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 –
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
Presenter: Linda Laux, M.D., Associate Professor of Pediatrics (Neurology and Epilepsy) at
Poster Number: 2.405
- Single doses of STK-001 up to 30mg, and three 20mg doses of STK-001 given every four weeks, were found to be well tolerated with no safety concerns related to the study drug.
- The most common treatment-emergent adverse events (TEAE) were headache, vomiting, seizure, irritability, and back pain.
- 18.2% (4/22) of patients experienced a TEAE that was related to study drug, none of which were severe.
- 22.7% (5/22) of patients had a serious treatment-emergent adverse event (SAE), none of which were related to study drug.
- 70.6% (12/17) of patients treated with single doses (10mg, 20mg, 30mg) or multiple doses (20mg) of STK-001 experienced a reduction from baseline in convulsive seizure frequency measured from Day 29 to Day 84 after receiving their first dose of STK-001.
- 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 observed among patients ages 13-18.
- Across all cohorts median reductions of 17% to 37% from baseline in convulsive seizure frequency from Day 29 to Day 84 were observed.
“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
“STK-001 is designed to target the underlying cause of Dravet syndrome to potentially address both seizures and non-seizure comorbidities,” said
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
Presenter: Colin Roberts, M.D., Director of the Doernbecher Childhood Epilepsy Program at
Poster Number: 2.22
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)
Session Date & Time: Monday, December 6 at
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.
Session Date & Time:
Presenter: Helen Cross, MB ChB, Ph.D., Professor, The
Poster Number: 2.219
Provides the trial design of the Company’s ongoing Phase 1/2a study (ADMIRAL) in the
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
Presenter: Elaine Wirrell, M.D., Director of Pediatric Epilepsy at
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 (
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 ethnic group.
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 (
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
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 (
The 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
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.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: the ability of STK-001 to treat Dravet syndrome and reduce seizures, the timing and expected progress of clinical trials, data readouts and presentations, and the timing or receipt of regulatory approval. Statements including words such as “believe,” “plan,” “will,” “continue,” “expect,” “may,” or “ongoing” and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Forward-looking statements are subject to risks and uncertainties that may cause the company’s actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties related to the Company’s ability to advance its product candidates, obtain regulatory approval of and ultimately commercialize its product candidates, the timing and results of preclinical and clinical trials, the company’s ability to fund development activities and achieve development goals, the company’s ability to protect intellectual property and other risks and uncertainties described under the heading “Risk Factors” in documents the company files from time to time with the
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