Core Insights - Stoke Therapeutics and Biogen announced longer-term follow-up analyses from ongoing open-label extension studies of zorevunersen, indicating its potential as a disease-modifying medicine for Dravet syndrome [1] Company Overview - Stoke Therapeutics is a biotechnology company focused on restoring protein expression through RNA medicine [1] - Biogen Inc. is a biotechnology company that collaborates with Stoke Therapeutics on the zorevunersen studies [1] Product Development - The ongoing studies of zorevunersen are aimed at evaluating its effectiveness in treating Dravet syndrome, a severe form of epilepsy [1] - The new results from the studies support the potential of zorevunersen as a disease-modifying treatment [1]

Core Insights - Stoke Therapeutics, Inc. (STOK) shares increased by 11.7% to close at $30.5, with a notable trading volume compared to normal sessions, and a total gain of 23.7% over the past four weeks [1][2] Company Developments - The rise in stock price is linked to increased investor confidence in Stoke Therapeutics' lead candidate, zorevunersen, which is being developed as a first-in-class potential disease-modifying therapy for Dravet syndrome [2] - The company appointed Ian F. Smith as the new chief executive officer earlier this week [2] Financial Expectations - The company is projected to report a quarterly loss of $0.56 per share, reflecting a year-over-year decline of 19.2%, while revenues are expected to reach $5.7 million, an increase of 16.6% from the previous year [3] - The consensus EPS estimate for the quarter has remained unchanged over the last 30 days, indicating that stock price movements may not sustain without trends in earnings estimate revisions [4] Industry Context - Stoke Therapeutics is part of the Zacks Medical - Biomedical and Genetics industry, which includes other companies like Janux Therapeutics, Inc. (JANX), whose stock closed 6.7% higher at $24.2, but has seen a return of -4.6% over the past month [5] - Janux Therapeutics' consensus EPS estimate has changed by +0.1% over the past month to -$0.6, representing a year-over-year change of -17.7% [6]

Core Insights - Stoke Therapeutics has appointed Ian F. Smith as Chief Executive Officer, who has been serving as Interim CEO since March 2025 and has been a board member since 2023 [1][3] - The company is advancing its lead investigational medicine, zorevunersen, in a global Phase 3 study for Dravet syndrome, a severe developmental and epileptic encephalopathy [2][8] - The collaboration with Biogen Inc. for zorevunersen allows Stoke to retain exclusive rights in the U.S., Canada, and Mexico, while Biogen holds rights for the rest of the world [2] Company Leadership - Ian F. Smith is recognized for his deep experience in rare disease drug development and has a strong track record in building and leading teams [3][4] - Arthur Tzianabos, who has been on the board since 2018, will resume his role as Chairman after serving as Executive Chairman during the CEO search [1][6] Clinical Development - The pivotal Phase 3 EMPEROR study for zorevunersen has commenced, contributing to the company's growth and value creation for shareholders [3] - Stoke is also expanding its pipeline with a second clinical program targeting Autosomal Dominant Optic Atrophy [3] Company Background - Stoke Therapeutics focuses on restoring protein expression through RNA medicine, utilizing its proprietary TANGO approach to develop antisense oligonucleotides [8] - The company is headquartered in Bedford, Massachusetts, and aims to address diseases caused by a loss of approximately 50% of normal protein levels [8]

Core Insights - Ultragenyx Pharmaceutical Inc. has appointed Eric Olson as chief business officer and executive vice president effective September 22, 2025, following the retirement of Thomas Kassberg [1][2] - Olson brings nearly two decades of experience in the biopharma industry, having led or supported over $15 billion in aggregate transaction value [2][3] - The company is focused on developing therapies for rare and ultra-rare genetic diseases, with a diverse portfolio aimed at addressing high unmet medical needs [4][5] Company Leadership Transition - Thomas Kassberg has contributed significantly to Ultragenyx over 14 years, helping to build the largest clinical pipeline in rare diseases [2] - Eric Olson's expertise in business development and strategic partnerships is expected to enhance the company's mission to deliver new therapies for rare diseases [2][3] Business Development Expertise - Olson previously served as CBO at Stoke Therapeutics, leading a major partnership with Biogen, and held key roles at Alnylam Pharmaceuticals and Takeda [2][3] - His background includes extensive experience in rare diseases and significant accomplishments in business development, including a $2.8 billion collaboration with Roche [2] Company Mission and Strategy - Ultragenyx is committed to accelerating innovation in rare diseases by overcoming scientific, development, and commercial challenges [3] - The company aims for time- and cost-efficient drug development to deliver safe and effective therapies urgently [5]

Summary of Stoke Therapeutics Conference Call Company Overview - **Company**: Stoke Therapeutics - **Focus**: Development of treatments for Dravet syndrome, a genetic condition affecting neurodevelopment and seizures [1][2][3] Key Points Leadership Transition - Ian Smith has taken on the role of Interim CEO, having been with the company for approximately two and a half years [2][3] - Smith's background includes significant experience in biotech, particularly with Vertex Pharmaceuticals, where he worked on cystic fibrosis treatments [3] Disease Focus: Dravet Syndrome - Dravet syndrome affects approximately 40,000 individuals across major global regions, with an incidence of about 1 in 15,000 to 16,000 births [6][7] - The disease is characterized by severe seizures and significant neurodevelopmental delays, with many children not developing beyond the cognitive level of a two-year-old [8][9] Treatment Landscape - Current treatments primarily focus on seizure management, with no existing therapies addressing neurodevelopmental aspects [10][12] - Stoke's drug, zorevunersen, aims to modify the disease by restoring functional protein levels in the brain, potentially improving both seizure control and neurodevelopment [10][12] Clinical Data and Efficacy - In clinical studies, zorevunersen has shown a median seizure reduction of 85% when administered at a 70 mg dose, on top of existing anti-seizure medications [13][14] - The drug has demonstrated durability in seizure reduction over a four-year follow-up period, which is critical given the high mortality rate (20%) associated with Dravet syndrome [15][17] - Improvements in neurodevelopmental outcomes have been observed, with patients scoring significantly higher on the Vineland-3 scale compared to baseline [29][31] Phase 3 Study: AMPRO - The AMPRO study is a 52-week trial designed to evaluate the efficacy of zorevunersen, with a primary endpoint focused on seizure reduction [36][37] - The study aims to enroll 170 patients and is currently progressing well, with over 150 patients already in pre-screening [37] Regulatory Considerations - Stoke Therapeutics has received breakthrough therapy designation from the FDA, which may facilitate a faster path to market [39][41] - A meeting with the FDA is anticipated to discuss expedited filing options based on the existing safety and efficacy data [41] Market Potential and Value Proposition - The potential for zorevunersen to be a high-value treatment is emphasized, particularly if it can demonstrate significant improvements in both seizure control and neurodevelopmental outcomes [44][45] - The company aims to position zorevunersen similarly to other high-impact therapies in the market, such as those for cystic fibrosis [45] Future Outlook - The company is focused on advancing the AMPRO study and hopes to bring the treatment closer to patients, with aspirations for regulatory filing in the near future [48] Additional Insights - The emotional and developmental impact of Dravet syndrome on patients and families is highlighted, underscoring the importance of effective treatment options [9][10] - The potential for zorevunersen to change the trajectory of neurodevelopment in affected children is a key motivating factor for the company's mission [35][48]

Core Insights - Zorevunersen shows potential as the first disease-modifying treatment for Dravet syndrome, with significant reductions in seizure frequency and improvements in cognitive and behavioral outcomes over three years of treatment [2][3][12] Efficacy Results - In Phase 1/2a studies, patients receiving initial doses of 70 mg of zorevunersen experienced a median seizure reduction of 84.8% and an increase of eight seizure-free days per 28 days at three months post-treatment [4] - In open-label extension studies, 94% of eligible patients continued treatment, with 77% remaining after three years, sustaining reductions in major motor seizure frequency [5] - Improvements in quality of life were noted, with an 18-point increase in EuroQol Visual Analog Scale (EQ-VAS) scores over three years [6] Safety Profile - Zorevunersen was 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 [7] - The most common TEAE was elevated cerebrospinal fluid (CSF) protein levels, occurring in 14% of patients in Phase 1/2a and 44% in open-label extension studies [7] Study Design - The Phase 1/2a studies involved 81 patients aged 2 to 18 with refractory Dravet syndrome, focusing on safety, pharmacokinetics, and seizure frequency [9] - The ongoing EMPEROR Phase 3 study aims to further evaluate zorevunersen's efficacy and safety in a larger population [13] Company Background - Biogen and Stoke Therapeutics are collaborating on the development of zorevunersen, which has received orphan drug designation and Breakthrough Therapy Designation from the FDA [12][14] - Stoke Therapeutics focuses on restoring protein expression through RNA medicine, with zorevunersen being their first investigational product [16]

Core Insights - Biogen Inc. and Stoke Therapeutics announced new clinical data for zorevunersen, an investigational treatment for Dravet syndrome, to be presented at the 36th International Epilepsy Congress [1][2] - Zorevunersen is being evaluated in the EMPEROR Phase 3 study, which aims to demonstrate its potential as a disease-modifying therapy [1][8] Company Overview - Biogen is a leading biotechnology company focused on innovative science to deliver new medicines and create shareholder value [9] - Stoke Therapeutics specializes in RNA medicine and is developing zorevunersen to restore protein expression in patients with Dravet syndrome [11] Clinical Data and Study Details - New clinical data show substantial and durable reductions in seizures and improvements in cognition and behavior for patients receiving zorevunersen alongside standard anti-seizure medications [2][4] - The EMPEROR Phase 3 study is a global, double-blind, sham-controlled trial evaluating zorevunersen's efficacy and safety in children with Dravet syndrome [8] Presentation Information - Presentations at the IEC will include data on zorevunersen's potential as a disease-modifying therapy and improvements in seizure-free days and quality of life [2][4] - Key presentations will be made by leading experts in the field, highlighting the significance of zorevunersen in treating Dravet syndrome [5][2]

Zorevunersen for Dravet Syndrome - Stoke Therapeutics is developing zorevunersen as a potential disease-modifying medicine for Dravet syndrome [16] - Initial 70mg doses of zorevunersen demonstrated substantial and sustained reductions in convulsive seizure frequency [18] - Ongoing zorevunersen treatment showed substantial and durable reductions in major motor seizure frequency in OLE studies [21] - 36-month OLE data shows continuing improvements in cognition and behavior with zorevunersen treatment [56] - The EMPEROR Phase 3 study is designed to assess disease modification in Dravet syndrome with a dosing regimen of 2x70mg followed by 2x45mg over a 52-week treatment period [31, 32] - The EMPEROR Phase 3 study has dosed its first patient in August 2025 and anticipates data in 2H 2027, randomizing approximately 170 patients across ~70 global sites [35] STK-002 for Autosomal Dominant Optic Atrophy (ADOA) - Approximately 65-90% of ADOA cases are caused by mutations in one allele of the OPA1 gene, leading to haploinsufficiency [64] - Up to 46% of ADOA patients are registered as legally blind [65] - Preclinical findings support further development of STK-002, showing increased OPA1 protein and ATP-linked respiration [70] - A Phase 1 study of STK-002 in ADOA patients is underway in the UK, involving 21 patients aged ≥18 to <55 years receiving single ascending doses (0.1, 0.3, 0.5, & 0.7 mg/eye) [76]

Core Insights - Biogen and Stoke Therapeutics have initiated the global Phase 3 EMPEROR study to evaluate the efficacy and safety of zorevunersen for treating Dravet syndrome, a rare genetic disease with no currently approved disease-modifying treatments [1][2][10] Company Overview - Biogen is a leading biotechnology company founded in 1978, focused on innovative science to deliver new medicines and create value for shareholders [5] - Stoke Therapeutics specializes in RNA medicine, aiming to restore protein expression and is developing zorevunersen as a potential treatment for Dravet syndrome [7] Study Design and Objectives - The EMPEROR study is a double-blind, sham-controlled trial involving children aged 2 to 18 with a confirmed SCN1A gene variant, randomized to receive either zorevunersen or a sham for a 52-week treatment period [10] - The primary endpoint is the change in major motor seizure frequency at week 28, with key secondary endpoints including improvements in behavior and cognition measured by Vineland-3 subdomains at week 52 [5][10] Disease Background - Dravet syndrome is characterized by severe, recurrent seizures and significant cognitive and behavioral impairments, primarily caused by mutations in the SCN1A gene [8] - Over 90% of patients continue to experience seizures despite existing anti-seizure medications, highlighting the urgent need for effective treatments [8] Mechanism of Action - Zorevunersen is designed to increase NaV1.1 protein production in brain cells, potentially reducing seizure frequency and improving neurodevelopment, cognition, and behavior [9] - The drug has received orphan drug designation from the FDA and EMA, as well as rare pediatric disease and Breakthrough Therapy Designations for Dravet syndrome [9]

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]