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© COPYRIGHT 2025 | STOKE THERAPEUTICS | © COPYRIGHT 2025 | STOKE THERAPEUTICS | 1 Stoke Therapeutics Third Quarter 2025 Business Update Webcast for Investors & Analysts November 4, 2025
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | Forward-Looking Statements and Other Legal Notices 2 This presentation has been prepared by Stoke Therapeutics, Inc. ("Stoke" or "us") for informational purposes only and not for any other purpose. Nothing contained in this presentation is, or should be construed as, a recommendation, promise or representation by the presenter(s) or Stoke or any officer, director, employee, agent or advisor o f Stoke. This presentation does not purport to be all-inclusive or to contain all of the information you may desire. Information provided in this presentation speaks only as of the date hereof. Stoke assumes no obligation to publicly update any information or forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments, subsequent events, or circumstances after the date hereof, or to reflect the occurrence of unanticipated events. This presentation contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: the ability of zorevunersen to treat the underlying causes of Dravet syndrome and reduce seizures or show improvements in behavior or cognition at the indic ated dosing levels or at all; the design, timing and results of clinical studies, data readouts, regulatory decisions and other presentations for zorevunersen and STK-002; the potential for zorevunersen to be a first-in-class, disease-modifying therapy for Dravet syndrome; our confidence in the demand for and the timing of enrollment in EMPEROR; timing of regulatory interactions or the outcomes thereof; the ability of STK-002 to treat the underlying causes of Autosomal Dominant Optic Atrophy (ADOA) and maintain or improve vision; the potential for us to advance and develop our research and development programs; our expectations, plans, aspiratio ns and goals, including those related to the potential of zorevunersen and our collaborations with Biogen and Acadia; the anticipated market for zorevunersen; our future operating results, financial position and cash runway and ability to fund operations to mid-2028. Statements including words such as "anticipate," "believe," "hope," "plan," "will," "continue," expect," "ongoing," or "potential" and statements in the future ten se are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they prove incorrect or do not fully materialize, could cause our results to differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, risks and uncertainties related to: our ability to advance, obtain regulatory approval of, and ultimately commercialize our product candidates, including zorevunersen and STK-002; the timing of data readouts and interim and final results of nonclinical and clinical studies; nonclinical and clinical data are voluminous and detailed, and regulatory authorities may interpret or weigh the importance of data differently and reach different conclusions than us or others, request additional information, have additional recommendations or change their guidance or requirements before or after approval; receiving Breakthrough Therapy Designation may not lead to a faster development or regulatory review or approval and does not mean zorevunersen will receive marketing approval; our ability to fund development activities and achieve development goals; our ability to protect our intellectual property; global business, political and macroeconomic conditions, including inflation, interest rate volatility, cybersecurity events, uncertainty with respect to the federal budget, instability in the global banking system and volatile market conditions, and global events, including public health crises and ongoing geopolitical conflicts, such as the conflicts in Ukraine and the Middle East; and other risks and uncertainties described under the heading "Risk Factors" in our Annual Report on Form 10-K for the year ended December 31, 2024, our quarterly reports on Form 10- Q and the other documentation we file from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this presentation, and we undertake no obligation to revise or update any forward- looking statements to reflect events or circumstances after the date hereof. By attending or receiving this presentation you acknowledge that you are cautioned not to place undue reliance on these forwa rd-looking statements, which speak only as of the date such statements are made, you will be solely responsible for your own assessment of the market and our market position, and that you will conduct your own analysis and be solely responsible for forming your own view of the potential future performance of Stoke. Certain information contained in or that may orally accompany this presentation relate to or are based on studies, research, publications, surveys and other data obtained from third-party sources and our own internal estimates and research. While we believe these third-party studies, research, publications, surveys and other data to be reliable as of the date of this presentation, we have not independently verified, and we make no representation as to the adequacy, fairness, accuracy or completeness of any information obtained from third-party sources. This presentation discusses product candidates, including zorevunersen and STK-002, that have not yet been approved for marketing by the U.S. Food and Drug Administration or any other regulatory age ncy.
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | © COPYRIGHT 2025 | STOKE THERAPEUTICS | 3 Opening Remarks Ian F. Smith, CEO & Director
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | Preparing for the Opportunity Stoke is on an Important Growth Trajectory 4 Understanding the Potential for zorevunersen • Enhanced medical & scientific educational efforts • Increasing awareness of Dravet syndrome & need for genetic diagnosis • Long-term longitudinal zorevunersen data support the potential for disease modification, in contrast to natural history • Establishing foundational capabilities to scale the business • Prioritizing executive leadership, Medical Affairs & Commercial builds • Continuing to strengthen financial position; cash runway to mid-2028 • FDA Breakthrough Therapy Designation granted Dec. 2024 • Phase 3 underway with strong caregiver and clinician demand • Preparations underway for FDA Multi-Disciplinary Meeting before year-end to include discussion of potential expedited regulatory pathways Urgency to Deliver for Patients
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | No disease modifying medicines are currently available Up to 57% of patients fail to achieve >50% reduction in seizure frequency2 • Mean 14.3 seizures per 28 days while receiving an average of 3.5 ASMs at baseline Developmental delays and cognitive impairment are persistent and cannot be treated today • Patients with Dravet syndrome fall further and further behind their neurotypical peers SIGNIFICANT UNMET NEED DESPITE ANTI-SEIZURE MEDICINES Significant Market Opportunity ~38K patients with Dravet syndrome across 7 major markets *Numbers may not add up due to rounding. EU4: Germany, France, Italy and Spain; ASMs: anti-seizure medications. 1 Based on preliminary management estimates, which scaled annual incidence to prevalence using country-specific live birth rates over the past 85 years and adjusted for Dravet-specific mortality. The estimate is based on incidence rates published by Wu et al., Pediatrics, 2015. Lagae et al., Developmental Medicine & Child Neurology, 2017; 2018 Health Advances Report; Dravet Syndrome Foundation Voice of the Patient Report. Sullivan, J. et al., 24-Month Analysis of BUTTERFLY. AES 2023. 2 Devinsky O, et al. Trial of Cannabidiol for Drug-Resistant Seizures in DS. N Engl J Med. 2017;376:2011–2020 16K US 16K EU4 + UK 7K Japan PREVALENCE OF DRAVET SYNDROME* 5 ~38K 1 PATIENTS
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | PROGRAM TARGET DISCOVERY & PRECLINICAL PHASE 1/2 PHASE 3 PARTNER CENTRAL NERVOUS SYSTEM Stoke: United States, Canada, Mexico Biogen: Rest of World Stoke: Acadia 50:50 Worldwide Stoke Global 100% OPHTHALMOLOGY Stoke Global 100% OTHER Stoke Global 100% Our Pipeline of First-in-Class Disease-Modifying Potential Medicines ADOA: Autosomal dominant optic atrophy 6 Dravet Syndrome SCN1A zorevunersen SYNGAP1 SYNGAP1 ADOA OPA1 STK-002 Undisclosed Cardiac Undisclosed DEE
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | Substantial, Durable Reductions in Seizures on Top of SOC Observed Through Three Years of Treatment with Zorevunersen OLE data cut 30 May 2025. One patient who received an incorrect dose of zorevunersen in Phase 1/2a, 3 patients who experienced less than the minimum number of convulsive seizures during Phase 1/2a baseline, and 1 patient who transferred into OLE with a delay of approximately 10 months were excluded. Patients were not included in 6M after last Ph1/2a dose time point if they didn’t enter OLE. No exclusions were made for ASM modification. Intervals with <50% diary data were excluded for individual patients. For all enrolled patients who received doses of less than 70 mg in Ph1/2a, n = 52, 53, 53, 53, 53, 52, 52, 52, 46, 46, 47, 47, 45, 45, 45, 41, 38, 41, 41, 40, 38, 39, 39, 39, 36, 36, 36, 36, 32, 30, 30, 30, 25, 20, 19, 19, 16 at each time point. For patients who received 70 mg (1, 2, or 3 doses) in Ph1/2a and up to 45 mg in OLE, n = 16, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 17, 16, 17, 17, 17, 15, 16, 16, 16, 16 at each time point. All enrolled patients received up to 45 mg zorevunersen in the OLEs. ASM, antiseizure medication; CI, confidence interval; M, month; OLE, open label extension; Ph1/2a, Phase 1/2a. 7 Data for all patients who continued treatment in the OLEs separated by dose received in the Ph1/2a studies -100 -75 -50 -25 0 25 Median % change from Ph1/2a baseline in convulsive seizure frequency (80% CI) M1 M2 M3 M5 M6 M7 M8 M9 M10 M11 M12 M13 M14 M15 M16 M17 M18 M19 M20 M21 M22 M23 M24M4 M25 M26 M27 M28 M29 M30 M31 M32 M33 M34 M35 M36 70 mg (1, 2, or 3 doses) in Ph1/2a and up to 45 mg in OLE (n=15–17) All enrolled patients who received doses of less than 70 mg in Ph1/2a (n=16–53) OLE study doses (once every 4 months) 6M after last Ph1/2a dose
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | Development in Patients with Dravet Syndrome Differs Markedly from that of Neurotypical Children 8 Comparison of developmental trajectory between neurotypical children and patients with Dravet syndrome Graph provided for illustrative purposes only. Sullivan et al Natural history of children and adolescents with Dravet syndrome: A 24-month follow-up. Submitted. Neurodevelopmental progress Age
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | The Vineland-3 Assessment Tool is Commonly Used to Evaluate Non-Seizure Outcomes in Dravet Syndrome 9 COMMUNICATION Receptive: Responds upon hearing name called Expressive: Says “Dada”, “Mama”, or caregiver name Written: Writes alphabet letters using correct orientation MOTOR SKILLS Gross Motor: Moves, scoots, or crawls across the floor Fine Motor: Picks up small objects with thumb and fingers SOCIALIZATION Interpersonal Relationships: Responds upon hearing name called Play and Leisure: Responds when parent or caregiver is playful Coping Skills: Transitions easily from one activity to another DAILY LIVING SKILLS Personal: Cooperates in dressing and undressing Domestic: Puts away books, toys, etc. when done Community: Talks with a familiar person using a phone DomainsSubdomains Vineland-3 Adaptive Behavior Scales* 1-to-3-point change per subdomain per year is considered clinically meaningful1 DS, Dravet syndrome; Vineland-3, Vineland Adaptive Behavior Scales, Third Edition. *Maladaptive Behavior is an additional optional domain of the Vineland-3 depending on age and developmental requirements. Its subdomains include Externalizing, Internalizing, and Other. 1Condon C, et al. Qualitative evaluation of meaningful change in Dravet syndrome as measured by the Vineland-3: Caregiver and clinician perspectives. Epilepsy & Behavior. 2025.
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | -3 0 3 6 9 12 15 Fine Motor Skills Gross Motor Skills Play and Leisure Coping Skills Personal Skills Interpersonal Relationships Receptive Communication Expressive Communication 2.3 2.1 5.1 5.4 6.0 5.1 2.4 3.2 4.4 2.4 4.9 5.2 5.2 5.2 4.8 6.9 5.9 8.9 9.7 7.4 6.2 4.3 6.1 7.6 Change in raw scores (95% CI) from OLE baseline 36 Month Data from Ongoing OLE Studies of Zorevunersen: Continuing Improvements in Cognition and Behavior OLE data cut: 30 May 2025. Mixed-effects model for repeated measures constructed using available data from enrolled patients in OLE studies. One patient who received incorrect dose in Ph1/2a study excluded; OLE sample sizes: n=74 at OLE baseline, n=66 at Month 12, n=44 at Month 24, and n=19 at Month 36. CI, confidence interval; OLE, open-label extension; Ph1/2a, Phase 1/2a; Vineland-3, Vineland Adaptive Behavior Scales – Third Edition. 10 Month 12 (n=66) Month 24 (n=44) Month 36 (n=19) EMPEROR Phase 3 Subdomains Vineland-3 subdomain results for 12, 24, and 36 months compared to OLE baseline
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | Substantial Improvements in Cognition and Behavior with Zorevunersen Treatment Support Phase 3 Design 11 Dravet syndrome natural history study patientsPatients treated with zorevunersen Expressive Communication Receptive Communication Interpersonal Relationships Personal Skills Coping Skills -10 0 10 20 9.1 8.7 8.8 10.4 LS mean change in Vineland-3 raw scores (95% CI) from baseline Patients receiving zorevunersen (3 × 45 mg or 2 × 70 mg loading doses followed by 2 × 45 mg maintenance doses) at Week 68 10.7 Expressive Communication Receptive Communication Interpersonal Relationships Personal Skills Coping Skills -10 0 10 20 -0.8 1.9 1.9 0.4 LS mean change in Vineland-3 raw scores (95% CI) from baseline Dravet syndrome natural history study (BUTTERFLY) -4.7 Phase 1/2a data cut: December 12, 2023 (after End of Study); OLE data cut: June 28, 2024. Mixed-effects models for repeated measures (MMRM) were developed using clinical data from the Phase 1/2a ADMIRAL study (n=18 at baseline) and LONGWING OLE study (n=13 at OLE Week 32). Ten patients in ADMIRAL who received 2 doses of 70mg (n=6) or 3 doses of 45mg (n=4) are represented on the left. Matching of baseline characteristics was performed using population-adjusted least squares means to allow for cross-trial comparison with the BUTTERFLY natural history study (right, n=36 at baseline, n=26-27 at Month 12, n=22 at Month 18). LS, least squares; OLE, open-label extension; Vineland-3, Vineland Adaptive Behavior Scales – Third Edition. Brunklaus A, et al. Zorevunersen demonstrates potential as a disease-modifying therapy in patients with Dravet syndrome. Presented at the 16th European Paediatric Neurology Society (EPNS) Congress; July 10, 2025. Due to differences between trials, cross-study comparisons may provide limited information on the efficacy or safety of a drug.
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | Zorevunersen Generally Well-Tolerated with Long-Term Dosing Phase 1/2a data cut: December 12, 2023 (after End of Study); OLE data cut: May 30, 2025. *≥1 CSF protein value >50 mg/dL. Percentage based on 72/75 patients who had ≥1 post-baseline CSF protein value in the OLE studies, of whom 62/72 (86.1%) had an elevation. CSF, cerebrospinal fluid; SUSAR, suspected unexpected serious adverse reaction; TEAE, treatment-emergent adverse event; TESAE, treatment-emergent serious adverse event. 12 ~800 doses Administered to date in the Phase 1/2 and OLE studies Patients have received treatment for up to 4.5 years • No new safety concerns have emerged • 29% of patients experienced a TESAE, all were unrelated to the study drug • CSF protein elevation* occurred in 86% of patients and was classified as a TEAE in 45% o No clinical manifestations associated with CSF protein elevation were observed o One patient discontinued treatment due to elevated CSF protein • 30% of patients experienced a study drug–related TEAE • Most common: CSF protein elevations (14%) and procedural vomiting (5%) • 22% of patients experienced a TESAE • All were unrelated to the study drug except for one patient with SUSARs Phase 1/2a studies (n=81) OLE studies (n=75)
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | Global Pivotal Phase 3 Study Underway 13 • First patient dosed in August 2025; >20 patients randomized as of October 2025 • Patient recruitment underway in the United States, United Kingdom and Japan; 30 sites initiated* • European sites expected to initiate in 1H2026 • High volume of caregiver inquiries and competitive site enrollment Awareness of zorevunersen and medical need are driving interest in EMPEROR “We’re eager to join EMPEROR as soon as possible—willing to travel to the UK or any participating center and fully comply with all requirements.” – Parent of a child with Dravet syndrome On-track to complete enrollment (n=170) in the second half of 2026 Briefing book submitted and preparations underway for our FDA Multi-Disciplinary Meeting to review our most recent data and discuss potential expedited regulatory pathways Urgency to Deliver * Additional steps may be required after completion of site initiation visit prior to active recruitment.
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | © COPYRIGHT 2025 | STOKE THERAPEUTICS | 14 $328.6M B/S Cash $48.7M via ATM Cash, Cash Equivalents, & Marketable Securities, as of 9/30/2025 $183M Revenue, YTD Current financial position anticipated to fund operations to mid-2028 Net Proceeds raised since 9/30/2025 $10.6M 3Q Revenue+ Third Quarter 2025 Financial Summary
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | 15 2025: A Defining Year for Stoke Positioned the Company to deliver long-term value to patients, employees and shareholders In the near team, we will continue our efforts to: 1. Bring awareness of Dravet syndrome 2. Use our data to support understanding of zorevunersen’s potential 3. Pursue opportunities to deliver zorevunersen to patients as fast as possible, including continued activation and enrollment of EMPEROR and regulatory interactions 4. Ensure continued financial and organizational strength
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© COPYRIGHT 2025 | STOKE THERAPEUTICS | © COPYRIGHT 2025 | STOKE THERAPEUTICS | 16 Q&A