# EDGAR Filing Document

**Accession Number:** 0001496201
**File Stem:** 0001496201-25-000017
**Filing Date:** 2025-11
**Character Count:** 15763
**Document Hash:** 2a6da005d27124316a336df7b3152fd1
**Contains OCR:** False
**Source Format:** 

## Filing Content

## Filing Summary
**0001496201-25-000017.hdr.sgml**: 20251114

**ACCESSION NUMBER**: 0001496201-25-000017

**CONFORMED SUBMISSION TYPE**: 13F-HR

**PUBLIC DOCUMENT COUNT**: 2

**CONFORMED PERIOD OF REPORT**: 20250930

**FILED AS OF DATE**: 20251114

**DATE AS OF CHANGE**: 20251114

**EFFECTIVENESS DATE**: 20251114

**FILER**: 

**COMPANY DATA:**
- **COMPANY CONFORMED NAME:** SPHERA FUNDS MANAGEMENT LTD.
- **CENTRAL INDEX KEY:** 0001496201

**ORGANIZATION NAME:**
- **EIN:** 000000000
- **STATE OF INCORPORATION:** L3

**FILING VALUES:**
- **FORM TYPE:** 13F-HR
- **SEC ACT:** 1934 Act
- **SEC FILE NUMBER:** 028-15863
- **FILM NUMBER:** 251485146

**BUSINESS ADDRESS:**
- **STREET 1:** 4 ITZHAK SADE BUILDING A
- **STREET 2:** 29TH FLOOR
- **CITY:** TEL AVIV
- **STATE:** L3
- **ZIP:** 6777520
- **BUSINESS PHONE:** 972-3-6845535

**MAIL ADDRESS:**
- **STREET 1:** 4 ITZHAK SADE BUILDING A
- **STREET 2:** 29TH FLOOR
- **CITY:** TEL AVIV
- **STATE:** L3
- **ZIP:** 6777520

### FORM 13F COVER PAGE

**Report for the Calendar Year or Quarter Ended:** 09-30-2025

**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.<br>**Address:** 4 ITZHAK SADE BUILDING A<br>29TH FLOOR<br>TEL AVIV, L3 6777520

**Form 13F File Number:** 028-15863

**CRD Number (if applicable):** 000312614

**SEC File Number (if applicable):** 802-120694

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:** Oshrat Levi<br>**Title:** Chief Financial Officer<br>**Phone:** 972 3 6845617

**Signature, Place, and Date of Signing:**

Oshrat Levi  Tel Aviv, L3  11-14-2025<br>[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 are reported 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:** 2

**Form 13F Information Table Entry Total:** 115

**Form 13F Information Table Value Total:** $474069298

      (round to nearest dollar)

**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.   | Name                                   | Form 13F File Number   |
|:---|:---|:---|
|  | Sphera Global Healthcare Management LP | 028-15865              |
|  | Sphera Global Healthcare GP Ltd.       | 028-15864              |

### FORM 13F INFORMATION TABLE

---

|  |  |  |  |  |  |  |  |  |  |  |  |  |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| NAME OF ISSUER | TITLE OF CLASS | CUSIP | FIGI | VALUE (x$1000) | SHRS OR PRN AMT | SH/PRN | PUT/CALL | INVESTMENT DISCRETION | OTHER MANAGER | VOTING AUTHORITY | VOTING AUTHORITY | VOTING AUTHORITY |
| NAME OF ISSUER | TITLE OF CLASS | CUSIP | FIGI | VALUE (x$1000) | SHRS OR PRN AMT | SH/PRN | PUT/CALL | INVESTMENT DISCRETION | OTHER MANAGER | SOLE | SHARED | NONE |
| 89BIO INC | COM | 282559103 |  | 583223 | 39675 | SH |  | DFND | 12 | 39675 | 0 | 0 |
| ABBVIE INC | COM | 00287Y109 |  | 5847774 | 25256 | SH |  | DFND | 12 | 25256 | 0 | 0 |
| ACADIA PHARMACEUTICALS INC | COM | 004225108 |  | 3177526 | 148900 | SH |  | DFND | 12 | 148900 | 0 | 0 |
| ADVANCED MICRO DEVICES INC | COM | 007903107 |  | 2502891 | 15470 | SH |  | DFND |  | 15470 | 0 | 0 |
| ALPHA COGNITION INC | COM NEW | 02074J501 |  | 2205276 | 338752 | SH |  | DFND | 12 | 338752 | 0 | 0 |
| AMAZON COM INC | COM | 023135106 |  | 3021283 | 13760 | SH |  | DFND |  | 13760 | 0 | 0 |
| AMGEN INC | COM | 031162100 |  | 2680900 | 9500 | SH |  | DFND | 12 | 9500 | 0 | 0 |
| AMICUS THERAPEUTICS INC | COM | 03152W109 |  | 7810199 | 991142 | SH |  | DFND | 12 | 991142 | 0 | 0 |
| ANNEXON INC | COM | 03589W102 |  | 5472880 | 1794387 | SH |  | DFND | 12 | 1794387 | 0 | 0 |
| APELLIS PHARMACEUTICALS INC | COM | 03753U106 |  | 1440626 | 63660 | SH |  | DFND | 12 | 63660 | 0 | 0 |
| APPLIED THERAPEUTICS INC | COM | 03828A101 |  | 30245 | 50000 | SH |  | DFND | 12 | 50000 | 0 | 0 |
| APREA THERAPEUTICS INC | COM NEW | 03836J201 |  | 398250 | 270000 | SH |  | DFND | 12 | 270000 | 0 | 0 |
| ARROWHEAD PHARMACEUTICALS IN | COM | 04280A100 |  | 430987 | 12496 | SH |  | DFND | 12 | 12496 | 0 | 0 |
| ASTRAZENECA PLC | SPONSORED ADR | 046353108 |  | 10361803 | 135060 | SH |  | DFND | 12 | 135060 | 0 | 0 |
| ASTRIA THERAPEUTICS INC | COM | 04635X102 |  | 1828918 | 251225 | SH |  | DFND | 12 | 251225 | 0 | 0 |
| BICARA THERAPEUTICS INC | COM | 055477103 |  | 1353945 | 85747 | SH |  | DFND | 12 | 85747 | 0 | 0 |
| BIOGEN INC | COM | 09062X103 |  | 11589939 | 82738 | SH |  | DFND | 12 | 82738 | 0 | 0 |
| BIOHAVEN LTD | COM | G1110E107 |  | 1368237 | 91155 | SH |  | DFND | 12 | 91155 | 0 | 0 |
| BRIDGEBIO PHARMA INC | COM | 10806X102 |  | 2116347 | 40746 | SH |  | DFND | 12 | 40746 | 0 | 0 |
| BRIDGEBIO PHARMA INC | COM | 10806X102 |  | 6752200 | 130000 | SH | Call | DFND | 12 | 0 | 0 | 0 |
| BRISTOL-MYERS SQUIBB CO | COM | 110122108 |  | 789250 | 17500 | SH |  | DFND | 12 | 17500 | 0 | 0 |
| BROADCOM INC | COM | 11135F101 |  | 2162560 | 6555 | SH |  | DFND |  | 6555 | 0 | 0 |
| CAMTEK LTD | ORD | M20791105 |  | 3051492 | 29048 | SH |  | DFND |  | 29048 | 0 | 0 |
| CELLDEX THERAPEUTICS INC NEW | COM NEW | 15117B202 |  | 5374855 | 207764 | SH |  | DFND | 12 | 207764 | 0 | 0 |
| CELLEBRITE DI LTD | ORDINARY SHARES | M2197Q107 |  | 5539506 | 298948 | SH |  | DFND |  | 298948 | 0 | 0 |
| CEVA INC | COM | 157210105 |  | 2141455 | 81085 | SH |  | DFND |  | 81085 | 0 | 0 |
| CHEMOMAB THERAPEUTICS LTD | SPONSORED ADS | 16385C203 |  | 471888 | 179425 | SH |  | DFND | 12 | 179425 | 0 | 0 |
| CIDARA THERAPEUTICS INC | COM NEW | 171757206 |  | 7253150 | 75743 | SH |  | DFND | 12 | 75743 | 0 | 0 |
| CIDARA THERAPEUTICS INC | COM NEW | 171757206 |  | 9576000 | 100000 | SH | Call | DFND | 12 | 0 | 0 | 0 |
| CLIMB BIO INC | COM | 28658R106 |  | 874022 | 434837 | SH |  | DFND | 12 | 434837 | 0 | 0 |
| COGENT BIOSCIENCES INC | COM | 19240Q201 |  | 1414833 | 98526 | SH |  | DFND | 12 | 98526 | 0 | 0 |
| CORVUS PHARMACEUTICALS INC | COM | 221015100 |  | 3004815 | 407709 | SH |  | DFND | 12 | 407709 | 0 | 0 |
| CYBIN INC | COM NEW | 23256X407 |  | 2181515 | 370376 | SH |  | DFND | 12 | 370376 | 0 | 0 |
| CYTOKINETICS INC | COM NEW | 23282W605 |  | 8876974 | 161517 | SH |  | DFND | 12 | 161517 | 0 | 0 |
| DAY ONE BIOPHARMACEUTICALS I | COM | 23954D109 |  | 1236366 | 175371 | SH |  | DFND | 12 | 175371 | 0 | 0 |
| DESIGN THERAPEUTICS INC | COM | 25056L103 |  | 165043 | 21918 | SH |  | DFND | 12 | 21918 | 0 | 0 |
| DYNE THERAPEUTICS INC | COM | 26818M108 |  | 5395453 | 426518 | SH |  | DFND | 12 | 426518 | 0 | 0 |
| ELBIT SYS LTD | ORD | M3760D101 |  | 3436052 | 6740 | SH |  | DFND |  | 6740 | 0 | 0 |
| ELEDON PHARMACEUTICALS INC | COM | 28617K101 |  | 3315803 | 1280233 | SH |  | DFND | 12 | 1280233 | 0 | 0 |
| ELEDON PHARMACEUTICALS INC | COM | 28617K101 |  | 518000 | 200000 | SH | Put | DFND | 12 | 200000 | 0 | 0 |
| ELI LILLY  CO | COM | 532457108 |  | 7660520 | 10040 | SH |  | DFND | 12 | 10040 | 0 | 0 |
| ENGENE HOLDINGS INC | COM | 29286M105 |  | 3445113 | 504409 | SH |  | DFND | 12 | 504409 | 0 | 0 |
| ENLIVEN THERAPEUTICS INC | COM | 29337E102 |  | 3413680 | 166765 | SH |  | DFND | 12 | 166765 | 0 | 0 |
| ENPHASE ENERGY INC | COM | 29355A107 |  | 944913 | 26700 | SH |  | DFND |  | 26700 | 0 | 0 |
| FORTE BIOSCIENCES INC | COM NEW | 34962G208 |  | 7114635 | 474309 | SH |  | DFND | 12 | 474309 | 0 | 0 |
| GSK PLC | SPONSORED ADR | 37733W204 |  | 5265520 | 122000 | SH |  | DFND | 12 | 122000 | 0 | 0 |
| IDEAYA BIOSCIENCES INC | COM | 45166A102 |  | 2721000 | 100000 | SH |  | DFND | 12 | 100000 | 0 | 0 |
| IMMATICS N.V | SHS | N44445109 |  | 4968055 | 583105 | SH |  | DFND | 12 | 583105 | 0 | 0 |
| IMMUNOME INC | COM | 45257U108 |  | 1723712 | 147200 | SH |  | DFND | 12 | 147200 | 0 | 0 |
| IMMUNOVANT INC | COM | 45258J102 |  | 4138697 | 256743 | SH |  | DFND | 12 | 256743 | 0 | 0 |
| INVESCO QQQ TR | UNIT SER 1 | 46090E103 |  | 13784495 | 22960 | SH |  | DFND |  | 22960 | 0 | 0 |
| ISHARES BITCOIN TRUST ETF | SHS BEN INT | 46438F101 |  | 1394575 | 21455 | SH |  | DFND |  | 21455 | 0 | 0 |
| ISHARES TR | 20 YR TR BD ETF | 464287432 |  | 4200390 | 47000 | SH | Call | DFND |  | 0 | 0 | 0 |
| JANUX THERAPEUTICS INC | COM | 47103J105 |  | 2097930 | 85840 | SH |  | DFND | 12 | 85840 | 0 | 0 |
| JASPER THERAPEUTICS INC | COM NEW | 471871202 |  | 1498139 | 629470 | SH |  | DFND | 12 | 629470 | 0 | 0 |
| JOHNSON  JOHNSON | COM | 478160104 |  | 7570884 | 40831 | SH |  | DFND | 12 | 40831 | 0 | 0 |
| KURA ONCOLOGY INC | COM | 50127T109 |  | 2172870 | 245522 | SH |  | DFND | 12 | 245522 | 0 | 0 |
| LARIMAR THERAPEUTICS INC | COM | 517125100 |  | 841044 | 260385 | SH |  | DFND | 12 | 260385 | 0 | 0 |
| MAZE THERAPEUTICS INC | COM | 578784100 |  | 4002114 | 154343 | SH |  | DFND | 12 | 154343 | 0 | 0 |
| MEDIWOUND LTD | SHS NEW | M68830112 |  | 3338565 | 185270 | SH |  | DFND | 12 | 185270 | 0 | 0 |
| MERCK  CO INC | COM | 58933Y105 |  | 4078998 | 48600 | SH |  | DFND | 12 | 48600 | 0 | 0 |
| MERUS N V | COM | N5749R100 |  | 14122500 | 150000 | SH | Call | DFND | 12 | 0 | 0 | 0 |
| META PLATFORMS INC | CL A | 30303M102 |  | 2881707 | 3924 | SH |  | DFND |  | 3924 | 0 | 0 |
| MILESTONE PHARMACEUTICALS IN | COM | 59935V107 |  | 1640000 | 820000 | SH |  | DFND | 12 | 820000 | 0 | 0 |
| MINERALYS THERAPEUTICS INC | COM | 603170101 |  | 8338987 | 219910 | SH |  | DFND | 12 | 219910 | 0 | 0 |
| MOONLAKE IMMUNOTHERAPEUTICS | CLASS A ORD | 61559X104 |  | 509142 | 71010 | SH |  | DFND | 12 | 71010 | 0 | 0 |
| MOONLAKE IMMUNOTHERAPEUTICS | CLASS A ORD | 61559X104 |  | 71700 | 10000 | SH | Call | DFND | 12 | 0 | 0 | 0 |
| NICE LTD | SPONSORED ADR | 653656108 |  | 22788372 | 157400 | SH |  | DFND |  | 157400 | 0 | 0 |
| NOVA LTD | COM | M7516K103 |  | 14031795 | 43896 | SH |  | DFND |  | 43896 | 0 | 0 |
| NOVARTIS AG | SPONSORED ADR | 66987V109 |  | 4744880 | 37000 | SH |  | DFND | 12 | 37000 | 0 | 0 |
| NOVO-NORDISK A S | ADR | 670100205 |  | 5864017 | 105677 | SH |  | DFND | 12 | 105677 | 0 | 0 |
| ONKURE THERAPEUTICS INC | COM CL A | 68277Q105 |  | 166249 | 60454 | SH |  | DFND | 12 | 60454 | 0 | 0 |
| ORIC PHARMACEUTICALS INC | COM | 68622P109 |  | 5180316 | 431693 | SH |  | DFND | 12 | 431693 | 0 | 0 |
| ORMAT TECHNOLOGIES INC | COM | 686688102 |  | 2791250 | 29000 | SH |  | DFND |  | 29000 | 0 | 0 |
| PEPGEN INC | COM | 713317105 |  | 792178 | 171467 | SH |  | DFND | 12 | 171467 | 0 | 0 |
| PERSPECTIVE THERAPEUTICS INC | COM NEW | 46489V302 |  | 1750476 | 510343 | SH |  | DFND | 12 | 510343 | 0 | 0 |
| PFIZER INC | COM | 717081103 |  | 2191280 | 86000 | SH |  | DFND | 12 | 86000 | 0 | 0 |
| PHARVARIS N V | COM | N69605108 |  | 2979180 | 119406 | SH |  | DFND | 12 | 119406 | 0 | 0 |
| PRAXIS PRECISION MEDICINES I | COM NEW | 74006W207 |  | 3068753 | 57901 | SH |  | DFND | 12 | 57901 | 0 | 0 |
| PRAXIS PRECISION MEDICINES I | COM NEW | 74006W207 |  | 2650000 | 50000 | SH | Call | DFND | 12 | 0 | 0 | 0 |
| PROMIS NEUROSCIENCES INC | COM NEW | 74346M406 |  | 125454 | 295187 | SH |  | DFND | 12 | 295187 | 0 | 0 |
| RAPPORT THERAPEUTICS INC | COM | 75383L102 |  | 4678730 | 157533 | SH |  | DFND | 12 | 157533 | 0 | 0 |
| REVOLUTION MEDICINES INC | COM | 76155X100 |  | 2802000 | 60000 | SH |  | DFND | 12 | 60000 | 0 | 0 |
| REZOLUTE INC | COM NEW | 76200L309 |  | 3421102 | 363947 | SH |  | DFND | 12 | 363947 | 0 | 0 |
| ROIVANT SCIENCES LTD | SHS | G76279101 |  | 644099 | 42571 | SH |  | DFND | 12 | 42571 | 0 | 0 |
| ROIVANT SCIENCES LTD | SHS | G76279101 |  | 2293708 | 151600 | SH | Call | DFND | 12 | 0 | 0 | 0 |
| SAB BIOTHERAPEUTICS INC | COM NEW | 78397T202 |  | 1138454 | 566395 | SH |  | DFND | 12 | 566395 | 0 | 0 |
| SANOFI SA | SPONSORED ADR | 80105N105 |  | 10361108 | 219515 | SH |  | DFND | 12 | 219515 | 0 | 0 |
| SAREPTA THERAPEUTICS INC | COM | 803607100 |  | 2890500 | 150000 | SH | Call | DFND | 12 | 0 | 0 | 0 |
| SAVARA INC | COM | 805111101 |  | 4820689 | 1350333 | SH |  | DFND | 12 | 1350333 | 0 | 0 |
| SKYE BIOSCIENCE INC | COM NEW | 83086J200 |  | 1882187 | 478928 | SH |  | DFND | 12 | 478928 | 0 | 0 |
| SOLAREDGE TECHNOLOGIES INC | NOTE 2.250% 7/0 | 83417MAE4 |  | 5332890 | 4000000 | SH |  | DFND |  | 4000000 | 0 | 0 |
| SOLAREDGE TECHNOLOGIES INC | COM | 83417M104 |  | 5215742 | 140966 | SH |  | DFND |  | 140966 | 0 | 0 |
| SOLENO THERAPEUTICS INC | COM | 834203309 |  | 2812566 | 41606 | SH |  | DFND | 12 | 41606 | 0 | 0 |
| STRUCTURE THERAPEUTICS INC | SPONSORED ADS | 86366E106 |  | 4870068 | 173931 | SH |  | DFND | 12 | 173931 | 0 | 0 |
| STRUCTURE THERAPEUTICS INC | SPONSORED ADS | 86366E106 |  | 1400000 | 50000 | SH | Call | DFND | 12 | 0 | 0 | 0 |
| SYNDAX PHARMACEUTICALS INC | COM | 87164F105 |  | 5965011 | 387716 | SH |  | DFND | 12 | 387716 | 0 | 0 |
| TAYSHA GENE THERAPIES INC | COM SHS | 877619106 |  | 1334637 | 408146 | SH |  | DFND | 12 | 408146 | 0 | 0 |
| TECTONIC THERAPEUTIC INC | COM | 878972108 |  | 1818597 | 115908 | SH |  | DFND | 12 | 115908 | 0 | 0 |
| TEVA PHARMACEUTICAL INDS LTD | SPONSORED ADS | 881624209 |  | 26401905 | 1307025 | SH |  | DFND |  | 1307025 | 0 | 0 |
| TEVA PHARMACEUTICAL INDS LTD | SPONSORED ADS | 881624209 |  | 4040000 | 200000 | SH |  | DFND | 12 | 200000 | 0 | 0 |
| TOWER SEMICONDUCTOR LTD | SHS NEW | M87915274 |  | 22543285 | 311802 | SH |  | DFND |  | 311802 | 0 | 0 |
| TRAVERE THERAPEUTICS INC | COM | 89422G107 |  | 2433020 | 101800 | SH | Call | DFND | 12 | 0 | 0 | 0 |
| TREVI THERAPEUTICS INC | COM | 89532M101 |  | 5892207 | 643957 | SH |  | DFND | 12 | 643957 | 0 | 0 |
| TREVI THERAPEUTICS INC | COM | 89532M101 |  | 1182180 | 129200 | SH | Call | DFND | 12 | 0 | 0 | 0 |
| ULTRAGENYX PHARMACEUTICAL IN | COM | 90400D108 |  | 10604945 | 352558 | SH |  | DFND | 12 | 352558 | 0 | 0 |
| UNIQURE NV | SHS | N90064101 |  | 1453413 | 24900 | SH |  | DFND | 12 | 24900 | 0 | 0 |
| UNIQURE NV | SHS | N90064101 |  | 4377750 | 75000 | SH | Put | DFND | 12 | 75000 | 0 | 0 |
| VARONIS SYS INC | COM | 922280102 |  | 4247033 | 73900 | SH |  | DFND |  | 73900 | 0 | 0 |
| VAXCYTE INC | COM | 92243G108 |  | 1801000 | 50000 | SH |  | DFND | 12 | 50000 | 0 | 0 |
| VENTYX BIOSCIENCES INC | COM | 92332V107 |  | 1368755 | 440114 | SH |  | DFND | 12 | 440114 | 0 | 0 |
| VERASTEM INC | COM NEW | 92337C203 |  | 691451 | 78307 | SH |  | DFND | 12 | 78307 | 0 | 0 |
| VOYAGER THERAPEUTICS INC | COM | 92915B106 |  | 932884 | 199761 | SH |  | DFND | 12 | 199761 | 0 | 0 |
| WAVE LIFE SCIENCES LTD | SHS | Y95308105 |  | 366000 | 50000 | SH |  | DFND | 12 | 50000 | 0 | 0 |
| WEREWOLF THERAPEUTICS INC | COM | 95075A107 |  | 1234816 | 626810 | SH |  | DFND | 12 | 626810 | 0 | 0 |

---