As filed with the Securities and Exchange Commission on August 5, 2026.

Registration No. 333-213120

Registration No. 333-216532

Registration No. 333-223500

Registration No. 333-230213

Registration No. 333-237066

Registration No. 333-254090

Registration No. 333-263097

Registration No. 333-270573

Registration No. 333-277409

Registration No. 333-285137

Registration No. 333-293749

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

POST-EFFECTIVE

AMENDMENT NO. 1 TO

FORM S-8 Registration No. 333-213120

FORM S-8 Registration No. 333-216532

FORM S-8 Registration No. 333-223500

FORM S-8 Registration No. 333-230213

FORM S-8 Registration No. 333-237066

FORM S-8 Registration No. 333-254090

FORM S-8 Registration No. 333-263097

FORM S-8 Registration No. 333-270573

FORM S-8 Registration No. 333-277409

FORM S-8 Registration No. 333-285137

FORM S-8 Registration No. 333-293749

REGISTRATION STATEMENT

UNDER

THE SECURITIES ACT OF 1933

PROTAGONIST THERAPEUTICS, INC.

(Exact name of Registrant as specified in its charter)

7707 Gateway Boulevard, Suite 140

Newark, California 94560

(510) 474-0170

(Address, including zip code and telephone number, of Registrant’s principal executive offices)

Protagonist Therapeutics, Inc. 2016 Equity Incentive Plan

Protagonist Therapeutics, Inc. 2026 Equity Incentive Plan

(Full title of the plans)

Dinesh V. Patel, Ph.D.

President and Chief Executive Officer

7707 Gateway Boulevard, Suite 140

Newark, California 94560

(510) 474-0170

(Name, address, including zip code and telephone number, including area code, of agent for service)

Copies to:

Ryan Murr

Gibson, Dunn & Crutcher LLP

One Embarcadero Center

Suite 2600

San Francisco, California 94111

415-393-8200

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ¨

EXPLANATORY NOTE

Protagonist Therapeutics, Inc., a Delaware corporation (the “Registrant”), filed a registration Statement on form S-8 (File No. 333-213120) with the Securities and Exchange Commission (the “Commission”) on August 15, 2016 (the “First Registration Statement”) for the purpose of registering 1,200,000 shares of common stock, $0.00001 par value per share (the “Common Stock”), issuable to eligible persons under the Registrant’s 2016 Equity Incentive Plan (the “Prior Plan”).

On March 8, 2017, the Registrant filed a registration statement on Form S-8 (File No. 333-216532) (the “Second Registration Statement”) with the Commission to register 668,891 shares of Common Stock issuable to eligible individuals under the Prior Plan.

On March 7, 2018, the Registrant filed a registration statement on Form S-8 (File No. 333-223500) (the “Third Registration Statement”) with the Commission to register 843,532 shares of Common Stock issuable to eligible individuals under the Prior Plan.

On March 12, 2019, the Registrant filed a registration statement on Form S-8 (File No. 333-230213) (the “Fourth Registration Statement”) with the Commission to register 927,488 shares of Common Stock issuable to eligible individuals under the Prior Plan.

On March 10, 2020, the Registrant filed a registration statement on Form S-8 (File No. 333-237066) (the “Fifth Registration Statement”) with the Commission to register 1,088,705 shares of Common Stock issuable to eligible individuals under the Prior Plan.

On March 10, 2021, the Registrant filed a registration statement on Form S-8 (File No. 333-254090) (the “Sixth Registration Statement”) with the Commission to register 1,749,818 shares of Common Stock issuable to eligible individuals under the Prior Plan.

On February 28, 2022, the Registrant filed a registration statement on Form S-8 (File No. 333-263097) (the “Seventh Registration Statement”) with the Commission to register 1,913,533 shares of Common Stock issuable to eligible individuals under the Prior Plan.

On March 15, 2023, the Registrant filed a registration statement on Form S-8 (File No. 333-270573) (the “Eighth Registration Statement”) with the Commission to register 1,973,570 shares of Common Stock issuable to eligible individuals under the Prior Plan.

On February 27, 2024, the Registrant filed a registration statement on Form S-8 (File No. 333-277409) (the “Ninth Registration Statement”) with the Commission to register 2,308,344 shares of Common Stock issuable to eligible individuals under the Prior Plan.

On February 21, 2025, the Registrant filed a registration statement on Form S-8 (File No. 333-285137) (the “Tenth Registration Statement”) with the Commission to register 2,441,405 shares of Common Stock issuable to eligible individuals under the Prior Plan.

On February 25, 2026, the Registrant filed a registration statement on Form S-8 (File No. 333-293749) (the “Eleventh Registration Statement” and, together with the First Registration Statement, Second Registration Statement, Third Registration Statement, Fourth Registration Statement, Fifth Registration Statement, Sixth Registration Statement, Seventh Registration Statement, Eight Registration Statement, Ninth Registration Statement and Tenth Registration Statement, the “Prior Registration Statements”) with the Commission to register 2,503,115 shares of Common Stock issuable to eligible individuals under the Prior Plan.

On June 17, 2026 (the “Effective Date”), the Registrant’s 2026 Equity Incentive Plan (the “2026 Plan”) became effective upon its approval by the Registrant’s stockholders. Under the terms of the 2026 Plan: (a) as of the Effective Date, no new awards may be granted under the Prior Plan (although outstanding awards granted under the Prior Plan prior to the Effective Date (the “Outstanding Awards”) will remain outstanding in accordance with their terms and those of the Prior Plan) and (b) any shares of Common Stock that remain available for grant under the Prior Plan as of the Effective Date plus any shares of Common Stock subject to Outstanding Awards that on or after the Effective Date expire or terminate for any reason or are forefeited, reacquired or withheld (or not issued) to satisfy tax withholding obligations or the purchase price or exercise price of an award will become available for issuance pursuant to awards granted under the 2026 Plan (any such shares of Common Stock that become available for issuance under the 2026 Plan in accordance with this clause (b), the “Rollover Shares”). As of the Effective Date, the maximum number of Rollover Shares that may become issuable under the 2026 Plan will not exceed 10,991,258 shares of Common Stock.

Accordingly, pursuant to the undertaking in Item 512(a)(1)(iii) of Regulation S-K that the Registrant disclose a material change in the plan of distribution as it was originally disclosed in the Prior Registration Statements and in accordance with Compliance and Disclosure Interpretation 126.43, the Registrant is filing this Post-Effective Amendment to the Prior Registration Statements to cover the offer and sale of the Rollover Shares under the 2026 Plan. No additional securities are being registered by this Post-Effective Amendment. The Registrant is concurrently filing a separate registration statement on Form S-8 to register the new shares of Common Stock for offer or sale pursuant to the 2026 Plan.

PART I

INFORMATION REQUIRED IN THE SECTION 10(a) PROSPECTUS

The information required by this Part I has been omitted from this Registration Statement pursuant to the Note to Part I of Form S-8.

PART II

INFORMATION REQUIRED IN THE REGISTRATION STATEMENT

The following documents filed by the Registrant with the Commission are incorporated by reference herein and shall be deemed to be a part hereof:

In addition, all documents filed by the Registrant pursuant to Sections 13(a), 13(c), 14 or 15(d) of the Exchange Act after the date hereof, but prior to the filing of a post-effective amendment to this Registration Statement that indicates that all securities offered hereby have been sold or that deregisters all such securities then remaining unsold, shall be deemed to be incorporated by reference in this Registration Statement and to be a part hereof from the date of filing of such documents. Notwithstanding the foregoing, unless specifically stated to the contrary in such filing, none of the information that the Registrant discloses under Items 2.02 or 7.01 of any Current Report on Form 8-K that it may from time to time furnish to the Commission will be incorporated by reference into, or otherwise be included in or deemed to be a part of, this Registration Statement.

For purposes of this Registration Statement, any document or any statement contained in a document incorporated or deemed to be incorporated herein by reference shall be deemed to be modified or superseded to the extent that a subsequently filed document or a statement contained herein or in any other subsequently filed document that also is or is deemed to be incorporated herein by reference modifies or supersedes such document or such statement in such document. Any statement so modified or superseded shall not be deemed, except as so modified or superseded, to constitute a part of this Registration Statement. Subject to the foregoing, all information in this Registration Statement is so qualified in its entirety by the information appearing in the documents incorporated herein by reference.

Not applicable.

Not applicable.

Section 145 of the Delaware General Corporation Law authorizes a court to award, or a corporation’s board of directors to grant, indemnity to directors and officers in terms sufficiently broad to permit such indemnification under certain circumstances for liabilities, including reimbursement for expenses incurred, arising under the Securities Act of 1933, as amended (the “Securities Act”).

The Registrant’s amended and restated certificate of incorporation and amended and restated bylaws provide that the Registrant will indemnify its directors and officers, and may indemnify its employees and other agents, to the fullest extent permitted by the Delaware General Corporation Law. However, Delaware law prohibits the Registrant’s certificate of incorporation from limiting the liability of the Registrant’s directors for the following:

The Registrant has entered into indemnification agreements with each of its directors and officers. These agreements provide for the indemnification of such persons for all reasonable expenses and liabilities incurred in connection with any action or proceeding brought against them by reason of the fact that they are or were serving in such capacity.

The Registrant may maintain insurance policies that indemnify its directors and officers against various liabilities arising under the Securities Act and the Exchange Act that might be incurred by any director or officer in his or her capacity as such. The Registrant has obtained director and officer liability insurance to cover liabilities directors and officers may incur in connection with their services to the Registrant.

Not applicable.

(a) The undersigned Registrant hereby undertakes:

(1) To file, during any period in which offers or sales are being made, a post-effective amendment to this Registration Statement:

(i) To include any prospectus required by Section 10(a)(3) of the Securities Act;

(ii) To reflect in the prospectus any facts or events arising after the effective date of this Registration Statement (or the most recent post-effective amendment thereof) which, individually or in the aggregate, represent a fundamental change in the information set forth in this Registration Statement.  Notwithstanding the foregoing, any increase or decrease in volume of securities offered (if the total dollar value of securities offered would not exceed that which was registered) and any deviation from the low or high end of the estimated maximum offering range may be reflected in the form of prospectus filed with the Commission pursuant to Rule 424(b) if, in the aggregate, the changes in volume and price represent no more than 20% change in the maximum aggregate offering price set forth in the “Calculation of Filing Fee Tables” in the effective registration statement; and

(iii)  To include any material information with respect to the plan of distribution not previously disclosed in this Registration Statement or any material change to such information in this Registration Statement;

provided, however, that paragraphs (a)(1)(i) and (a)(1)(ii) do not apply if the information required to be included in a post-effective amendment by those paragraphs is contained in reports filed with or furnished to the Commission by the Registrant pursuant to Section 13 or Section 15(d) of the Exchange Act that are incorporated by reference in this Registration Statement;

(2) That, for the purpose of determining any liability under the Securities Act, each such post-effective amendment shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof; and

(3) To remove from registration by means of a post-effective amendment any of the securities being registered which remain unsold at the termination of the offering.

(b) The undersigned Registrant hereby undertakes that, for purposes of determining any liability under the Securities Act, each filing of the Registrant’s annual report pursuant to Section 13(a) or Section 15(d) of the Exchange Act (and, where applicable, each filing of an employee benefit plan’s annual report pursuant to Section 15(d) of the Exchange Act) that is incorporated by reference in this Registration Statement shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.

(c) Insofar as indemnification for liabilities arising under the Securities Act may be permitted to directors, officers and controlling persons of the Registrant pursuant to the foregoing provisions, or otherwise, the Registrant has been advised that in the opinion of the Commission such indemnification is against public policy as expressed in the Securities Act and is, therefore, unenforceable.  In the event that a claim for indemnification against such liabilities (other than the payment by the Registrant of expenses incurred or paid by a director, officer or controlling person of the Registrant in the successful defense of any action, suit or proceeding) is asserted by such director, officer or controlling person in connection with the securities being registered, the Registrant will, unless in the opinion of its counsel the matter has been settled by controlling precedent, submit to a court of appropriate jurisdiction the question whether such indemnification by it is against public policy as expressed in the Securities Act and will be governed by the final adjudication of such issue.

SIGNATURES

Pursuant to the requirements of the Securities Act, the Registrant certifies that it has reasonable grounds to believe that it meets all of the requirements for filing on Form S-8 and has duly caused this Post-Effective Amendment to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Newark, State of California, on this 5^th day of August, 2026.

POWER OF ATTORNEY

KNOW ALL PERSONS BY THESE PRESENTS, that each person whose signature appears below constitutes and appoints Dinesh V. Patel, Ph.D. and Asif Ali, and each or any one of them, as his or her true and lawful attorney-in-fact and agent, each with full power of substitution and resubstitution, for him or her and in his or her name, place and stead, in any and all capacities, to sign this Post-Effective Amendment to the Prior Registration Statements and any and all amendments (including post-effective amendments) thereto, and to file the same, with all exhibits thereto, and other documents in connection therewith, with the Commission, granting unto said attorneys-in-fact and agents, and each of them, full power and authority to do and perform each and every act and thing requisite and necessary to be done in connection therewith, as fully to all intents and purposes as he or she might or could do in person, hereby ratifying and confirming all that said attorneys-in-fact and agents, or any of them, or their or his substitutes or substitute, may lawfully do or cause to be done by virtue hereof.

Pursuant to the requirements of the Securities Act, this Post-Effective Amendment has been signed by the following persons in the capacities and on the dates indicated.

ATTACHMENTS / EXHIBITS

EXHIBIT 5.1

EXHIBIT 23.2