Summary of Stokes Therapeutics Conference Call Company Overview - **Company**: Stokes Therapeutics - **Industry**: Biotechnology, specifically focusing on genetic diseases such as Dravet syndrome and ADOA (autosomal dominant optic atrophy) [5][51] Key Points and Arguments 1. **Dravet Syndrome Treatment**: - Stokes Therapeutics is developing a disease-modifying medicine for Dravet syndrome, showing significant reductions in seizures over three to four years of treatment [5][6] - The medicine also demonstrates cognitive and behavioral benefits, improving neurodevelopment in affected children [6][7] - The mechanism involves upregulating Nav 1.1 in the brain, addressing the root cause of Dravet syndrome [7] 2. **Phase III Program**: - The company has commenced a Phase III clinical trial with 150 patients already in pre-screening, aiming for full recruitment by the second half of next year [9][13][36] - The trial is designed to measure seizure reductions and cognitive benefits over a 52-week period [36][42] 3. **FDA Interaction and Breakthrough Designation**: - The FDA granted breakthrough designation for the treatment, acknowledging its potential to address both seizures and cognitive challenges in Dravet syndrome [11] - Stokes plans to discuss data with the FDA in the second half of the year to expedite patient access [12][21] 4. **Financial Position**: - The company ended the quarter with $355 million in capital and is fully funded through mid-2028, covering the Phase III trial and beyond [8][9] 5. **Partnership with Biogen**: - Stokes has a collaboration with Biogen, which funds 30% of the Dravet development and provides infrastructure for faster patient access outside North America [25][27] - The partnership aims to leverage Biogen's existing market presence to expedite the delivery of the medicine globally [27][30] 6. **ADOA Program**: - Stokes is initiating a clinical program for ADOA, focusing on improving vision by upregulating OPA1 and enhancing mitochondrial function [8][51] - Preclinical data from nonhuman primates showed improved vision, prompting the move into clinical trials [52][53] Additional Important Content - **Clinical Data and Biomarkers**: - The company does not have a measurable biomarker for NAV1.1, which complicates the pathway for accelerated approval [19][20] - Clinical data shows significant improvements in Vineland scores, particularly in expressive and receptive communication, which are critical for assessing treatment efficacy [45][46] - **Safety Profile**: - Over 800 doses have been administered with no significant clinical manifestations of elevated cerebrospinal fluid levels observed [50][51] - **Regulatory Landscape**: - The company remains optimistic about regulatory flexibility from the FDA, especially for rare pediatric diseases with significant unmet needs [14][15] - **Global Market Strategy**: - The partnership with Biogen allows Stokes to access over 70 markets globally, enhancing their ability to deliver the treatment quickly post-approval [27][30] This summary encapsulates the critical insights from the conference call, highlighting the company's strategic direction, clinical advancements, and market positioning.

Core Insights - The analysis of the Phase 3 zorevunersen dosing regimen indicates improvements in cognition and behavior at Week 68, supporting its potential as a disease-modifying treatment for Dravet syndrome [1][2][4] - Zorevunersen has shown substantial and durable reductions in major motor seizure frequency and improvements in cognitive and behavioral measures over two years of treatment [2][4] - The Phase 3 EMPEROR study will assess key secondary endpoints related to cognition and behavior, which are critical for evaluating the treatment's effectiveness [3][5] Company Overview - Biogen Inc. and Stoke Therapeutics are collaborating on the development of zorevunersen, an investigational therapy aimed at addressing the underlying causes of Dravet syndrome [1][8] - Stoke Therapeutics focuses on restoring protein expression through RNA medicine, with zorevunersen being their first medicine in development [9] - Biogen is a leading biotechnology company that aims to deliver innovative treatments and create value for shareholders [10] Disease Context - Dravet syndrome is a severe neurodevelopmental disorder characterized by recurrent seizures and significant cognitive and behavioral impairments, affecting an estimated 38,000 individuals in the U.S., UK, EU-4, and Japan [3][7] - The condition is primarily caused by mutations in the SCN1A gene, leading to insufficient NaV1.1 protein levels in neuronal cells [7][8] - Current treatments primarily focus on seizure control, with no approved therapies addressing the cognitive and behavioral aspects of the disease [3][7] Clinical Study Insights - The Phase 3 EMPEROR study is designed to evaluate the effects of zorevunersen on cognition and behavior, with a focus on five sub-domains of the Vineland-3 Adaptive Behavior Scales [5][6] - The dosing regimen includes two loading doses of 70mg followed by maintenance doses of 45mg, which has shown promising results in previous studies [4][5] - The analysis utilized a mixed-effects model for repeated measures to assess the potential effects of the dosing regimen on patient outcomes [4]