Stoke Therapeutics, Inc. · NASDAQ:STOK
Stoke Therapeutics — Investor Presentation (January 2021)
29 slides from Stoke Therapeutics's investor presentation, Jan 11, 2021
Slide 1: Stoke Therapeutics January 2021
Stoke Therapeutics NASDAQ: STOK January 2021 © Copyright 2021 Stoke Therapeutics Exhibit 99.1
Slide 2: Disclaimer
Disclaimer © Copyright 2021 Stoke Therapeutics 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 represen
Slide 3: Boldly Restoring Genetic Health
© Copyright 2021 Stoke Therapeutics STOKE THERAPEUTICS Boldly Restoring Genetic Health Addressing the underlying cause of severe diseases by up-regulating protein expression with RNA-based medicines.
Slide 4: Stoke Therapeutics Highlights
© Copyright 2021 Stoke Therapeutics A Differentiated Platform for the Discovery and Development of Novel RNA-based Medicines Proprietary RNA therapeutics platform Targets pre-mRNA splicing to restore target protein to near normal levels Disease-modifying approach Our compounds address the underlying
Slide 5: Targeted Augmentation of Nuclear Gene Output
© Copyright 2021 Stoke Therapeutics Targeted Augmentation of Nuclear Gene Output Our compounds aim to restore protein levels by increasing protein production from the functional copy of a gene and: Selectively boost expression only in tissues where the protein is normally expressed Offer one drug fo
Slide 6: TANGO ASOs Demonstrate Dose-Dependent Increases in Protein Expression
Genetic epilepsy – haploinsufficiency NT ASO nM NT ASO nM NT ASO nM Pathway target – wild-type NT ASO nM NT ASO nM NT ASO nM SCN1A SYNGAP1 CD274 PCCA Lim et al., Nat Comm, 2020 Correlation between event abundance (+CHX) & upregulation SYNGAP1 non-productive event productive mRNA protein Liver target
Slide 7: 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 8: 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 9: Haploinsufficiency without TANGO-ASO = 50% functional protein
Haploinsufficiency without TANGO-ASO = 50% functional protein
Slide 10: Haploinsufficiency with TANGO-ASO ~100% functional protein
Haploinsufficiency with TANGO-ASO ~100% Functional protein
Slide 11: STK-001 Restores NaV1.1 to Near Normal Levels for >3 Months in DS Mice
Percentage of Nav1.1 protein in wild-type brain 150 100 50 0 Placebo 7 WEEKS STK-001 Placebo STK-001 14 WEEKS © Copyright 2021 Stoke Therapeutics STK-001 Restores NaV1.1 to Near Normal Levels for >3 Months in Dravet Syndrome (DS) Mice after a Single Dose Sources: Han et al., Science Trans Med, 2020
Slide 12: STK-001 Significantly Reduces Premature Mortality in DS Mice
© Copyright 2021 Stoke Therapeutics Significant improvements in survival after STK-001 administration at postnatal day 2 © Copyright 2021 Stoke Therapeutics STK-001 Significantly Reduces Premature Mortality in DS Mice After a Single Dose Postnatal days Survival (%) PBS STK-001 STK-001 PBS wild-type
Slide 13: STK-001 Administration Reduces Seizure Frequency in DS Mice
Wild Type DS Seizure frequency per day 1.0 0.8 0.6 0.4 0.2 0.0 -0.2 STK-001 Administration Reduces Seizure Frequency in DS Mice Source: Targeted Augmentation of Nuclear Gene Output (TANGO) of SCN1A reduces seizures and rescues parvalbumin positive interneuron firing frequency in a mouse model of Dra
Slide 14: STK-001 Achieves Broad Distribution and Increases Nav1.1 in NHPs
© Copyright 2021 Stoke Therapeutics Study 1: Exposure of STK-001 observed in all brain regions Study 2: Nav1.1 protein levels increased up to 3-fold NHP = Non-human primate Source (left graph): Stoke data Source (right graph) TANGO oligonucleotides for the treatment of Dravet Syndrome: Safety, biodi
Slide 15: Toxicology Studies in NHPs Showed STK-001 Well-Tolerated
Source: Stoke data Single and Multiple-Dose Toxicology Studies in NHPs Showed STK-001 Well-Tolerated © Copyright 2021 Stoke Therapeutics ü ü ü Key safety findings from GLP studies* No observed adverse events at highest dose tested No change in platelet counts or renal/hepatic function No adverse his
Slide 16: STK-001 Has Potential to Address the Genetic Cause of Dravet Syndrome
© Copyright 2021 Stoke Therapeutics STK-001 Has Potential to Address the Genetic Cause of Dravet Syndrome (DS) ü ü ü Single dose restores NaV1.1 to near normal levels for >3 months in DS mice Significantly reduces mortality and seizure frequency in DS mice Achieves broad distribution and increases N
Slide 17: Non-Seizure Comorbidities of DS are Progressive and Measurable
© Copyright 2021 Stoke Therapeutics Non-Seizure Comorbidities of DS are Progressive and Measurable * VABS = Vineland Adaptive Behavior Scales * ABC score based on Communication, Daily Living, and Socialization domains and expressed relative to normative mean of 100 Source: Observational Study to Inv
Slide 18: Enrollment and Dosing in MONARCH Phase 1/2a Trial is Ongoing
Open-label evaluation of single and multiple ascending doses of STK-001 (up to 30mg) SAD: Currently enrolling MAD: Planned initiation 2H 2021 Doses >30mg remain on FDA partial clinical hold ~48 children and adolescents ages 2-18 years old with Dravet syndrome and confirmed SCN1a variant Safety and t
Slide 19: Autosomal Dominant Optic Atrophy (ADOA): A Severe, Progressive Optic Nerve Disorder
people are affected globally with a higher incidence of ~1 out of 10,000 in Denmark due to a founder effect Sources: Yu-Wai-Man P et al. Ophthalmology, 2010; Yu-Wai-Man P, Chinnery PF. Ophthalmology, 2013; P. Amati-Bonneau P et al. The International Journal of Biochemistry & Cell Biology, 2009; Lena
Slide 20: No Approved Disease-Modifying Therapies for ADOA
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 low-vision aids are offered for patients Healthy ADOA patient © Copyright 2021 Stoke Therapeutics No App
Slide 21: OPA1 is Critical for Normal Mitochondrial Function and Cellular Metabolism
ADOA OPA1 +/- Mitochondrial Bioenergetic Dysfunction Cristae Structural Disruption Oxidative Stress OPA1 is Critical for Normal Mitochondrial Function and Cellular Metabolism © Copyright 2021 Stoke Therapeutics Cell Death Cell Survival Retinal ganglion cells have very high energy (ATP) requirements
Slide 22: TANGO ASO Demonstrates Dose-Dependent OPA1 Protein Increases in Rabbit Retina
TANGO ASO Demonstrates Dose-Dependent OPA1 Protein Increases in Rabbit Retina Target engagement Day 29 OPA1 protein Day 29 ASO exposure in retina Day 29 NMD = nonsense mediated decay Source: TANGO oligonucleotides for the treatment of Dravet Syndrome: Safety, biodistribution and pharmacology in the
Slide 23: TANGO ASO Partially Restores ATP and Protein Levels in Human OPA1+/- Cells
TANGO ASO Partially Restores ATP and Protein Levels in Human OPA1 +/- Cells N= 3 *one-way ANOVA # t-test Source: Stoke data © Copyright 2021 Stoke Therapeutics ASO treatment increased ATP levels in OPA1 deficient cells ASO treatment increased OPA1 protein levels ATP/total protein Mock ASO-14 Mock OP
Slide 24: TANGO ASOs Have the Potential to Address the Genetic Cause of ADOA
TANGO ASOs Have the Potential to Address the Genetic Cause of ADOA ü ü ü Dose-dependent increases in OPA1 protein expression in rabbit retina Increases ATP and protein levels in human OPA1 +/- cells Well tolerated for up to 29 days after intravitreal injection in rabbit Lead optimization is underway
Slide 25: Broad Therapeutic Potential for TANGO
Stoke identified a variety of non-productive alternative-splicing events that lead to mRNA degradation and limit protein production. Broad Therapeutic Potential for TANGO © Copyright 2021 Stoke Therapeutics Genetic diseases are caused by mutations in a single gene 10K+ Monogenic disease genes contai
Slide 26: 2021 Milestones
2021 Milestones 1H2021 2H2021 2H2021 2H2021 YE2021 Initiate Swallowtail Open Label Extension (OLE) study of STK-001 Initiate multiple ascending dose (MAD) study of STK-001 Preliminary safety and PK data from Phase 1/2a MONARCH study of STK-001 Initiate ADOA natural history data collection Complete l
Slide 27: Current Financials Anticipated to Fund Operations into 2024
Current Financials Anticipated to Fund Operations into 2024 $287.6M 36.6M Cash, Cash Equivalents & Restricted Cash as of 12/31/2020 Common Shares Outstanding as of 12/31/2020 © Copyright 2021 Stoke Therapeutics
Slide 28: We Are Stoke
We Are Stoke United in our mission to address the underlying cause of severe diseases by up-regulating protein expression with RNA-based medicines. © Copyright 2021 Stoke Therapeutics
Slide 29: © Copyright 2021 Stoke Therapeutics
© Copyright 2021 Stoke Therapeutics
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