Stoke Therapeutics (STOK) Q3 2025: R&D Spend Jumps 70% as Phase III Enrollment Surges Past 200 Patients

November 4, 2025 | By EarningsIQ Research

Stoke Therapeutics accelerated its transition to a late-stage CNS platform company in Q3, with R&D expense up sharply to support rapid enrollment in its pivotal EMPEROR trial for Dravet syndrome. Strong patient demand, deepening physician engagement, and a robust cash runway position STOK for a pivotal regulatory inflection as it seeks expedited FDA review, even as the company resists shortcuts on its disease-modifying label ambitions. Management’s conviction in long-term data and pipeline focus highlight a maturing commercial strategy ahead of key FDA and clinical milestones.

Summary

• Clinical Momentum Accelerates: EMPEROR Phase III trial enrollment and prescreening outpaced expectations, reflecting high patient and caregiver demand.
• Strategic Capital Deployment: Substantial R&D and SG&A investment signal Stoke’s pivot toward commercial readiness and pipeline expansion.
• Regulatory Inflection Ahead: Upcoming FDA meeting could define the accelerated approval path, with management emphasizing totality of long-term efficacy and safety data.

Performance Analysis

Stoke’s Q3 financials underscore a decisive investment phase, with total revenue of $10.6 million, up from $4.9 million in the prior year, primarily reflecting increased collaboration revenue from Biogen for Zoriva Nursing. Net loss widened to $38.3 million as R&D spend surged 70% year-over-year, driven by the EMPEROR Phase III trial, early-stage pipeline progress, and R&D hiring. SG&A rose to $16 million, reflecting foundational buildout of commercial infrastructure and leadership. The company ended the quarter with $328.6 million in cash, augmented by a $48.7 million ATM raise, extending its runway into mid-2028.

Operationally, EMPEROR trial enrollment outpaced internal forecasts, with more than 200 patients identified in prescreening, over 20 randomized, and 35+ in formal screening. The trial now spans 30 sites across the US, UK, and Japan, with European sites set to open in 2026. Clinical engagement is robust, as evidenced by nearly 400 medical information requests since June, half from caregivers seeking trial access. Longitudinal data from Zoriva Nursing’s open-label extension (OLE) studies continue to show durable seizure reduction and meaningful cognitive and behavioral gains, supporting the Phase III design and regulatory dialogue.

• R&D Investment Surge: Phase III EMPEROR trial and pipeline advancement drove a 70% YoY increase in R&D expense, reflecting Stoke’s late-stage pivot.
• Commercial Infrastructure Build: SG&A growth tracked new leadership hires in market access, pricing, and medical affairs, setting the stage for launch readiness.
• Robust Cash Position: Cash runway now extends into mid-2028, supporting continued trial execution and pipeline investment without near-term dilution risk.

Stoke’s financial discipline and clinical execution are converging as the company enters a defining regulatory and commercial phase, with the EMPEROR trial and FDA engagement acting as key catalysts.

Executive Commentary

Strategic Positioning

1. EMPEROR Trial as Value Catalyst

The EMPEROR Phase III trial for Zoriva Nursing is Stoke’s central value driver, with enrollment momentum exceeding expectations and broadening global reach. Over 200 patients have been prescreened, and 30 sites are now active, with European expansion slated for 2026. Stoke’s focus on disease-modifying endpoints, rather than short-term seizure reduction alone, reflects a strategic bet on durable, differentiated clinical benefit as the basis for regulatory and commercial success.

2. Regulatory Pathway and FDA Engagement

Stoke is leveraging its breakthrough therapy designation to seek an expedited FDA pathway, submitting a comprehensive four-year data package ahead of its December multidisciplinary meeting. Management is clear that approval will not be sought solely on seizure reduction, but on the totality of disease-modifying data, including cognitive and behavioral gains measured by Vineland-3. The company is prepared for multiple regulatory scenarios, from accelerated review to amendments in trial design or data cuts, signaling flexibility and readiness for iterative FDA dialogue.

3. Commercial and Pipeline Readiness

Stoke is actively building commercial infrastructure, with new leadership across market access, pricing, and medical affairs. Early market shaping includes the “Unseen” disease awareness campaign, targeting increased Dravet diagnosis via genetic testing. Beyond Dravet, pipeline programs in autosomal dominant optic atrophy (ADOA) and Syngap syndrome are advancing, with Phase I for STK002 underway and preclinical work in Syngap targeting a 2026 clinical nomination. The company’s focus on haploinsufficient CNS, eye, and cardiac diseases leverages platform learnings from Zoriva Nursing.

4. Data-Driven Credibility and Stakeholder Engagement

Stoke’s robust longitudinal clinical data have been central to its dialogue with clinicians, caregivers, and regulators, with published studies validating the clinical meaningfulness of Vineland-3 gains. High levels of caregiver engagement and medical inquiries reflect strong patient advocacy and unmet need, reinforcing the urgency and potential scale of the opportunity.

Key Considerations

Stoke’s Q3 marks an inflection in its evolution from a clinical-stage biotech to a late-stage CNS platform company, with the EMPEROR trial, regulatory strategy, and commercial buildout converging as key value drivers.

Key Considerations:

• Trial Execution Outpaces Expectations: EMPEROR enrollment and site activation are running ahead of plan, de-risking timelines and supporting regulatory optionality.
• Strategic Refusal to Shortcut Label: Management’s commitment to a full disease-modifying label, rather than seizure reduction alone, may delay approval but aims for long-term differentiation and pricing power.
• Cash Runway Supports Multiple Programs: Funding into mid-2028 enables full execution of EMPEROR, commercial preparations, and advancement of ADOA and Syngap programs without near-term capital constraints.
• Data Transparency and Stakeholder Buy-In: Frequent data disclosures, peer-reviewed publications, and direct engagement with caregivers and clinicians bolster credibility ahead of regulatory milestones.

Risks

Regulatory risk remains central, as the FDA’s acceptance of disease-modifying endpoints, rather than seizure reduction alone, is not guaranteed. Operational risks include potential enrollment slowdowns, evolving trial design requirements, and the challenge of translating robust OLE data into registrational endpoints. Pipeline expansion into new therapeutic areas carries inherent uncertainties in target selection and development timelines.

Forward Outlook

For Q4 and into 2026, Stoke guided to:

• Completion of EMPEROR trial enrollment in the second half of 2026
• Data readout expected in the second half of 2027, with NDA filing targeted for late 2027 or early 2028

For full-year 2025, management maintained guidance of:

• Cash runway into mid-2028

Management highlighted several forward drivers:

• December FDA multidisciplinary meeting as a potential regulatory inflection
• Ongoing expansion of commercial and medical affairs teams to support future launch

Takeaways

Stoke’s late-stage pipeline execution, robust cash position, and refusal to compromise on label ambition set the stage for a pivotal regulatory year. Clinical and commercial infrastructure investments are de-risking the transition to a commercial CNS company, while the company’s platform approach and data-driven engagement with regulators and stakeholders build long-term credibility.

• EMPEROR Trial Momentum: Enrollment and engagement trends suggest Stoke is well positioned for regulatory dialogue and future launch, even as management resists shortcuts on label scope.
• Platform and Pipeline Depth: Early-stage programs in ADOA and Syngap, plus a focus on haploinsufficiency, diversify Stoke’s future opportunity set beyond Dravet syndrome.
• FDA Meeting as Near-Term Catalyst: The December FDA meeting will clarify regulatory timelines and may unlock accelerated pathways, with management’s strategic flexibility as a key asset.

Conclusion

Stoke Therapeutics is entering a critical phase, with clinical, regulatory, and commercial investments converging to support its transition into a late-stage CNS leader. The company’s disciplined approach to data, label ambition, and capital allocation positions it for long-term value creation as EMPEROR and the FDA dialogue unfold.

Industry Read-Through

Stoke’s experience underscores the importance of robust, long-term data and stakeholder engagement in rare CNS disease drug development. Its refusal to pursue narrow endpoints for short-term approval may set a precedent for other disease-modifying therapies seeking durable differentiation and pricing leverage. Biotech investors should note the value of early commercial buildout, cross-functional regulatory preparation, and platform focus on genetically defined, haploinsufficient diseases. Stoke’s regulatory and clinical playbook offers a template for other late-stage rare disease developers navigating similar inflection points.

STOK Healthcare Biotechnology Rare Disease Clinical Trials Regulatory CNS Pipeline