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Executive Officer nd 42 Annual J.P. Morgan Healthcare Conference January 10, 2024 Copyr i g Ch op t 2024 yrightS 2024 toke T Sh tok era ep T e h u e tr ic as peutic1 s
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ability of 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 timing and expected progress of clinical trials, data readouts and
presentations for STK-001 and STK-002; the timing of regulatory interactions or the outcomes thereof; our future operating results, financial position and cash runway; and our expectations, plans, aspirations and goals, including those related to
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potential future performance of Stoke. Copyright 2024 Stoke Therapeutics 2
C Cop opyr yri ig gh ht t 2024 2024 S St tok oke e T Th he
er ra ap pe eu ut ti ic cs s 3 3
1 out of 16,000 babies are born with Dravet syndrome Dravet syndrome is
not concentrated in a particular geographic area or ethnic group ~35,000 people affected in: United States Canada Japan Germany France United Kingdom Sources: 2018 Health Advances Report C Cop opyr yri ig gh ht t 2024 2024 S St tok oke
e T Th he er ra ap pe eu ut ti ic cs s 4 4
50% of Epilepsies are Unknown or Idiopathic; Majority of These are Now
Thought to be Genetic Epilepsy affects approximately 1.2 % ~85% of the US population Causes: of Dravet cases caused by a HAPLOINSUFFICIENCY Trauma of the SCN1A gene Tumor Stroke Resulting in Infection
Developmental abnormalities of brain However, 50% of epilepsies are due 50% to genetic mutations (previously known as cryptogenic) Na 1.1 protein V expression Sources: The Epilepsy Foundation; Centers for Disease Control and Prevention; Nabbout et
al., Orphanet Journal of Rare Diseases, 2013; C Cop opyr yri ig gh ht t 2024 2024 S St tok oke e T Th he er ra ap pe eu ut ti ic cs s 5 5 Dravet Syndrome Foundation Voice of the Patient Report
Our Goal: Upregulate Protein Expression to Treat the Underlying Cause of
Severe Genetic Diseases Mechanism of action for TANGO Non-productive exons control protein levels by alternative splicing pre-mRNA mRNA Full-length functional protein (productive splicing) PTC triggers degradation via NMD (non-productive splicing)
TANGO ASOs skip out non-productive exons pre-mRNA mRNA Full-length functional protein (productive splicing) TANGO ASO TANGO: Targeted Augmentation of Nuclear Gene Output C Cop opyr yri ig gh ht t 2024 2024 S St tok oke e T Th he er ra
ap pe eu ut ti ic cs s 6 6 PTC: premature termination codon NMD: nonsense-mediated mRNA decay
The Effects of Dravet Go Beyond "Just Seizures" Growth Time
Defects Loss Intellectual Disruptions Disability & Side Effects of Autonomic Developmental Nervous Delays ~20% of children and adolescents System with Dravet syndrome die before Direct Home 1 Medical adulthood, due to SUDEP , prolonged
Modifications Burden on Costs Movement seizures, seizure-related accidents or Caregiver & Balance infections Burden on Career Seizures are not Siblings Sacrifices ER Visits adequately controlled in Mood Sleep Disorders Abnormalities Language
& ~90% Speech Keto Diet Multiple Forced Disturbances Daily Retirement Medicines of people with Dravet syndrome 1 Sudden Unexpected Death in Epilepsy. C Cop opyr yri ig gh ht t 2024 2024 S St tok oke e T Th he er ra ap pe eu ut ti
ic cs s 7 7 Sources: Lagae et al., Developmental Medicine & Child Neurology, 2017; 2018 Health Advances Report; Dravet Syndrome Foundation Voice of the Patient Report
STK-001 is on Track to be the First Disease-Modifying Treatment for
Dravet Syndrome Multiple medicines available for No medicines available for Seizure management Syndrome management Available medicines used to control seizures: Acetazolamide Felbamate Rufinamide Benzodiazepines
Fenfluramine Stiripentol STK-001 Brivaracetam Lamotrigine Topiramate Cannabidiol Levetiracetam Valproate products The first potential disease-modifying Carbamazepine
Mesuximide Zonisamide approach to address the genetic cause Clobazam Oxcarbazepine of Dravet syndrome Ethosuximide Phenytoin Despite these treatments, seizures are not adequately controlled in 90% of patients
with Dravet syndrome C Cop opyr yri ig gh ht t 2024 2024 S St tok oke e T Th he er ra ap pe eu ut ti ic cs s 8 8
Data Support the Potential for Disease Modification with STK-001
BUTTERFLY Natural History Data Data from Phase 1/2a and OLE (patients 2-18 taking standard anti-seizure medicines) Clinical Studies Safety Generally well-tolerated No meaningful improvement in seizure Substantial and sustained reductions in studies
to date frequency in seizures with initial treatment (70mg) Median reductions observed among all patients at 3 and at 6 months Sustain reductions with ongoing treatment PK data Higher drug exposure Widening gap in cognition and
behavior: Substantial improvements in measures of in brain leads to cognition and behavior: greater reductions in Expressive communication Expressive communication seizure frequency Receptive communication Receptive
communication Gross motor skills Gross motor skills C Cop opyr yri ig gh ht t 2024 2024 S St tok oke e T Th he er ra ap pe eu ut ti ic cs s 9 9
No Improvement in Convulsive Seizure Frequency Despite Treatment with
Standard Anti-Seizure Medicines Over 2 Years BUTTERFLY natural history study of 2-18 years old patients with Dravet syndrome Patients were treated with the 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 (%) Clobazam 25 (69.4%) Fenfluramine 16 (44.4%) Stiripentol 14 (38.9%) Valproic Acid 14 (38.9%) Cannabidiol 12 (33.3%) Levetiracetam 8 (22.2%) Source: 24-Month
Analysis of BUTTERFLY: A Prospective, Observational Study to Investigate Cognition and Other Non-seizure Comorbidities in Children and Adolescents with Dravet Syndrome (DS), AES 2023. Copyright 2024 Stoke Therapeutics 10
Substantial Reductions in Seizure Frequency Observed in Patients
Treated with 2 or 3 Initial Doses of STK-001 (70mg) Data as of July 2023. All patients have now completed the study. End of study data anticipated 1Q 2024. 6 patients 3 patients *D1-D28: +825%, D29-D56: +626%, D57-D84: +1125%, D85-D112: +717%
Source: MONARCH and ADMIRAL: Phase 1/2a Studies in US and UK Investigating Safety and Drug Exposure of STK-001, an Antisense Oligonucleotide (ASO), in Children and Adolescents with Copyright 2024 Stoke Therapeutics 11 Dravet Syndrome (DS),
Median Reductions in Convulsive Seizure Frequency Observed Among All
Patients with 2 or 3 Doses of 70mg at 3 and at 6 Months 6 Patients at 3 Months 3 Patients at 6 Months After Last Dose After Last Dose Ages 2 to 12 Years Ages 2 to 12 Years Ages 13 to 18 Years Ages 13 to 18 Years -50% -50% *28-day interval prior to 3
months or 6 months After Last Dose for all patients. 1 patient in 70 mg cohort received Dose 3 late; therefore, interval does not extend fully to 3 and 6 months After Last Dose for this patient. Data cutoff dates: MONARCH 13APR2023; ADMIRAL
12APR2023 and 21JUN2023 Source: MONARCH and ADMIRAL: Phase 1/2a Studies in US and UK Investigating Safety and Drug Exposure of STK-001, an Antisense Oligonucleotide (ASO), in Children and Adolescents with Copyright 2024 Stoke Therapeutics 12
Dravet Syndrome (DS), AES 2023.
OLE Data: Sustained Reductions in Convulsive Seizure Frequency Effects
observed with ongoing treatment with STK-001 at 30mg, 45mg Weeks Weeks Weeks Weeks Weeks Weeks Weeks Weeks Weeks Weeks Weeks Weeks 1-4 5-8 9-12 13-16 17-20 21-24 25-28 29-32 33-36 37-40 41-44 45-48 SWALLOWTAIL: Maintenance Dose (30mg or 45mg) Every
4 Months STK-001 STK-001 STK-001 *No exclusion for AED modification in MONARCH or SWALLOWTAIL. Data cutoff dates: MONARCH 13APR2023; SWALLOWTAIL 24MAR2023 Source: SWALLOWTAIL and LONGWING: Open-Label Extension (OLE) Studies for Children and
Adolescents with Dravet Syndrome (DS) who Previously Participated in a Study of Antisense Copyright 2024 Stoke Therapeutics 13 Oligonucleotide (ASO) STK-001, AES 2023. MONARCH 6 Months After Last Dose
Natural History Shows Widening Gap in Cognition and Behavior Compared
to Neurotypical Peers Dravet patients were taking standard anti-seizure medicines throughout the 2-years of study Source: 24-Month Analysis of BUTTERFLY: A Prospective, Observational Study to Investigate Cognition and Other Non-seizure Comorbidities
Copyright 2024 Stoke Therapeutics 14 in Children and Adolescents with Dravet Syndrome (DS), AES 2023.
OLE Data (30mg, 45mg): Substantial Improvements in Communication and
Gross Motor Skills with Ongoing Treatment Improving 12.25 11.00 7.32 10.16 6.25 5.63 5.07 4.50 4.28 -1.00 -2.09 -2.30 -2.95 -3.21 -3.94 -12.58 -13.34 -13.95 Worsening BUTTERFLY (Natural History) SWALLOWTAIL (STK-001) *Mixed model repeated measures
with AR(1) covariance structure. Baseline covariates in BUTTERFLY matched to SWALLOWTAIL. Analysis includes patients who received 30 or 45 mg for all doses in SWALLOWTAIL; BUTTERFLY sample size: n=36 at screen, n=27 at Month 12; SWALLOWTAIL sample
size: n=24 at screen, n=9 at Week 48 and n=5 at Week 64. GSV = Growth Scale Value. Copyright 2024 Stoke Therapeutics 15 Source: SWALLOWTAIL and LONGWING: Open-Label Extension (OLE) Studies for Children and Adolescents with Dravet Syndrome
(DS) who Previously Participated in a Study of Antisense Oligonucleotide (ASO) STK-001, AES 2023.
OLE Data (30mg, 45mg): Substantial Improvements in Executive Function
with Ongoing Treatment Worsening 5.29 2.83 0.95 -3.99 -5.01 -6.54 Improving SWALLOWTAIL (STK-001) BUTTERFLY (Natural History) *Mixed model repeated measures with AR(1) covariance structure. Baseline covariates in BUTTERFLY matched to SWALLOWTAIL.
Analysis includes all patients who received 30 or 45 mg for all doses in SWALLOWTAIL; BUTTERFLY sample size: n=36 at screen, n=30 at Month 12; SWALLOWTAIL sample size: n=25 at screen, n=9 at Week 48 and n=5 at Week 64. Copyright 2024 Stoke
Therapeutics 16 BRIEF-P measures executive function in children, such as the ability to organize thoughts and have working memory. Source: SWALLOWTAIL and LONGWING: Open-Label Extension (OLE) Studies for Children and Adolescents with Dravet Syndrome
(DS) who Previously Participated in a Study of Antisense Oligonucleotide (ASO) STK-001, AES 2023.
OLE Data (30mg, 45mg): Substantial Improvements in Overall Condition
Compared to BUTTERFLY Natural History Results Consistent responses across caregiver and clinician ratings Very much worse 4.48 4.40 4.32 No change 4.24 4.23 3.98 2.80 2.68 2.50 2.23 1.95 1.53 Very much improved SWALLOWTAIL (STK-001) BUTTERFLY
(Natural History) *Mixed model repeated measures with AR(1) covariance structure. Baseline covariates in BUTTERFLY matched to SWALLOWTAIL. Analysis includes all patients who received 30 or 45 mg for all doses in SWALLOWTAIL. For CGI-C, BUTTERFLY
sample size: n=32 at Month 3, n=29 at Month 12; and for CaGI-C, BUTTERFLY sample size: n=27 at Month 3, n=24 at Month 12. For both CGI-C and CaGI-C, SWALLOWTAIL sample size: n=25 at Week 16, n=9 at Week 48 and n=5 at Week 64. CGI and CaGI in
BUTTERFLY were adapted for cognition. CGI-C=Clinical Global Impression of Copyright 2024 Stoke Therapeutics 17 Change and CaGI-C=Caregiver Global Impression of Change. Sources: SWALLOWTAIL and LONGWING: Open-Label Extension (OLE) Studies for
Children and Adolescents with Dravet Syndrome (DS) who Previously Participated in a Study of Antisense Oligonucleotide (ASO) STK-001, AES 2023.
Higher Brain Exposure Leads to Greater Seizure Reduction PK Modeling of
exposure-seizure relationship 300 R=-0.23, p=0.00000000025 200 100 0 Baseline -100 Seizure Free Average Concentration of Mean Brain Regions, excluding Thalamus Copyright 2024 Stoke Therapeutics 18 Source: Utilization of a Pharmacokinetic (PK)
Model for STK-001 in Patients with Dravet Syndrome (DS) To Support Selection of Dosing Regimens in Clinic, AES 2023. Percentage of Change from Baseline in Cumulative Seizure Frequency
Summary of Key Clinical Data from Ongoing Studies Single and multiple
doses of 10mg to 70mg were generally well-tolerated Patients treated with 2 or 3 doses of 70mg experience STK-001 Has Potential to substantial and sustained reductions in convulsive Address the Genetic Cause seizures Reductions in
seizure frequency were maintained of Dravet Syndrome with ongoing treatment at lower doses (30mg, 45mg) Improvements in assessments of cognition and behavior as measured by VABS-III* & BRIEF-P** *Vineland Adaptive Behavior Scale
(VABS-III), an assessment of adaptive behavior which refers to an individual's ability to undertake daily activities appropriate for their age group. **Behavior Rating Inventory of Executive Function-Preschool Version, an assessment of
pediatric executive function. C Cop opyr yri ig gh ht t 2024 2024 S St tok oke e T Th he er ra ap pe eu ut ti ic cs s 19 19
Q1 2024 Data Readout & Next Steps Rest of Year Q1 2024 Phase 3
Preparations Key Anticipated Data Safety, pharmacokinetic (PK) modeling, Global regulatory interactions and cerebrospinal fluid (CSF) Chronic toxicology data Seizure frequency from ~20 patients who Protocol
finalization/submission received 1, 2, or 3 initial doses of STK-001 (70mg) and were followed for six months Investigator brochure Seizure frequency, cognition and behavior Seek IRB approvals from patients treated in the OLE
studies C Cop opyr yri ig gh ht t 2024 2024 S St tok oke e T Th he er ra ap pe eu ut ti ic cs s 20 20
2024 Summary of Priorities Advance STK-002 for ADOA Advance STK-001 for
Dravet Initiate Phase 1 study (OSPREY) in 2024 Syndrome to Pivotal Develop & Expand Pipeline Q1 Data Readout Execute on collaboration with Acadia to advance 3 Pending data, request Phase 3 neurodevelopmental
programs including Rett planning meetings with regulators syndrome and Syngap1 programs Expand TANGO ASOs as a first-in-class disease- modifying approach for additional genetic diseases Current Liquidity Anticipated to Fund Operations to the
End of 2025 $214.7M in Cash, Cash Equivalents, and Marketable Securities as of 9/30/23 C Cop opyr yri ig gh ht t 2024 2024 S St tok oke e T Th he er ra ap pe eu ut ti ic cs s 21 21 ADOA: Autosomal dominant optic atrophy
Q&A Copyright 2024 Stoke Therapeutics 22