Stoke Therapeutics is an early-stage biotechnology company leveraging its proprietary Targeted Augmentation of Nuclear Gene Output platform to develop novel RNA-based therapies for severe genetic diseases. The company’s strategy centers on advancing its clinical pipeline and forging partnerships to accelerate commercialization opportunities. With a focused approach on rare neurological disorders, Stoke Therapeutics positions itself as an innovator within the biopharmaceutical sector.It serves patients affec ...

UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM 10-K (Mark One) ☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 For the fiscal year ended December 31, 2025 OR ☐ TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934 FOR THE TRANSITION PERIOD FROM TO Commission File Number 001-38938 Stoke Therapeutics, Inc. (Exact name of Registrant as specified in its Charter) Delaware 47-1144582 (State or other jurisdictio ...

Core Insights - The investigational medicine zorevunersen shows potential for disease modification in Dravet syndrome, a severe genetic neurodevelopmental disorder, with significant reductions in seizures and improvements in cognition and behavior [1][4][10] Company Overview - Stoke Therapeutics, a biotechnology company focused on RNA medicine, is developing zorevunersen to restore protein expression and treat Dravet syndrome [1][14] - Biogen Inc. collaborates with Stoke Therapeutics to develop and commercialize zorevunersen, retaining exclusive rights in certain regions [10][15] Clinical Study Results - Data from Phase 1/2a studies indicate that zorevunersen led to substantial and durable reductions in seizure frequency, particularly with initial doses of 70 mg [4][11] - Improvements in neurodevelopment, functioning, and quality of life were observed over three years of treatment in open-label extension studies [5][12] Safety Profile - Zorevunersen has been generally well tolerated, with 81 patients evaluated for safety and over 800 doses administered [6][11] - The most common adverse event was elevated cerebrospinal fluid protein levels, with no related clinical manifestations reported [6][12] Future Developments - The ongoing Phase 3 EMPEROR study aims to further evaluate the efficacy and safety of zorevunersen, with results expected in mid-2027 [8][13] - The study will enroll approximately 150 patients and assess the percentage change in major motor seizure frequency as the primary endpoint [13]

Core Insights - The Innovator IBD 50 ETF (FFTY) has outperformed the S&P 500 significantly, returning 19.2% this year compared to the S&P 500's 0.7% return [1] - The strong performance of the IBD 50 index is attributed to its heavy weighting in gold stocks, which are not included in the S&P 500 [1] Performance Comparison - The IBD 50 ETF is the top performer among actively traded U.S. diversified ETFs, followed by Schwab US Dividend Equity (SCHD) with a return of 16.2% [1] - Coeur Mining (CDE) is the top position in the IBD 50 index, with a weight of 3.75% and a share price increase of over 35% this year [1] - IamGold (IAG) is the second-largest position, with a weight of 3.6% and a share price increase of 36% over the past year [1] Key Holdings - The third largest position in the ETF is Stoke Therapeutics (STOK), which has seen a price increase of over 6% this year [1] - Micron Technology (MU) is also a significant holding, with a weight of 3.3% in the IBD 50 ETF and a share price increase of 33% this year [1] - Other notable positions include AngloGold Ashanti (AU), Kinross Gold (KGC), and Applied Optoelectronics (AAOI), all contributing to the ETF's strong performance [1]

Summary of Stoke Therapeutics FY Conference Call Company Overview - **Company**: Stoke Therapeutics (NasdaqGS:STOK) - **Focus**: Development of treatments for Dravet syndrome and Autosomal Dominant Optic Atrophy (ADOA) Key Points on Dravet Syndrome - **Market Opportunity**: Approximately 35,000-40,000 patients in the core geographies (U.S., Japan, U.K., EU 4) with about 16,000 in the U.S. and a similar number in the EU 4 [85][86] - **Addressable Patients**: 6,000 patients are immediately addressable upon launch, with 4,000 being pediatric patients aged 18 and younger [85][86] - **FDA Interactions**: Ongoing discussions with the FDA regarding the potential success of the phase 3 study and the importance of the label for pricing and promotion [15][71] - **Clinical Data**: Phase 1, 2 studies show robust seizure reduction and improvements in cognition and behavior, with a focus on longitudinal data over a 5-year period [17][19][20] - **Primary Endpoint**: Seizure reduction at 26 weeks, with secondary endpoints including cognition and behavior assessed at 52 weeks [48][55] - **Vineland Assessment**: Statistical improvements observed in Vineland scores, indicating cognitive and behavioral benefits [23][25] Phase 3 Study (EMPEROR) - **Enrollment Status**: Approximately 160 patients enrolled in the U.S. and Europe, with completion expected in mid-2027 [26][27] - **Study Design**: Includes lumbar puncture sham control patients and additional cohorts for regulatory compliance [27][35] - **Powering of Study**: Designed for a 90% confidence level with a p-value of 0.01 for secondary endpoints, ensuring robust statistical significance [48][52] Pricing and Market Dynamics - **Pricing Strategy**: Aiming for a price reflective of the value provided by the treatment, potentially aligning with other genetically targeted disease-modifying treatments rather than traditional anti-seizure medications [103][105] - **Comparison with SPINRAZA**: Pricing expected to be in line with other ASOs like SPINRAZA, which is priced around $600 per dose [118][105] Autosomal Dominant Optic Atrophy (ADOA) - **Patient Population**: Approximately 13,000 patients in the U.S. and Europe, with a significant risk of legal blindness [127] - **Phase 1 Study**: Ongoing dose escalation study with initial dosing completed, aiming to demonstrate efficacy in improving eyesight [128][129] Additional Insights - **Long-term Development**: The treatment aims to provide more years of neurotypical development for children with Dravet syndrome, addressing both seizure control and cognitive development [20][71] - **Genetic Testing**: Increased access and utilization of genetic testing are expected to enhance patient identification, particularly in adults who may have been misdiagnosed [88][90] Conclusion - Stoke Therapeutics is positioned to address significant unmet needs in the treatment of Dravet syndrome and ADOA, with ongoing clinical studies and strategic planning for market entry and pricing. The company emphasizes the importance of robust clinical data to support its treatment's efficacy and market potential.

Core Insights - Principal Financial Group Inc. acquired 45,205 shares of Stoke Therapeutics, valued at approximately $1,062,000, representing about 0.08% of the company [2] - Several institutional investors have increased their stakes in Stoke Therapeutics, indicating growing interest in the company [3] - Research firms have provided positive ratings and price targets for Stoke Therapeutics, suggesting a favorable outlook for the stock [4] Institutional Investment - Marshall Wace LLP increased its position by 7.9%, owning 2,300,554 shares valued at $26,111,000 after acquiring an additional 168,771 shares [3] - Goldman Sachs Group Inc. raised its stake by 21.4%, now holding 1,662,039 shares worth $11,053,000 after purchasing 293,072 shares [3] - Assenagon Asset Management S.A. boosted its position by 67.3%, owning 900,272 shares valued at $21,156,000 after acquiring 362,299 shares [3] Analyst Ratings - Guggenheim initiated coverage with a "buy" rating and a price target of $60.00 [4] - JPMorgan Chase & Co. raised its price target from $15.00 to $25.00, maintaining a "neutral" rating [4] - The consensus rating for Stoke Therapeutics is "Moderate Buy" with a target price of $39.18 [4] Stock Performance - Stoke Therapeutics shares opened at $30.98, with a 52-week low of $5.35 and a high of $38.69 [5] - The company has a market capitalization of $1.77 billion and a PE ratio of 46.24 [5] - The 50-day moving average price is $31.54, while the 200-day moving average price is $27.33 [5] Insider Activity - Director Edward M. Md Kaye sold 13,430 shares at an average price of $32.27, resulting in a 21.47% decrease in his position [6] - General Counsel Jonathan Allan sold 3,978 shares at an average price of $32.28, leading to a 25.16% decrease in his ownership [6] - Over the last 90 days, insiders sold 58,302 shares valued at $1,826,430, with insiders owning 9.50% of the company's stock [6] Company Overview - Stoke Therapeutics is a clinical-stage biopharmaceutical company focused on developing genetic medicines for rare neuromuscular and neurological disorders [8] - The company utilizes its proprietary TANGO™ platform to design antisense oligonucleotides that enhance protein expression [8] - The lead program, STK-001, targets the sodium channel protein SCN1A for the treatment of Dravet syndrome [9]

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 Viewpoint - Stoke Therapeutics has initiated the Phase 1 OSPREY study for STK-002, targeting Autosomal Dominant Optic Atrophy (ADOA), a rare genetic condition leading to vision loss [1] Company Summary - Stoke Therapeutics is focused on restoring protein expression through RNA medicine [1] - The company has announced the dosing of the first patient in its clinical trial for STK-002 [1] Industry Summary - ADOA is characterized as a rare genetic disease that results in progressive and irreversible vision loss, typically beginning in early childhood [1]

Company Overview - Stoke Therapeutics is a biotechnology company focused on restoring protein expression through RNA medicine, with its lead investigational medicine, zorevunersen, aimed at treating Dravet syndrome, a severe neurodevelopmental disorder characterized by recurrent seizures and cognitive impairments [3][9] - The company was founded in 2015 and has advanced zorevunersen from early clinical testing to late-stage development, preparing for commercialization in the United States [4][9] New Headquarters - Stoke Therapeutics has secured a long-term lease for a new 98,500 square-foot headquarters at 245 Fifth Avenue in Waltham, Massachusetts, which is one of the largest leases in the Greater Boston life sciences sector over the past year [1][2] - The relocation is set to occur when the current lease in Bedford, Massachusetts ends in late 2026 [1] Growth and Research Expansion - The new headquarters will support Stoke's growth trajectory as it prepares to commercialize zorevunersen and expand research efforts for additional medicines targeting severe diseases [5] - The Waltham area is recognized as a resilient hub for life sciences, providing operational efficiency and access to top talent, which aligns with Stoke's strategic goals [5] Infrastructure and Sustainability - The new property is LEED Gold and WiredScore Platinum certified, emphasizing sustainability and connectivity, with modern infrastructure designed for lab-ready use [5] Market Context - Despite a moderation in the national life sciences market, the Greater Boston area, particularly Waltham and the Route 128 corridor, continues to demonstrate strength and resilience in supporting the biotech industry [5]

Core Insights - Stoke Therapeutics is a clinical-stage biotechnology company focused on developing disease-modifying therapies for Dravet syndrome and ADOA using its TANGO RNA platform [1] Company Overview - The company is currently advancing Zorevunersen, which is in Phase 3 clinical trials and has presented four-year positive Open Label Extension (OLE) data [1]