Summary of Stoke Therapeutics Conference Call Company Overview - **Company**: Stoke Therapeutics (NasdaqGS:STOK) - **Focus**: Development of treatments for genetic diseases, specifically Dravet syndrome and Autosomal Dominant Optic Atrophy (ADOA) [2][6] Key Points on Dravet Syndrome - **Disease Understanding**: Dravet syndrome is a severe form of epilepsy affecting young children, leading to significant developmental challenges [2][3] - **Clinical Data**: Initial phase 1/2 data showed an 80% reduction in seizures on top of standard care medications, with durable effects observed over nearly four years [4][9] - **Cognitive and Behavioral Benefits**: Improvements in cognition and behavior were noted, measured by the Vineland-3 assessment, indicating potential for neurodevelopmental progress in children who typically plateau after 18 months [5][10] - **Phase 3 Program**: Enrollment for the phase 3 study is expected to complete in Q2 2026, with data anticipated in mid-2027 [6][28] Market Opportunity - **Patient Population**: Approximately 36,000-40,000 patients globally, with 16,000 in the U.S. and 6,000 currently addressable [50][51] - **Pricing Strategy**: The company aims to position its treatment as a disease-modifying therapy, potentially aligning pricing with similar therapies like Spinraza [52][54] Regulatory Pathway - **FDA Interaction**: The company is pursuing accelerated approval but faced challenges due to the FDA's request for additional data. A follow-up discussion is planned to present data against patient baseline rather than cross-study comparisons [34][35][36] - **Optimal Label**: The goal is to achieve a label that reflects both seizure reduction and cognitive improvements, which is crucial for market positioning and pricing discussions [41][42] ADOA Development - **New Indication**: The first patient for ADOA was dosed recently, targeting a genetic loss of eyesight by upregulating the OPA1 gene to improve mitochondrial function and vision [56][57] - **Market Size**: The ADOA market is estimated at around 16,000 patients in the top seven geographies [58] Financial Position - **Cash Reserves**: The company reported approximately $400 million in cash at the end of 2025, with funding from Biogen covering 30% of Dravet R&D costs, providing a runway into 2028 [60]

Core Insights - Zorevunersen shows potential as a disease-modifying treatment for Dravet syndrome, with significant improvements in cognition and behavior observed over two years, contrasting with minimal changes in standard care [1][2][3] - In open-label extension studies, 95% of patients reported improvements in overall clinical status after three years of treatment with zorevunersen [1][2] Company Overview - Biogen Inc. and Stoke Therapeutics are collaborating on the development of zorevunersen, an investigational antisense oligonucleotide aimed at treating Dravet syndrome by increasing functional NaV1.1 protein production [8][9] - Zorevunersen has received orphan drug designation from the FDA and EMA, as well as Breakthrough Therapy Designation for specific mutations in the SCN1A gene [8] Clinical Data - The ongoing open-label extension studies indicate long-term benefits of zorevunersen on seizures, cognition, and behavior, supporting its potential for disease modification [3][4] - Safety data from the studies show that zorevunersen is generally well tolerated, with treatment-emergent adverse events (TEAEs) reported in 30% of patients in Phase 1/2a studies and 53% in open-label extension studies [4] Disease Context - Dravet syndrome is characterized by severe seizures and significant cognitive and behavioral impairments, with over 90% of patients experiencing seizures despite the best available treatments [7] - The estimated prevalence of Dravet syndrome in the U.S. is around 16,000 patients, with no approved disease-modifying therapies currently available [7][17]