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Stoke Therapeutics and Biogen Announce Presentations of Clinical Data from Studies of Zorevunersen f
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# Stoke Therapeutics and Biogen Announce Presentations of Clinical Data from Studies of Zorevunersen for the Potential Treatment of Dravet Syndrome at the 36th International Epilepsy Congress **Date:** 2025-08-25 07:00:00 **Company:** Biogen Inc. **Ticker:** BIIB **Source URL:** https://www.businesswire.com/news/home/20250825375131/en/Stoke-Therapeutics-and-Biogen-Announce-Presentations-of-Clinical-Data-from-Studies-of-Zorevunersen-for-the-Potential-Treatment-of-Dravet-Syndrome-at-the-36th-International-Epilepsy-Congress/ --- - # **Stoke Therapeutics and Biogen Announce Presentations of Clinical Data from Studies of Zorevunersen for the Potential Treatment of Dravet Syndrome at the 36th International Epilepsy Congress** Share * * * _– 3-year data from open-label extension (OLE) studies demonstrate the potential for disease modification with durable seizure reductions and improvements in cognition and behavior on top of standard anti-seizure medicines –_ _– Substantial improveme...
# Stoke Therapeutics and Biogen Announce Presentations of Clinical Data from Studies of Zorevunersen for the Potential Treatment of Dravet Syndrome at the 36th International Epilepsy Congress **Date:** 2025-08-25 07:00:00 **Company:** Biogen Inc. **Ticker:** BIIB **Source URL:** https://www.businesswire.com/news/home/20250825375131/en/Stoke-Therapeutics-and-Biogen-Announce-Presentations-of-Clinical-Data-from-Studies-of-Zorevunersen-for-the-Potential-Treatment-of-Dravet-Syndrome-at-the-36th-International-Epilepsy-Congress/ --- - # **Stoke Therapeutics and Biogen Announce Presentations of Clinical Data from Studies of Zorevunersen for the Potential Treatment of Dravet Syndrome at the 36th International Epilepsy Congress** Share * * * _– 3-year data from open-label extension (OLE) studies demonstrate the potential for disease modification with durable seizure reductions and improvements in cognition and behavior on top of standard anti-seizure medicines –_ _– Substantial improvement in overall seizure burden and seizure free days observed with ongoing treatment –_ BEDFORD, Mass. & CAMBRIDGE, Mass.--( [BUSINESS WIRE](https://www.businesswire.com/))-- [Stoke Therapeutics](https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.stoketherapeutics.com%2F&esheet=54311931&newsitemid=20250825375131&lan=en-US&anchor=Stoke+Therapeutics&index=1&md5=c0c91152ae4d708d4494a2b6cd4b6ed7), Inc. (Nasdaq: STOK), a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine, and [Biogen Inc.](https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.biogen.com%2F&esheet=54311931&newsitemid=20250825375131&lan=en-US&anchor=Biogen+Inc.&index=2&md5=ed33434d2ee5ee1d4c964021e3f124f0) (Nasdaq: BIIB), today announced presentations of new clinical data from studies of zorevunersen at the 36th International Epilepsy Congress (IEC), taking place August 30 – September 3, 2025 in Lisbon, Portugal. Zorevunersen, an investigational antisense oligonucleotide, is being evaluated as a potential disease-modifying medicine for the treatment of Dravet syndrome in the global pivotal EMPEROR Phase 3 study. “With these additional clinical data, we are developing a long-term understanding of the potential for zorevunersen to improve outcomes for patients by addressing the underlying genetic cause of Dravet syndrome,” said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “The substantial and durable reductions in seizures and improvements in cognition and behavior in patients already receiving standard anti-seizure medicines support the potential for disease modification. We look forward to sharing and discussing our latest zorevunersen data, including new analyses related to improvements in seizure free days and quality of life, with the world’s leading epilepsy experts at this premier congress.” “The zorevunersen data generated to date are encouraging and support the design of the Phase 3 EMPEROR study now enrolling and dosing patients,” said Katherine Dawson, M.D., Head of the Therapeutics Development Unit at Biogen. “The effects observed so far are bringing greater awareness to Dravet syndrome as a neurodevelopmental disorder while generating increasing interest in EMPEROR.” Details of the presentations at IEC are as follows: - **Title:** [Zorevunersen demonstrates potential as a disease‑modifying therapy in patients with Dravet syndrome through durable seizure reduction and improvements in cognition, behavior, and functioning with up to 36 months of maintenance dosing in open-label extension studies](https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fiec2025.abstractserver.com%2Fprogramme%2F%23%2Fdetails%2Fpresentations%2F521&esheet=54311931&newsitemid=20250825375131&lan=en-US&anchor=Zorevunersen+demonstrates+potential+as+a+disease%26%238209%3Bmodifying+therapy+in+patients+with+Dravet+syndrome+through+durable+seizure+reduction+and+improvements+in+cognition%2C+behavior%2C+and+functioning+with+up+to+36+months+of+maintenance+dosing+in+open-label+extension+studies&index=3&md5=7876c9a0514cfbb7b382a8b8dd8a742f) **Oral Presentation Date & Time:** Sunday, August 31, 3:15 – 4:15 PM WEST/GMT +1 (10:15 – 11:15 AM ET) **Oral Presenter:** Andreas Brunklaus, M.D., Consultant Paediatric Neurologist at the Royal Hospital for Children, Glasgow, Honorary Professor at the University of Glasgow, member of Dravet Syndrome UK's Medical Advisory Board - **Title:** [Substantial improvements in overall seizure burden and seizure free days in patients with Dravet syndrome treated with zorevunersen: Results from Phase 1/2a and open-label extension studies](https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fiec2025.abstractserver.com%2Fprogramme%2F%23%2Fdetails%2Fpresentations%2F920&esheet=54311931&newsitemid=20250825375131&lan=en-US&anchor=Substantial+improvements+in+overall+seizure+burden+and+seizure+free+days+in+patients+with+Dravet+syndrome+treated+with+zorevunersen%3A+Results+from+Phase+1%2F2a+and+open-label+extension+studies&index=4&md5=884ab551959b9bbf3c67a53a3b393b93) **Poster Presentation Date & Time:** Monday, September 1, 1:45 – 3:15 PM WEST/ GMT +1 (8:45 – 10:15 AM ET) **Poster Presenter:** J 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:** P351 - **Title:** [EMPEROR Phase 3 study design: Evaluation of zorevunersen as a potential disease-modifying therapy for Dravet syndrome](https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fiec2025.abstractserver.com%2Fprogramme%2F%23%2Fdetails%2Fpresentations%2F917&esheet=54311931&newsitemid=20250825375131&lan=en-US&anchor=EMPEROR+Phase+3+study+design%3A+Evaluation+of+zorevunersen+as+a+potential+disease-modifying+therapy+for+Dravet+syndrome&index=5&md5=f3555cea01991b41da1423d39e9bdde0) **Poster Presentation Date & Time:** Monday, September 1, 1:45 – 3:15 PM WEST/ GMT +1 (8:45 – 10:15 AM ET) **Poster Presenter:** Joseph Sullivan, M.D., FAES, Professor of Neurology and Pediatrics and Director of the Pediatric Epilepsy Center of Excellence at the University of California San Francisco **Poster Number:** P358 **Additional Company Presentation:** - **Title:** [Emerging Concepts and Therapeutics in Dravet Syndrome: From Burden to Breakthroughs](https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fiec2025.abstractserver.com%2Fprogramme%2F%23%2Fdetails%2Fsessions%2F152&esheet=54311931&newsitemid=20250825375131&lan=en-US&anchor=Emerging+Concepts+and+Therapeutics+in+Dravet+Syndrome%3A+From+Burden+to+Breakthroughs&index=6&md5=b572d7967842227c26cdda5db33d5d1e) **Date & Time:** Tuesday, September 2, 1:55 – 3:05 PM WEST/ GMT +1 (8:55 – 10:05 ET) **Presenters:** Stéphane Auvin, M.D., Ph.D., FAES, Epileptologist and Child Neurologist, Chair of the Pediatric Neurology Department at Robert Debré University Hospital & Université Paris; Kelly G. Knupp, M.D., Professor, Pediatrics-Neurology, University of Colorado Anschutz Medical Campus, Children’s Hospital Colorado; and Scott Perry, M.D., Medical Director, Neurology; Co-Director, Jane and John Justin Neurosciences Center; Medical Director, Genetic Epilepsy Clinic **,** Cook Children's Hospital **About Dravet Syndrome** Dravet syndrome is a severe developmental and epileptic encephalopathy (DEE) characterized by severe, 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. More than 90 percent of patients continue to experience seizures despite treatment with the best available anti-seizure medicines. 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. 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.1 **About Zorevunersen** Zorevunersen is an investigational antisense oligonucleotide that is designed to treat the underlying cause of Dravet syndrome by increasing NaV1.1 protein production in brain cells from the non-mutated (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 EMPEROR Study** The EMPEROR Phase 3 Study (NCT06872125) is a global, double-blind, sham-controlled study evaluating the efficacy, safety and tolerability of zorevunersen in children ages 2 to <18 with Dravet syndrome with a confirmed variant in the _SCN1A_ gene not associated with gain-of-function. The trial is expected to enroll participants across the United States, Japan, United Kingdom and European Union, with participants being randomized 1:1 to receive either zorevunersen via intrathecal administration or a sham comparator for a 52-week treatment period following an 8-week baseline period. Following the completion of the study, eligible participants will be offered ongoing treatment with zorevunersen as part of an OLE study. The primary endpoint of the study is percent change from baseline in major motor seizure frequency at week 28 in patients receiving zorevunersen as compared to sham. The key secondary endpoints are the durability of effect on major motor seizure frequency and improvements in behavior and cognition as measured by Vineland-3 subdomains, including expressive communication, receptive communication, interpersonal relationships, coping skills and personal skills. Additional endpoints include safety, Clinician Global Impression of Change (CGI-C), Caregiver Global Impression of Change (CaGI-C), and the Bayley Scales of Infant Development (BSID-IV). For more information, visit [https://www.emperorstudy.com/](https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.emperorstudy.com%2F&esheet=54311931&newsitemid=20250825375131&lan=en-US&anchor=https%3A%2F%2Fwww.emperorstudy.com%2F&index=7&md5=604edf3efbc211f977975217f66172d6). **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/](https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.stoketherapeutics.com%2F&esheet=54311931&newsitemid=20250825375131&lan=en-US&anchor=https%3A%2F%2Fwww.stoketherapeutics.com%2F&index=8&md5=812bd6343af3178c88b4a46c77ccbc07). **About Biogen** Founded in 1978, Biogen is a leading biotechnology company that pioneers innovative science to deliver new medicines to transform patients’ lives and to create value for shareholders and our communities. We apply deep understanding of human biology and leverage different modalities to advance first-in-class treatments or therapies that deliver superior outcomes. Our approach is to take bold risks, balanced with return on investment to deliver long-term growth. We routinely post information that may be important to investors on our website at [www.biogen.com](https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fwww.globenewswire.com%2FTracker%3Fdata%3DNETrezJbdYrVoi5ddDQzntWHpjrTeUkS3vgJ9QKdurYMhloN73X4BFRV8yzGC0wqvtNEu4MPUqhIMFKW3ObunLzxJnuJrprTyyDTr1gh3QI%3D&esheet=54311931&newsitemid=20250825375131&lan=en-US&anchor=www.biogen.com&index=9&md5=715289d1b717068aa7f221feb7c8d32b). 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Statements including words such as “plan,” “potential,” “will,” “continue,” “expect,” 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: Stokes ability to advance, obtain regulatory approval and ultimately commercialize its product candidates; that if Biogen were to breach or terminate the collaboration, Stoke would not obtain the anticipated financial or other benefits; the possibility that Stoke and Biogen may not be successful in their development of zorevunersen and that, even if successful, they may be unable to successfully commercialize zorevunersen; 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 to mid-2028; and the other risks and uncertainties described under the heading “Risk Factors” in its 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. **Biogen Safe Harbor** This news release contains forward-looking statements, including, among others, relating to: the potential clinical effects of zorevunersen; the potential for zorevunersen to improve outcomes and for patients of Dravet syndrome; the potential benefits, safety and efficacy of zorevunersen and continued treatment with zorevunersen; potential regulatory discussions, submissions and approvals and the timing thereof; the treatment of Dravet syndrome; the anticipated benefits, risks and potential of Biogen's collaboration arrangements with Stoke Therapeutics; the potential of Biogen's commercial business and pipeline programs, including zorevunersen; and risks and uncertainties associated with drug development and commercialization. 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Given their forward-looking nature, these statements involve substantial risks and uncertainties that may be based on inaccurate assumptions and could cause actual results to differ materially from those reflected in such statements. These forward-looking statements are based on management’s current beliefs and assumptions and on information currently available to management. Given their nature, we cannot assure that any outcome expressed in these forward-looking statements will be realized in whole or in part. We caution that these statements are subject to risks and uncertainties, many of which are outside of our control and could cause future events or results to differ materially from those stated or implied in this document, including, among others, uncertainty of our long-term success in developing, licensing, or acquiring other product candidates or additional indications for existing products; expectations, plans, prospects and timing of actions relating to product approvals, approvals of additional indications for our existing products, sales, pricing, growth, reimbursement and launch of our marketed and pipeline products; the potential impact of increased product competition in the biopharmaceutical and healthcare industry, as well as any other markets in which we compete, including increased competition from new originator therapies, generics, prodrugs and biosimilars of existing products and products approved under abbreviated regulatory pathways; our ability to effectively implement our corporate strategy; difficulties in obtaining and maintaining adequate coverage, pricing, and reimbursement for our products; the drivers for growing our business, including our dependence on collaborators and other third parties for the development, regulatory approval, and commercialization of products and other aspects of our business, which are outside of our full control; risks related to commercialization of biosimilars, which is subject to such risks related to our reliance on third-parties, intellectual property, competitive and market challenges and regulatory compliance; the risk that positive results in a clinical trial may not be replicated in subsequent or confirmatory trials or success in early stage clinical trials may not be predictive of results in later stage or large scale clinical trials or trials in other potential indications; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; and the occurrence of adverse safety events, restrictions on use with our products, or product liability claims; and any other risks and uncertainties that are described in other reports we have filed with the U.S. Securities and Exchange Commission, which are available on the SEC’s website at [www.sec.gov](https://cts.businesswire.com/ct/CT?id=smartlink&url=http%3A%2F%2Fwww.sec.gov&esheet=54311931&newsitemid=20250825375131&lan=en-US&anchor=www.sec.gov&index=14&md5=381063f171049dcb12b13c4ce6f4b367). These statements speak only as of the date of this press release and are based on information and estimates available to us at this time. Should known or unknown risks or uncertainties materialize or should underlying assumptions prove inaccurate, actual results could vary materially from past results and those anticipated, estimated or projected. Investors are cautioned not to put undue reliance on forward-looking statements. A further list and description of risks, uncertainties and other matters can be found in our Annual Report on Form 10-K for the fiscal year ended December 31, 2024 and in our subsequent reports on Form 10-Q. Except as required by law, we do not undertake any obligation to publicly update any forward-looking statements whether as a result of any new information, future events, changed circumstances or otherwise. Reference: 1. Based on Stoke Therapeutics’ preliminary estimates, which scaled annual incidence to prevalence using country-specific live birth rates over the past 85 years and adjusted for Dravet-specific mortality. The estimate is based on incidence rates published by [Wu et al., Pediatrics, 2015](https://cts.businesswire.com/ct/CT?id=smartlink&url=https%3A%2F%2Fpublications.aap.org%2Fpediatrics%2Farticle-abstract%2F136%2F5%2Fe1310%2F33828%2FIncidence-of-Dravet-Syndrome-in-a-US-Population%3FredirectedFrom%3Dfulltext%3Fautologincheck%3Dredirected&esheet=54311931&newsitemid=20250825375131&lan=en-US&anchor=Wu+et+al.%2C+Pediatrics%2C+2015&index=15&md5=693da438283c64a507ee8e699f169a7c). ## Contacts **Stoke Media & Investor Contacts:** Dawn Kalmar Chief Communications Officer [dkalmar@stoketherapeutics.com](mailto:dkalmar@stoketherapeutics.com) 781-303-8302 Doug Snow Director, Communications & Investor Relations [IR@stoketherapeutics.com](mailto:IR@stoketherapeutics.com) 508-642-6485 **Biogen Media Contact:** Madeleine Shin [Public.affairs@biogen.com](mailto:Public.affairs@biogen.com) \+ 1 781 464 3260 **Biogen Investor Contact:** Tim Power [IR@biogen.com](mailto:IR@biogen.com) +1 781 464 2442 Industry: - [Science](https://www.businesswire.com/newsroom?industry=1050101) - [Biotechnology](https://www.businesswire.com/newsroom?industry=1000039) - [Research](https://www.businesswire.com/newsroom?industry=1000159) - [Pharmaceutical](https://www.businesswire.com/newsroom?industry=1000146) - [Health](https://www.businesswire.com/newsroom?industry=1000088) - [FDA](https://www.businesswire.com/newsroom?industry=1050070) - [Genetics](https://www.businesswire.com/newsroom?industry=1000082) - [Clinical Trials](https://www.businesswire.com/newsroom?industry=1000045) [](https://www.stoketherapeutics.com/) ### Stoke Therapeutics, Inc. NASDAQ:STOK * * * Release Versions [English](https://www.businesswire.com/news/home/20250825375131/en/Stoke-Therapeutics-and-Biogen-Announce-Presentations-of-Clinical-Data-from-Studies-of-Zorevunersen-for-the-Potential-Treatment-of-Dravet-Syndrome-at-the-36th-International-Epilepsy-Congress) * * * ### Contacts **Stoke Media & Investor Contacts:** Dawn Kalmar Chief Communications Officer [dkalmar@stoketherapeutics.com](mailto:dkalmar@stoketherapeutics.com) 781-303-8302 Doug Snow Director, Communications & Investor Relations [IR@stoketherapeutics.com](mailto:IR@stoketherapeutics.com) 508-642-6485 **Biogen Media Contact:** Madeleine Shin [Public.affairs@biogen.com](mailto:Public.affairs@biogen.com) \+ 1 781 464 3260 **Biogen Investor Contact:** Tim Power [IR@biogen.com](mailto:IR@biogen.com) +1 781 464 2442 More News From Stoke Therapeutics, Inc. 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[**Stoke Therapeutics Announces Inducement Grants Under Nasdaq Listing Rule 5635(C)(4)**](https://www.businesswire.com/news/home/20260317412877/en/Stoke-Therapeutics-Announces-Inducement-Grants-Under-Nasdaq-Listing-Rule-5635C4) BEDFORD, Mass.--( [BUSINESS WIRE](https://www.businesswire.com/))--Stoke Therapeutics, Inc. (Nasdaq: STOK) is a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine and has a lead investigational medicine, zorevunersen, in development as a first-in-class potential disease-modifying treatment for Dravet syndrome. The Company today announced that, effective on March 16, 2026, it granted stock options to purchase an aggregate of 58,650 shares of common stock to six ne...  [Back to Newsroom](https://www.businesswire.com/newsroom) [](https://www.stoketherapeutics.com/) ### Stoke Therapeutics, Inc. NASDAQ:STOK * * * Release Versions [English](https://www.businesswire.com/news/home/20250825375131/en/Stoke-Therapeutics-and-Biogen-Announce-Presentations-of-Clinical-Data-from-Studies-of-Zorevunersen-for-the-Potential-Treatment-of-Dravet-Syndrome-at-the-36th-International-Epilepsy-Congress) * * * ### Contacts **Stoke Media & Investor Contacts:** Dawn Kalmar Chief Communications Officer [dkalmar@stoketherapeutics.com](mailto:dkalmar@stoketherapeutics.com) 781-303-8302 Doug Snow Director, Communications & Investor Relations [IR@stoketherapeutics.com](mailto:IR@stoketherapeutics.com) 508-642-6485 **Biogen Media Contact:** Madeleine Shin [Public.affairs@biogen.com](mailto:Public.affairs@biogen.com) \+ 1 781 464 3260 **Biogen Investor Contact:** Tim Power [IR@biogen.com](mailto:IR@biogen.com) +1 781 464 2442
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