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© COPYRIGHT 2026 | STOKE THERAPEUTICS | © COPYRIGHT 2026 | STOKE THERAPEUTICS | Stoke Therapeutics Third Quarter 2026 Business Update Webcast for Investors & Analysts October 29, 2026 1
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© COPYRIGHT 2026 | 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, ag ent or advisor of Stoke. This presentation does not purport to be all-inclusive or contain all of the information you may desire. Information provided in this presentation speaks only as of the date hereof. S toke 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 develo pments, 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, statements regarding: the ability of zorevunersen to treat the underlying causes of Dravet syndrome and reduce seizures or show improvements in behavior or cognition at the in dicated dosing levels or at all; the potential benefits, safety and efficacy of zorevunersen; the design, timing and results of clinical studies, enrollment timelines, data readouts, regulatory submissions or decision s and other presentations for zorevunersen and STK-002; our ability to achieve an NDA submission or approval on the expedited timeframe disclosed or at all, and the assoc iated timing, if any, of a potential U.S. commercial launch; 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, aspirations and goals, including those related to the potential of zorevunersen, STK-002 or our other product candidates and our collaborations with Biogen and Acadia; the anticipated market, access, reimbursement and label, if any, for zorevunersen; our future operating results, financial position and cash runway and ability to fund operations through to early 2028. Statements including words such as “anticipate,” “believe,” "expect," “hope,” “plan,” “will,” “continue,” “ongoing,” or “potential,” and statements in the future tense 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 materializ e, 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 re gulatory 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 cli nical data being voluminous and detailed, and regulatory authorities may interpret or weigh the importance of data differently and reach different conclusions than us or others, request addition al 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 reg ulatory 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 inte llectual property; 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, 2025, our quarterly reports on Form 10-Q and the other documentation we file form 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 obliga tion 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 the forward -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 accompany this presentation relate to or are based on studies, research, publica tions, 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, and 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 fr om 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 2026 | STOKE THERAPEUTICS | © COPYRIGHT 2026 | STOKE THERAPEUTICS | Opening Remarks Ian F. Smith Chief Executive Officer & Director 3
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | Advancing Zorevunersen to Patients 4 EMPEROR Phase 3 Progress FDA Meeting to Prepare for NDA Commercial Readiness ~110 Patients Through Week 28 measurement of primary endpoint ~20 Patients Through Week 52 completion of efficacy treatment period and measurement of key secondary endpoints No Treatment Discontinuations Reviewed 5 Years of Clinical Data from Phase 1/2 and ongoing OLE studies Multicomponent Assessment will analyze changes in cognition and behavior, a key secondary endpoint in EMPEROR Active Engagement with FDA and planned submission of data throughout H1 2027 ~6,000 Patients addressable at launch Strong Awareness and Understanding of Zorevunersen among clinicians and caregivers Field Market Access Team built out to support payer engagement and information exchange All ~20 Continuing into OLE Data Readout in Q3 2027 Completion of NDA in H2 2027 Potential U.S. Launch in Early 2028 New Stakeholder Initiatives including American Epilepsy Society’s Presidential Task Force
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | 5 Expanding Our Research and Building Our Pipeline Phase 1 Study Underway of STK-002 in Patients with ADOA Preclinical data support advancement of OSPREY Initial safety and efficacy data anticipated in H1 2027 Dosing of third cohort underway; completion expected by year-end Initiation of fourth cohort expected in early 2027 Severe genetic diseases Caused by haploinsufficiency Focused on CNS With an Emphasis On Rare, genetic disease No approved treatments Most common optic nerve disorder Primarily caused by haploinsufficiency of OPA1 protein
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | © COPYRIGHT 2026 | STOKE THERAPEUTICS | 6 Phase 3 EMPEROR Progress Barry Ticho, M.D., Ph.D. Chief Medical Officer
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | EMPEROR: A Global, Double-Blind, Sham Controlled Phase 3 Study In patients 2 to <18 years old with a confirmed SCN1A gene variant not associated with gain of function 7 LOADING DOSES (sham or 70mg zorevunersen) MAINTENANCE DOSES (sham or 45mg zorevunersen) Baseline screening Dose 1 D1 Dose 4 W40 Dose 2 W8 Dose 3 W24 Open-label extension 1:1 randomization Primary Endpoint W28 Secondary Endpoints W52
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | Patient Progression Through Key EMPEROR Timepoints No Discontinuations to Date 8 LOADING DOSES (sham or 70mg zorevunersen) MAINTENANCE DOSES (sham or 45mg zorevunersen) Baseline screening Dose 1 D1 Dose 4 W40 Dose 2 W8 Dose 3 W24 Open-label extension 1:1 randomization Primary Endpoint W28 Secondary Endpoints W52 162 ~130 ~110 ~20 Patient Progress Through Key Study Milestones ~65
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | EMPEROR is Designed to Evaluate the Disease-Modifying Potential of Zorevunersen 9 PRIMARY KEY SECONDARY KEY SECONDARY Study Endpoints Percent change from baseline in major motor seizure frequency at Week 28 Durability of effect on major motor seizure frequency at Week 52 Change in behavior & cognition measured by multicomponent assessment of four Vineland-3 subdomains at Week 52 Multicomponent Assessment Four Vineland-3 Subdomains: • Expressive Communication • Receptive Communication • Interpersonal Relationships • Personal Skills Individual treatment effect for each subdomain is calculated, then all four scores are averaged to produce a single score that reflects overall treatment effect
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | MARGIN MARGIN MARGIN MARGIN Matching Adjusted Indirect Comparison of Patient Data Supported Phase 3 Selection of Dose and Vineland Subdomains 10 Dravet syndrome natural history study patientsPatients treated with zorevunersen Expressive Communication Receptive Communication Interpersonal Relationships Personal Skills -10 0 10 20 9.1 8.7 8.8 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 -10 0 10 20 -0.8 1.9 1.9 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. Treatment group (left, n=7 at Week 68) includes patients who received loading doses of 2x70mg or 3x45mg plus two maintenance doses of 45mg. 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. 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 2026 | STOKE THERAPEUTICS | MARGIN MARGIN MARGIN MARGIN Statistically Significant Improvements in Cognition and Behavior Using a Multicomponent Assessment Support Planned Phase 3 Analysis Phase 1/2a data cut: December 12, 2023 (after End of Study); OLE data cut: February 19, 2026. Month 18: Week 68 in ADMIRAL/LONGWING to Week 78 in BUTTERFLY. Treatment group (n=7 at Week 68) includes patients who received loading doses of 2x70mg or 3x45mg plus two maintenance doses of 45mg. Propensity score weighting with weighted mixed repeated-measures model (MMRM) was employed to balance baseline characteristics for cross-trial comparison with the BUTTERFLY. MMRM used unstructured covariance. CI, confidence interval; Vineland-3, Vineland Adaptive Behavior Scales – Third Edition 11 Treatment effect in Phase 1/2 and OLE patients who received cumulative doses of zorevunersen consistent with Phase 3, compared to natural history at 18 months Vineland-3 Treatment Effect (95% CI) -3 0 3 6 9 12 15 18 21 Multicomponent Expressive Receptive Interpersonal Personal P-value <0.0001 0.0103 0.0075 0.0174 0.0041 Effect (95% CI) 7.13 (3.83, 10.44) 7.75 (2.16, 13.34) 5.38 (0.98, 9.77) 6.33 (1.56, 11.10) 9.08 (3.01, 15.16)
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | EMPEROR is Powered to Detect Statistically Significant Treatment Effects in Primary and Key Secondary Endpoints 12 Patient enrollment and progression with no discontinuations, combined with planned multicomponent assessment, enhance statistical power Minimum Detectable Treatment Effect Modeled with 150 evaluable patients at 90% power PRIMARY KEY SECONDARY KEY SECONDARY Endpoints Percent change from baseline in major motor seizure frequency at Week 28 Durability of effect on major motor seizure frequency at Week 52 Change in behavior & cognition measured by multicomponent assessment of four Vineland-3 subdomains at Week 52 46% 53% α=0.05 α=0.01 Relative reduction between treatment arms Difference in raw score points 1.8 2.1
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | © COPYRIGHT 2026 | STOKE THERAPEUTICS | Advancing STK-002 for ADOA Barry Ticho, M.D., Ph.D. Chief Medical Officer 13
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | MARGIN MARGIN MARGIN MARGIN Autosomal Dominant Optic Atrophy (ADOA): A Progressive Vision Disorder Primarily Caused by OPA1 Haploinsufficiency Sources: 1. Kjer. Acta Ophthalmologica Scandinavica. 1996; 2. Yu-Wai-Man P et al. Ophthalmology, 2010; 3. Yu-Wai-Man P, Chinnery PF. Ophthalmology, 2013; 4. Physician and Payer Interviews; 5. P. Amati-Bonneau P et al. The International Journal of Biochemistry & Cell Biology, 2009; 6. Lenaers G, Hamel C, Delettre C, et al. Orphanet J Rare Dis, 2012; 7. Chun BY and Rizzo JF III. Curr Opin Ophthalmol, 2016; 8. Le Roux B, Lenaers G, Zanlonghi X et al. Orphanet J Rare Dis, 2019; 9. “What is ADOA?” Autosomal Dominant Optic Atrophy Association. Accessed August 11, 2025, from https://www.adoaa.org/what-is-adoa 14 Disease and Cause Epidemiology Burden of cases caused by mutations in one copy of the OPA1 gene, most of which lead to haploinsufficiency functional OPA1 protein and disease manifestation Resulting in 1 out of 25,000 people are affected globally with a higher incidence of ~1 out of 10,000 in Denmark due to a founder effect ~13,000 people affected in the U.S., UK, EU-4, and Denmark up to of patients are registered legally blind of patients are symptomatic by age 10 >600 Different OPA1 mutations reported in ADOA patients 65-90% 50% 46% 80%
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | MARGIN MARGIN MARGIN MARGIN STK-002 Shows Statistically Significant Increases in OPA1 Protein and Improvements in Mitochondrial Function in ADOA Patient‐Derived Cells 1. Mean (SD) OPA1 protein levels (n=9) plotted relative to WT Vehicle group. Statistical analysis by unpaired t-tests. 2. Mean (SD) maximal respiration determined by OCR (pmol/min/cell) under basal and stress conditions, normalized to cell count (n=3) plotted relative to Vehicle (1.0) for each cell type. Statistical analysis by ordinary one-way ANOVA and Dunnett’s multiple comparison test. ADOA, autosomal dominant optic atrophy; FS, frameshift; mRNA, messenger ribonucleic acid; OCR, oxygen consumption rate; OPA1, OPA1 mitochondrial dynamin like GTPase; SD, standard deviation; WT, wild-type. Figures adapted from Venkatesh A et al. Nucleic Acid Ther 2024; 34 (5): 221–236. Licensed under CC BY 4.0. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/ 15 Improved mitochondrial functionIncreased OPA1 protein expression 0.0 0.5 1.0 1.5 2.0 WT F34 (splice) F35 (FS) F36 (FS) Vehicle STK-002 40 nM Relative OPA1 protein1 OPA1 variant P<0.01 P<0.0001 P<0.05 P<0.01 0.0 0.5 1.0 1.5 2.0 20 40 60 20 40 60 20 40 60 P<0.01 P<0.05 P<0.001 P<0.001 Relative mitochondrial function (maximal respiration,pmol/min/cell)2 Dose (nM) F34 (splice) F35 (FS) F36 (FS) OPA1 variant STK-002 demonstrated activity across cells carrying different OPA1 variants
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | MARGIN MARGIN MARGIN MARGIN A Single Intravitreal Dose of STK-002 Increased Retinal OPA1 Protein by 47% at 4 Weeks in Wild-Type Non-Human Primates Versus Control Retinas were collected at 4 or 8 weeks after intravitreal dosing. OPA1, OPA1 mitochondrial dynamin like GTPase; PBS, phosphate-buffered saline; RGC, retinal ganglion cell. Figures are adapted from Venkatesh A et al. Nucleic Acid Ther 2024; 34 (5): 221–236. Licensed under CC BY 4.0. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/ 16 OPA1 protein in RGC layerSTK-002 detected in RGC layer OPA1 protein in retinal lysates 0 2 4 6 8 10 Vehicle 0.1mg 0.3mg 1mg 0.3mg 1mg OPA1 protein (µg/mg) P<0.05 P<0.05 Week 4 Week 8
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | MARGIN MARGIN MARGIN MARGIN Phase 1 OSPREY Study of STK-002 in Patients with ADOA Eight clinical trial sites are active in the UK, Germany, Denmark, Italy, and Austria. a. Patients will receive a single intravitreal injection of STK-002 to the most affected or, if both eyes are of equal severity, the non-dominant eye. ADOA, autosomal dominant optic atrophy; LCVA, low contrast visual acuity; OCT, optical coherence tomography; OPA1, OPA1 mitochondrial dynamin like GTPase. 17 Principal focus Other measures • Safety and tolerability • Visual function – LCVA • Ocular structure – OCT • Mitochondrial stress – OcuMet BeaconTM imaging Recruitment ongoing Part A: Adults (≥18 to <55 years) 4 ascending dose cohorts Part A data will determine Part B starting dose STK-002 dose escalation Single intravitreal dose (0.1–0.7 mg/eye)a + + Part B: Children/adolescents (≥6 to <18 years) Day 1 First patient in cohort dosed N=1 Screening & Baseline Up to 29 days Safety review Day 4 Safety review Day 29 Remaining patients in cohort dosed N=2
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | MARGIN MARGIN MARGIN MARGIN OSPREY: Dose Escalation Continuing with Initial Safety & Efficacy Data Expected in H1 2027 18 Cohorts 3 and 4 have the potential to reach therapeutic levels of dosing FutureStatusSignificance May demonstrate whether STK-002’s ability to upregulate OPA1 expression translates into measurable effects on visual function Inform dose selection and future clinical development of this novel RNA-based potentially disease-modifying approach Dosing complete in cohorts #1 and #2 Cohort #3 expected to complete by the end of 2026 Initial data expected in H1 2027
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | © COPYRIGHT 2026 | STOKE THERAPEUTICS | 19 Preparing for a Potential U.S. Launch Jason Hoitt Chief Patient Officer
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | Significant Market Opportunity 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. 2 Numbers may not add up due to rounding. EU4: Germany, France, Italy and Spain 3 De-identified U.S. medical and pharmacy claims database, Oct 2022 – Sep 2026. Patients with a first observed ICD-10 Dravet syndrome code (G40.833/G40.834) per month; observed, unprojected counts. 20 ~38K patients with Dravet syndrome across 7 major geographic markets 16K US 16K EU4 + UK 7K Japan Prevalence of Dravet Syndrome2 ~38K 1 Patients ~6,000 patients immediately addressable at launch • <25 years old and likely in the care of a pediatric provider • Insights into where ~80% of these patients are being cared for today ICD10 code established in 2020 will continue to increase patient identification • 40-50 new patients3 entering claims databases every month Concentrated U.S. Market
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | “We’ve used Spinraza for years and we’ve already established the infrastructure of recurrent intrathecal injections for these patients. I can’t imagine that I’m going to need a completely different infrastructure." Established Infrastructure at Key Sites of Care Provides Foundation for Early Adoption Sources: Stoke primary research, July 2026; Komodo claims-based site model, Dec 2025; Field Medical insights. Quote from qualitative HCP interviews 21 Treating Sites Existing Infrastructure Zorevunersen Experience ~50% of identified U.S. patients are cared for by the top 50 sites 100% of top 50 sites have established intrathecal administration infrastructure ~50% of top 50 sites have participated in zorevunersen clinical studies
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | Preparing to Deliver Zorevunersen 22 Collaborative EffortsAdding Capabilities Expanding Education Two additional studies of zorevunersen in adults and infants & toddlers anticipated to initiate by year -end Patient Services to enable timely access Payer Account Team to educate medical directors at insurers Continuing engagement with HCPs Expansion into broader neurology community Genetic testing initiatives Medical society leadership initiatives
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | © COPYRIGHT 2026 | STOKE THERAPEUTICS | Financial Summary Thomas Leggett Chief Financial Officer 23
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | © COPYRIGHT 2026 | STOKE THERAPEUTICS | $358.8 Million Cash, Cash Equivalents, & Marketable Securities Current financial position anticipated to fund operations through to early 2028 Third Quarter 2026 Financial Summary as of September 30, 2026 24Note: Excludes $3.2 million of restricted cash.
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© COPYRIGHT 2026 | STOKE THERAPEUTICS | © COPYRIGHT 2026 | STOKE THERAPEUTICS | Q&A 25