Summary of Stoke Therapeutics FY Conference Call Company Overview - **Company**: Stoke Therapeutics (NasdaqGS:STOK) - **CEO**: Ian Smith, in role since March 2025 - **Focus**: Upregulating protein expression for haplo-insufficient diseases, primarily targeting genetic conditions like Dravet syndrome and Autosomal Dominant Optic Atrophy (ADOA) [2][3] Key Developments - **Lead Medicine**: Zorevunersen, targeting Dravet syndrome by upregulating the SCN1A gene to increase NaV1.1 expression, aiming to reduce seizures and improve neurodevelopment [3][4] - **Clinical Trials**: - Currently in Phase 3 for Dravet syndrome with a target enrollment of 150 patients, approximately 60 patients have been randomized, and another 60 are in the screening phase [5][6] - Enrollment expected to complete by Q2 2026, with potential NDA submission in 2027 or early 2028 [6][20] - **Long-term Data**: Patients have been followed for up to four years, showing durability in seizure reduction (up to 85%) and improvements in neurocognition [7][10][18] Financial Position - **Funding**: Approximately $400 million available, sufficient to fund operations through 2028 [8][9] - **Collaboration**: Partnership with Biogen, which licensed commercial rights to zorevunersen and funds 30% of R&D development [21][22] Market Opportunity - **Patient Population**: Estimated 40,000 patients with Dravet syndrome across key geographies (15-20,000 in the U.S. and Europe) [20][21] - **Commercial Potential**: Anticipated robust demand for a disease-modifying treatment, with market research indicating high clinician willingness to prescribe [41][42] Regulatory Pathway - **Breakthrough Designation**: Zorevunersen has received this designation, allowing for expedited development discussions with the FDA [27][28] - **FDA Interaction**: Productive discussions with the FDA regarding the potential for filing based on Phase 1, 2, and OLE data, although the timeline for filing may not be significantly shortened [28][30] Pipeline and Future Plans - **Next Steps**: - Completion of Phase 3 enrollment and subsequent NDA filing [24][25] - Initiation of clinical trials for ADOA (STK-002) and SYNGAP1, with expectations for early efficacy results by the end of 2026 [50][51] - **Regulatory Strategy**: Focus on demonstrating improvement in vision for ADOA, which could shorten clinical study durations [52][53] Additional Insights - **Data Integrity**: Emphasis on the importance of long-term data and observed outcomes in regulatory discussions to support claims of disease modification [45][46] - **Market Positioning**: Differentiation from existing seizure medications by positioning zorevunersen as a true disease-modifying treatment [48][49] This summary encapsulates the critical points discussed during the Stoke Therapeutics FY Conference Call, highlighting the company's strategic focus, clinical advancements, financial health, and regulatory strategies.