Full Press Release Details
Stoke Therapeutics Presents Data from the Phase 1/2a MONARCH Study of STK-001 in Children and
Adolescents with Dravet Syndrome at the American Epilepsy Society (AES) 2021 Annual Meeting
Single doses of STK-001 up to 30mg and multiple doses of 20mg were well tolerated with no safety concerns related to study drug
70.6% (12/17) of patients treated with STK-001 experienced a reduction from baseline in
convulsive seizure frequency measured from Day 29 to Day 84
All patients ages 2-12 (n=7) experienced reductions in seizure frequency
Additional data to be
presented include pharmacokinetic (PK) modeling data of STK-001, initial safety data from the SWALLOWTAIL open-label extension study and three-month data from the BUTTERFLY observational study
BEDFORD, Mass., December 3, 2021 Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company dedicated to
addressing the underlying cause of severe diseases by upregulating protein expression with RNA-based medicines, today announced highlights from five presentations related to the ongoing clinical
development of STK-001 being made at the American Epilepsy Society (AES) 2021 Annual Meeting, December 3 7. STK-001 has the potential to be the first
disease-modifying therapy to target the underlying cause of Dravet syndrome, which is a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures beginning within the first year of life. The disease is
classified as a developmental and epileptic encephalopathy due to the developmental delays and cognitive impairment associated with the disease.
Interim Safety, PK, and CSF Exposure Data from the Phase 1/2a MONARCH Study of STK-001, an Antisense
Oligonucleotide (ASO), in Children and Adolescents with Dravet Syndrome (DS)
Session Date & Time:
Sunday, December 5 at 12:00 p.m. CT
Presenter: Linda Laux, M.D., Associate Professor of Pediatrics (Neurology and Epilepsy)
at Northwestern University Feinberg School of Medicine and Attending Physician at Ann & Robert H. Lurie Children s Hospital of Chicago
Poster Number: 2.405
Dravet syndrome is characterized by frequent, prolonged and intractable seizures, but some of the most
devastating effects relate to non-seizure comorbidities such as developmental delays and cognitive impairment, said Linda Laux, M.D., Associate Professor of Pediatrics (Neurology and Epilepsy)
at Northwestern University Feinberg School of Medicine, Attending Physician at Ann & Robert H. Lurie Children s Hospital of Chicago, and the MONARCH study lead investigator. Seeing an early trend toward reduction in seizure
frequency at these relatively low dose levels is very encouraging, especially given that more than 90 percent of patients were taking three or more concomitant anti-seizure medications as maintenance
therapy during the study.
STK-001 is designed to target the underlying cause of Dravet syndrome to
potentially address both seizures and non-seizure comorbidities, said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. These initial data give us confidence that STK-001 is having an effect on the disease. Based on our pharmacokinetic model, we believe that sustained higher exposure levels in the brain may lead to greater reductions in seizure frequency and potentially also
improvements in some of the non-seizure comorbidities. We are pleased with the initial clinical findings from MONARCH, and the SWALLOWTAIL open-label extension study, and look forward to continuing our
clinical progress in collaboration with the Dravet community.
Additional posters include:
SWALLOWTAIL: An Open-Label Extension (OLE) Study for Patients with Dravet Syndrome (DS) who Previously Participated in Studies of STK-001
Session Date & Time: Sunday, December 5 at 12:00 p.m. CT
Presenter: Colin Roberts, M.D., Director of the Doernbecher Childhood Epilepsy Program at Oregon Health & Science University
Clinical data from the continued
administration of STK-001 to patients previously treated in the Phase 1/2a MONARCH study demonstrated that multiple doses up to 30mg of STK-001 were well tolerated with
no safety concerns related to the study drug. Additionally, dosing of STK-001 intrathecally (IT) every four months appears to be well tolerated. No patients have discontinued treatment in SWALLOWTAIL.
A Pharmacokinetic (PK) Model for STK-001, an Antisense
Oligonucleotide (ASO), Based on Data from Non-human Primates (NHP) Enables Dose Selection in Patients with Dravet Syndrome (DS)
Date & Time: Monday, December 6 at 12:00 p.m. CT
Presenter: Meena, Ph.D., Vice President of Bioanalytical, DMPK
and Biomarker Development at Stoke Therapeutics
Poster Number: 3.264
A population pharmacokinetic model for intrathecal STK-001 was developed using
non-human primate data and was scaled and adjusted using clinical data to predict STK-001 concentrations in plasma, CSF and brain in pediatric patients with Dravet
syndrome. STK-001 levels in plasma and CSF in patients treated with STK-001 correlated very well with model predictions, indicating that plasma and CSF levels observed
in patients are good predictors of STK-001 brain levels in patients. Modeling of clinical data also suggest that more than 95% of patients are predicted to have pharmacologically active STK-001 brain levels following three doses of 30mg administered one month apart and half of all patients are anticipated to maintain greater than minimum pharmacologically active levels of STK-001 for approximately three months after their last dose.
ADMIRAL: A UK Open-Label Study to Investigate the
Safety and Pharmacokinetics (PK) of Multiple Ascending Doses of Antisense Oligonucleotide (ASO) STK-001 in Children and Adolescents with Dravet Syndrome
Session Date & Time: Sunday, December 5 at 12:00 p.m. CT
Presenter: Helen Cross, MB ChB, Ph.D., Professor, The Prince of Wales s Chair of Childhood Epilepsy and Head of the Developmental Neuroscience
Programme at University College London Great Ormond Street Institute of Child Health, Honorary Consultant in Paediatric Neurology, President of the International League Against Epilepsy
Poster Number: 2.219
Provides the trial design of the
Company s ongoing Phase 1/2a study (ADMIRAL) in the United Kingdom. This study is evaluating multiple doses of up to 70mg of STK-001. The primary endpoints are safety and tolerability of STK-001 as well as to determine the PK in plasma and exposure in CSF. The impact of STK-001 on frequency of convulsive seizures and quality of life are secondary endpoints of
this study. Enrollment and dosing in ADMIRAL is ongoing.
BUTTERFLY, An Observational Study to Investigate Cognition and Other Non-seizure
Comorbidities in Children and Adolescents with Dravet Syndrome
Session Date & Time: Monday, December 6 at 12:00
Presenter: Elaine Wirrell, M.D., Director of Pediatric Epilepsy at Mayo Clinic, Director of the Child and Adolescent Neurology Residency
Training Program at Mayo Clinic
Poster Number: 3.278
Three-month data suggest that commonly used cognition assessments including the VABS-III (Vineland Adaptive Behavior
Scales, Third Edition), BSID-III (Bayley Scales of Infant Development, Third Edition), and WPPSI-IV (Wechsler Preschool and Primary Scale of Intelligence, Fourth
Edition) may be useful for clinical studies assessing neurodevelopment and adaptive behavior in patients with Dravet syndrome. All three assessments showed relatively low intra-patient variability and no significant change from baseline three months
after baseline assessments for all 36 patients enrolled.
All Company posters presented at AES 2021 will be available on the Investors & News section of
Stoke s website at https://investor.stoketherapeutics.com/.
About Dravet Syndrome
Dravet syndrome is a severe and progressive genetic epilepsy characterized by frequent, prolonged and refractory seizures, beginning within the first year of
life. Dravet syndrome is difficult to treat and has a poor long-term prognosis. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. The effects of the disease go beyond seizures and often
include intellectual disability, developmental delays, movement and balance issues, language and speech disturbances, growth defects, sleep abnormalities, disruptions of the autonomic nervous system and mood disorders. The disease is classified as a
developmental and epileptic encephalopathy due to the developmental delays and cognitive impairment associated with the disease. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden
unexpected death in epilepsy, or SUDEP. There are no approved disease-modifying therapies for people living with Dravet syndrome. One out of 16,000 babies are born with Dravet syndrome, which is not concentrated in a particular geographic area or
STK-001 is an investigational new medicine for the treatment of Dravet syndrome currently being evaluated in ongoing
clinical trials. Stoke believes that STK-001, a proprietary antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. STK-001 is designed to upregulate NaV1.1 protein expression by leveraging the non-mutant (wild-type) copy of
the SCN1A gene to restore physiological NaV1.1 levels, thereby reducing both occurrence of seizures and significant non-seizure
comorbidities. Stoke has generated preclinical data demonstrating proof-of-mechanism and
proof-of-concept for STK-001. STK-001 has been granted orphan drug designation by the FDA
as a potential new treatment for Dravet syndrome.
About Phase 1/2a MONARCH Study (United States)
The MONARCH study is a Phase 1/2a open-label study of children and adolescents ages 2 to 18 who have an established diagnosis of Dravet syndrome and have
evidence of a pathogenic genetic mutation in the SCN1A gene. The primary objectives for the study are to assess the safety and tolerability of STK-001, as well as to determine the pharmacokinetics in
plasma and exposure in cerebrospinal fluid. A secondary objective is to assess the efficacy as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency over a 12-week treatment period. Stoke also intends to measure non-seizure aspects of the disease, such as quality of life, as secondary endpoints. Stoke plans to enroll
approximately 90 patients in the study across 20 sites in the United States. Additional information about the MONARCH study can be found at https://www.monarchstudy.com/.
Patients who participated in the MONARCH study are eligible to continue treatment in SWALLOWTAIL, an open
label extension (OLE) study designed to evaluate the long-term safety and tolerability of repeat doses of STK-001. Enrollment and dosing in SWALLOWTAIL are underway.
About Phase 1/2a ADMIRAL Study (United Kingdom)
ADMIRAL study is a Phase 1/2a open-label study of children and adolescents ages 2 to <18 who have an established diagnosis of Dravet syndrome and have evidence of a genetic mutation in the SCN1A gene. The primary objectives for the study
are to assess the safety and tolerability of multiple doses of STK-001, as well as to determine the pharmacokinetics in plasma and exposure in cerebrospinal fluid. A secondary objective is to assess the effect
of multiple doses of STK-001 as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency over a 24-week
treatment period. Stoke also intends to measure non-seizure aspects of the disease, such as overall clinical status and quality of life, as secondary endpoints. Stoke plans to enroll up to 60 patients in the
study across multiple sites in the United Kingdom. Additional information about the ADMIRAL study can be found at https://www.admiralstudy.com.
TANGO (Targeted Augmentation of Nuclear Gene
Output) is Stoke s proprietary research platform. Stoke s initial application for this technology are diseases in which one copy of a gene functions normally and the other is mutated, also called haploinsufficiencies. In these cases, the
mutated gene does not produce its share of protein, resulting in disease. Using the TANGO approach and a deep understanding of RNA science, Stoke researchers design antisense oligonucleotides (ASOs) that bind to
pre-mRNA and help the functional (or wild-type) genes produce more protein. TANGO aims to restore missing proteins by increasing or stoking protein output from healthy genes, thus compensating
for the mutant copy of the gene.
About Stoke Therapeutics
Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company dedicated to addressing the underlying cause of severe diseases by upregulating protein
expression with RNA-based medicines. Using the Company s proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides (ASOs) to selectively