Stoke Therapeutics Inc【STOK】株式ニュース

The New England Journal of Medicine Publishes First Data to Demonstrate the Potential for Disease Modification in Dravet SyndromeMarch 4, 2026 5:06 PM
Business Wire
–Results show that targeting the underlying cause of Dravet syndrome with zorevunersen may improve outcomes for people with this rare, devastating genetic neurodevelopmental disease–

–Data support ongoing global Phase 3 EMPEROR study–

Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine, and Biogen Inc. (NASDAQ: BIIB), today announced the publication of data from studies of the investigational medicine zorevunersen in The New England Journal of Medicine (NEJM). The publication includes results from two completed Phase 1/2a and ongoing open-label extension (OLE) studies that demonstrate, for the first time, the potential for disease modification in people living with Dravet syndrome. These data showed substantial and durable reductions in seizures and improvements across multiple measures of cognition and behavior that began in the Phase 1/2a treatment period and continued through three additional years of treatment in the OLEs. The effects were shown in people treated with zorevunersen on top of standard of care anti-seizure medicines (ASMs).

Dravet syndrome is a severe developmental and epileptic encephalopathy (DEE) in which people experience severe and recurrent seizures and a plateauing in their neurodevelopment around the age of two. Over time, children with Dravet syndrome fall further and further behind their neurotypical peers in their ability to achieve developmental milestones. There are currently no approved disease-modifying medicines to treat Dravet syndrome.

“These data mark a potential turning point in the treatment of Dravet syndrome,” said Helen Cross, MB ChB, Ph.D., corresponding author of the NEJM publication and The Prince of Wales’s Chair of Childhood Epilepsy and Director of University College London Great Ormond Street Institute of Child Health, Honorary Consultant in Paediatric Neurology at Great Ormond Street Hospital. “While reducing seizures is still critical, the improvements in cognition, behavior and quality of life seen in these studies suggest we may be changing the course of the disease and therefore the lives of patients and their families.”

“Dravet syndrome arrives without warning for families, just as it did for our family more than 25 years ago when my son began having seizures,” said Mary Anne Meskis, Chief Executive Officer of the Dravet Syndrome Foundation. “While awareness, diagnosis and medical care have advanced significantly over the years, the realities of Dravet syndrome remain severe and life-altering for patients and their families. A treatment that could help someone like my son dress himself independently or better communicate with his parents would profoundly change the cadence and quality of our everyday lives.”

Efficacy Results

The Phase 1/2a studies evaluated single and multiple doses of zorevunersen up to 70 mg with a primary endpoint of safety. Change in major motor seizure frequency was assessed as a secondary endpoint. Substantial reductions in seizures were observed among zorevunersen-treated patients in the Phase 1/2a studies and continued through three years of treatment in the OLEs. The most substantial reductions in seizure frequency were observed among patients treated with initial doses of 70 mg in the Phase 1/2a studies.

Changes in neurodevelopment, functioning, clinical status and quality of life for all patients were assessed as additional endpoints in the OLEs using standard clinical assessments. Improvements in communication, motor skills, socialization, daily living and quality of life continued through three additional years of treatment.

Summary of Safety Data

Zorevunersen has been generally well tolerated across the Phase 1/2a and OLE studies. Eighty-one patients received at least one dose of zorevunersen and were evaluated for safety, and more than 800 doses have been administered across these studies to date. The most common treatment-related adverse event was cerebrospinal fluid (CSF) protein elevations with a higher incidence observed in the OLE studies (44%, n=33/75). No related clinical manifestations have been observed, although one patient discontinued treatment due to elevated CSF protein levels. All serious adverse events were assessed to be unrelated to zorevunersen except in one patient who experienced suspected unexpected serious adverse reactions (SUSARs).

“The discovery of the genetic cause of Dravet syndrome 25 years ago changed how researchers thought about the disease and how to treat it,” said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “By targeting the underlying genetic cause of the disease, zorevunersen has the potential to be the first disease-modifying medicine for the treatment of Dravet syndrome. We look forward to the results of our Phase 3 EMPEROR study expected in mid-2027.”

“This publication in NEJM demonstrates an appreciation of the severity of Dravet syndrome and the potential of this novel approach to transform the way the disease is treated,” said Katherine Dawson, M.D., Head of Therapeutics Development Unit at Biogen. “For more than 10 years Biogen has been advancing cutting-edge research to address some of the most rare, devastating and neglected diseases, and we are proud to partner with Stoke on this first-of-its-kind investigational drug.”

The full publication titled, “Zorevunersen in Children and Adolescents with Dravet Syndrome,” appears in the March 5 issue of The New England Journal of Medicine.

About Dravet Syndrome

Dravet syndrome is a severe developmental and epileptic encephalopathy (DEE) characterized by recurrent seizures as well as significant cognitive and behavioral impairments. Most cases of Dravet are caused by mutations in one copy of the SCN1A gene, leading to insufficient levels of NaV1.1 protein in neuronal cells in the brain. Even when treated with the best available anti-seizure medicines (ASMs), up to 57 percent of patients with Dravet syndrome do not achieve ≥50 percent reduction in seizure frequency. Complications of the disease often contribute to a poor quality of life for patients and their caregivers. Developmental and cognitive impairments 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. Compared with the general epilepsy population, people living with Dravet syndrome have a higher risk of sudden unexpected death in epilepsy, or SUDEP; up to 20 percent of children and adolescents with Dravet syndrome die before adulthood due to SUDEP, prolonged seizures, seizure-related accidents or infections 1. Dravet syndrome occurs globally and is not concentrated in a particular geographic area or ethnic group. Currently, it is estimated that up to 38,000 people are living with Dravet syndrome in the U.S. (~16,000), UK, EU-4 and Japan 2. There are no approved disease-modifying therapies for people living with Dravet syndrome.

About Zorevunersen

Zorevunersen is an investigational antisense oligonucleotide that is designed to treat the underlying cause of Dravet syndrome by increasing functional NaV1.1 protein production in brain cells from the unaffected (wild-type) copy of the SCN1A gene. This highly differentiated mechanism of action aims to reduce seizure frequency beyond what has been achieved with anti-seizure medicines and to improve neurodevelopment, cognition and behavior. Zorevunersen has demonstrated the potential for disease modification and has been granted orphan drug designation by the FDA and the EMA. The FDA has also granted zorevunersen rare pediatric disease designation and Breakthrough Therapy Designation for the treatment of Dravet syndrome with a confirmed mutation not associated with gain-of-function, in the SCN1A gene. Stoke has a strategic collaboration with Biogen to develop and commercialize zorevunersen for Dravet syndrome. Under the collaboration, Stoke retains exclusive rights for zorevunersen in the United States, Canada, and Mexico; Biogen receives exclusive rest of world commercialization rights.

About the Phase 1/2a and Open-Label Extension Studies of Zorevunersen

Two Phase 1/2a open-label, multicenter studies were conducted and evaluated the effects of zorevunersen in patients with highly refractory Dravet syndrome ages 2 to 18 years (N=81). Primary endpoints were the safety profile, plasma pharmacokinetics (PK) and exposure in cerebrospinal fluid (CSF) of single and multiple doses of zorevunersen. Secondary endpoints included percentage change from baseline in major motor seizure frequency, overall clinical status (a measure of patients’ overall functioning) and quality of life. The ADMIRAL Phase 1/2a study included an exploratory endpoint to evaluate changes in neurodevelopmental status (cognition & behavior) as measured by Vineland Adaptive Behavior Scales, Third Edition (Vineland-3). The Phase 1/2a studies were completed in November 2023.

Following treatment in the Phase 1/2a studies, eligible patients continued treatment with zorevunersen every four months in one of two OLEs. There was at least a 6-month gap between the last dose administered in the Phase 1/2a studies and the first dose administered in the OLEs. The primary endpoints are the safety profile of multiple doses of zorevunersen. Secondary endpoints include PK parameters, percentage change from baseline in major motor seizure frequency, change in overall clinical status, and change from baseline in quality of life. Exploratory endpoints include changes in neurodevelopment status as measured by Vineland-3. The OLE studies are ongoing.

About the Phase 3 EMPEROR Study

The Phase 3 EMPEROR Study (NCT06872125) is a global, double-blind, sham-controlled study evaluating the efficacy, safety and tolerability of zorevunersen in children ages 2 to

Stoke Therapeutics Announces First Patient Dosed in Phase 1 Study of STK-002, a Potential Disease-Modifying Medicine for the Treatment of Autosomal Dominant Optic Atrophy (ADOA)February 11, 2026 7:30 AM
Business Wire
–Dose-escalating study will evaluate the safety, tolerability and exposure of STK-002 in people with ADOA–

–Changes in visual function, ocular structure and quality of life to be evaluated as secondary objectives–

–ADOA is the most common inherited optic nerve disorder and is primarily caused by variants in the OPA1 gene that result in progressive and irreversible vision loss–

Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine, today announced that the first patient has been dosed in the Phase 1 OSPREY study of STK-002, an investigational medicine for the treatment of Autosomal Dominant Optic Atrophy (ADOA). ADOA is a rare genetic disease that causes progressive and irreversible vision loss in both eyes starting in the first decade of life. Approximately 80 percent of people with ADOA are symptomatic by age 10, and approximately half are expected to become legally blind. There are currently no approved treatments for ADOA.

“Data from our natural history study suggest that for some people affected by ADOA, the disease progresses more rapidly than previously thought. Based on a growing understanding of the disease biology, we believe that increasing naturally occurring OPA1 protein may help restore vision in people with ADOA,” said the lead principal investigator of the study Dr. Patrick Yu-Wai-Man, M.D., Ph.D., Professor of Ophthalmology at the University of Cambridge and honorary consultant neuro-ophthalmologist at Addenbrooke’s Hospital, Moorfields Eye Hospital, and the UCL Institute of Ophthalmology, United Kingdom. “There are currently no medicines available for people living with ADOA, and there is a lot of interest in this study from the ADOA community given the potential for STK-002 to restore vision by addressing the root cause of the disease.”

The OSPREY study is a Phase 1, dose-escalating open-label study of children and adults ages 6 to 55 who have an established diagnosis of ADOA and have a confirmed disease-causing variant in the OPA1 gene. The primary objectives for the study are to assess the safety and tolerability of single ascending doses of STK-002, as well as to determine the exposure in blood. Secondary objectives are to assess changes in visual function, ocular structure and quality of life after single doses of STK-002. The OSPREY study follows a standard dose escalation design with participants enrolled into sequential cohorts receiving increasing dose levels of STK-002. Dose escalation of the first four cohorts will continue through 2026 and early 2027, pending safety and tolerability assessments. Data from the OSPREY study will help to inform potential future development of STK-002.

“ADOA is a haploinsufficient disease, one of many that we believe are ideally suited for our ASOs that are designed to increase naturally occurring protein levels to improve health,” said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “We are pleased to be expanding our approach into a new disease area, leveraging our learnings from Dravet syndrome and applying them to the development of a potential disease-modifying medicine for people living with ADOA.”

The OSPREY study is actively recruiting in the United Kingdom and Germany. Additional European sites are expected to activate in the coming months.

About Autosomal Dominant Optic Atrophy (ADOA)

ADOA is the most common inherited optic nerve disorder, affecting approximately one in 30,000 people globally with a higher incidence of one in 10,000 in Denmark due to a founder effect. It is a rare disease that causes progressive and irreversible vision loss in both eyes starting in the first decade of life. Severity can vary and the rate of vision loss can be difficult to predict. Approximately half of people with ADOA fail driving standards and up to 46% are registered as legally blind. More than 400 different disease-causing OPA1 variants have been reported in people diagnosed with ADOA. Currently there are no approved treatments for people living with ADOA.

About STK-002

STK-002 is a proprietary antisense oligonucleotide (ASO) in clinical development for the treatment of ADOA. Stoke believes that STK-002 has the potential to be the first disease-modifying therapy for people living with ADOA. An estimated 65% to 90% of ADOA cases are caused by variants in the OPA1 gene, most of which lead to a haploinsufficiency resulting in 50% OPA1 protein expression and disease manifestation. STK-002 is designed to upregulate OPA1 protein expression by leveraging the non-mutant (wild-type) copy of the OPA1 gene to restore OPA1 protein expression with the aim to maintain or improve vision in people with ADOA. Stoke has generated preclinical data demonstrating proof-of-mechanism and proof-of-concept for STK-002. STK-002 has been granted orphan drug designation by the U.S. Food and Drug Administration (FDA) as a potential new treatment for ADOA. A Phase 1 study (OSPREY) of STK-002 in people with ADOA is now underway.

About the Phase 1 OSPREY Study

The OSPREY study is a Phase 1, dose-escalating open-label study of children and adults ages 6 to 55 who have an established diagnosis of ADOA and have a confirmed disease-causing variant in the OPA1 gene. The primary objectives for the study are to assess the safety and tolerability of single ascending doses of STK-002, as well as to determine the exposure in blood. Secondary objectives are to assess changes in visual function, ocular structure and quality of life after single doses of STK-002. The OSPREY study follows a standard dose escalation design with participants enrolled into sequential cohorts receiving increasing dose levels of STK-002. Dose escalation of the first four cohorts will continue through 2026 and early 2027, pending safety and tolerability assessments. Data from the OSPREY study will help to inform potential future development of STK-002. The OSPREY study is actively recruiting in the United Kingdom and Germany. Additional European sites are expected to activate in the coming months.

For more information on the OSPREY study, please visit:

https://www.ospreyclinicaltrial.com/

https://www.isrctn.com/ISRCTN41725621

About Stoke Therapeutics

Stoke Therapeutics (Nasdaq: STOK), is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine. Using Stoke’s proprietary TANGO (Targeted Augmentation of Nuclear Gene Output) approach, Stoke is developing antisense oligonucleotides (ASOs) to selectively restore naturally-occurring protein levels. Stoke’s first medicine in development, zorevunersen, has demonstrated the potential for disease modification in patients with Dravet syndrome and is currently being evaluated in a Phase 3 study. Stoke’s initial focus are diseases of the central nervous system and the eye that are caused by a loss of ~50% of normal protein levels (haploinsufficiency). Proof of concept has been demonstrated in other organs, tissues, and systems, supporting broad potential for Stoke’s proprietary approach. Stoke is headquartered in Bedford, Massachusetts. For more information, visit https://www.stoketherapeutics.com/.

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-002 to treat the underlying cause of ADOA and maintain or improve vision; and the timing, details and expected progress of clinical trials for STK-002. Statements including words such as “anticipate,” “potential”, “could,” “expect,” “plan,” “will,” “may” or similar words 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 prove incorrect or do not fully materialize, could cause Stoke’s results to differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, risks and uncertainties related to: Stoke’s ability to advance, obtain regulatory approval and ultimately commercialize its product candidates; that if Stoke’s collaborators were to breach or terminate their agreements, it would not obtain the anticipated financial or other benefits; the possibility that Stoke and its collaborators may not be successful in their development of product candidates and that, even if successful, they may be unable to successfully commercialize such product candidates; positive results in a clinical trial may not be replicated in subsequent trials or successes in early stage clinical trials may not be predictive of results in later stage trials; Stoke’s ability to protect its intellectual property; Stoke’s ability to fund development activities and achieve development goals into 2028; and the other risks and uncertainties described under the heading “Risk Factors” in Stoke’s Annual Report on Form 10-K for the year ended December 31, 2024, its quarterly reports on Form 10-Q, and the other documents it files with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and Stoke undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof.

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Original: Stoke Therapeutics Announces First Patient Dosed in Phase 1 Study of STK-002, a Potential Disease-Modifying Medicine for the Treatment of Autosomal Dominant Optic Atrophy (ADOA)