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Forward-Looking Statements and Other Legal Notices 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 of 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 advantages that may be achieved with TANGO; the ability of TANGO to develop medicines for other genetic diseases and the opportunity thereof; the ability of zorevunersen (STK-001) to treat the
underlying causes of Dravet syndrome and reduce seizures or show improvements in behavior or cognition at the indicated dosing levels or at all; the design, timing and results of the Phase 3 study, data readouts, regulatory decisions and other
presentations for zorevunersen; the potential for zorevunersen to be a first-in-class, disease-modifying therapy for Dravet syndrome; the timing of regulatory interactions or the outcomes thereof; our expectations, plans, aspirations 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 beyond
Phase 3 and into launch readiness to mid-2028. Statements including words such as anticipate, believe, hope, plan, will, continue, expect, 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 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; 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
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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
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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, that have not yet been approved for marketing by the U.S. Food and Drug
Administration or any other regulatory agency. COPYRIGHT 2025 | STOKE THERAPEUTICS | 2
OUR GOAL Restore protein expression by harnessing the body's
potential with RNA medicine Stoke's pipeline offers potential first-in-class disease modifying new medicines for diseases caused by protein insufficiency STK-002 for Autosomal zorevunersen Dominant Optic Atrophy SYNGAP1 And beyond for
Dravet syndrome (ADOA) A severe genetic developmental A severe and rare genetic The most common inherited ~6,500 add'l genes with epileptic encephalopathy neurodevelopmental disease optic nerve disorder TANGO target signatures
COP COPY YR RI IG GH HT T 2 20 02 25 5 | | S ST TOKE OKE T TH HER ERA AP PEU EUT TI ICS CS | | 3
ADVANTAGES OF STOKE'S APPROACH vs. OTHER GENETIC APPROACHES
Selectively boosts expression No observed unwanted Utility across small and only in tissues where the protein off-target genetic effects large gene targets and is normally expressed mutations Does not alter DNA Ability to control dose level Simple
and scalable and duration manufacturing COP COPY YR RI IG GH HT T 2 20 02 25 5 | | S ST TOKE OKE T TH HER ERA AP PEU EUT TI ICS CS | | 4
Dravet Syndrome: A Severe, Progressive Genetic Epilepsy 2 2 ~38,000 1
OUT OF 15,600 babies are born with Dravet syndrome Patients with Dravet syndrome in of cases caused by a the U.S., Japan, Germany, France, HAPLOINSUFFICIENCY Italy, Spain and UK of the SCN1A gene of children and adolescents with UP TO Dravet
syndrome die before adulthood, RESULTING IN 1 4 due to SUDEP , prolonged seizures, seizure- 20% related accidents or infections Seizures are not adequately controlled in of people with 4 Na 1.1 protein V Dravet syndrome is not concentrated in a
Dravet syndrome 90% expression particular geographic area or ethnic group 1 Sudden Unexpected Death in Epilepsy 2 Based on preliminary management estimates, which scaled annual incidence to prevalence using country-specific live birth rates over the
past 85 years and 3 adjusted for Dravet-specific mortality. The estimate is based on incidence rates published by Wu et al., Pediatrics, 2015 4 Symonds, J. et al. Brain, 2021. 2018 Health Advances Report; Dj mi et al., Molecular Genetics
& Genomic Medicine, 2016; Lagae et al., Developmental COPYRIGHT 2025 | STOKE THERAPEUTICS | 5 Medicine & Child Neurology, 2017; Nabbout et al., Orphanet Journal of Rare Diseases, 2013; Epilepsy, Behav. 2016; Dravet Syndrome
Current Treatments For Dravet Aim to Reduce Seizures Leaving a
Significant Gap in Treatment of the Syndrome MULTIPLE MEDICINES available for Currently NO MEDICINES available for Seizure Management Syndrome Management Bromide Cannabinoid Clobazam Diazepam Fenfluramine Levetiracetam Stiripentol Topiramate ?
Valproate Zonisamide ASM, antiseizure medication; DS, Dravet syndrome; SOC, standard of care. COPYRIGHT 2025 | STOKE THERAPEUTICS | 6 1. Lagae L, et al. Dev Med Child Neurol 2018; 60 (1): 63-72. Appendix S4. 2. Lagae L, et al. Dev Med
Child Neurol 2018; 60 (1): 63-72.
The Effects of Dravet Go Beyond "Just Seizures" All aspects
of life are affected, not only for the individual living with DS, but for their caregivers and families Seizures Stress Developmental Financial deficits burden Behavioral Work Difficulties with changes productivity Social balance, walking, isolation
and gait Mental health Polytherapy strain Communication Family and speech dynamics challenges Sleep disruptions DS, Dravet syndrome. Voice of the patient report. Externally-Led Patient-Focused Drug Development Meeting on Dravet Syndrome. Available
at: COPYRIGHT 2025 | STOKE THERAPEUTICS | 7 https://dravetfoundation.org/dsf-funded-research/externally-led-pfdd-meeting/. Accessed March 2025.
Natural History Data: Despite Standard Anti-Seizure Medicines, No
Meaningful Improvement in Convulsive Seizure Frequency Patients were treated with the Change in Convulsive Seizure Frequency best available anti-seizure medicines Median baseline convulsive seizure frequency per 28 days (95% CI), n=26 10.0 (5.50,
15.5) Most common ongoing anti-seizure medicines, n (%) ZZ Clobazam 25 (69.4%) Fenfluramine 16 (44.4%) Stiripentol 14 (38.9%) Valproic Acid 14 (38.9%) Month Cannabidiol 12 (33.3%) Mean progression of BUTTERFLY patients Levetiracetam 8 (22.2%)
Source: 24-Month Analysis of BUTTERFLY: A Prospective, Observational Study to Investigate Cognition and Other Non-seizure COPYRIGHT 2025 | STOKE THERAPEUTICS | 8 Comorbidities in Children and Adolescents with Dravet Syndrome (DS), AES 2023.
Percent change from baseline in convulsive seizure frequency
Compelling Clinical Data and Key Stakeholder Engagement Underscore the
Potential for Zorevunersen FDA Breakthrough Biogen Phase 3 Study Clinical Data Underway Therapy Collaboration for Substantial and durable reductions in seizure Designation Zorevunersen First sites initiated in the frequency and continuing U.S. in
May 2025 Indicates that zorevunersen Brings global commercial improvements across may demonstrate expertise with high-value, multiple measures of substantial improvement disease-modifying cognition and behavior are over available therapy medicines,
Stoke retains full evidence of disease rights in U.S., Canada, and modification Mexico First-ever Phase 3 study of Disease modification would represent a major step a potential disease-modifying medicine KEY TAKEAWAYS forward in the treatment of
Dravet syndrome for Dravet syndrome now underway *Breakthrough Therapy Designation is not the same as drug approval. Zorevunersen is an investigational drug candidate. COPYRIGHT 2025 | STOKE THERAPEUTICS | Regulatory discussions ongoing.
Initial 70mg Doses of Zorevunersen Demonstrated Substantial and
Sustained Reductions in Convulsive Seizure Frequency on Top of Standard of Care Medicines Median percent change in convulsive seizure frequency 70 mg 1 dose from baseline in Phase 1/2a studies 70 mg 2 dose 50 70 mg 3 dose 0 ZZ -50 -100 M1 M2 M3 M4
M5 M6 M7 M8 M9 Dose 1 Dose 2 Dose 3 Laux, L et al. Zorevunersen (STK-001) demonstrates potential for disease modification including reductions in seizures and improvements in cognition and COPYRIGHT 2025 | STOKE THERAPEUTICS | 10 behavior in
children and adolescents with Dravet syndrome (presentation). American Epilepsy Society Annual Meeting, December 6-10, 2024 (Los Angeles, USA). Median % change in convulsive seizure frequency from Ph1/2a baseline (80% CI)
Ongoing Treatment Demonstrated Substantial and Durable Reductions in
Convulsive Seizure Frequency 70 mg 1 dose* Initial 2 & 3 doses of 70mg in Ph1/2 followed by 45mg 70 mg 2 dose in OLE demonstrated up to 87% reduction at Month 8 70 mg 3 dose 0 -25 ZZ -50 -75 -100 M1 M2 M3 M4 M5 M6 M7 M8 End of 45mg* 45mg* Ph1/2a
*Patients from the single dose 70mg cohort received 30mg doses at M1 and M5. Patients with Dravet syndrome in open-label extension studies of zorevunersen (STK-001) have durable reductions in seizure COPYRIGHT 2025 | STOKE THERAPEUTICS | 11
frequency and ongoing improvements in cognition and behavior. AES 2024 Median % change in convulsive seizure frequency from Ph1/2a baseline (80% CI)
Substantial, Durable Reductions in Seizures On Top of SOC Observed
Through Two Years of Treatment with Zorevunersen Enrolled patients Data for all patients who continued treatment in the OLEs 70 mg in Ph 1/2a and 30 mg in OLE 0 -25 ZZ -50 -75 -100 M1 M2 M3 M4 M5 M6 M7 M8 M9 M10 M11 M12 M13 M14 M15 M16 M17
M18 M19 M20 M21 M22 M23 M24 End of Dose Dose Dose Dose Dose Dose 1 2 3 4 5 6 Ph1/2a Orange: Enrolled Patients (n=70 M1 and 17 at M24 based on study progression) Black: 70mg Cohorts from Ph1/2a who received 30 mg in OLE (n=16 - 17 at
each timepoint) Ph1/2a End of Study results.; OLE data cut: June 28, 2024. COPYRIGHT 2025 | STOKE THERAPEUTICS | 12 Sullivan, J et al. Patients with Dravet syndrome in open-label extension studies of zorevunersen (STK-001) have durable
reductions in seizure frequency and ongoing improvements in cognition and behavior (poster). American Epilepsy Society Annual Meeting, December 6-10, 2024 (Los Angeles, USA). Median % change in convulsive seizure frequency from Ph1/2a baseline (80%
The Vineland-3 Assessment Tool is Commonly Used to Evaluate Non-seizure
Outcomes in Dravet Syndrome Vineland-3 Adaptive Behavior Scales* COMMUNICATION MOTOR SKILLS SOCIALIZATION DAILY LIVING SKILLS Receptive: Gross Motor: Interpersonal Personal: Responds upon hearing Moves, scoots, or crawls Relationships: Cooperates in
dressing and across the floor Responds upon hearing undressing name called name called Expressive: Fine Motor: Domestic: Says "Dada", "Mama", Picks up small objects with Play and Leisure: Puts away books, toys, etc. thumb and
fingers Responds when parent when done or caregiver name or caregiver is playful Written: Community: Writes alphabet letters Coping Skills: Talks with a familiar person using correct orientation Transitions easily from one using a phone activity to
another DS, Dravet syndrome; Vineland-3, Vineland Adaptive Behavior Scales, Third Edition. *Maladaptive Behavior is an additional optional domain of the Vineland-3 COPYRIGHT 2025 | STOKE THERAPEUTICS | 13 depending on age and developmental
requirements. Its subdomains include Externalizing, Internalizing, and Other. Subdomains Domains
Adaptive Functioning and Neurodevelopment Plateau in Patients with
Dravet Syndrome Widening development gap over time in patients with Dravet syndrome relative to neurotypical peers DS, Dravet syndrome; Vineland-3, Vineland Adaptive Behavior Scales, Third Edition. 1. Sullivan J et al. Poster P788 Presented at EEC
2024; Rome, Italy, 7-11 September 2024. 2. Sullivan J, Wirrell E, Knupp KG, et al. Epilepsy COPYRIGHT 2025 | STOKE THERAPEUTICS | 14 Behav 2024;151:109604; 3. Sullivan J, Wirrell E, Knupp KG, et al. Epilepsy Behav 2022;137(Pt
Improvements in Cognition and Behavior Within 9 Months Continuing
Improvements Throughout the OLEs Vineland-3 GSV scores in OLE build on improvements already observed in Phase 1/2 2 1 Open-label extension studies Phase 1/2a study Month 12 Month 24 LS mean change from Phase 1/2a baseline in GSV (95%CI) at Month 9
Change in GSV (95%CI) from OLE baseline to Month 24 1 Machine learning model constructed using data from EOS Ph1/2a ADMIRAL (all dose cohorts) and data through Month 4 visit in LONGWING OLE (as of Nov. 2023) COPYRIGHT 2025 | STOKE
THERAPEUTICS | 15 2 Mixed-effects model for repeated measures constructed using data through Month 24 from enrolled patients in OLE studies. Data cutoff 28 June 2024.
Zorevunersen Generally Well-Tolerated Across Studies Phase TEAEs 1/2a
30% of patients experienced a study drug-related TEAE To date, Most common: CSF protein elevations (13.6%) and procedural vomiting (4.9%) studies (n=81) >700 doses of TESAEs zorevunersen 22% of patients experienced
a TESAE All were unrelated to study drug except for 1 patient with SUSARs have been administered; 3 years of treatment in Findings consistent with Ph1/2, with the exception of a higher incidence of CSF protein OLE elevation some patients
studies 79% (56/71*) of patients in the OLEs had at least 1 CSF protein value >50 mg/dL (n=74) No clinical manifestations have been observed in these patients One patient discontinued treatment due to elevated CSF protein
levels End of Phase 1/2a study data. Datacut June 28, 2024, for OLEs. *71/74 patients had 1 post-baseline CSF protein value in the OLEs Number of doses to date includes doses administered after the June 28, 2024, safety datacut for the
OLEs. CSF, cerebrospinal fluid; OLE, open-label extension; SUSAR, suspected unexpected serious adverse reaction; TEAE, treatment-emergent adverse event; COPYRIGHT 2025 | STOKE THERAPEUTICS | 16 TESAE, treatment-emergent serious adverse
EMPEROR Phase 3 Study Overview Phase 3 design and dose regimen aligned
with Ph1/2 and OLE studies Primary endpoint Key secondaries Study Design: Sham-controlled, 1:1 randomization Seizures Durability of effect on Dosing Regimen: 2x70mg + 2x45mg major motor seizure Percent change from Study Start: May 2025 frequency
measured at baseline in major motor Week 52 Population: 2 to <18 years with a confirmed seizure frequency in variant in the SCN1A gene not associated with gain patients receiving Improvements in of function zorevunersen as behavior &
cognition compared to sham measured by Vineland- Number of Patients Randomized: ~150 measured at Week 28 3 subdomains Sites: ~60 globally Other Endpoints Duration: 8-week baseline, 52-week efficacy treatment period Safety, CGI-C, CaGI-C, BSID-IV,
and others Data Anticipated: 2H 2027 COPYRIGHT 2025 | STOKE THERAPEUTICS | 17 Regulatory discussions ongoing
First Phase 3 Study Designed to Assess Disease Modification in Dravet
Syndrome Dosing Regimen of 2x70mg followed by 2x45mg based on positive data from Phase 1/2a and OLE studies 8-week baseline period 1:1 randomization 52-WEEK EFFICACY TREATMENT PERIOD D1 W8 W24 W40 Dose Dose Dose Dose 1 2 3 4 MAINTENANCE DOSES
LOADING DOSES (sham or 45mg zorevunersen) (sham or 70mg zorevunersen) COPYRIGHT 2025 | STOKE THERAPEUTICS | 18 Regulatory discussions ongoing
Zorevunersen is Positioned to Change the Treatment of Dravet Syndrome
SIGNIFICANT NEED CLINICAL DATA STAKEHOLDER SUPPORT Current treatments focus on Substantial and durable reductions HCPs and caregivers have had an reducing seizure frequency. in seizures and continuing overwhelming positive reaction to There is
nothing available to improvements in cognition and the zorevunersen profile as a 1 treat the entire syndrome. behavior on top of standard of disease-modifying medicine. care anti-seizure medicines. Phase 3 study now underway. Pivotal data
anticipated in 2H 2027 Regulatory discussions ongoing COPYRIGHT 2025 | STOKE THERAPEUTICS | 19 1. Based on Company sponsored interviews using a Product X profile based on MONARCH and ADMIRAL study results.