Unverricht-Lundborg Syndrome

BEDFORD, Mass.--(BUSINESS WIRE)-- 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 presentations related to the ongoing clinical development of STK-001, the first potential new medicine to treat the underlying cause of Dravet syndrome. A total of seven posters will be presented at the American Epilepsy Society (AES) 2022 Annual Meeting, December 2-6. Dravet syndrome 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. “Dravet syndrome is a complex and devastating disease that presents challenges for clinicians, patients and their caregivers,” said Barry Ticho, Ph.D., M.D., Chief Medical Officer of Stoke Therapeutics. “To curb the seizures, patients typically take multiple anti-seizure medicines which often produce additional challenges and side effects that impact their quality of life and overall health. STK-001 represents an entirely new approach to treatment, one that aims to treat the syndrome, not just the seizures. At the highest dose level, we observed a 55% median reduction in convulsive seizure frequency, with all but one patient responding to treatment with STK-001. Demonstrating this level of effect in highly refractory patients, who have already taken multiple standard anti-seizure medicines, including fenfluramine, has not been seen before.” Topline data from a combined interim analysis of the Phase 1/2a MONARCH and ADMIRAL studies showed single and multiple doses of STK-001 up to 45mg were well-tolerated. Reductions in seizure frequency were observed among patients who received multiple doses of STK-001 (20mg, 30mg, 45mg). The effects were more evident at the highest dose (45mg) and in younger patients and were observed on top of standard treatments. Half of the patients in these studies were taking four or more anti-seizure medicines, including fenfluramine. An interim analysis of six patients treated with three doses of 45mg was presented and showed: A 55% median reduction from baseline in convulsive seizure frequency from Day 29 after the first dose to three months after receiving the last dose. Reductions from baseline in convulsive seizure frequency in 5/6 (83%) patients. A greater than 50% reduction in convulsive seizure frequency in 4/6 (67%) patients. Reductions in seizure frequency began after the first dose and continued with additional treatment, consistent with the anticipated mechanism of action of STK-001. The interim safety analysis of patients treated in MONARCH and ADMIRAL showed that 27% (15/55) of patients experienced a treatment-emergent adverse event (TEAE) that was related to study drug. All adverse events related to study drug were mild to moderate in severity. No TEAEs led to study drug withdrawal. Preliminary data from a small cohort of patients in the open-label SWALLOWTAIL study showed the effects of ongoing treatment with STK-001 (30mg), including: Reductions in convulsive seizure frequency that were observed in MONARCH were maintained with ongoing treatment in the SWALLOWTAIL open-label extension study. A trend toward improvement in non-seizure comorbidities as measured by the BRIEF-P, an assessment of executive function, was observed among patients in the SWALLOWTAIL open-label extension study. One-year data from the BUTTERFLY observational study, which did not include treatment with STK-001, showed little change from baseline to 12 months in the mean BRIEF-P scores and other commonly used cognition assessments. Safety pro with MONARCH and ADMIRAL. Seven presentations related to the Company’s work in Dravet syndrome will be presented during the AES Annual Meeting and can be found on the Stoke Therapeutics website under the Investors & News tab. Title MONARCH and ADMIRAL Interim Analyses: Phase 1/2a Studies Investigating Safety and Drug Exposure of STK-001, an Antisense Oligonucleotide (ASO), in Children and Adolescents with Dravet Syndrome (DS) 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: 1.215 Saturday, Dec. 3 12:00 PM CST Title MONARCH and ADMIRAL Interim Analyses: Phase 1/2a Studies Investigating Safety and Drug Exposure of STK-001, an Antisense Oligonucleotide (ASO), in Children and Adolescents with Dravet Syndrome (DS) 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: 1.227 Saturday, Dec. 3 12:00 PM CST Title SWALLOWTAIL: An Open-Label Extension (OLE) Study for Children and Adolescents with Dravet Syndrome (DS) who Previously Participated in a Study of Antisense Oligonucleotide (ASO) STK-001 Presenter Colin Roberts​, M.D., Director of the Doernbecher Childhood Epilepsy Program at Oregon Health & Science University Poster Number: 1.216 Saturday, Dec. 3 12:00 PM CST Title Utilization of Pharmacokinetic (PK) Model for STK-001 in Patients with Dravet Syndrome (DS) to Predict Pharmacological Active Dose in Clinic Presenter Meena, Ph.D., Senior Vice President of Bioanalytical, DMPK and Biomarker Development at Stoke Therapeutics Poster Number: 1.134 Saturday, Dec. 3 12:00 PM CST Title Twelve-month Analysis of BUTTERFLY: An Observational Study to Investigate Cognition and Other Non-seizure Comorbidities in Children and Adolescents with Dravet Syndrome (DS) Presenter Joseph Sullivan, M.D., Professor of Neurology and Pediatrics and Director of the University of California San Francisco Pediatric Epilepsy Center of Excellence Poster Number: 1.228 Saturday, Dec. 3 12:00 PM CST Title Quantitative EEG Analysis Patients with Dravet Syndrome (DS) Treated in the Phase 1/2a MONARCH Study of STK-001, an Antisense Oligonucleotide (ASO) Presenter Kimberly Parkerson, M.D., Ph.D., Vice President, Head of Neurology Clinical Development at Stoke Therapeutics Poster Number: 3.225 Monday, Dec. 5 12:00 PM CST Title STK-001 Surrogate Restores the Excitability of Parvalbumin-positive Fast-spiking Interneurons in a Mouse Model of Dravet Syndrome Presenter Luis Lopez-Santiago, Ph.D., Associate Research Scientist at University of Michigan Medical School Poster Number: 3.050 Monday, Dec. 5 12:00 PM CST 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. About STK-001 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 and the EMA, and rare pediatric disease 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 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. Stoke also intends to measure non-seizure aspects of the disease, such as quality of life, as secondary endpoints. Additional information about the MONARCH study can be found at https://www.monarchstudy.com/. Patients who participated in the MONARCH study and meet study entry criteria 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. We expect that SWALLOWTAIL will also provide valuable information on the preliminary effects of STK-001 on seizures along with non-seizure aspects of the disease, such as quality of life and cognition. Enrollment and dosing in SWALLOWTAIL are underway. About Phase 1/2a ADMIRAL Study (United Kingdom) 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. Stoke also intends to measure non-seizure aspects of the disease, such as overall clinical status and quality of life, as secondary endpoints. Additional information about the ADMIRAL study can be found at https://www.admiralstudy.com. Patients who participated in the ADMIRAL study and meet study entry criteria are eligible to continue treatment in LONGWING, an open-label extension (OLE) study designed to evaluate the long-term safety and tolerability of repeat doses of STK-001. We expect that LONGWING will also provide valuable information on the preliminary effects of STK-001 on seizures along with non-seizure aspects of the disease, such as quality of life and cognition. Enrollment and dosing in LONGWING are underway. 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 Stoke’s proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides (ASOs) to selectively restore protein levels. Stoke’s first compound, STK-001, is in clinical testing for the treatment of Dravet syndrome, a severe and progressive genetic epilepsy. Dravet syndrome is one of many diseases caused by a haploinsufficiency, in which a loss of ~50% of normal protein levels leads to disease. Stoke is pursuing the development of STK-002 for the treatment of autosomal dominant optic atrophy (ADOA), the most common inherited optic nerve disorder. Stoke’s initial focus is haploinsufficiencies and diseases of the central nervous system and the eye, although proof of concept has been demonstrated in other organs, tissues, and systems, supporting its belief in the broad potential for its proprietary approach. Stoke is headquartered in Bedford, Massachusetts with offices in Cambridge, Massachusetts. For more information, visit https://www.stoketherapeutics.com/ or follow Stoke on Twitter at @StokeTx Poster Number: 1.215 Saturday, Dec. 3 12:00 PM CST Poster Number: 1.215 Saturday, Dec. 3 12:00 PM CST Poster Number: 1.215 Saturday, Dec. 3 12:00 PM CST Poster Number: 1.215 Saturday, Dec. 3 12:00 PM CST

Researchers from the University of Eastern Finland (UEF) and Kuopio University Hospital published a study that found a wearable device used at home can help monitor symptoms of a progressive form of epilepsy. The study published in Clinical Neurophysiology found that a wearable developed at UEF correlated positively with experienced physician assessments of muscular jerks in the arms of patients with progressive myoclonic epilepsy (EPM1). EPM1 patients experience “myoclonus”: sudden muscle jerks. These jerks can be positive, when the muscle contracts, or negative, when a patient loses muscle control. Negative myoclonic jerks can result in a patient dropping something, losing their grip, falling, or being unable to control an object they were managing. Part of the EPM1 treatment process involves monitoring positive and negative myoclonic jerks. In standard clinical practice, a physician observes video of a patient and scores the symptoms with the Unified Myoclonus Scale (UMRS). The UMRS assessment assists healthcare teams in tracking the progress of the disease and treatment effectiveness. In the UEF study, 23 EPM1 patients wore a device for 48 hours. The wearable measured skin surface electromyography (electrical impulses) and 3-dimensional acceleration. The sensor patches attached at the biceps brachii (BB) of the dominant arm and the extensor digitorum communis (forearm) of the non-dominant arm. Patients also self-reported on their own myoclonic jerks in a diary once an hour. The researchers video-recorded the patients during the 48 hours. A physician experienced in UMRS assessments scored the recorded video. According to the study, myoclonic jerk assessments based on the objective data from the wearable correlated well with the experienced physician assessments and with the patients’ own evaluation of their symptoms. Researchers and other participants in this study included personnel from three universities and eight companies, all in Finland. Study subject self-reporting is not generally considered terribly valid or reliable because of its subjective nature. This study, however, found general agreement in three levels of data, ranging from the subjective patient reporting, professional assessments by physicians experienced with the UMRS modality, and objective sensor data. According to the researchers, because the wearable successfully detected both positive and negative myoclonic jerks, the technology is suitable for monitoring treatment effects at home and the progression of the disease. The UEF study is another example of wearables playing a positive role supporting remote patient care and remote patient monitoring RPM. It will support longer periods of observation — presumably while a patient goes about normal daily activities — and produce a richer set of data for physicians to use in analyzing a patient’s condition.