3-2cad-7dc3-92ea-88a1d4b56fba" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_ClassOfWarrantOrRightExercisePriceOfWarrantsOrRights1_01a0edc3-2cad-7dc3-92ea-88a1d4b56fba" xlink:type="arc" order="12"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RepaymentsOfConvertibleDebt_01a0edc3-2cad-7e45-81cf-c45b6b2c2d19" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RepaymentsOfConvertibleDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_RepaymentsOfConvertibleDebt_01a0edc3-2cad-7e45-81cf-c45b6b2c2d19" xlink:type="arc" order="13"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_01a0edc3-2cad-76f6-8f87-0f8436e56a45" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_01a0edc3-2cad-76f6-8f87-0f8436e56a45" xlink:type="arc" order="14"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ProceedsFromIssuanceOfWarrants_01a0edc3-2cad-72d8-ab45-e2afdb90e8de" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ProceedsFromIssuanceOfWarrants"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_ProceedsFromIssuanceOfWarrants_01a0edc3-2cad-72d8-ab45-e2afdb90e8de" xlink:type="arc" order="15"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTerm_01a0edc3-6be0-7b85-8c3f-12e64d87794d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentTerm"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_DebtInstrumentTerm_01a0edc3-6be0-7b85-8c3f-12e64d87794d" xlink:type="arc" order="16"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseDebt_01a0edc3-6be0-7e83-93f8-52b845dbbd0f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestExpenseDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_InterestExpenseDebt_01a0edc3-6be0-7e83-93f8-52b845dbbd0f" xlink:type="arc" order="17"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_InterestExpenseDebtExcludingAmortization_01a0edc3-6be0-7fc4-9934-a5be8247be16" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_InterestExpenseDebtExcludingAmortization"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_InterestExpenseDebtExcludingAmortization_01a0edc3-6be0-7fc4-9934-a5be8247be16" xlink:type="arc" order="18"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_01a0edc3-9942-7237-bb97-8fe36dcb21a9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_LineOfCreditFacilityMaximumBorrowingCapacity_01a0edc3-9942-7237-bb97-8fe36dcb21a9" xlink:type="arc" order="19"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LineOfCreditFacilityCovenantMinimumConsolidatedEBITDA_01a143ed-761e-7129-b9ce-4170ebca04cb" xlink:href="lgnd-20260930.xsd#lgnd_LineOfCreditFacilityCovenantMinimumConsolidatedEBITDA"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_lgnd_LineOfCreditFacilityCovenantMinimumConsolidatedEBITDA_01a143ed-761e-7129-b9ce-4170ebca04cb" xlink:type="arc" order="20"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_DebtInstrumentCovenantComplianceConsolidatedLeverageRatioMaximum_01a0edc3-9942-7899-995c-1ee05c7a7626" xlink:href="lgnd-20260930.xsd#lgnd_DebtInstrumentCovenantComplianceConsolidatedLeverageRatioMaximum"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_lgnd_DebtInstrumentCovenantComplianceConsolidatedLeverageRatioMaximum_01a0edc3-9942-7899-995c-1ee05c7a7626" xlink:type="arc" order="21"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_01a18e6e-fa8a-75ed-aec6-1b2929ff5b93" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_LongTermDebt_01a18e6e-fa8a-75ed-aec6-1b2929ff5b93" xlink:type="arc" order="22"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LettersOfCreditOutstandingAmount_01a0edc3-b172-7a5c-82d1-bf0830ed7889" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LettersOfCreditOutstandingAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_LettersOfCreditOutstandingAmount_01a0edc3-b172-7a5c-82d1-bf0830ed7889" xlink:type="arc" order="23"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity_01a0edc3-b172-776b-b6ac-01f28feefbaa" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_LineOfCreditFacilityRemainingBorrowingCapacity_01a0edc3-b172-776b-b6ac-01f28feefbaa" xlink:type="arc" order="24"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SeniorLongTermNotes_01a18e76-59e3-788c-a22d-35ffbdece2e2" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SeniorLongTermNotes"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_SeniorLongTermNotes_01a18e76-59e3-788c-a22d-35ffbdece2e2" xlink:type="arc" order="25"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_DebtConversionConvertedInstrumentAmountAbovePrincipal_01a18e79-39fd-720d-8577-01f356809756" xlink:href="lgnd-20260930.xsd#lgnd_DebtConversionConvertedInstrumentAmountAbovePrincipal"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_lgnd_DebtConversionConvertedInstrumentAmountAbovePrincipal_01a18e79-39fd-720d-8577-01f356809756" xlink:type="arc" order="26"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SharePrice_01a18e7b-d341-7680-9791-c855f4576e97" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SharePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LineOfCreditFacilityLineItems_01a0edc2-de88-7e16-bd98-b8465e49fe12" xlink:to="loc_us-gaap_SharePrice_01a18e7b-d341-7680-9791-c855f4576e97" xlink:type="arc" order="27"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/DebtConvertibleDebtScheduleDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#DebtConvertibleDebtScheduleDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/DebtConvertibleDebtScheduleDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentLineItems_01a01583-c0a6-7563-bca3-54ce107cba49" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentTable_01a01583-c0a6-7985-8146-a9aa62e8e782" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a01583-c0a6-7563-bca3-54ce107cba49" xlink:to="loc_us-gaap_DebtInstrumentTable_01a01583-c0a6-7985-8146-a9aa62e8e782" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_01a01583-c0a6-77c7-901f-95d9cd2edd9e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_01a01583-c0a6-7985-8146-a9aa62e8e782" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_01a01583-c0a6-77c7-901f-95d9cd2edd9e" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_01a01583-c0a6-77c7-901f-95d9cd2edd9e_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_01a01583-c0a6-77c7-901f-95d9cd2edd9e" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_01a01583-c0a6-77c7-901f-95d9cd2edd9e_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_01a01583-c0a6-77a5-bba7-99cbc085b677" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_01a01583-c0a6-77c7-901f-95d9cd2edd9e" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_01a01583-c0a6-77a5-bba7-99cbc085b677" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleNotesPayableMember_01a01583-c0a6-74a0-b11c-ae426263092e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConvertibleNotesPayableMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_01a01583-c0a6-77a5-bba7-99cbc085b677" xlink:to="loc_us-gaap_ConvertibleNotesPayableMember_01a01583-c0a6-74a0-b11c-ae426263092e" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_01a01583-c0a6-7420-9a04-b45d077522d7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_DebtInstrumentTable_01a01583-c0a6-7985-8146-a9aa62e8e782" xlink:to="loc_us-gaap_DebtInstrumentAxis_01a01583-c0a6-7420-9a04-b45d077522d7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a01583-c0a6-7420-9a04-b45d077522d7_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a01583-c0a6-7420-9a04-b45d077522d7" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a01583-c0a6-7420-9a04-b45d077522d7_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a01583-c0a6-73c1-a279-e4ef9cd61aeb" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a01583-c0a6-7420-9a04-b45d077522d7" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a01583-c0a6-73c1-a279-e4ef9cd61aeb" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ConvertibleSeniorNotesDue2031Member_01a01583-c0a6-7018-a8d6-16f88defa749" xlink:href="lgnd-20260930.xsd#lgnd_ConvertibleSeniorNotesDue2031Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a01583-c0a6-73c1-a279-e4ef9cd61aeb" xlink:to="loc_lgnd_ConvertibleSeniorNotesDue2031Member_01a01583-c0a6-7018-a8d6-16f88defa749" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_ConvertibleSeniorNotesDue2030Member_01a01583-c0a6-74d4-94d3-e934958ef9a1" xlink:href="lgnd-20260930.xsd#lgnd_ConvertibleSeniorNotesDue2030Member"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a01583-c0a6-73c1-a279-e4ef9cd61aeb" xlink:to="loc_lgnd_ConvertibleSeniorNotesDue2030Member_01a01583-c0a6-74d4-94d3-e934958ef9a1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermNotesPayableCurrentAndNoncurrentTotalAbstract_01a01583-c0a6-78ca-a4d0-e0f46abe1ebf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermNotesPayableCurrentAndNoncurrentTotalAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a01583-c0a6-7563-bca3-54ce107cba49" xlink:to="loc_us-gaap_LongtermNotesPayableCurrentAndNoncurrentTotalAbstract_01a01583-c0a6-78ca-a4d0-e0f46abe1ebf" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentCarryingAmount_01a01583-c0a6-77fe-bb1f-48f72628601a" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentCarryingAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermNotesPayableCurrentAndNoncurrentTotalAbstract_01a01583-c0a6-78ca-a4d0-e0f46abe1ebf" xlink:to="loc_us-gaap_DebtInstrumentCarryingAmount_01a01583-c0a6-77fe-bb1f-48f72628601a" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_01a01583-c0a6-7ec7-8c73-529bdec97f76" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermNotesPayableCurrentAndNoncurrentTotalAbstract_01a01583-c0a6-78ca-a4d0-e0f46abe1ebf" xlink:to="loc_us-gaap_DebtInstrumentUnamortizedDiscountPremiumAndDebtIssuanceCostsNet_01a01583-c0a6-7ec7-8c73-529bdec97f76" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtCurrent_01a18e6e-3665-75c6-9a98-a0d99c3c24a7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongTermDebtCurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermNotesPayableCurrentAndNoncurrentTotalAbstract_01a01583-c0a6-78ca-a4d0-e0f46abe1ebf" xlink:to="loc_us-gaap_LongTermDebtCurrent_01a18e6e-3665-75c6-9a98-a0d99c3c24a7" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtNoncurrent_01a18e6d-b15f-7ba8-ab08-8ecdd67b13e8" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongTermDebtNoncurrent"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermNotesPayableCurrentAndNoncurrentTotalAbstract_01a01583-c0a6-78ca-a4d0-e0f46abe1ebf" xlink:to="loc_us-gaap_LongTermDebtNoncurrent_01a18e6d-b15f-7ba8-ab08-8ecdd67b13e8" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebt_01a01583-c0a6-7a3b-af29-8e0c54271ec1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongTermDebt"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermNotesPayableCurrentAndNoncurrentTotalAbstract_01a01583-c0a6-78ca-a4d0-e0f46abe1ebf" xlink:to="loc_us-gaap_LongTermDebt_01a01583-c0a6-7a3b-af29-8e0c54271ec1" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongTermDebtFairValue_01a01583-c0a6-7407-af34-d5a01afd73b5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongTermDebtFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentLineItems_01a01583-c0a6-7563-bca3-54ce107cba49" xlink:to="loc_us-gaap_LongTermDebtFairValue_01a01583-c0a6-7407-af34-d5a01afd73b5" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/IncomeTaxDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#IncomeTaxDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/IncomeTaxDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowanceLineItems_01a18e3c-2252-7c58-b389-f3fdbfa032cf" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ValuationAllowanceLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ValuationAllowanceTable_01a18e3c-2252-7ca7-b15a-98dc51ec4cce" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ValuationAllowanceTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ValuationAllowanceLineItems_01a18e3c-2252-7c58-b389-f3fdbfa032cf" xlink:to="loc_us-gaap_ValuationAllowanceTable_01a18e3c-2252-7ca7-b15a-98dc51ec4cce" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAxis_01a18e3c-2252-750f-9df6-5c75dd3ddcce" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ValuationAllowanceTable_01a18e3c-2252-7ca7-b15a-98dc51ec4cce" xlink:to="loc_us-gaap_BusinessAcquisitionAxis_01a18e3c-2252-750f-9df6-5c75dd3ddcce" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e3c-2252-750f-9df6-5c75dd3ddcce_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e3c-2252-750f-9df6-5c75dd3ddcce" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e3c-2252-750f-9df6-5c75dd3ddcce_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e3c-2252-7c7d-a81f-9eafbacfd3d7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessAcquisitionAcquireeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_BusinessAcquisitionAxis_01a18e3c-2252-750f-9df6-5c75dd3ddcce" xlink:to="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e3c-2252-7c7d-a81f-9eafbacfd3d7" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_XOMAAcquisitionMember_01a18e3c-3b03-7e0c-96c7-1390981c3ecd" xlink:href="lgnd-20260930.xsd#lgnd_XOMAAcquisitionMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_BusinessAcquisitionAcquireeDomain_01a18e3c-2252-7c7d-a81f-9eafbacfd3d7" xlink:to="loc_lgnd_XOMAAcquisitionMember_01a18e3c-3b03-7e0c-96c7-1390981c3ecd" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EffectiveIncomeTaxRateContinuingOperations_01a01583-c0a6-72ca-bdcb-d0d32f1ebda6" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EffectiveIncomeTaxRateContinuingOperations"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationAllowanceLineItems_01a18e3c-2252-7c58-b389-f3fdbfa032cf" xlink:to="loc_us-gaap_EffectiveIncomeTaxRateContinuingOperations_01a01583-c0a6-72ca-bdcb-d0d32f1ebda6" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxAssets_01a18e3c-2252-7ddd-b0cb-5282ea2a0a6c" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxAssets"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ValuationAllowanceLineItems_01a18e3c-2252-7c58-b389-f3fdbfa032cf" xlink:to="loc_us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxAssets_01a18e3c-2252-7ddd-b0cb-5282ea2a0a6c" xlink:type="arc" order="1"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/StockholdersEquityNarrativeDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#StockholdersEquityNarrativeDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/StockholdersEquityNarrativeDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_01a0ed14-d4a0-73ad-b3aa-800eed687455" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_01a0ed14-d4a0-7fc5-b21a-646ec59065ea" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a0ed14-d4a0-73ad-b3aa-800eed687455" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_01a0ed14-d4a0-7fc5-b21a-646ec59065ea" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameAxis_01a0ed14-d4a0-707d-bc71-6147ad88c582" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_01a0ed14-d4a0-7fc5-b21a-646ec59065ea" xlink:to="loc_us-gaap_PlanNameAxis_01a0ed14-d4a0-707d-bc71-6147ad88c582" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_01a0ed14-d4a0-707d-bc71-6147ad88c582_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_PlanNameAxis_01a0ed14-d4a0-707d-bc71-6147ad88c582" xlink:to="loc_us-gaap_PlanNameDomain_01a0ed14-d4a0-707d-bc71-6147ad88c582_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PlanNameDomain_01a0ed14-d4a0-7ae1-a010-766a1e2d9455" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_PlanNameAxis_01a0ed14-d4a0-707d-bc71-6147ad88c582" xlink:to="loc_us-gaap_PlanNameDomain_01a0ed14-d4a0-7ae1-a010-766a1e2d9455" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_LigandPharmaceuticalsIncorporated2002StockIncentivePlanMember_01a0ed14-d4a0-7f09-a002-cade0d04ae84" xlink:href="lgnd-20260930.xsd#lgnd_LigandPharmaceuticalsIncorporated2002StockIncentivePlanMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_01a0ed14-d4a0-7ae1-a010-766a1e2d9455" xlink:to="loc_lgnd_LigandPharmaceuticalsIncorporated2002StockIncentivePlanMember_01a0ed14-d4a0-7f09-a002-cade0d04ae84" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AmendedESPPMember_01a0ed14-f545-7afb-a126-65e7b7b6cd05" xlink:href="lgnd-20260930.xsd#lgnd_AmendedESPPMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_PlanNameDomain_01a0ed14-d4a0-7ae1-a010-766a1e2d9455" xlink:to="loc_lgnd_AmendedESPPMember_01a0ed14-f545-7afb-a126-65e7b7b6cd05" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsidiarySaleOfStockAxis_01a0ed14-f545-7c39-9227-f1583cab6330" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SubsidiarySaleOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_01a0ed14-d4a0-7fc5-b21a-646ec59065ea" xlink:to="loc_us-gaap_SubsidiarySaleOfStockAxis_01a0ed14-f545-7c39-9227-f1583cab6330" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_01a0ed14-f545-7c39-9227-f1583cab6330_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_01a0ed14-f545-7c39-9227-f1583cab6330" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_01a0ed14-f545-7c39-9227-f1583cab6330_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SaleOfStockNameOfTransactionDomain_01a0ed14-f545-778f-90bb-9f53512a29f9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SaleOfStockNameOfTransactionDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsidiarySaleOfStockAxis_01a0ed14-f545-7c39-9227-f1583cab6330" xlink:to="loc_us-gaap_SaleOfStockNameOfTransactionDomain_01a0ed14-f545-778f-90bb-9f53512a29f9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AtTheMarketEquityOfferingMember_01a0ed14-f545-7b00-8de4-6afa6493017b" xlink:href="lgnd-20260930.xsd#lgnd_AtTheMarketEquityOfferingMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SaleOfStockNameOfTransactionDomain_01a0ed14-f545-778f-90bb-9f53512a29f9" xlink:to="loc_lgnd_AtTheMarketEquityOfferingMember_01a0ed14-f545-7b00-8de4-6afa6493017b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ShareRepurchaseProgramAxis_01a0ed14-f545-7c0c-b67c-0e6f1b9ca610" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ShareRepurchaseProgramAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_01a0ed14-d4a0-7fc5-b21a-646ec59065ea" xlink:to="loc_srt_ShareRepurchaseProgramAxis_01a0ed14-f545-7c0c-b67c-0e6f1b9ca610" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ShareRepurchaseProgramDomain_01a0ed14-f545-7c0c-b67c-0e6f1b9ca610_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ShareRepurchaseProgramDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_ShareRepurchaseProgramAxis_01a0ed14-f545-7c0c-b67c-0e6f1b9ca610" xlink:to="loc_srt_ShareRepurchaseProgramDomain_01a0ed14-f545-7c0c-b67c-0e6f1b9ca610_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_ShareRepurchaseProgramDomain_01a0ed14-f545-7690-a72b-f88ed3fddda0" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_ShareRepurchaseProgramDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_ShareRepurchaseProgramAxis_01a0ed14-f545-7c0c-b67c-0e6f1b9ca610" xlink:to="loc_srt_ShareRepurchaseProgramDomain_01a0ed14-f545-7690-a72b-f88ed3fddda0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_April2023RepurchaseAgreementMember_01a0ed14-f545-7b56-b4e1-d57eccdd1f55" xlink:href="lgnd-20260930.xsd#lgnd_April2023RepurchaseAgreementMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_ShareRepurchaseProgramDomain_01a0ed14-f545-7690-a72b-f88ed3fddda0" xlink:to="loc_lgnd_April2023RepurchaseAgreementMember_01a0ed14-f545-7b56-b4e1-d57eccdd1f55" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_01a0ed15-0f4e-79f4-966d-676b1687895d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_01a0ed14-d4a0-7fc5-b21a-646ec59065ea" xlink:to="loc_us-gaap_StatementClassOfStockAxis_01a0ed15-0f4e-79f4-966d-676b1687895d" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a0ed15-0f4e-79f4-966d-676b1687895d_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a0ed15-0f4e-79f4-966d-676b1687895d" xlink:to="loc_us-gaap_ClassOfStockDomain_01a0ed15-0f4e-79f4-966d-676b1687895d_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a0ed15-0f4e-7446-bd3a-bb64da061773" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a0ed15-0f4e-79f4-966d-676b1687895d" xlink:to="loc_us-gaap_ClassOfStockDomain_01a0ed15-0f4e-7446-bd3a-bb64da061773" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_CommonStockMember_01a0ed15-0f4e-7e33-ba3e-ca50d546eac4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_CommonStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_01a0ed15-0f4e-7446-bd3a-bb64da061773" xlink:to="loc_us-gaap_CommonStockMember_01a0ed15-0f4e-7e33-ba3e-ca50d546eac4" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_01a0ed14-d4a0-717b-8aec-3b9b318e533d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a0ed14-d4a0-73ad-b3aa-800eed687455" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfAdditionalSharesAuthorized_01a0ed14-d4a0-717b-8aec-3b9b318e533d" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_01a0ed14-f545-71d2-963f-3bfabb5dcb50" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a0ed14-d4a0-73ad-b3aa-800eed687455" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber_01a0ed14-f545-71d2-963f-3bfabb5dcb50" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_01a0ed14-f545-7171-9a09-eb5e998d6f28" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a0ed14-d4a0-73ad-b3aa-800eed687455" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice_01a0ed14-f545-7171-9a09-eb5e998d6f28" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_EmployeeStockPurchasePlanAbstract_01a0ed19-651a-7e48-a186-248c9b9dfdb8" xlink:href="lgnd-20260930.xsd#lgnd_EmployeeStockPurchasePlanAbstract"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a0ed14-d4a0-73ad-b3aa-800eed687455" xlink:to="loc_lgnd_EmployeeStockPurchasePlanAbstract_01a0ed19-651a-7e48-a186-248c9b9dfdb8" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardDiscountFromMarketPricePurchaseDate_01a0ed14-f545-7c8b-9795-6fdd2aa13783" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardDiscountFromMarketPricePurchaseDate"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_EmployeeStockPurchasePlanAbstract_01a0ed19-651a-7e48-a186-248c9b9dfdb8" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardDiscountFromMarketPricePurchaseDate_01a0ed14-f545-7c8b-9795-6fdd2aa13783" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_EmployeeServiceShareBasedCompensationEstimatedQuantityOfSharesToBeRepurchasedInFollowingPeriod_01a0ed14-f545-7a23-ad68-1fbd79420d15" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_EmployeeServiceShareBasedCompensationEstimatedQuantityOfSharesToBeRepurchasedInFollowingPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_lgnd_EmployeeStockPurchasePlanAbstract_01a0ed19-651a-7e48-a186-248c9b9dfdb8" xlink:to="loc_us-gaap_EmployeeServiceShareBasedCompensationEstimatedQuantityOfSharesToBeRepurchasedInFollowingPeriod_01a0ed14-f545-7a23-ad68-1fbd79420d15" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_SaleOfStockAuthorizedOfferingAmount_01a0ed14-f545-715e-961c-a610003fce8c" xlink:href="lgnd-20260930.xsd#lgnd_SaleOfStockAuthorizedOfferingAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a0ed14-d4a0-73ad-b3aa-800eed687455" xlink:to="loc_lgnd_SaleOfStockAuthorizedOfferingAmount_01a0ed14-f545-715e-961c-a610003fce8c" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_StockRepurchaseProgramAuthorizedAmount1_01a0ed14-f545-7848-9169-0c2e0f5d0050" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_StockRepurchaseProgramAuthorizedAmount1"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a0ed14-d4a0-73ad-b3aa-800eed687455" xlink:to="loc_srt_StockRepurchaseProgramAuthorizedAmount1_01a0ed14-f545-7848-9169-0c2e0f5d0050" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_01a0ed15-0f4e-70bf-845a-d796c0e4b377" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsForRepurchaseOfCommonStock"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a0ed14-d4a0-73ad-b3aa-800eed687455" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfCommonStock_01a0ed15-0f4e-70bf-845a-d796c0e4b377" xlink:type="arc" order="6"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockRepurchasedDuringPeriodShares_01a0ed15-0f4e-756b-975b-1d875af18c24" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockRepurchasedDuringPeriodShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a0ed14-d4a0-73ad-b3aa-800eed687455" xlink:to="loc_us-gaap_StockRepurchasedDuringPeriodShares_01a0ed15-0f4e-756b-975b-1d875af18c24" xlink:type="arc" order="7"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_TreasuryStockAcquiredAverageCostPerShare_01a0ed15-0f4e-71fd-8aa0-4d932dcd6c17" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_TreasuryStockAcquiredAverageCostPerShare"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a0ed14-d4a0-73ad-b3aa-800eed687455" xlink:to="loc_us-gaap_TreasuryStockAcquiredAverageCostPerShare_01a0ed15-0f4e-71fd-8aa0-4d932dcd6c17" xlink:type="arc" order="8"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/StockholdersEquityStockOptionPlanandRestrictedStockActivityDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#StockholdersEquityStockOptionPlanandRestrictedStockActivityDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/StockholdersEquityStockOptionPlanandRestrictedStockActivityDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockLineItems_01a01583-c0a6-71c1-ba3f-5997d965c320" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ScheduleOfStockByClassTable_01a01583-c0a6-740b-b169-12f4f072ca7e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ScheduleOfStockByClassTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a01583-c0a6-71c1-ba3f-5997d965c320" xlink:to="loc_us-gaap_ScheduleOfStockByClassTable_01a01583-c0a6-740b-b169-12f4f072ca7e" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_AwardTypeAxis_01a01583-c0a6-7de5-861b-21ca8789e280" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_AwardTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_ScheduleOfStockByClassTable_01a01583-c0a6-740b-b169-12f4f072ca7e" xlink:to="loc_us-gaap_AwardTypeAxis_01a01583-c0a6-7de5-861b-21ca8789e280" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-c0a6-7de5-861b-21ca8789e280_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_AwardTypeAxis_01a01583-c0a6-7de5-861b-21ca8789e280" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-c0a6-7de5-861b-21ca8789e280_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-c0a6-7db0-ba82-8b72329eba26" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_AwardTypeAxis_01a01583-c0a6-7de5-861b-21ca8789e280" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-c0a6-7db0-ba82-8b72329eba26" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_RestrictedStockMember_01a01583-c0a6-7ae2-a650-22501e6ae62b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_RestrictedStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_01a01583-c0a6-7db0-ba82-8b72329eba26" xlink:to="loc_us-gaap_RestrictedStockMember_01a01583-c0a6-7ae2-a650-22501e6ae62b" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_01a01583-c0a6-75ca-9c2f-4c882d80aa23" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a01583-c0a6-71c1-ba3f-5997d965c320" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_01a01583-c0a6-75ca-9c2f-4c882d80aa23" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_01a01583-c0a6-7c82-9e89-e72df8e1f9b1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_01a01583-c0a6-75ca-9c2f-4c882d80aa23" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_01a01583-c0a6-7c82-9e89-e72df8e1f9b1" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_01a01583-c0a6-7341-8e0d-20fe819d5e6d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_01a01583-c0a6-75ca-9c2f-4c882d80aa23" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross_01a01583-c0a6-7341-8e0d-20fe819d5e6d" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_01a01583-c0a6-7cf4-b8ff-83ac7903dea3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_01a01583-c0a6-75ca-9c2f-4c882d80aa23" xlink:to="loc_us-gaap_StockIssuedDuringPeriodSharesStockOptionsExercised_01a01583-c0a6-7cf4-b8ff-83ac7903dea3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod_01a01583-c0a6-760f-966c-28045ec8c7c9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward_01a01583-c0a6-75ca-9c2f-4c882d80aa23" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod_01a01583-c0a6-760f-966c-28045ec8c7c9" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber_01a01583-c0a6-7806-a88f-f851a9cdde54" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_01a01583-c0a6-793d-8008-e551b34bf630" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a01583-c0a6-71c1-ba3f-5997d965c320" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_01a01583-c0a6-793d-8008-e551b34bf630" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_01a01583-c0a6-7bbf-9a19-fe3c53219498" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_01a01583-c0a6-793d-8008-e551b34bf630" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_01a01583-c0a6-7bbf-9a19-fe3c53219498" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_01a01583-c0a6-7e61-a22f-43a046ec335b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_01a01583-c0a6-793d-8008-e551b34bf630" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice_01a01583-c0a6-7e61-a22f-43a046ec335b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_01a01583-c0a6-70ca-82a0-d353d88c2b54" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_01a01583-c0a6-793d-8008-e551b34bf630" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsExercisesInPeriodWeightedAverageExercisePrice_01a01583-c0a6-70ca-82a0-d353d88c2b54" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice_01a01583-c0a6-72e0-bef9-6a7fe1ccb693" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward_01a01583-c0a6-793d-8008-e551b34bf630" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice_01a01583-c0a6-72e0-bef9-6a7fe1ccb693" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice_01a01583-c0a6-7d65-9b85-a0758db58492" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_01a01583-c0a6-74a7-b0b7-496643bb940b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a01583-c0a6-71c1-ba3f-5997d965c320" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_01a01583-c0a6-74a7-b0b7-496643bb940b" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_01a01583-c0a6-776a-bfe5-7b3b3e432d93" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_01a01583-c0a6-74a7-b0b7-496643bb940b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_01a01583-c0a6-776a-bfe5-7b3b3e432d93" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_01a01583-c0a6-79c9-b996-b6908abd52d7" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_01a01583-c0a6-74a7-b0b7-496643bb940b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriod_01a01583-c0a6-79c9-b996-b6908abd52d7" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_01a01583-c0a6-7999-a3ae-7c47e0ccbc33" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_01a01583-c0a6-74a7-b0b7-496643bb940b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriod_01a01583-c0a6-7999-a3ae-7c47e0ccbc33" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_01a01583-c0a6-74af-86db-9a1e87cd8e69" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedRollForward_01a01583-c0a6-74a7-b0b7-496643bb940b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeitedInPeriod_01a01583-c0a6-74af-86db-9a1e87cd8e69" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber_01a01583-c0a6-7b4a-9d96-385acbe0fe87" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedNumber"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a01583-c0a6-7426-b3a1-0d4b1f9cd82b" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockLineItems_01a01583-c0a6-71c1-ba3f-5997d965c320" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a01583-c0a6-7426-b3a1-0d4b1f9cd82b" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_01a01583-c0a6-77af-ba12-2dd12ab7398d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a01583-c0a6-7426-b3a1-0d4b1f9cd82b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_01a01583-c0a6-77af-ba12-2dd12ab7398d" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_01a01583-c0a6-7fc4-8ad5-febf570b6a5e" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a01583-c0a6-7426-b3a1-0d4b1f9cd82b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsGrantsInPeriodWeightedAverageGrantDateFairValue_01a01583-c0a6-7fc4-8ad5-febf570b6a5e" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_01a01583-c0a6-7fb8-aeb0-0adfa0e48db4" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a01583-c0a6-7426-b3a1-0d4b1f9cd82b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsVestedInPeriodWeightedAverageGrantDateFairValue_01a01583-c0a6-7fb8-aeb0-0adfa0e48db4" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_01a01583-c0a6-7e86-9857-c68aed6f0bc5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValueRollForward_01a01583-c0a6-7426-b3a1-0d4b1f9cd82b" xlink:to="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsForfeituresWeightedAverageGrantDateFairValue_01a01583-c0a6-7e86-9857-c68aed6f0bc5" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue_01a01583-c0a6-7e3d-9472-f498b53dccb9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardEquityInstrumentsOtherThanOptionsNonvestedWeightedAverageGrantDateFairValue"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/CommitmentandContingenciesDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#CommitmentandContingenciesDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/CommitmentandContingenciesDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingenciesLineItems_01a01583-c0a6-7b16-8b35-3f89a82e8640" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LossContingenciesLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingenciesTable_01a01583-c0a6-7fac-897e-c2ea87527154" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LossContingenciesTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_LossContingenciesLineItems_01a01583-c0a6-7b16-8b35-3f89a82e8640" xlink:to="loc_us-gaap_LossContingenciesTable_01a01583-c0a6-7fac-897e-c2ea87527154" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_LitigationCaseAxis_01a01583-c0a6-7ee3-abed-37b19eca964b" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_LitigationCaseAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_LossContingenciesTable_01a01583-c0a6-7fac-897e-c2ea87527154" xlink:to="loc_srt_LitigationCaseAxis_01a01583-c0a6-7ee3-abed-37b19eca964b" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_LitigationCaseTypeDomain_01a01583-c0a6-7ee3-abed-37b19eca964b_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_LitigationCaseTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_LitigationCaseAxis_01a01583-c0a6-7ee3-abed-37b19eca964b" xlink:to="loc_srt_LitigationCaseTypeDomain_01a01583-c0a6-7ee3-abed-37b19eca964b_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_LitigationCaseTypeDomain_01a01583-c0a6-7f56-bbd4-ae530f0a46b0" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_LitigationCaseTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_LitigationCaseAxis_01a01583-c0a6-7ee3-abed-37b19eca964b" xlink:to="loc_srt_LitigationCaseTypeDomain_01a01583-c0a6-7f56-bbd4-ae530f0a46b0" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_USDistrictCourtForTheNorthernDistrictOfOhioMember_01a01583-c0a6-7bf0-a2b1-3b00df4e36b8" xlink:href="lgnd-20260930.xsd#lgnd_USDistrictCourtForTheNorthernDistrictOfOhioMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_LitigationCaseTypeDomain_01a01583-c0a6-7f56-bbd4-ae530f0a46b0" xlink:to="loc_lgnd_USDistrictCourtForTheNorthernDistrictOfOhioMember_01a01583-c0a6-7bf0-a2b1-3b00df4e36b8" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LossContingencyNewClaimsFiledNumber_01a01583-c0a6-77f5-9cbb-822bc0977054" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LossContingencyNewClaimsFiledNumber"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LossContingenciesLineItems_01a01583-c0a6-7b16-8b35-3f89a82e8640" xlink:to="loc_us-gaap_LossContingencyNewClaimsFiledNumber_01a01583-c0a6-77f5-9cbb-822bc0977054" xlink:type="arc" order="0"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://www.ligand.com/role/SubsequentEventsDetails" xlink:type="simple" xlink:href="lgnd-20260930.xsd#SubsequentEventsDetails"/>
  <link:definitionLink xlink:role="http://www.ligand.com/role/SubsequentEventsDetails" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventLineItems_01a01583-c0a6-74c8-9421-e470163c9e2d" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SubsequentEventLineItems"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTable_01a01583-c0a6-7e4a-92e7-b852072a9891" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SubsequentEventTable"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" xlink:from="loc_us-gaap_SubsequentEventLineItems_01a01583-c0a6-74c8-9421-e470163c9e2d" xlink:to="loc_us-gaap_SubsequentEventTable_01a01583-c0a6-7e4a-92e7-b852072a9891" xlink:type="arc" order="1" xbrldt:closed="true" xbrldt:contextElement="segment"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeAxis_01a01583-c0a6-7444-b170-b7416185b887" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SubsequentEventTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_01a01583-c0a6-7e4a-92e7-b852072a9891" xlink:to="loc_us-gaap_SubsequentEventTypeAxis_01a01583-c0a6-7444-b170-b7416185b887" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_01a01583-c0a6-7444-b170-b7416185b887_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_01a01583-c0a6-7444-b170-b7416185b887" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_01a01583-c0a6-7444-b170-b7416185b887_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventTypeDomain_01a01583-c0a6-7816-b69f-6273dfdd9da9" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SubsequentEventTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_SubsequentEventTypeAxis_01a01583-c0a6-7444-b170-b7416185b887" xlink:to="loc_us-gaap_SubsequentEventTypeDomain_01a01583-c0a6-7816-b69f-6273dfdd9da9" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_SubsequentEventMember_01a01583-c0a6-7775-9cb1-ea0b8b0252f1" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_SubsequentEventMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventTypeDomain_01a01583-c0a6-7816-b69f-6273dfdd9da9" xlink:to="loc_us-gaap_SubsequentEventMember_01a01583-c0a6-7775-9cb1-ea0b8b0252f1" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentAxis_01a18e43-80d5-7485-9290-2b1eb8db13d0" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_01a01583-c0a6-7e4a-92e7-b852072a9891" xlink:to="loc_us-gaap_DebtInstrumentAxis_01a18e43-80d5-7485-9290-2b1eb8db13d0" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a18e43-80d5-7485-9290-2b1eb8db13d0_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a18e43-80d5-7485-9290-2b1eb8db13d0" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a18e43-80d5-7485-9290-2b1eb8db13d0_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentNameDomain_01a18e43-80d5-7f93-b499-249fbc5d3ebc" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_DebtInstrumentAxis_01a18e43-80d5-7485-9290-2b1eb8db13d0" xlink:to="loc_us-gaap_DebtInstrumentNameDomain_01a18e43-80d5-7f93-b499-249fbc5d3ebc" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_CCBNotesMember_01a18e43-a63e-7351-8bfc-fcc836dfb880" xlink:href="lgnd-20260930.xsd#lgnd_CCBNotesMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_DebtInstrumentNameDomain_01a18e43-80d5-7f93-b499-249fbc5d3ebc" xlink:to="loc_lgnd_CCBNotesMember_01a18e43-a63e-7351-8bfc-fcc836dfb880" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeAxis_01a18e43-bf4d-70b4-8b6d-9ebab81c96f3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_01a01583-c0a6-7e4a-92e7-b852072a9891" xlink:to="loc_us-gaap_LongtermDebtTypeAxis_01a18e43-bf4d-70b4-8b6d-9ebab81c96f3" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_01a18e43-bf4d-70b4-8b6d-9ebab81c96f3_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_01a18e43-bf4d-70b4-8b6d-9ebab81c96f3" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_01a18e43-bf4d-70b4-8b6d-9ebab81c96f3_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_LongtermDebtTypeDomain_01a18e43-bf4d-70e6-a55f-a9e848a3ab6f" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_LongtermDebtTypeDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_LongtermDebtTypeAxis_01a18e43-bf4d-70b4-8b6d-9ebab81c96f3" xlink:to="loc_us-gaap_LongtermDebtTypeDomain_01a18e43-bf4d-70e6-a55f-a9e848a3ab6f" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ConvertibleDebtMember_01a18e43-e73d-75d0-abf7-fbd3a1bc1cba" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ConvertibleDebtMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_LongtermDebtTypeDomain_01a18e43-bf4d-70e6-a55f-a9e848a3ab6f" xlink:to="loc_us-gaap_ConvertibleDebtMember_01a18e43-e73d-75d0-abf7-fbd3a1bc1cba" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_StatementClassOfStockAxis_01a18e4a-610f-726d-9389-ba74309b70fd" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_StatementClassOfStockAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_01a01583-c0a6-7e4a-92e7-b852072a9891" xlink:to="loc_us-gaap_StatementClassOfStockAxis_01a18e4a-610f-726d-9389-ba74309b70fd" xlink:type="arc" order="4"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a18e4a-610f-726d-9389-ba74309b70fd_default" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a18e4a-610f-726d-9389-ba74309b70fd" xlink:to="loc_us-gaap_ClassOfStockDomain_01a18e4a-610f-726d-9389-ba74309b70fd_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfStockDomain_01a18e4a-610f-72d7-9755-9d6ba18700d3" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfStockDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_us-gaap_StatementClassOfStockAxis_01a18e4a-610f-726d-9389-ba74309b70fd" xlink:to="loc_us-gaap_ClassOfStockDomain_01a18e4a-610f-72d7-9755-9d6ba18700d3" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_SeriesBConvertiblePreferredStockMember_01a18e4a-b801-762b-ac84-20571fe3c5da" xlink:href="lgnd-20260930.xsd#lgnd_SeriesBConvertiblePreferredStockMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_ClassOfStockDomain_01a18e4a-610f-72d7-9755-9d6ba18700d3" xlink:to="loc_lgnd_SeriesBConvertiblePreferredStockMember_01a18e4a-b801-762b-ac84-20571fe3c5da" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_CounterpartyNameAxis_01a18e4b-0751-7e43-b610-12be97768679" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_CounterpartyNameAxis"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:from="loc_us-gaap_SubsequentEventTable_01a01583-c0a6-7e4a-92e7-b852072a9891" xlink:to="loc_srt_CounterpartyNameAxis_01a18e4b-0751-7e43-b610-12be97768679" xlink:type="arc" order="5"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e4b-0751-7e43-b610-12be97768679_default" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:from="loc_srt_CounterpartyNameAxis_01a18e4b-0751-7e43-b610-12be97768679" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e4b-0751-7e43-b610-12be97768679_default" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e4b-0751-7016-aab8-08d4b55ddc11" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-2026.xsd#srt_RepurchaseAgreementCounterpartyNameDomain"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:from="loc_srt_CounterpartyNameAxis_01a18e4b-0751-7e43-b610-12be97768679" xlink:to="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e4b-0751-7016-aab8-08d4b55ddc11" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_PelthosMember_01a18e4b-325c-785f-bc00-ae90b1bbbbbc" xlink:href="lgnd-20260930.xsd#lgnd_PelthosMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_srt_RepurchaseAgreementCounterpartyNameDomain_01a18e4b-0751-7016-aab8-08d4b55ddc11" xlink:to="loc_lgnd_PelthosMember_01a18e4b-325c-785f-bc00-ae90b1bbbbbc" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentFaceAmount_01a18e42-779f-7f8a-852d-9b3f88a487a5" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentFaceAmount"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_01a01583-c0a6-74c8-9421-e470163c9e2d" xlink:to="loc_us-gaap_DebtInstrumentFaceAmount_01a18e42-779f-7f8a-852d-9b3f88a487a5" xlink:type="arc" order="0"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_01a18e42-efbc-7066-b052-3822130e9b02" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_DebtInstrumentInterestRateStatedPercentage"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_01a01583-c0a6-74c8-9421-e470163c9e2d" xlink:to="loc_us-gaap_DebtInstrumentInterestRateStatedPercentage_01a18e42-efbc-7066-b052-3822130e9b02" xlink:type="arc" order="1"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_SecuritiesPurchaseAgreementNumberOfShares_01a18e4a-32dd-7a67-9538-a95af4f8c8b9" xlink:href="lgnd-20260930.xsd#lgnd_SecuritiesPurchaseAgreementNumberOfShares"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_01a01583-c0a6-74c8-9421-e470163c9e2d" xlink:to="loc_lgnd_SecuritiesPurchaseAgreementNumberOfShares_01a18e4a-32dd-7a67-9538-a95af4f8c8b9" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_01a18e45-60f5-73fb-b622-171641053595" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_01a01583-c0a6-74c8-9421-e470163c9e2d" xlink:to="loc_us-gaap_ClassOfWarrantOrRightNumberOfSecuritiesCalledByWarrantsOrRights_01a18e45-60f5-73fb-b622-171641053595" xlink:type="arc" order="3"/>
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_PaymentsForRepurchaseOfEquity_01a18e48-2b49-7582-adc7-68e241707f18" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_PaymentsForRepurchaseOfEquity"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_SubsequentEventLineItems_01a01583-c0a6-74c8-9421-e470163c9e2d" xlink:to="loc_us-gaap_PaymentsForRepurchaseOfEquity_01a18e48-2b49-7582-adc7-68e241707f18" xlink:type="arc" order="4"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://fasb.org/srt/role/srt-eedm/ExtensibleEnumerationLists" xlink:type="simple" xlink:href="https://xbrl.fasb.org/srt/2026/elts/srt-roles-2026.xsd#eedm1"/>
  <link:definitionLink xlink:role="http://fasb.org/srt/role/srt-eedm/ExtensibleEnumerationLists" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_us-gaap_IncomeStatementAbstract" xlink:href="https://xbrl.fasb.org/us-gaap/2026/elts/us-gaap-2026.xsd#us-gaap_IncomeStatementAbstract"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_NonCashChangeInEstimatedFairValueOfContingentValueRights_01a01583-bdf6-7bc5-a72f-012533563372" xlink:href="lgnd-20260930.xsd#lgnd_NonCashChangeInEstimatedFairValueOfContingentValueRights"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_us-gaap_IncomeStatementAbstract" xlink:to="loc_lgnd_NonCashChangeInEstimatedFairValueOfContingentValueRights_01a01583-bdf6-7bc5-a72f-012533563372" xlink:type="arc" order="691"/>
  </link:definitionLink>
  <link:roleRef roleURI="http://xbrl.sec.gov/ecd/role/IndividualsOnly" xlink:type="simple" xlink:href="https://xbrl.sec.gov/ecd/2026/ecd-2026.xsd#IndividualsOnly"/>
  <link:definitionLink xlink:role="http://xbrl.sec.gov/ecd/role/IndividualsOnly" xlink:type="extended">
    <link:loc xlink:type="locator" xlink:label="loc_ecd_AllIndividualsMember" xlink:href="https://xbrl.sec.gov/ecd/2026/ecd-2026.xsd#ecd_AllIndividualsMember"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_AndrewReardonMember_01a18e2a-6ec7-7f50-ae29-72b803548e06" xlink:href="lgnd-20260930.xsd#lgnd_AndrewReardonMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_lgnd_AndrewReardonMember_01a18e2a-6ec7-7f50-ae29-72b803548e06" xlink:type="arc" order="2"/>
    <link:loc xlink:type="locator" xlink:label="loc_lgnd_JohnKozarichMember_01a01583-bea2-7118-bf6d-0c3bb7a048c5" xlink:href="lgnd-20260930.xsd#lgnd_JohnKozarichMember"/>
    <link:definitionArc xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" xlink:from="loc_ecd_AllIndividualsMember" xlink:to="loc_lgnd_JohnKozarichMember_01a01583-bea2-7118-bf6d-0c3bb7a048c5" xlink:type="arc" order="3"/>
  </link:definitionLink>
</link:linkbase>
