Slide 1: Zorevunersen Regulatory Alignment & Phase 3 Plans
Zorevunersen Regulatory Alignment & Phase 3 Plans Virtual Event for Investors & Analysts January 7, 2025 Exhibit 99.2
Slide 2: Agenda
The Potential for Disease Modification in the Treatment of Dravet Syndrome: Clinical Data and Phase 3 Plan Barry Ticho, M.D., Ph.D., FACC, Chief Medical Officer Kimberly Parkerson, M.D., Ph.D., SVP, Head of Neurology Clinical Development Zorevunersen Commercial Opportunity Jason Hoitt, Chief Commerc
Slide 3: Forward-Looking Statements and Other Legal Notices
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 repre
Slide 4: Opening Remarks
Opening Remarks Edward M. Kaye, M.D. Chief Executive Officer
Slide 5: Our Goal: Restore protein expression with RNA medicine
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 zorevunersen for Dravet syndrome STK-002 for Autosomal Dominant Optic Atrophy (ADOA)
Slide 6: Key Takeaways
Clinical Data Substantial and durable reductions in seizure frequency and continuing improvements across multiple measures of cognition and behavior are evidence of disease modification Breakthrough Therapy Designation Indicates that zorevunersen may demonstrate substantial improvement over availabl
Slide 7: Breakthrough Therapy Designation (BTD)
Breakthrough Therapy Designation (BTD) Qualifying Criteria A drug that is intended to treat a serious condition AND preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinically significant endpoint(s) over available therapies Status Granted December 2
Slide 8: Zorevunersen Clinical Data
Zorevunersen Clinical Data Barry Ticho, M.D., Ph.D. Chief Medical Officer
Slide 9: Current Treatments For Dravet Aim to Reduce Seizures
Current Treatments For Dravet Aim to Reduce Seizures Leaving a Significant Gap in Treatment of the Syndrome ASM, antiseizure medication; DS, Dravet syndrome; SOC, standard of care. 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;
Slide 10: Initial 70mg Doses Demonstrated Substantial and Sustained Seizure Reductions
ZZ Initial 70mg Doses of Zorevunersen Demonstrated Substantial and Sustained Reductions in Convulsive Seizure Frequency Laux, L et al. Zorevunersen (STK-001) demonstrates potential for disease modification including reductions in seizures and improvements in cognition and behavior in children and ad
Slide 11: Ongoing Treatment Demonstrated Durable Reductions in Convulsive Seizure Frequency
ZZ Ongoing Treatment Demonstrated Substantial and Durable Reductions in Convulsive Seizure Frequency *Patients from the single dose 70mg cohort received 30mg doses at M1 and M5. Sullivan, J et al. Patients with Dravet syndrome in open-label extension studies of zorevunersen (STK-001) have durable re
Slide 12: Durable Seizure Reductions Through Two Years of Treatment
ZZ Durable, Substantial Reductions in Seizures On Top of SOC Observed Through Two Years of Treatment with Zorevunersen 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 S
Slide 13: Zorevunersen Generally Well-Tolerated Across Studies
Zorevunersen Generally Well-Tolerated Across Studies 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, cereb
Slide 14: Potential for Disease Modification
Potential for Disease Modification Kimberly Parkerson, M.D., Ph.D. Head of Neurology Clinical Development
Slide 15: Vineland-3 Used to Assess Cognitive & Developmental Outcomes
Vineland-3 is Commonly Used to Assess Cognitive & Developmental Outcomes Receptive — Responds upon hearing name called Expressive — Says “Dada”, “Mama”, or caregiver name Written — Writes alphabet letters using correct orientation Communication Interpersonal Relationships — Tries to interact with ot
Slide 16: Improvements in Cognition and Behavior Within Months
Improvements in Cognition and Behavior Within 9 Months Continuing Improvements Throughout the OLEs 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) 2 Mixed-effects model for repeated measures c
Slide 17: Handwriting Before and After Treatment with Zorevunersen
Handwriting from a 12 year-old before and after treatment with zorevunersen* AFTER 9mo of Treatment November 2023 BEFORE Treatment November 2022 Images captured during the Phase 1/2a ADMIRAL study independently by the investigator. Brunklaus A, et al, British Paediatric Neurology Association Confere
Slide 18: Strong Regulatory Alignment
Strong Regulatory Alignment Regulatory discussions ongoing Global Alignment FOR EMPEROR Phase 3 Protocol PMDA EMA FDA
Slide 19: Emperor Clinical Study Design
Emperor Clinical Study Design First Phase 3 study of a potential disease-modifying medicine for Dravet syndrome 1:1 randomization 52-WEEK TREATMENT PERIOD LOADING DOSES (sham or 70mg zorevunersen) MAINTENANCE DOSES (sham or 45mg zorevunersen) 8-week baseline period TOTAL STUDY DURATION: 60 WEEKS Dos
Slide 20: EMPEROR Phase 3 Study Overview
Primary endpoint Seizures Percent change from baseline in major motor seizure frequency in patients receiving zorevunersen as compared to sham Key secondaries Durability of effect on major motor seizure frequency Improvements in behavior & cognition measured by Vineland-3 subdomains Other Endpoints
Slide 21: Operational Optimization Strategies for Emperor Start-Up
Rapid-start sites identified Returning Ph1/2a sites Streamlined document submissions to sites Pre-screening process to expedite enrollment Site visits to ensure quality and compliance Pursue as many centralized IRB sites as possible Electronic informed consent Clinical Trial Educators Travel concier
Slide 22: Commercial Opportunity
Commercial Opportunity Jason Hoitt Chief Commercial Officer
Slide 23: Zorevunersen Positioned to Change Treatment of Dravet Syndrome
Zorevunersen is Positioned to Change the Treatment of Dravet Syndrome, Representing Blockbuster Potential SIGNIFICANT NEED Current treatments focus on reducing seizure frequency. There is nothing available to treat the entire syndrome. CLINICAL DATA Substantial and durable reductions in seizures and
Slide 24: No disease modifying medicines are currently available
No disease modifying medicines are currently available Seizures are inadequately controlled in 90% of patients Mean 14.3 seizures per 28 days while receiving an average of 3.5 ASMs at baseline Developmental delays and cognitive impairment are persistent and cannot be treated today Patients with Drav
Slide 25: Current Treatment Paradigm is Burdensome and Ineffective
Once Diagnosed, the Current Treatment Paradigm is Burdensome and Ineffective Most patients are on 3 anti-seizure medicines Adapted from Wirrell et al. International consensus on diagnosis and management of Dravet syndrome. May 2022. Comments extracted from company sponsored interviews using a Produc
Slide 26: Approximately 90% of HCPs See a Significant Unmet Need
Approximately 90% of HCPs See a Significant Unmet Need for Patients with Dravet Syndrome *Based on Stoke quantitative market research with 135 HCP participants who treat Dravet syndrome in the US and EU in 2024. Most pressing unmet needs identified by HCPs* Percent of respondents
Slide 27: Support for a Disease Modifying Therapy for Dravet Syndrome
Support for a Disease Modifying Therapy for Dravet Syndrome Based on Company sponsored interviews using a Product X profile based on MONARCH and ADMIRAL study results. Zorevunersen is an investigational drug candidate and is not approved for marketing by the FDA or any other regulatory agency. Careg
Slide 28: Closing Remarks
Closing Remarks Edward M. Kaye, M.D. Chief Executive Officer
Slide 29: Stoke Therapeutics
* STOKE ‘ THERAPEUTICS