Stoke Therapeutics Reports Durable Dravet Data, Expects Phase 3 Enrollment Completion in Q2 2026

Stoke Therapeutics used its presentation at the Guggenheim Emerging Outlook Biotech Summit 2026 to highlight long-term clinical findings for its lead program in Dravet syndrome, outline the design and objectives of its ongoing Phase 3 trial, and discuss early progress in a second clinical program in autosomal dominant optic atrophy (ADOA). The company's stock has demonstrated notable resilience, currently trading at €29.40 and hovering just below its 52-week high of €30.20, with a gain of approximately 17.6% over the past 30 trading days.

Chief Executive Officer Ian Smith said investor attention has increasingly centered on longitudinal results from the company's Phase 1/2 Dravet program and its open-label extension (OLE). Smith noted that patients originally enrolled in dose escalation were rolled into an OLE and have now been followed for three years in that extension, representing close to four years since the Phase 1/2 period.

According to Smith, Stoke has reported seizure reductions of roughly up to 80% on top of standard-of-care anti-seizure medicines, and he described the effect as durable through the OLE follow-up. He emphasized that many trial participants were already receiving approved Dravet therapies, noting that about 50% of patients in Stoke's studies were on Fintepla.

Smith also discussed measured changes in cognition and behavior, citing assessments on the Vineland-3 scale. He said the company has observed improvements over the three-year OLE period, contrasting those improvements with what he described as typical developmental "plateauing" in Dravet beginning around 18 months to two years of age. Smith said the company has seen Vineland changes "up to 10 and 11" over 12 to 18 months in its longitudinal assessments.

In response to questions about how investors should think about magnitude and durability versus standard of care, Smith tied the seizure effect to the company's proposed mechanism: Dravet's pathophysiology involves reduced expression of NaV1.1, and Stoke's approach is intended to upregulate the SCN1A gene to increase NaV1.1 expression. Smith said this "root cause" approach underpins both the magnitude of seizure reduction and the durability once patients reach steady state.

He further linked the same mechanism to neurocognitive and behavioral changes, characterizing the observed changes as improvement rather than merely slowing disease progression. As an example of functional change, Smith described a patient case presented by physicians at medical conferences in which a child who did not respond to name or gestures at baseline later demonstrated responses to the same prompts after a year on therapy.

Smith said Stoke is well into its Phase 3 Dravet program and expects to complete enrollment in the second quarter of the year, with data anticipated in mid-2027. He described the pivotal study as a 52-week trial with a primary endpoint measured at week 28 focused on seizure reduction, and secondary endpoints at week 52 that include Vineland. Smith said the timing reflects the mechanism of action: seizure suppression is expected to occur earlier, while cognitive and behavioral assessments are scheduled later to allow time for drug exposure and steady-state effects.

The Phase 3 "EMPEROR" trial is evaluating zorevunersen, Stoke's lead candidate being developed in collaboration with Biogen. Smith said the trial is enrolling about 150–160 patients and includes different sham-control approaches by region: U.S., U.K., and Japan use lumbar puncture sham control, while four European countries use needle-prick sham control, reflecting European preference versus lumbar puncture.

On powering and statistical assumptions, Smith said the study is "interestingly powered to one of the secondary endpoints," specifying a receptive communication endpoint at week 52, targeting a p-value of 0.01 with 90% confidence and aiming to achieve a Vineland score of at least 2. He added that overall trial success is driven by the primary endpoint, while also pointing to the importance of long-term "observed data" in supporting labeling, payer discussions, uptake, and pricing.

Smith addressed a recent FDA interaction focused on accelerated approval pathways. He said the company met with the FDA in December in a multidisciplinary meeting required after receiving breakthrough designation. Given the magnitude and durability of its long-term data, Stoke asked whether the existing dataset could support filing an NDA; Smith said the FDA's pushback was that the submission relied on post hoc analysis and cross-study comparison, which the agency found challenging within its framework.

Smith said the accelerated approval path remains open and that the company plans to return to the FDA with additional analyses comparing patients to their own baselines, rather than to a propensity-matched natural history cohort. However, he noted that as Phase 3 enrollment has accelerated, the practical timeline benefit of an expedited pathway may narrow.

Beyond the flagship program, the candidate STK-002 is gaining attention. It is being investigated in the Phase 1 "OSPREY" study for the treatment of Autosomal Dominant Optic Atrophy (ADOA). Stoke dosed the first patient in its ADOA Phase I/II dose‑escalation program targeting OPA1 upregulation and expects potentially efficacious doses by late 2026/early 2027.

The company ended 2025 with approximately $400 million in cash—sufficient runway into 2028—with Biogen funding approximately 30% of Dravet R&D. Stoke Therapeutics, headquartered in Bedford, Massachusetts, is a clinical-stage biotech firm whose proprietary TANGO platform leverages RNA-based technology.