Detailed Narrative
EMPEROR Study Progress and Confidence
The Phase III EMPEROR study for zorevunersen in Dravet syndrome has completed enrollment of 162 patients in just 10 months, exceeding the target of 150. Management highlighted zero treatment discontinuations to date, compared to an initial assumption of a 15% discontinuation rate, reinforcing confidence in the study's powering. Over 140 patients have completed week 8, and approximately 60 have reached the week 28 primary endpoint time point for major motor seizure frequency. The study remains on track for a Q3 2027 data readout.
Long-term OLE Data and Disease Modification
Data from the ongoing open-label extension (OLE) studies for zorevunersen now extend to 4 years, demonstrating statistically significant improvements in cognition and behavior as measured by Vineland-3, and durable seizure control. Of the 81 patients in Phase I/IIa studies, 93% (75 patients) continued into OLE, with 57 remaining. Over 930 doses have been administered, with some patients treated for more than 5 years, showing no new safety findings and continued general tolerability. These longitudinal data are considered crucial for understanding chronic treatment benefits and supporting the NDA.
Regulatory Strategy and Pre-NDA Meeting
A pre-NDA meeting with the FDA is scheduled for H2 2026 to discuss the rolling NDA submission plan, which is expected to begin in Q1 2027 with the CMC package and conclude in Q3 2027 with clinical data. Key discussion points include the statistical analysis plan (SAP) for secondary endpoints, specifically whether to use a hierarchical analysis of individual Vineland domains or a composite approach. The importance of the 4-year OLE data in demonstrating long-term efficacy and safety for a chronically administered drug will also be a focus.
STK-002 Advancement for ADOA
STK-002, an investigational medicine for autosomal dominant optic atrophy (ADOA), is progressing in a Phase I dose escalation study in the U.K. and Europe. The first cohort of 3 patients has completed dosing, and the study is moving into a higher dose in the second cohort. Management anticipates early safety and efficacy results in H1 2027, which will guide further development steps. Preclinical data suggests that upregulation of OPA1 proteins has disease-modifying potential for ADOA.
Commercial Readiness and Market Opportunity
Stoke Therapeutics estimates approximately 16,000 Dravet syndrome patients in the U.S., with 6,000 under the age of 25 considered immediately addressable at launch. The company notes that 50% of identified U.S. patients are cared for by the top 50 sites experienced in intrathecal therapies, providing a strong foundation for early adoption with a lean commercial infrastructure of approximately 25 sales representatives. Management expects a broad label for zorevunersen, consistent with its breakthrough therapy designation, and anticipates a significant increase in genetic testing with the introduction of a disease-modifying treatment.
Pipeline Expansion and Financial Position
Beyond zorevunersen and STK-002, the company is expanding early research efforts into new haploinsufficient CNS diseases and aims to select a development candidate for SYNGAP1-related disorders in 2027. The business investment is well-supported by a pro forma cash position of approximately $420 million, including $65.7 million raised through an ATM program post-quarter-end. This cash runway is expected to fund operations through the potential U.S. launch of zorevunersen in early 2028, supplemented by Biogen reimbursements and potential milestone payments.