Stoke Therapeutics (NASDAQ:STOK) 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).
Long-term Dravet data: seizure reduction and functional measures
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.
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.
Rationale for a “disease-modifying” framing
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. He also described how Vineland scoring works at the item level and said the company has seen Vineland changes “up to 10 and 11” over 12 to 18 months in its longitudinal assessments.
EMPEROR Phase 3 design and endpoints
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.
Smith said the trial is enrolling about 150–160 patients and includes different sham-control approaches by region:
- U.S., U.K., and Japan: lumbar puncture sham control
- Four European countries: 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.
FDA discussions and labeling priorities
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, particularly if the company prioritizes what he described as an “optimal label” reflecting not only seizure reduction but also neurodevelopmental benefit.
In describing a preferred label outcome, Smith outlined a combination of a statistically strong primary endpoint, supportive secondary endpoints, and inclusion of longer-term observed data—potentially in a Section 14 context—provided the FDA is comfortable with the integrity and GCP conduct of the longitudinal dataset and it is supported through publication and physician engagement.
Commercial framing, pipeline update, and cash runway
On commercial opportunity in Dravet, Smith estimated a global prevalence of roughly 36,000–40,000 patients, including about 16,000 in North America, about 7,000 in Japan, and the remainder across other major geographies. He said Stoke retained North American rights in its collaboration with Biogen and described an immediately addressable U.S. population of about 6,000 patients identified through treatment coding, plus another approximately 2,000 patients aged 18–24 that the company anticipates treating. He characterized growth beyond that addressable base as dependent on increased screening and awareness.
On pricing benchmarks, Smith pointed to disease-modifying genetic medicines, citing Vertex’s cystic fibrosis portfolio as an analogue and referencing Spinraza as a comparator “range,” while emphasizing that pricing ultimately depends on data.
Stoke also announced progress in ADOA, a genetic form of vision loss. Smith said the company issued a press release the same morning and that the first patient was dosed the prior week. He described the program as targeting upregulation of OPA1, with the goal of improving mitochondrial function in the eye and, in turn, improving vision. He cited non-human primate studies using flavoprotein fluorescence as a readout of mitochondrial function. The company has initiated a dose-escalation Phase I/II study with four planned dose levels, starting at 0.1 mg and rising to 0.7 mg administered by injection into the eye. Smith said he expects efficacious dosing may be around the third and fourth doses, with timing toward the end of the year or in the first half of 2027. He estimated the ADOA market at around 16,000 patients in the top seven geographies.
Finally, Smith said Stoke ended 2025 with approximately $400 million in cash. He noted that Biogen funds 30% of Dravet R&D and said the company’s cash runway extends into 2028.
About Stoke Therapeutics (NASDAQ:STOK)
Stoke Therapeutics, headquartered in Bedford, Massachusetts, is a clinical-stage biopharmaceutical company focused on developing genetic medicines to upregulate protein production for the treatment of rare neuromuscular and neurological disorders. Founded in 2014, the company applies its proprietary Targeted Augmentation of Nuclear Gene Output (TANGO™) platform to design antisense oligonucleotides that selectively modulate RNA splicing and enhance expression of functional proteins.
The company’s lead program, STK-001, is an antisense oligonucleotide therapy designed to increase production of the sodium channel protein SCN1A and is currently in clinical development for Dravet syndrome, a severe childhood-onset epilepsy.
