Stoke Therapeutics, Inc. · NASDAQ:STOK

Stoke Therapeutics — J.P. Morgan 2020 Healthcare Conference

31 slides from Stoke Therapeutics's conference presentation, Jan 13, 2020

1. Slide 1: J.P. Morgan 2020 Healthcare Conference

   Stoke Therapeutics Edward M. Kaye, M.D. Chief Executive Officer J.P. Morgan 2020 Healthcare Conference January 14, 2020 © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved. Nasdaq: STOK Exhibit 99.1

2. Slide 2: Disclaimer

   Disclaimer © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved This presentation has been prepared by Stoke Therapeutics, Inc. (“Stoke”) for informational purposes only and not for any other purpose. Nothing contained in this presentation is, or should be construed as, a recommendation, pr

3. Slide 3: Stoke Therapeutics: Amplifying Science to Transform the Experience of Life

   Stoke Therapeutics Amplifying Science to Transform the Experience of Life Stoke is making a new generation of RNA-based genetic medicines that up-regulate protein expression to restore human health. © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved

4. Slide 4: Foundational Elements of Stoke

   Foundational Elements of Stoke © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved Experienced Leaders in Innovation Differentiated Platform with Broad Applicability Strong Financial Position to Support Growth Focused Development Program to transform the experience of life. Amplifying Scie

5. Slide 5: Efficient Execution Since 2018 Launch of Stoke

   Efficient Execution Since 2018 Launch of Stoke © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved 2019 2018 Completed $163.3M Initial Public Offering Received FDA orphan drug designation for STK-001, a potential disease modifying medicine for Dravet syndrome Enrolled first patient in the

6. Slide 6: Experienced Leaders in Innovation

   Experienced Leaders in Innovation © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved Edward Kaye, M.D. Chief Executive Officer and Director Huw Nash, Ph.D. Chief Operating Officer and Chief Business Officer Barry Ticho, M.D., Ph.D. Chief Medical Officer Steve Tulipano, CPA Chief Financial

7. Slide 7: TANGO: An RNA-Based Genetic Medicine Platform for Protein Upregulation

   TANGO: An RNA-Based Genetic Medicine Platform for Protein Upregulation © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved Targeted Augmentation of Nuclear Gene Output Addresses underlying cause of disease Applicable to most loss-of-function mutations Applies equally to small or large gene

8. Slide 8: TANGO Restores Protein Levels by Stoking Output From Healthy Genes

   © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved TANGO Restores Protein Levels by Stoking Output From Healthy Genes Stoke’s ASOs bind to specific stretches of pre-mRNA to reduce non-productive mRNA and increase productive mRNA The increased levels of productive mRNA from the functional

9. Slide 9: Transformative Potential of TANGO Technology for Haploinsufficiencies

   Transformative Potential of TANGO Technology for Haploinsufficiencies © Copyright 2019 Stoke Therapeutics, Inc. All rights reserved. Wild-type pre-mRNA Mutant pre-mRNA Nucleus Cytoplasm pre-mRNA splicing Extracellular fluid 50% protein Wild-type (normal) and mutant allele TANGO mechanism for increas

10. Slide 10: Transformative Potential of TANGO Technology for Haploinsufficiencies

    Transformative Potential of TANGO Technology for Haploinsufficiencies © Copyright 2019 Stoke Therapeutics, Inc. All rights reserved. Wild-type pre-mRNA Mutant pre-mRNA Nucleus Cytoplasm pre-mRNA splicing ASO Extracellular fluid ~100% protein TANGO mechanism for increasing protein synthesis in a pros

11. Slide 11: Robust Target Identification Process Utilizing Proprietary Bioinformatics

    Robust Target Identification Process Utilizing Proprietary Bioinformatics Approximately 50% of human genes contain a TANGO signature Cross-referencing with genetic disease databases identifies approximately 2,900 monogenic diseases amenable to TANGO Enables rapid and systematic identification of cli

12. Slide 12: Stoke is Initially Focused on Dravet Syndrome and Other Genetic Epilepsies

    Targets Time Horizon Stoke is Initially Focused on Dravet Syndrome and Other Genetic Epilepsies © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved Immediate focus Near-term focus Near-to-mid-term focus & collaborations GENETIC EPILEPSIES HAPLOINSUFFICIENCIES PATHWAY UPREGULATION DRAVET SY

13. Slide 13: Significant Unmet Need in Genetic Epilepsies

    Significant Unmet Need in Genetic Epilepsies © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved 50 million people globally affected by epilepsy 50% of patients with epilepsy have significant cognitive problems 0 Source: WHO 2018 fact sheet; Sirven, Cold Spring Harbor Perspectives in Medic

14. Slide 14: Dravet Syndrome: A Severe, Progressive Genetic Epilepsy

    Dravet Syndrome: A Severe, Progressive Genetic Epilepsy © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved 85% 1 out of 16,000 babies are born with Dravet syndrome 20% Sources: Source: 2018 Health Advances Report; Djémié et al., Molecular Genetics & Genomic Medicine 2016; Lagae et al., De

15. Slide 15: Non-Seizure Comorbidities of Dravet Syndrome Are Not Addressed by Current Therapies

    Non-Seizure Comorbidities of Dravet Syndrome Are Not Addressed by Current Therapies © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved Dravet is Not Limited to Seizures: More than 90% of patients suffer from at least one non-seizure comorbidity, including Severe intellectual disabilities

16. Slide 16: STK-001 Significantly Reduces Premature Mortality in Dravet Syndrome Mice

    STK-001 Significantly Reduces Premature Mortality in Dravet Syndrome Mice © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved Significant improvements in survival among Dravet syndrome mice after STK-001 administration (20µg) at postnatal day 2 ****p<0.0001 Source: Stoke data, presented at

17. Slide 17: STK-001 Significantly Reduces Premature Mortality in Dravet Syndrome Mice

    STK-001 Significantly Reduces Premature Mortality in Dravet Syndrome Mice © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved **p<0.005 Significant improvements in survival among Dravet syndrome mice after STK-001 administration (60µg) at postnatal day 14 Source: Stoke data, presented at A

18. Slide 18: STK-001 Significantly Reduces Spontaneous Seizures in Dravet Syndrome Mice

    Source: Stoke data, presented at AES 2019 STK-001 Significantly Reduces Spontaneous Seizures in Dravet Syndrome Mice © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved 76% of mice treated with STK-001 were seizure-free compared to 48% of placebo-treated mice 48% 76% 38% 14% 80% reduction

19. Slide 19: STK-001 Achieves Broad Distribution and Increases Nav1.1 Protein Expression in NHPs

    STK-001 Achieves Broad Distribution and Increases Nav1.1 Protein Expression in NHPs (n=3) © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved Exposure of STK-001 observed in all brain regions except pons and thalamus Nav1.1 protein levels increased up to 3-fold Source: Stoke data, presente

20. Slide 20: Preclinical Studies Show STK-001 Well-Tolerated in NHPs

    Preclinical Studies Show STK-001 Well-Tolerated at a Pharmacologically Active Dose in NHPs Key safety measures No complement activation No decrease in platelet counts No change in renal or hepatic function No clinical signs or symptoms over 28-day period after administration Normal histopathology in

21. Slide 21: STK-001 Has Potential to Address the Genetic Cause of Dravet Syndrome

    STK-001 Has Potential to Address the Genetic Cause of Dravet Syndrome © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved Preclinical data support the use of STK-001 in Dravet syndrome: Significant reduction in mortality and seizure frequency in Dravet syndrome mouse model Broad distributi

22. Slide 22: Several Factors De-Risk STK-001 Clinical Development for Dravet Syndrome

    Several Factors De-Risk STK-001 Clinical Development for Dravet Syndrome Defined patient population: Genetic testing routine in epilepsy diagnostic workups Established regulatory pathway: Existing medicines are approved for Dravet syndrome Validated chemistry and delivery to CNS: Years of experience

23. Slide 23: BUTTERFLY Observational Study Ongoing

    BUTTERFLY Observational Study Ongoing © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved Two-year observational study of children and adolescents ages 2-18 Designed to evaluate seizure frequency and non-seizure comorbidities associated with Dravet syndrome, including: Intellectual disabil

24. Slide 24: On-Track to Enroll First Patient in MONARCH Phase 1/2a Trial in 2Q/3Q 2020

    On-Track to Enroll First Patient in MONARCH Phase 1/2a Trial in 2Q/3Q 2020 Pre-IND meeting conducted and IND on track GLP single-dose toxicology studies completed Overview of study design: Analogous trial design and endpoints to recently approved antiepileptic drugs for Dravet syndrome Open label Pl

25. Slide 25: Expanding the Pipeline Using Stoke's Proprietary Bioinformatics and TANGO

    Targets Time Horizon PATHWAY UPREGULATION GENETIC EPILEPSIES HAPLOINSUFFICIENCIES DRAVET SYNDROME Expanding the Pipeline Using Stoke’s Proprietary Bioinformatics and TANGO Immediate focus Near-term focus Near-to-mid-term focus & collaborations Longer-term focus & collaborations We plan to expand the

26. Slide 26: TANGO is Applicable to a Broad Range of Targets

    TANGO is Applicable to a Broad Range of Targets © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved Genetic epilepsy – haploinsufficiency SYNGAP1 non-productive event productive mRNA protein NT ASO nM NT ASO nM NT ASO nM Pathway target – wild type NT ASO nM NT ASO nM NT ASO nM CD274 (PD-L1

27. Slide 27: Business Development Vision – Sector Expert & Collaborator of Choice

    Business Development Vision – Sector Expert & Collaborator of Choice Numerous validated targets in therapeutic areas outside of Stoke’s internal scope: metabolic, renal, immunology, cancer, hematology, neuromuscular, as well as partner-proprietary targets Explore alternative drug delivery approaches

28. Slide 28: Stoke Becomes a Clinical-Stage Company in 2020

    2020 Early 2020: File IND with FDA 2Q/3Q 2020: Enroll first patient in MONARCH Mid-2020: Nominate new candidate for preclinical development in an additional genetic disease Continuously evaluate potential collaborations to expand the pipeline Build the organization and capabilities to scale as a cli

29. Slide 29: Cash Expected to be Sufficient to Fund Operations into 2023

    Cash Expected to be Sufficient to Fund Operations into 2023 © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved Cash, Cash Equivalents and Restricted Cash as of 09/30/2019 $233.2 million Common Shares Outstanding as of 09/30/2019 32,724,153 Raised $151.9 million in net proceeds in June 201

30. Slide 30: The Commitment that Drives Stoke

    The Commitment that Drives Stoke © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved

31. Slide 31: .

    © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved © Copyright 2020 Stoke Therapeutics, Inc. All rights reserved.

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