The Securities and Exchange Commission has not necessarily reviewed the information in this filing and has not determined if it is accurate and complete.
The reader should not assume that the information is accurate and complete.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 13F

FORM 13F COVER PAGE

OMB APPROVAL
OMB Number: 3235-0006
Expires: July 31, 2015
Estimated average burden
hours per response: 23.8

Report for the Calendar Year or Quarter Ended: 03-31-2022
Check here if Amendment   Amendment Number:
This Amendment (Check only one.):   is a restatement.
  adds new holdings entries.
Institutional Investment Manager Filing this Report:
Name: SPHERA FUNDS MANAGEMENT LTD.
Address: 21 HA'ARBA'AH STREET
TEL AVIV , L364739
Form 13F File Number: 028-15863

The institutional investment manager filing this report and the person by whom it is signed hereby represent that the person signing the report is authorized to submit it, that all information contained herein is true, correct and complete, and that it is understood that all required items, statements, schedules, lists, and tables, are considered integral parts of this form.

Person Signing this Report on Behalf of Reporting Manager:
Name: Israel Mor
Title: Partner
Phone: 972 3 6845535
Signature, Place, and Date of Signing:
Israel Mor Tel Aviv , L3 05-16-2022
[Signature] [City, State] [Date]
Report Type (Check only one.):
X 13F HOLDINGS REPORT. (Check here if all holdings of this reporting manager are reported in this report.)
  13F NOTICE. (Check here if no holdings reported are in this report, and all holdings are reported by other reporting manager(s).)
  13F COMBINATION REPORT. (Check here if a portion of the holdings for this reporting manager are reported in this report and a portion are reported by other reporting manager(s).)
Form 13F Summary Page
Report Summary:
Number of Other Included Managers: 3
Form 13F Information Table Entry Total: 66
Form 13F Information Table Value Total: 707,568
(thousands)
List of Other Managers Reporting for this Manager:
[If there are no entries in this list, omit this section.]
Form 13F File Number Name
028-15865 Sphera Global Healthcare Management LP
028-15864 Sphera Global Healthcare GP Ltd.
028-21415 Sphera Healthcare US Inc.

List of Other Included Managers:
Provide a numbered list of the name(s) and Form 13F file number(s) of all institutional investment managers with respect to which this report is filed, other than the manager filing this report.
[If there are no entries in this list, state “NONE” and omit the column headings and list entries.]
No. Form 13F File Number Name
1 028-15865 Sphera Global Healthcare Management LP
2 028-15864 Sphera Global Healthcare GP Ltd.
3 028-21415 Sphera Healthcare US Inc.


SEC FORM 13F-HR

The Securities and Exchange Commission has not necessarily reviewed the information in this filing and has not determined if it is accurate and complete.
The reader should not assume that the information is accurate and complete.

UNITED STATES SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 13F

FORM 13F INFORMATION TABLE

OMB APPROVAL
OMB Number: 3235-0006
Expires: July 31, 2015
Estimated average burden
hours per response: 23.8

COLUMN 1 COLUMN 2 COLUMN 3 COLUMN 4 COLUMN 5 COLUMN 6 COLUMN 7 COLUMN 8
VALUE SHRS OR SH/ PUT/ INVESTMENT OTHER VOTING AUTHORITY
NAME OF ISSUER TITLE OF CLASS CUSIP (x$1000) PRN AMT PRN CALL DISCRETION MANAGER SOLE SHARED NONE
ABBVIE INC COM 00287Y109 30,962 190,994 SH DFND 1,2,3 190,994 0 0
ADVANCED MICRO DEVICES INC COM 007903107 10,934 100,000 SH DFND 100,000 0 0
AIRBNB INC COM CL A 009066101 5,153 30,000 SH DFND 30,000 0 0
AIRBNB INC CALL 009066901 4,174 24,300 SH Call DFND 0 0 24,300
ALNYLAM PHARMACEUTICALS INC COM 02043Q107 4,044 24,768 SH DFND 1,2,3 24,768 0 0
ALTIMMUNE INC COM NEW 02155H200 7,959 1,306,953 SH DFND 1,2,3 1,306,953 0 0
ARBE ROBOTICS LTD ORDINARY SHARES M1R95N100 300 43,165 SH DFND 43,165 0 0
ASCENDIS PHARMA A/S SPONSORED ADR 04351P101 3,113 26,529 SH DFND 1,2,3 26,529 0 0
ASTRAZENECA PLC SPONSORED ADR 046353108 55,514 836,817 SH DFND 1,2,3 836,817 0 0
AYALA PHARMACEUTICALS INC COM 05465V108 995 250,000 SH DFND 1,2,3 250,000 0 0
BIOMARIN PHARMACEUTICAL INC COM 09061G101 16,293 211,326 SH DFND 1,2,3 211,326 0 0
C4 THERAPEUTICS INC COM STK 12529R107 8,795 362,528 SH DFND 1,2,3 362,528 0 0
CAESARSTONE LTD ORD SHS M20598104 4,503 428,046 SH DFND 428,046 0 0
CATERPILLAR INC COM 149123101 2,674 12,000 SH DFND 12,000 0 0
CHINOOK THERAPEUTICS INC COM 16961L106 8,077 493,677 SH DFND 1,2,3 493,677 0 0
CRINETICS PHARMACEUTICALS IN COM 22663K107 11,457 521,947 SH DFND 1,2,3 521,947 0 0
CYCLACEL PHARMACEUTICALS INC COM 23254L603 1,550 508,322 SH DFND 1,2,3 508,322 0 0
FATE THERAPEUTICS INC COM 31189P102 3,467 89,425 SH DFND 1,2,3 89,425 0 0
FIVE9 INC COM 338307101 3,279 29,699 SH DFND 29,699 0 0
FIVE9 INC CALL 338307101 27,479 248,900 SH Call DFND 0 0 248,900
FIVERR INTL LTD NOTE 11/0 33835LAA3 4,227 4,951,000 SH DFND 4,951,000 0 0
GENERAC HLDGS INC COM 368736104 12,548 42,211 SH DFND 42,211 0 0
IMMATICS N.V *W EXP 07/01/202 N44445117 175 100,000 SH DFND 1,2,3 100,000 0 0
IMMATICS N.V SHS N44445109 4,969 621,925 SH DFND 1,2,3 621,925 0 0
IMMUNIC INC COM 4525EP101 6,590 583,206 SH DFND 1,2,3 583,206 0 0
INVESCO QQQ TR PUT 46090E103 45,680 126,000 SH Put DFND 126,000 0 0
IRONSOURCE LTD CL A ORD SHS M5R75Y101 2,976 620,000 SH DFND 620,000 0 0
IVERIC BIO INC COM 46583P102 13,029 774,130 SH DFND 1,2,3 774,130 0 0
JOHNSON & JOHNSON COM 478160104 52,287 295,023 SH DFND 1,2,3 295,023 0 0
KEROS THERAPEUTICS INC COM 492327101 7,590 139,581 SH DFND 1,2,3 139,581 0 0
KEZAR LIFE SCIENCES INC COM 49372L100 3,118 187,599 SH DFND 1,2,3 187,599 0 0
KRYSTAL BIOTECH INC COM 501147102 1,684 25,310 SH DFND 1,2,3 25,310 0 0
KURA ONCOLOGY INC COM 50127T109 9,941 618,244 SH DFND 1,2,3 618,244 0 0
KYMERA THERAPEUTICS INC COM 501575104 15,576 368,061 SH DFND 1,2,3 368,061 0 0
LIANBIO SPONSORED ADS 53000N108 1,020 275,007 SH DFND 1,2,3 275,007 0 0
LILLY ELI & CO COM 532457108 20,130 70,295 SH DFND 1,2,3 70,295 0 0
MAGIC SOFTWARE ENTERPRISES L ORD 559166103 1,401 81,293 SH DFND 81,293 0 0
MASTERCARD INCORPORATED CL A 57636Q104 4,324 12,100 SH DFND 12,100 0 0
MERCK & CO INC COM 58933Y105 22,826 278,200 SH DFND 1,2,3 278,200 0 0
MERUS N V COM N5749R100 10,818 409,141 SH DFND 1,2,3 409,141 0 0
NAUTILUS BIOTECHNOLOGY INC COM 63909J108 3,646 840,000 SH DFND 1,2,3 840,000 0 0
NICE SYS INC NOTE 1.250% 1/1 65366HAB9 662 250,000 SH DFND 250,000 0 0
NOVO-NORDISK A S ADR 670100205 26,363 237,400 SH DFND 1,2,3 237,400 0 0
ONCORUS INC COM 68236R103 962 540,258 SH DFND 1,2,3 540,258 0 0
OTONOMO TECHNOLOGIES LTD ORDINARY SHARES M7571L103 772 391,863 SH DFND 391,863 0 0
OUTBRAIN INC COM 69002R103 564 52,531 SH DFND 52,531 0 0
PERION NETWORK LTD SHS NEW M78673114 6,883 306,051 SH DFND 306,051 0 0
PFIZER INC COM 717081103 26,665 515,070 SH DFND 1,2,3 515,070 0 0
RELMADA THERAPEUTICS INC COM 75955J402 7,861 291,252 SH DFND 1,2,3 291,252 0 0
REPLIMUNE GROUP INC COM 76029N106 3,611 212,640 SH DFND 1,2,3 212,640 0 0
SANOFI SPONSORED ADR 80105N105 49,924 972,415 SH DFND 1,2,3 972,415 0 0
SENTINELONE INC CL A 81730H109 2,518 65,000 SH DFND 65,000 0 0
SPRINGWORKS THERAPEUTICS INC COM 85205L107 25,964 460,025 SH DFND 1,2,3 460,025 0 0
SPRINGWORKS THERAPEUTICS INC CALL 85205L107 7,055 125,000 SH Call DFND 1,2,3 0 0 125,000
SUNRUN INC COM 86771W105 4,556 150,000 SH DFND 150,000 0 0
SUNRUN INC CALL 86771W105 6,924 228,000 SH Call DFND 0 0 228,000
SYNDAX PHARMACEUTICALS INC COM 87164F105 22,201 1,277,413 SH DFND 1,2,3 1,277,413 0 0
TEVA PHARMACEUTICAL INDS LTD SPONSORED ADS 881624209 7,821 832,878 SH DFND 832,878 0 0
TEVA PHARMACEUTICAL INDS LTD CALL 881624209 17,747 1,890,000 SH Call DFND 0 0 1,890,000
TEVA PHARMACEUTICAL INDS LTD PUT 881624209 1,972 210,000 SH Put DFND 210,000 0 0
VERONA PHARMA PLC SPONSORED ADS 925050106 3,325 666,339 SH DFND 1,2,3 666,339 0 0
VINCERX PHARMA INC COM NEW 92731L106 2,881 720,161 SH DFND 1,2,3 720,161 0 0
VISA INC COM CL A 92826C839 5,589 25,200 SH DFND 25,200 0 0
VISTAGEN THERAPEUTICS INC COM NEW 92840H202 6,140 4,951,423 SH DFND 1,2,3 4,951,423 0 0
WEREWOLF THERAPEUTICS INC COM 95075A107 2,570 584,203 SH DFND 1,2,3 584,203 0 0
ZIM INTEGRATED SHIPPING SERV SHS M9T951109 10,761 148,000 SH DFND 148,000 0 0