Stoke Therapeutics, Inc. Q3 FY2026 earnings call

• Phase 3 EMPRA Study Progress: Approximately 110 of 162 enrolled patients have completed the Week 28 visit (primary endpoint timepoint for seizure frequency), and ~20 patients have completed the Week 52 visit (secondary endpoint timepoint). There have been zero treatment discontinuations to date.
• FDA Interaction & NDA Planning: Stoke held a successful meeting with the FDA regarding its 2027 US NDA submission for Zareva-Nersen. The FDA agreed to accept a multi-component assessment (MC4) of Vineland-3 data for cognition and behavior, acknowledging the disease's complexity. This approach averages four subdomains rather than using a hierarchical model.
• Timeline Maintenance: Management reiterates the timeline for a data readout in Q3 2027, followed by an NDA submission in the second half of 2027, and potential US approval in early 2028.
• Commercial Readiness: The company is expanding its field market access team and engaging with top 50 treatment centers to prepare infrastructure for intrathecal administration. Educational efforts with payers and clinicians are ongoing, showing high conviction in the drug's disease-modifying potential.
• Pipeline Update (STK002/ADOA): Dosing is underway in the third cohort of the Phase 1 Osprey study for STK002 (Autosomal Dominant Optic Atrophy). The fourth cohort is expected to begin in early 2027. Initial safety and efficacy data are anticipated in H1 2027.
• Additional Clinical Studies: Two additional studies for Zareva-Nersen (in adults and infants/toddlers) will initiate by end of 2026 to support label breadth and reimbursement.

Stoke Therapeutics is a clinical-stage biopharmaceutical company with no commercial revenue. The transcript does not provide financial performance for product segments in absolute terms or as a percentage of revenue contribution, as the company is pre-commercial. Financial highlights focus on operational costs and cash position.

• Data Readout: Confirmed for Q3 2027.
• NDA Submission: Planned for the second half of 2027, with rolling submissions starting in the first half of 2027.
• Potential Approval: Targeting early 2028 in the US.
• Cash Runway: Current cash position ($358.8 million) plus Biogen reimbursements/milestones is expected to fund operations into early 2028.
• Quarterly Spend: Management suggests modeling Q4 2026 spend based on Q3 2026 levels, indicating a quarter-over-quarter increase trend.

• Clinical Trial Risk: While no discontinuations have occurred, the trial is long-term (52 weeks + open label), and patient retention or protocol deviations remain inherent risks.
• Regulatory Risk: The shift to a multi-component endpoint (MC4) for cognition/behavior is a new approach; while FDA-aligned, there is always risk associated with novel statistical endpoints in rare diseases.
• Commercial Execution Risk: Launching an intrathecal therapy requires significant site infrastructure changes. Although sites are engaged, execution delays could impact launch speed.
• Competitive/Market Evolution: The landscape for genetic epilepsies is evolving rapidly with increased awareness and new therapies, requiring continuous education and adaptation of commercial strategy.

Q: Analyst asked about the statistical design of the multi-component Vineland-3 assessment (MC4), specifically how it handles subdomain contributions and whether missing one domain affects the overall significance compared to individual hierarchical testing. / A: Management explained that MC4 averages four subdomains equally, providing greater statistical power than hierarchical testing. Even if individual domains miss significance due to variability, the composite score can still achieve statistical significance (p<0.01). This approach better reflects the heterogeneous nature of Dravet syndrome symptoms.

Q: Analyst inquired about the FDA meeting outcomes beyond the endpoint change, specifically regarding the inclusion of long-term Open Label Extension (OLE) data in the final label and the possibility of an Advisory Committee meeting. / A: CEO confirmed no AdCom is anticipated. Regarding OLE data, the FDA indicated that including the five-year chronic dosing data would be a "review issue," meaning it will be considered during labeling discussions. This supports the argument for a broad label without upper age limits, emphasizing the cumulative benefits of long-term treatment.

Q: Analyst asked about the clinical meaningfulness of seizure reduction targets and whether success is defined by p<0.05 or p<0.01. / A: Management stated that clinically meaningful improvement is generally viewed as a 40-50% additional reduction over standard of care. Statistically, the primary endpoint and key secondary endpoints require a p-value of less than 0.05 for significance. The study is powered to detect a 46-53% relative reduction in seizures.

Q: Analyst sought clarification on the STK002 program for Autosomal Dominant Optic Atrophy (ADOA), asking what data from the upcoming cohorts will drive the next development decision and if OPA1 protein levels are being measured. / A: CMO clarified that the Phase 1 study is primarily a safety study, but visual acuity and mitochondrial function biomarkers are key efficacy indicators. They are not directly measuring retinal OPA1 protein levels in humans yet but are looking for functional improvements. Decisions on dose selection for pivotal trials will depend on the safety and efficacy signals from cohorts 3 and 4 in H1 2027.

Q: Analyst asked about the alignment with partner Biogen on pricing and differentiation, particularly in ex-US markets where value propositions might differ. / A: CEO noted that while Biogen controls European filings, the US value proposition relies on the totality of data (including OLE data). He acknowledged that achieving differential pricing and demonstrating value is more challenging in single-payer European systems compared to the US, where they have direct engagement capabilities.