Business Context and Reporting Period
Company: Stoke Therapeutics, Inc. (STOK)
Filing Type: Form 10-K (Annual Report)
Reporting Period: Fiscal year ended December 31, 2025
Business Overview: Stoke is a late-stage clinical biotechnology company developing RNA-based medicines using its proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) platform to upregulate protein expression in genetic diseases. The company focuses on autosomal dominant haploinsufficiency diseases of the central nervous system and the eye.
- Lead Asset (Zorevunersen/STK-001): A disease-modifying therapy for Dravet syndrome. The global Phase 3 EMPEROR study was initiated in May 2025, with the first patient dosed in August 2025. Enrollment of ~150 patients is expected in Q2 2026, with data anticipated in mid-2027.
- Second Asset (STK-002): A therapy for Autosomal Dominant Optic Atrophy (ADOA). The Phase 1 OSPREY study dosed its first patient in February 2026.
- Collaborations: Active agreements with Biogen (global development outside North America for zorevunersen) and Acadia Pharmaceuticals (SYNGAP1 program).
Key Financial Metrics
| Metric (in millions) | 2025 | 2024 |
|---|---|---|
| Revenue | $184.4 | $36.6 |
| Net Loss | $(6.9) | $(89.0) |
| Operating Loss | $(20.6) | $(101.4) |
| Research & Development Expenses | $137.9 | $89.1 |
| Sales, General & Administrative Expenses | $67.1 | $48.8 |
| Cash, Cash Equivalents & Marketable Securities | $390.9 | $246.7 |
| Accumulated Deficit | $(497.7) | $(490.8) |
Liquidity: As of December 31, 2025, the company held $390.9 million in cash and marketable securities. Management believes this capital is sufficient to fund operations into 2028.
Material Changes vs. Prior Period
- Revenue Surge: Revenue increased by $147.8 million (404%) to $184.4 million. This was primarily driven by the February 2025 Biogen collaboration agreement, which generated $168.3 million in revenue (including $150.8 million for the IP license and $17.5 million for development activities). This offset a decrease in revenue from the Acadia collaboration.
- Improved Net Loss: Net loss narrowed significantly from $89.0 million in 2024 to $6.9 million in 2025, largely due to the substantial revenue recognition from the Biogen deal.
- Increased R&D Spend: R&D expenses rose by $48.8 million to $137.9 million, driven by a $33.8 million increase in costs for the zorevunersen program (Phase 3 trial initiation) and higher personnel costs.
- Collaboration Updates: In September 2025, Acadia terminated the MECP2 and undisclosed neurodevelopmental programs under their agreement; rights to these targets returned to Stoke. The SYNGAP1 collaboration remains active.
Guidance, Outlook, and Risks
Outlook and Milestones:
- Zorevunersen: Phase 3 EMPEROR study enrollment completion expected in Q2 2026. Pivotal data anticipated mid-2027 to support a rolling NDA submission in H1 2027.
- STK-002: Phase 1 OSPREY study ongoing; first patient dosed February 2026.
- Capital Needs: The company expects to require additional financing to advance clinical development and commercialization efforts beyond 2028.
Key Risks and Contingencies:
- Clinical Trial Risk: Success in early trials does not guarantee Phase 3 success. Failure to demonstrate efficacy or safety could halt development.
- Regulatory Risk: Approval timelines are uncertain; regulatory authorities may require additional studies or reject applications.
- Collaboration Dependence: Future revenue relies heavily on milestone payments and royalties from Biogen and Acadia, which are contingent on achieving development and commercial milestones.
- Intellectual Property: The company relies on licensed IP from the University of Southampton; disputes or expiration could impact commercialization.
- Profitability: The company has a history of operating losses and expects to continue incurring losses for the foreseeable future.
Investor Verification Checklist
- Biogen Revenue Recognition: Verify the accounting treatment of the $165 million upfront payment and the allocation of the transaction price between the IP license and development services under ASC 606.
- Phase 3 Enrollment Progress: Monitor the EMPEROR study enrollment rates to ensure the Q2 2026 completion target is met.
- Cash Burn Rate: Assess the sustainability of the $390.9 million cash balance against the projected increase in R&D and SG&A expenses through 2028.
- Acadia Termination Impact: Confirm the financial impact of the terminated MECP2 programs and the status of the remaining SYNGAP1 collaboration.
- Patent Expirations: Review the expiration dates of key patents (ranging from 2035 to 2046) and the status of the University of Southampton license.