Slide 1: MONARCH study in Dravet Syndrome Interim Analysis
MONARCH study in Dravet Syndrome Interim Analysis September 21, 2021 Exhibit 99.1
Slide 2: Agenda
Agenda Introduction Eric Rojas, Head of Investor Relations Disease Overview, Patient Need, and STK-001 Mechanism of Action Edward M. Kaye, M.D., Chief Executive Officer Phase 1/2a MONARCH Interim Analysis Barry Ticho, M.D., Ph.D., Chief Medical Officer Closing Remarks Edward M. Kaye, M.D., Chief Exe
Slide 3: Forward Looking Statements
Forward Looking Statements This presentation has been prepared by Stoke Therapeutics, Inc. (“Stoke” or “our”) 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 presen
Slide 4: Dravet Syndrome Disease Overview and STK-001 Mechanism of Action
Dravet Syndrome Disease Overview STK-001 Mechanism of Action Edward M. Kaye, M.D. Chief Executive Officer
Slide 5: Dravet Syndrome: A Severe, Progressive Genetic Epilepsy
1 Sudden Unexpected Death in Epilepsy Sources: 2018 Health Advances Report; Djémié et al., Molecular Genetics & Genomic Medicine, 2016; Lagae et al., Developmental Medicine & Child Neurology, 2017; Nabbout et al., Orphanet Journal of Rare Diseases, 2013 ~35,000 Seizures are not adequately controlled
Slide 6: 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 2021 Stoke Therapeutics No Approved Disease-Modifying Therapies for Dravet Syndrome Intellectual disability Developmental delays Movement and balance issues Language and speech disturbances Growth defects
Slide 7: Haploinsufficiency without TANGO-ASO = 50% functional protein
Haploinsufficiency without TANGO-ASO = 50% functional protein © Copyright 2021 Stoke Therapeutics
Slide 8: Haploinsufficiency with TANGO-ASO ~100% Functional protein
Haploinsufficiency with TANGO-ASO ~100% Functional protein © Copyright 2021 Stoke Therapeutics
Slide 9: Studies of STK-001 Ongoing in the U.S. and UK
Studies of STK-001 Ongoing in the U.S. and UK Open-label evaluation of single and multiple ascending doses of STK-001 in the U.S. Interim results show single doses of STK-001 up to 30mg and multiple doses of 20mg were well-tolerated with no safety concerns related to the study drug First patient dos
Slide 10: Phase 1/2a MONARCH Interim Analysis
Phase 1/2a MONARCH Interim Analysis Barry Ticho, M.D., Ph.D. Chief Medical Officer
Slide 11: MONARCH Study Design and Objectives
MONARCH Study Design and Objectives Design: Multi-center, open-label, SAD and MAD study of STK-001 in patients with Dravet syndrome conducted in U.S. SAD: 3 cohorts (10 mg, 20mg, 30mg) with study drug administration at Day 1 MAD: 2 cohorts (20mg, 30mg) with study drug administrations at Day 1, Week
Slide 12: MONARCH SAD and MAD Study Assessments
MONARCH SAD Study Assessments = Study Drug Administration Baseline Seizure Diary Seizure Diary Seizure Diary D-28 D-1 D2 D4 D8 D29 D57 D85 D113 D141 D169 D1 AE monitoring, Physical Examination, Clinical laboratories, Plasma PK CSF collection CSF collection CSF collection MONARCH MAD Study Assessment
Slide 13: MONARCH Interim Analysis Included Patients with Severe Disease Despite Anti-Seizure Medications
MONARCH Study Interim Analysis Included 21 Patients, All of Whom Had Severe Disease Despite Use of Anti-Seizure Medications Analysis conducted 3-months after the last patient was treated with 30mg (SAD) Age at Screening, years Median (min, max) 13.0 (2, 18) Age of onset of first seizure type (months
Slide 14: Single Doses up to 30mg and Multiple Doses of 20mg Were Well-Tolerated
Single Doses of STK-001 up to 30mg and Multiple Doses of 20mg Were Well-Tolerated and No Safety Concerns Related to STK-001 3 of 21 (14.3%) patients experienced a TEAE related to study drug None observed in 30mg SAD or 20mg MAD cohorts 4 of 21 (19.0%) patients had a treatment-emergent SAE None relat
Slide 15: Increases in Plasma Exposure and Mean CSF Concentration Observed
Increases in Plasma Exposure and Mean CSF Concentration Observed in Patients Who Received Doses From 10mg to 30mg A dose-proportional increase in study drug exposure was observed in plasma PK Dose (mg) Plasma PK parameters Dose N AUClast (h*ng/mL) (Mean ± SD) 10 4 2450 ± 1690 20 4 6460 ± 2820 30 5 1
Slide 16: Observed Plasma and CSF Levels Correlated Well with Model Predictions
Observed Plasma and CSF Levels in Patients Correlated Well with Model Predictions Comparison of PK Model Predictions With Mean Observed Plasma Data Comparison of PK Model Predictions With Mean Observed CSF Data CSF was drawn on Days 85 and 169 post single dose for STK-001 analyses Solid lines repres
Slide 17: Steady State Plasma and CSF Levels Predict Brain Levels
Steady State Plasma and CSF STK-001 Levels are Good Predictors of STK-001 Brain Levels in Patients Projected plasma, CSF, and brain levels were strongly correlated across time and dose groups following single IT STK-001 doses Therefore, CSF and/or plasma levels in MONARCH can be used to estimate STK
Slide 18: Monthly 30mg Doses Achieve Projected Active Brain Levels in 95% of Patients
3 Monthly Doses of STK-001 (30mg) Achieve Projected Pharmacologically Active Brain Levels in 95% of Patients ~50% of patients anticipated to remain at active levels approximately 3 months after their last dose Pharmacologic effect likely lasts beyond timepoint when STK-001 brain concentration falls
Slide 19: Secondary Endpoint: Trend Toward Seizure Reduction Observed
Secondary Endpoint: Trend Toward Seizure Reduction Observed 8/11 patients experienced a reduction in convulsive seizure frequency Trend more evident in patients 2 to 12 years old Patients in the study were taking multiple anti-seizure medicines: 85% on >3 and 67% >4 Data being prepared for presentat
Slide 20: Dravet Syndrome Program Continues to Progress
Dravet Syndrome Program Continues to Progress All patients who have completed dosing in the SAD portion of MONARCH have continued treatment in SWALLOWTAIL First patient dosed in MONARCH MAD at 30mg FDA will allow the evaluation of STK-001 up to 45mg in MONARCH First patient dosed at 30mg in ADMIRAL
Slide 21: Acknowledgements
Acknowledgements STOKE
Slide 22: Closing Remarks
Closing Remarks Edward M. Kaye, M.D. Chief Executive Officer
Slide 23: Overall Summary of MONARCH Interim Analysis Results
Overall Summary of MONARCH Interim Analysis Results Single doses of STK-001 up to 30mg and multiple doses of 20mg were well-tolerated and no safety concerns related to the study drug Interim analysis confirms our pre-clinical work and gives us greater understanding of dose levels that are likely to
Slide 24: 2021 Milestones as of September 2021
2021 Milestones as of September 2021 1H2021 Initiate Swallowtail Open Label Extension (OLE) study of STK-001 2H2021 Initiate MAD study of STK-001 (MONARCH) – COMPLETED IN 1H2021 3Q2021 Preliminary safety, PK, CSF, and modeling data from SAD portion of MONARCH 2H2021 Initiate MAD study of STK-001 in
Slide 25: Q&A
Q&A ‘opyright 2021 Stoke Therapeutics | 25.