Full Press Release Details
Stoke Therapeutics Edward M. Kaye, M.D.
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Stoke Therapeutics Amplifying Science
Foundational Elements of Stoke
life. Amplifying Science
Efficient Execution Since 2018 Launch
first patient in the BUTTERFLY observational study Presented preclinical data supporting efficacy of STK-001 Completed IND-enabling studies for STK-001 Stoke is Poised to Enter the Clinic Closed $40M Series A financing Nominated Dravet syndrome as
lead program; generated in-vivo proof of concept Completed FDA pre-IND meeting Closed $90M Series B financing Built robust intellectual property estate Stoke is Launched
Experienced Leaders in Innovation
Tulipano, CPA Chief Financial Officer Gene Liau, Ph.D. Executive Vice President, Head of Research and Preclinical Development Robin Walker, J.D. Senior Vice President, Chief Legal Officer and Chief Compliance Officer
TANGO: An RNA-Based Genetic Medicine
small or large gene targets Gene and tissue specific Controllable dose and duration Can address wide array of diseases Simple and scalable manufacturing TANGO Stoke uses RNA science to restore missing proteins by increasing - or stoking
- protein output from healthy genes.
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productive mRNA from the functional copy of the gene result in increased protein production For haploinsufficiences, TANGO restores the target protein to near-normal levels
Transformative Potential of TANGO
mechanism for increasing protein synthesis in a prospective haploinsufficient patient. Wild-type productive mRNA Wild-type non-productive mRNA Mutant mRNA Mutant non-productive mRNA
Transformative Potential of TANGO
protein synthesis in a prospective haploinsufficient patient. Wild-type productive mRNA Mutant mRNA Wild-type (normal) and mutant allele
Robust Target Identification Process
Utilizing Proprietary Bioinformatics Approximately 50% of human genes contain a TANGO signature Cross-referencing with genetic disease databases identifies approximately 2,900 monogenic diseases amenable to TANGO Enables rapid and systematic
identification of clinically relevant targets RNA sequencing and in silico discovery datasets Proprietary bioinformatics analysis Universe of non-productive splicing events Genetic disease databases TANGO amenability assessment TANGO targets Cell
Targets Time Horizon Stoke is
PATHWAY UPREGULATION DRAVET SYNDROME Longer-term focus & collaborations
Significant Unmet Need in Genetic
Perspectives in Medicine 2015; Pal et al., Nature Reviews Neurology 2010; Chen et al., JAMA Neurology 2018; Lagae et al., Developmental Medicine & Child Neurology 2017; Vlaskamp et al., Neurology 2019; Reddy SD et al., J Pharmacol Exp Ther 2018;
NIH Genetics Home Reference; Company websites While genetic mechanisms are often well understood genetically-targeted therapies for epilepsies are available >30% of patients are refractory to medical treatment, especially those with a
genetic epilepsy Up to >50% of epilepsies have an identified genetic cause and many of these are haploinsufficiencies Diagnostic work-up of epilepsy routinely includes genetic testing for more than 180 disease associated genes
Dravet Syndrome: A Severe,
& Genomic Medicine 2016; Lagae et al., Developmental Medicine & Child Neurology 2017; Nabbout et al., Orphanet Journal of Rare Diseases 2013 of children and adolescents with Dravet die before adulthood, due to SUDEP, prolonged seizures,
seizure-related accidents or infections ~35,000 Seizures are not adequately controlled in 90% of people with Dravet of cases caused by a haploinsufficiency of the SCN1A gene 50% NaV1.1 protein expression results in people affected in the U.S.,
Canada, Japan, Germany, France and the UK Up to Dravet syndrome is not concentrated in a particular geographic area or ethnic group.
Non-Seizure Comorbidities of Dravet
Severe intellectual disabilities Severe developmental disabilities Motor impairment Speech impairment Autism Behavioral difficulties Sleep abnormalities High Incidence of Premature Death: Up to 20% of children and adolescents die before adulthood,
due to: SUDEP1 Prolonged seizures Seizure-related accidents Infections Note: 1 Sudden Unexpected Death in Epilepsy Sources: Source: 2018 Health Advances Report; Dj mi et al., Molecular Genetics & Genomic Medicine 2016; Lagae et al.,
Developmental Medicine & Child Neurology 2017; Nabbout et al., Orphanet Journal of Rare Diseases 2013; Licheni et al, Developmental Medicine & Child Neurology 2018
STK-001 Significantly Reduces
****p<0.0001 Source: Stoke data, presented at AES 2019
STK-001 Significantly Reduces
Source: Stoke data, presented at AES 2019
Source: Stoke data, presented at AES
14% 80% reduction in the average number of spontaneous seizures compared to placebo (p<0.05) As measured between postnatal days (PND) 22 and 46 in Dravet syndrome mice after a single 20 g injection of STK-001 at PND 2 Placebo
STK-001 Achieves Broad Distribution
Stoke data, presented at AES 2019
Preclinical Studies Show STK-001
Well-Tolerated at a Pharmacologically Active Dose in NHPs Key safety measures No complement activation No decrease in platelet counts No change in renal or hepatic function No clinical signs or symptoms over 28-day period after administration Normal
STK-001 Has Potential to Address the
model Broad distribution to the brains of non-human primates with intrathecal delivery Ability to dose titrate with wide therapeutic window Effects persisting for at least 14 weeks in Dravet syndrome mice following a single dose Well-tolerated at
pharmacologically-active dose levels in non-human primates Selective target engagement may limit potential off-target effects
Several Factors De-Risk STK-001
Clinical Development for Dravet Syndrome Defined patient population: Genetic testing routine in epilepsy diagnostic workups Established regulatory pathway: Existing medicines are approved for Dravet syndrome Validated chemistry and delivery to CNS:
BUTTERFLY Observational Study
including: Intellectual disabilities Developmental disabilities Motor impairment Speech impairment Behavioral problems Sleep abnormalities
On-Track to Enroll First Patient in
MONARCH Phase 1/2a Trial in 2Q/3Q 2020 Pre-IND meeting conducted and IND on track GLP single-dose toxicology studies completed Overview of study design: Analogous trial design and endpoints to recently approved antiepileptic drugs for Dravet
syndrome Open label Plan to enroll ~40 patients aged 2-18 at ~20 sites in the U.S. For each dose level, sentinel group ages 13-18, followed by group ages 2-12 Primary endpoint: safety and tolerability of a single-ascending dose Secondary endpoints:
Targets Time Horizon PATHWAY
UPREGULATION GENETIC EPILEPSIES HAPLOINSUFFICIENCIES DRAVET SYNDROME Expanding the Pipeline Using Stoke's Proprietary Bioinformatics and TANGO Immediate focus Near-term focus Near-to-mid-term focus & collaborations Longer-term focus &
the capabilities to take our first 2-3 medicines from discovery to the clinic.
TANGO is Applicable to a Broad Range
NT ASO nM NT ASO nM CD274 (PD-L1) non-productive event productive mRNA protein Correlation between event abundance (+CHX) & upregulation SCN1A SYNGAP1 CD274 PCCA NT: non-targeting ASO control, all experiments n = 3, in vitro Liver target -
autosomal recessive PCCA non-productive event productive mRNA protein NT ASO nM NT ASO nM NT ASO nM
Business Development Vision -
Sector Expert & Collaborator of Choice Numerous validated targets in therapeutic areas outside of Stoke's internal scope: metabolic, renal, immunology, cancer, hematology, neuromuscular, as well as partner-proprietary targets Explore
alternative drug delivery approaches to expand into tissues poorly accessed by ASOs and provide improved product profiles Strategic collaborations in above areas will bolster our pipeline and more fully exploit the potential of our TANGO platform
2020 Early 2020: File IND with FDA
2Q/3Q 2020: Enroll first patient in MONARCH Mid-2020: Nominate new candidate for preclinical development in an additional genetic disease Continuously evaluate potential collaborations to expand the pipeline Build the organization and capabilities
Clinic Stoke is Launched
Cash Expected to be Sufficient to
net proceeds in June 2019 initial public offering
The Commitment that Drives Stoke
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