Stoke Therapeutics, Inc. · NASDAQ:STOK
Stoke Therapeutics — 40th Annual J.P. Morgan Healthcare Conference (January 2022)
29 slides from Stoke Therapeutics's conference presentation, Jan 10, 2022
Slide 1: Stoke Therapeutics at 40th Annual J.P. Morgan Healthcare Conference
Exhibit 99.1 Stoke Therapeutics NASDAQ: STOK Edward M. Kaye, M.D. Chief Executive Officer th 40 Annual J.P. Morgan Healthcare Conference January 10, 2022 © Copyr © igh Cot p2022 yrigh t S2022 toke T Sh to er ke ap T eh ue tic ras peutics 1
Slide 2: Disclaimer
Disclaimer 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 presenter or Stoke or
Slide 3: Boldly Restoring Genetic Health
Addressing the underlying cause of severe diseases by upregulating protein expression with RNA-based medicines Execute in the clinic with STK-001, the first potential disease-modifying approach for the treatment of Dravet syndrome Boldly Restoring Advance to the clinic with STK-002, the first potent
Slide 4: A Differentiated Platform for Discovery and Development of Novel RNA-Based Medicines
A Differentiated Platform for the Discovery and Development of Novel RNA-Based Medicines Proprietary RNA therapeutics platform Disease-modifying approach (TANGO) We aim to address the underlying Targets pre-mRNA splicing to restore cause of severe diseases target protein to near-normal levels Clinic
Slide 5: Targeted Augmentation of Nuclear Gene Output
Our compounds aim to restore protein Targeted levels by increasing protein production from the functional copy of a gene and: Augmentation of Selectively boost expression only in tissues Nuclear where the protein is normally expressed Offer one drug for diseases caused by many Gene different loss-of
Slide 6: Haploinsufficiency
Haploinsufficiency Haploinsufficiency without TANGO-ASO with TANGO-ASO = 50% increased functional functional protein expression protein 6
Slide 7: 2021 Execution
2021 Execution Initiated Swallowtail Open Label Extension (OLE) study of STK-001 1H2021 ✓ 2H2021 Initiated multiple ascending dose (MAD) study of STK-001 (MONARCH) ✓ 3Q2021 Reported preliminary safety, PK, and CSF data (SAD portion of MONARCH) ✓ 2H2021 Initiated (MAD) study of STK-001 in the U.K. (A
Slide 8: Dravet Syndrome: A Severe, Progressive Genetic Epilepsy
Dravet Syndrome: A Severe, Progressive Genetic Epilepsy 1 out of 16,000 ~35,000 85% babies are born with Dravet syndrome of cases caused by a people affected in the U.S., Canada, HAPLOINSUFFICIENCY Japan, Germany, France and the UK of the SCN1A gene of children and adolescents with Dravet Up to synd
Slide 9: No Approved Disease-Modifying Therapies for Dravet Syndrome
No Approved Disease-Modifying Therapies for Dravet Syndrome Non-Seizure Comorbidities of Dravet Syndrome Are Not Addressed by Current Therapies • Intellectual disability • Developmental delays • Movement and balance issues • Language and speech disturbances • Growth defects • Sleep abnormalities • D
Slide 10: Non-Seizure Comorbidities of DS are Progressive and Measurable
Non-Seizure Comorbidities of DS are Progressive and Measurable Gap in overall intellectual development and adaptive function between patients and neurotypical children appears to widen with age Results from the VABS Assessment Adaptive Behavior Composite (ABC)* 100 80 60 Initial findings showed: • V
Slide 11: STK-001 Significantly Reduces Premature Mortality in DS Mice After a Single Dose
STK-001 Significantly Reduces Premature Mortality in DS Mice After a Single Dose Significant improvements in survival after STK-001 administration at postnatal day 2 p<0.0001 PBS wild-type (n=46) STK-001 wild-type (n=27) +/- STK-001 SCN1a (n=34) +/- PBS SCN1a (n=62) Postnatal days Sources: Z. Han, C
Slide 12: Preclinical Findings Support Clinical Development of STK-001
Single dose restores Na 1.1 to near- V ✓ normal levels for >3 months in DS mice Significantly reduces mortality and ✓ seizure frequency in DS mice Preclinical Findings Support Clinical Development Achieves broad distribution and increases ✓ Na 1.1 protein expression in NHPs V of STK-001 Well-tolerat
Slide 13: Phase 1/2a Trials of STK-001 for Dravet Syndrome are Ongoing
Phase 1/2a Trials of STK-001 for Dravet Syndrome are Ongoing Parallel studies in the US & UK evaluating children and adolescents ages 2 to 18 years old Design Evaluation of STK-001 (up to 45mg*) Evaluation of STK-001 (up to 70mg) • SAD: Enrollment ongoing @45mg Status • MAD: Enrollment and dosing on
Slide 14: Patients Treated with STK-001 Experienced Reductions in Convulsive Seizure Frequency
Patients Treated with STK-001 Experienced Reductions in Convulsive Seizure Frequency 70.6% (12/17) of patients including all patients ages 2-12 (n=7) experienced a reduction from baseline in convulsive seizure frequency measured from Day 29 to Day 84 Reductions in seizure frequency were also observe
Slide 15: Median % Change from Baseline in Seizure Frequency More Evident >4 Weeks After Dosing
Median % Change from Baseline in Seizure Frequency More Evident >4 Weeks After Dosing Patients (All Ages) Combined by Cohort: Patients (All Ages) Combined by Cohort: Day 29-84 Day 1-84 0 0 -17% -25 -25 -37% -50 -50 Day 29-84 Day 1-84 © Copyright 2022 Stoke Therapeutics 15 Source: Interim Safety, PK,
Slide 16: Monthly 30mg Doses Projected to Achieve Pharmacologically Active Brain Levels
3 Monthly 30mg Doses of STK-001 Projected to Achieve Pharmacologically Active Brain Levels in >95% of Patients Plasma and CSF exposure data from MONARCH can be used to predict STK-001 brain levels in patients Pharmacologically active range Pharmacologic effect likely lasts beyond timepoint when STK-
Slide 17: Summary of Ph1/2a MONARCH Interim Data
Summary of Ph1/2a MONARCH Interim Data Single doses up to 30mg and three 20mg doses were well tolerated with no safety concerns ✓ related to study drug STK-001 Has Potential to Plasma and CSF data from MONARCH correlated well with model and likely predict STK-001 brain ✓ Address the Genetic Cause le
Slide 18: Autosomal Dominant Optic Atrophy (ADOA): A Severe, Progressive Optic Nerve Disorder
Autosomal Dominant Optic Atrophy (ADOA): A Severe, Progressive Optic Nerve Disorder 65-90% 1 out of 30,000 ~18,000 of cases caused by mutations in one allele Up to people affected in the U.S., Canada, people are affected globally with a of the OPA1 gene, most Japan, Germany, France and the UK higher
Slide 19: No Approved Disease-Modifying Therapies for ADOA
No Approved Disease-Modifying Therapies for ADOA Simulation of Optic Neuropathy Healthy Vision • Most common inherited optic nerve disorder • Leads to central field defects and reduced color vision in both eyes • Severity can vary; rate of vision loss difficult to predict • Supportive services and l
Slide 20: OPA1 is Critical for Normal Mitochondrial Function and Cellular Metabolism
OPA1 is Critical for Normal Mitochondrial Function and Cellular Metabolism Healthy ADOA • Retinal ganglion cells have very high energy (ATP) requirements • Impaired mitochondrial function leads to cell death OPA1 +/+ OPA1 +/- • OPA1 is critical for Mitochondrial Bioenergetics Functional Mitochondria
Slide 21: TANGO ASO Increases OPA1 Protein and ATP Linked Mitochondrial Respiration
TANGO ASO Increases OPA1 Protein and ATP Linked Mitochondrial Respiration in ADOA Patient Cells ASO treatment increased OPA1 protein levels in ASO treatment increased ATP linked respiration OPA1 deficient ADOA patient cells in OPA1 deficient ADOA patient cells 200 ** **** **** 140 150 120 100 * heal
Slide 22: Summary of Key Preclinical Data
Summary of Key Preclinical Data Increase OPA1 protein and ATP linked ✓ respiration in ADOA patient cells Result in dose-dependent increases in ✓ TANGO ASOs Have the OPA1 protein expression in rabbit retina Potential to Address the Were well tolerated for up to 29 days ✓ Genetic Cause of ADOA after i
Slide 23: Collaboration with Acadia Pharmaceuticals
Collaboration with Acadia Pharmaceuticals to Pursue RNA-Based Treatments for Severe & Rare Genetic Neurodevelopmental Diseases Collaboration leverages Stoke’s proprietary TANGO research platform and Acadia’s expertise in neurology drug development and commercialization 3 targets focused on severe an
Slide 24: Rett Syndrome: A Severe, Debilitating Neurological Disorder
Rett Syndrome: A Severe, Debilitating Neurological Disorder females are born with Rett 2 1 out of 10,000 to15,000 syndrome ~33% of cases caused by hypomorphic 3 Symptoms include : mutations of the MECP2 1 • Loss of purposeful hand use gene Period of rapid • Involuntary hand movements such as handwri
Slide 25: SYNGAP1 Syndrome: A Severe ID/DEE
SYNGAP1 Syndrome: A Severe Intellectual Disability / Developmental and Epileptic Encephalopathy (ID/DEE) >80% ~1-2 out of 100,000 children are born with SYNGAP1-ID/DEE of cases caused by a HAPLOINSUFFICIENCY 1 of the SYNGAP1 gene 100% 1-2% of patients have developmental delay of all intellectual dis
Slide 26: Investing In Our Pipeline
Investing In Our Pipeline PROGRAM TARGET DISCOVERY & PRECLINICAL PHASE 1/2 PHASE 3 PARTNER Central Nervous System 100% Stoke Dravet Syndrome SCN1A STK-001 Global Stoke: Acadia SYNGAP1 SYNGAP1 Syndrome 50:50 Acadia Rett Syndrome MECP2 Worldwide License Acadia Undisclosed Undisclosed Worldwide License
Slide 27: Our Strategy For 2022
Our Strategy For 2022 Advance our wholly owned CNS and eye programs and expand the scope of our drug discovery efforts Develop & Expand Advance STK-001 for Advance STK-002 for Pipeline Dravet Syndrome ADOA • Additional clinical data on STK-001 • Conduct preclinical toxicology studies • Continue disc
Slide 28: Current Liquidity Anticipated to Fund Operations into Second Half of 2024
Current Liquidity Including Upfront from Acadia Anticipated to Fund Operations into the Second Half of 2024 $220.4M* 36.9M Cash, Cash Equivalents, Common Shares Outstanding Marketable Securities, and Restricted Cash (unaudited) as of 12/31/2021 (unaudited) as of 12/31/2021 © © C Co op pyr yrigh ight
Slide 29: Q&A
Q&A © Copyright 2022 Stoke Therapeutics 29
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