Stoke Therapeutics, Inc. (STOK) Earnings

Management highlights

### Clinical Progress: Lead Asset (zurivinersen for Dravet Syndrome) - Completed enrollment of 162 patients in the Phase III EMPEROR study 10 months after initiation, with no patient treatment discontinuations to date (vs. original 15% discontinuation assumption in power calculations). Over 140 patients have completed Week 8, over half have only one dose remaining in the 52-week treatment period, and ~60 patients have completed the Week 28 primary endpoint visit. An additional 30-patient European cohort is on track to complete enrollment in Q3 2026. - Long-term open-label extension (OLE) study data (four years of follow-up) demonstrates durable seizure reduction on top of standard-of-care anti-seizure medications, and statistically significant annual improvements in adaptive cognition/behavior (measured via Vineland-3) through four years of treatment. 93% of original Phase 1/2 patients continued in the OLE, with 57 still active; over 930 total doses have been administered (some patients for over five years), with no new safety signals and continued good tolerability. These long-term data were published in the *New England Journal of Medicine* earlier in 2026. - New planned studies: A study in infants/toddlers under 24 months will initiate in late 2026 to support early intervention labeling, and an adult Dravet study will also initiate by end of 2026 to support adult access and reimbursement. ### Pipeline Progress - STK002 for autosomal dominant optic atrophy (ADOA, an orphan haploinsufficiency disease with no approved treatments): The Phase 1 single ascending dose study completed dosing of the first 3-patient cohort, and the second higher-dose cohort initiated dosing in Q3 2026. Early safety and efficacy results are expected in H1 2027. - SYNGAP1-related neurodevelopmental disorder: Five preclinical candidates are under evaluation; a development candidate is planned for selection in 2027 to advance to clinical testing. The company is also expanding early research into additional CNS haploinsufficient disease targets. ### Regulatory & Commercial Preparation - A pre-NDA meeting with the FDA is scheduled for late 2026. A rolling NDA submission will initiate in Q1 2027 (starting with the CMC module), with the full submission completed in Q3 2027 following EMPEROR readout, and potential FDA approval by early 2028. The company plans to include long-term OLE data in the NDA submission to support labeling. - Commercial preparations: Approximately 16,000 total Dravet patients in the U.S., 6,000 of whom are under 25 and immediately addressable at launch. 50% of U.S. patients are concentrated at the top 50 treatment centers, all of which already have experience administering intrathecal therapies. A lean commercial infrastructure of ~25 sales reps will leverage existing medical affairs relationships with treating physicians. Biogen holds commercialization rights for ex-U.S. markets. - Completed commercial-scale manufacturing validation for both drug substance and drug product, and is finalizing product specifications. ### Leadership Update - Added Tom McCauley as Chief Scientific Officer in July 2026 to lead platform expansion and translational research.

Guidance

- The Phase III EMPEROR study remains on track for a data readout in Q3 2027. - Rolling NDA submission for zurivinersen will initiate in Q1 2027 (starting with CMC) and complete in Q3 2027 after EMPEROR data is available, with potential FDA approval and U.S. launch in early 2028. - The $420 million pro forma cash position is expected to fund all operating activities through the planned early 2028 U.S. launch. - Early safety and efficacy data for STK002 (ADOA) is expected in H1 2027. - The infant/toddler and adult Dravet studies for zurivinersen are both expected to initiate in late 2026. - A development candidate for SYNGAP1-related disorders is targeted for selection in 2027 to advance to clinical testing.

Segment performance

Stoke Therapeutics is a clinical-stage biotech with a single product candidate (zurivinersen for Dravet syndrome) in late-stage development, plus one earlier clinical asset (STK002 for ADOA) and preclinical pipeline programs. No product segments have generated commercial revenue to date. The company ended Q2 2026 with $354.3 million in cash, cash equivalents, and marketable securities; after an additional $65.7 million in net proceeds from an ATM offering post-quarter, pro forma total cash is $420 million.

Risks & headwinds

- All clinical results are forward-looking; actual study outcomes (including meeting primary and secondary endpoint efficacy and safety targets) may differ from management expectations, which could delay or prevent regulatory approval of zurivinersen. - Successful FDA approval depends on agency agreement with the company’s proposed Statistical Analysis Plan, inclusion of long-term OLE data in the labeling, and acceptability of the EMPEROR study data, which cannot be guaranteed. - The company is dependent on the success of its lead asset zurivinersen; all pipeline assets are still in early development, and there is no guarantee they will meet clinical endpoints or advance to approval.

Analyst Q&A

• Q: What key takeaways should investors draw from EMPEROR study progress, and what alignment is management seeking at the upcoming pre-NDA meeting? /

  A: Management confirms the trial is progressing well, with 162 enrolled patients (over the 150 target), no discontinuations (vs. 15% assumed for powering), and most patients advancing through key milestones on schedule. This reinforces confidence that the well-tolerated drug will meet trial endpoints. For the pre-NDA meeting, management is seeking alignment on three priorities: 1) the sequence of modules for the rolling NDA submission (CMC first in Q1 2027, clinical data last in Q3 2027), 2) details of the Statistical Analysis Plan, specifically how to present the secondary Vineland-3 adaptive function endpoints (either hierarchical or composite analysis), and 3) inclusion of the five-year long-term OLE data demonstrating durable seizure reduction and sustained cognitive improvements.

• Q: What gives management confidence that the 52-week timepoint will show separation between active and sham for secondary endpoints, and how will disease modification labeling impact potential pricing? /

  A: The EMPEROR study was powered for >90% confidence to detect a 2-3 point delta in Vineland scores, with an original assumption of only 125-130 evaluable patients after 15% discontinuation. With 162 patients enrolled and zero discontinuations, the study is overpowered for all endpoints, and historical OLE data shows far larger effect sizes than the minimum delta the trial is powered to detect. For pricing, payers and providers find the five-year published OLE data the most compelling evidence of value, regardless of whether it is included in the label. Management expects zurivinersen will command rare disease, genetically targeted, disease-modifying pricing consistent with current market precedent for similar assets.

• Q: What is the status of site capacity for intrathecal delivery of zurivinersen, and what impact could this have on launch? /

  A: All of the top 50 U.S. Dravet treatment centers that care for 50% of U.S. patients already have extensive experience administering intrathecal therapies (including Spinraza for SMA) and have existing protocols in place for these procedures. The fast enrollment of the EMPEROR study confirms site capacity is sufficient to handle robust launch demand. Management will continue site readiness and qualification work over the next 12 months, and enters launch with a major advantage from existing infrastructure, limiting logistical constraints.

• Q: Can you provide an update on the STK002 Phase 1 study for ADOA, and what is the proof-of-concept threshold? /

  A: The first 3-patient sentinel cohort has completed dosing, and the safety monitoring committee reviewed data and approved dose escalation to the second cohort. Preclinical data in non-human primates with the same genetic mutation showed improved mitochondrial and optic nerve function, which gave management confidence to advance. Management expects potential efficacy signals may emerge in the third or fourth higher dose cohorts, with full early data readout expected in H1 2027, when the study will assess safety and changes in visual acuity and mitochondrial function.