EX-99.1

EX-99.1 2 d39993dex991.htm EX-99.1 EX-99.1

Exhibit 99.1 Stoke Therapeutics NASDAQ: STOK Edward M. Kaye, M.D. Chief 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

Disclaimer 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 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 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 the goals of our collaboration with Acadia. Statements including words such as anticipate, plan, will, continue, expect, or ongoing 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: Stoke's ability to advance, obtain regulatory approval of, and ultimately commercialize its produce candidates; the timing of data readouts and interim and final results of preclinical and clinical trials; positive results in a clinical trial may not be replicated in subsequent trials or successes in early stage clinical trials may not be predictive of results in later stage trials; preliminary interim data readouts of ongoing trials may show results that change when such trials are completed; Stoke's ability to fund development activities and achieve development goals into 2025; Stoke's ability to protect its 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 Stoke's Annual Report on Form 10-K for the year ended December 31, 2022, its quarterly reports on Form 10-Q and the other documentation Stoke files 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 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. © Copyright 2024 Stoke Therapeutics 2

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), AES 2023.

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 ü generally well-tolerated Patients treated with 2 or 3 doses of 70mg experience STK-001 Has Potential to substantial and sustained reductions in convulsive ü Address the Genetic Cause seizures Reductions in seizure frequency were maintained of Dravet Syndrome ü with ongoing treatment at lower doses (30mg, 45mg) Improvements in assessments of cognition and ü 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 qSafety, pharmacokinetic (PK) modeling, q Global regulatory interactions and cerebrospinal fluid (CSF) q Chronic toxicology data qSeizure frequency from ~20 patients who q Protocol finalization/submission received 1, 2, or 3 initial doses of STK-001 (70mg) and were followed for six monthsq Investigator brochure qSeizure frequency, cognition and behavior q 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