Slide 1: Analysis of STK-001 for the Treatment of Dravet Syndrome
Analysis of STK-001 for the Treatment of Dravet Syndrome Stoke Therapeutics July 25, 2023 Exhibit 99.2
Slide 2: Agenda
Agenda Introduction Eric Rojas, Head of Investor Relations Introductory Remarks Edward M. Kaye, M.D., Chief Executive Officer Phase 1/2a Interim Analysis Barry Ticho, M.D., Ph.D., Chief Medical Officer Kimberly Parkerson, M.D., Ph.D., Head of Neurology Clinical Development Closing Remarks Edward M.
Slide 3: Forward Looking Statements
Forward Looking Statements This presentation has been prepared by Stoke Therapeutics, Inc. (“Stoke” or “we”) for information purposes only and for no other purpose. Nothing contain in this presentation is, or should be construed as, a recommendation, promise or representation by the presenter or Sto
Slide 4: Introductory Remarks
Introductory Remarks Edward M. Kaye, M.D. Chief Executive Officer
Slide 5: STK-001: First Potential Medicine to Treat the Underlying Cause of Dravet Syndrome
STK-001: First Potential Medicine to Treat the Underlying Cause of Dravet Syndrome Patients treated with 2 or 3 initial doses of STK-001 (70mg) experienced substantial and sustained reductions in convulsive seizure frequency, outperforming all prior dose groups Sustained reductions in convulsive sei
Slide 6: Seizures are not adequately controlled in 90% of people with Dravet syndrome
~35,000 Seizures are not adequately controlled in 90% of people with Dravet syndrome 85% of cases caused by a HAPLOINSUFFICIENCY of the SCN1A gene people affected in the U.S., Canada, Japan, Germany, France and the UK of children and adolescents with Dravet syndrome die before adulthood, due to SUDE
Slide 7: Our Goal: Syndrome Management, Not Just Seizures
Our Goal: Syndrome Management, Not Just Seizures No medicines available for Syndrome management STK-001 The only potential disease-modifying approach currently in the clinic for Dravet syndrome Available medicines used to control seizures: Acetazolamide Benzodiazepines Brivaracetam Cannabidiol Carba
Slide 8: TANGO-ASO mechanism: increased functional protein expression
Nonsense mediated decay (NMD) exon without TANGO-ASO Increased functional protein expression Nonsense mediated decay (NMD) exon with TANGO-ASO = 50% functional protein NMD: nonsense-mediated decay
Slide 9: Analysis of Phase 1/2a MONARCH and ADMIRAL Studies of STK-001
Analysis of Phase 1/2a MONARCH and ADMIRAL Studies of STK-001 Barry Ticho, M.D., Ph.D. Chief Medical Officer
Slide 10: Phase 1/2a Study Designs: MONARCH (US) and ADMIRAL (UK)
Phase 1/2a Study Designs: MONARCH (US) and ADMIRAL (UK) *Study protocol for ADMIRAL was amended to allow investigators to decide whether to administer two or three doses of STK-001 (70mg) in the ADMIRAL study before patients would be eligible to enroll in the LONGWING OLE. * SAD MAD MAD
Slide 11: Demographics for Patients Treated With ≥1 Dose of STK-001
Demographics for 74 Patients Treated With ≥1 Dose of STK-001 Enrolled Patients Have Severe Disease and are Refractory to Standard Treatments Data cutoff dates: MONARCH 13APR2023; ADMIRAL 12APR2023 and 21JUN2023 Total, n (%) N 74 Age at Screening, y Mean (SD) 10.2 years (5.05) Median (min, max
Slide 12: Observed Effect of STK-001 on Convulsive Seizure Frequency
Observed Effect of STK-001 on Convulsive Seizure Frequency: Available Data from 30mg, 45mg and 70mg Multiple Dose Cohorts *Dosing in Monarch at D1, D29, and D57; Dosing in Admiral at D1, D57, and D85; 70 mg patients received 2 or 3 doses; Monarch Study Ends at D224 and Admiral Study Ends at D252 n=n
Slide 13: Differentiated Pattern of Response With 2 or 3 Doses of 70mg
Differentiated Pattern of Response With 2 or 3 Doses of 70mg Dosing in Monarch at D1, D29, and D57; Dosing in Admiral at D1, D57, and D85; 70 mg patients received 2 or 3 doses; Monarch Study Ends at D224 and Admiral Study Ends at D252
Slide 14: Available Data For All Patients Treated With 2 or 3 Doses of 70mg
Available Data For All Patients Treated With 2 or 3 Doses of 70mg *Dosing in Admiral at D1, D57, and D85; 70 mg patients received 2 or 3 doses; Admiral Study Ends at D252 **D1-D28: +825%, D29-D56: +626%, D57-D84: +1125%, D85-D112: +717%
Slide 15: Median percent change from baseline in convulsive seizure frequency
Median percent change from baseline in convulsive seizure frequency *Dosing in MONARCH at D1, D29, and D57; Dosing in ADMIRAL at D1, D57, and D85; 70 mg patients received 2 or 3 doses; 1 patient in 70 mg cohort received Dose 3 late; therefore, interval does not fully extend to 3 Months After Last Do
Slide 16: Substantial & Sustained Effects at 3 and 6 Months After Last Dose
Analysis of Data Captured at 3 and at 6 Months After Last Dose Showed Substantial & Sustained Effects With 2 or 3 Doses of 70mg Median reductions of 80% at 3 months (n=6), 89% at 6 months (n=3) *28-day interval prior to 3 months and 6 months After Last Dose for all patients. 1 patient in 70 mg cohor
Slide 17: Median Reductions in Convulsive Seizure Frequency by Age Group
*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. 70mg MAD Ages 2 to 12 Years Ages 13 to 18 Years Ages 2 to 12 Years Ages 13 to
Slide 18: Analyses of SWALLOWTAIL OLE
Analyses of SWALLOWTAIL OLE Kimberly Parkerson, M.D., Ph.D. Head of Neurology Clinical Development
Slide 19: SWALLOWTAIL open-label extension study design
An open-label extension study designed to evaluate the long-term safety and tolerability of repeat doses of STK-001
Slide 20: OLE Data: Sustained Reductions in Convulsive Seizure Frequency
Effects observed with STK-001 doses of 30mg or 45mg every four months *No exclusion for AED modification in MONARCH or SWALLOWTAIL Data cutoff dates: MONARCH 13APR2023; SWALLOWTAIL 24MAR2023 Weeks 1-4 Weeks 5-8 Weeks 9-12 Weeks 13-16 Weeks 17-20 Weeks 21-24 Weeks 25-28 Weeks 29-32 Weeks 33-36 Weeks
Slide 21: Dravet Syndrome is More Than "Just Seizures"
Dravet Syndrome is More Than “Just Seizures” Source: Voice of the Patient Report Published by the Dravet Syndrome Foundation, May 2022 Intellectual Disability & Developmental Delays “Over time, we have seen slow, steady decline in all areas, from speech, to mobility, endurance, loss of energy, toler
Slide 22: Vineland Adaptive Behavior Scale (VABS-III)
Vineland Adaptive Behavior Scale (VABS-III) An all-around measure of how a person performs in daily situations I would love to see him regain some speech so he can communicate and be less frustrated. Communication Daily living skills Socialization Motor skills – Barbara S., Mom of son with Dravet sy
Slide 23: SWALLOWTAIL OLE: Improvements in Receptive & Expressive Communication
-2.95 -2.09 4.50 5.63 7.32 -1.00 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 samp
Slide 24: SWALLOWTAIL OLE: Substantial Improvements in Gross Motor Skills
SWALLOWTAIL OLE: Substantial Improvements in Gross Motor Skills *Mixed model repeated measures with AR(1) covariance structure. Baseline covariates in BUTTERFLY matched to SWALLOWTAIL. Analysis includes all patients who received 30 mg or 45 mg for all doses in SWALLOWTAIL; for gross motor, BUTTERFLY
Slide 25: SWALLOWTAIL OLE: Substantial Improvements in Executive Function
SWALLOWTAIL OLE: Substantial Improvements in Executive Function 0.95 -3.99 -5.01 5.29 2.83 -6.54 Worsening Improving BUTTERFLY (Natural History) SWALLOWTAIL (STK-001) BRIEF-P measures executive function in children, such as the ability to organize thoughts and have working memory. *Mixed model repea
Slide 26: SWALLOWTAIL OLE: Substantial Improvements in Overall Condition
No change Very much worse Very much improved BUTTERFLY (Natural History) SWALLOWTAIL (STK-001) SWALLOWTAIL OLE: Substantial Improvements in Overall Condition Clinician and Caregiver Global Impression of Change scales measure a patient’s overall condition *Mixed model repeated measures with AR(1) cov
Slide 27: Single & Multiple Doses up to 70mg Were Generally Well Tolerated
Single & Multiple Doses up to 70mg Were Generally Well Tolerated MONARCH and ADMIRAL (n=74) 32% (24/74) of patients experienced a treatment-emergent adverse event (TEAE) related to study drug Most common TEAEs related to study drug were CSF protein elevations, vomiting, and irritability 20% (15/74)
Slide 28: Key Takeaways
Key Takeaways Data to date support STK-001 as the first potential disease-modifying therapy for Dravet syndrome Efficacy Reductions in seizures and improvements in assessments of cognition and behavior suggest clinical benefit for patients ages 2 to 18 years old Median reductions of 80% at 3 months
Slide 29: Closing Remarks
Closing Remarks Edward M. Kaye, M.D. Chief Executive Officer
Slide 30: Next Steps and Path to Phase 3
Next Steps and Path to Phase 3 Dosing complete in 70mg SAD in the US and 70mg MAD in the UK Additional data in Q1 2024 : End of study data from ADMIRAL and MONARCH More OLE data from SWALLOWTAIL (30mg, 45mg) and LONGWING (45mg) Engage with regulatory agencies to agree on Phase 3 design, including do
Slide 31: Therapeutics
THERAPEUTICS
Slide 32: Stoke
STOKE THE RAG EU Tilve Ss Copyright Stoke Therapeutics, Inc. Not for publication or distribution