Osprey: An open-label study to investigate the safety, tolerability, and exposure of single ascending doses of the antisense oligonucleotide STK-002 in patients with autosomal dominant optic atrophy

开始日期2024-12-31

申办/合作机构

Stoke Therapeutics, Inc.

100 项与 STK-002 相关的临床结果

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100 项与 STK-002 相关的转化医学

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100 项与 STK-002 相关的专利（医药）

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项与 STK-002 相关的文献（医药）

2024-10-01·Nucleic Acid Therapeutics

Antisense Oligonucleotide STK-002 Increases OPA1 in Retina and Improves Mitochondrial Function in Autosomal Dominant Optic Atrophy Cells

Article

作者: Ravipaty, Shobha ; Jacobson, Sarah ; Lin, Qian ; Aznarez, Isabel ; Sonntag, Donna ; Ali, Syed ; Kach, Jacob ; Huryn, Laryssa A. ; Anderson, Karen ; McKenty, Taylor ; Srinivasan, Vaishnavi ; Li, Zhiyu ; Liau, Gene ; Hoger, Jeff ; Christiansen, Anne ; Hufnagel, Robert B. ; Venkatesh, Aditya ; Slate, Deirdre ; Zinshteyn, Boris ; Lim, Kian Huat ; Cui, Yanyan

Autosomal dominant optic atrophy (ADOA) is an inherited optic neuropathy most frequently associated with OPA1 mutations. Most variants result in haploinsufficiency, and patient cells express roughly half of the normal levels of OPA1 protein. OPA1 is a mitochondrial GTPase that is essential for normal mitochondrial function. We identified and characterized STK-002, an antisense oligonucleotide (ASO) designed to prevent the incorporation of a naturally occurring alternatively spliced nonproductive exon in OPA1. STK-002 dose dependently reduced the inclusion of this exon, and increased OPA1 protein in human cells, including ADOA patient-derived fibroblasts. ADOA patient cells manifest reduced mitochondrial respiration, and treatment with STK-002 improved the parameters of mitochondrial respiratory function in these cells. Since STK-002 increases OPA1 through the wild-type allele, we assessed retinal OPA1 in wild-type cynomolgus monkeys and rabbits after intravitreal administration of STK-002 or a rabbit-specific surrogate. Increased OPA1 protein was produced in retinal tissue in both species at 4 weeks after ASO injection and persisted in monkeys at 8 weeks. STK-002 and enhanced OPA1 immunofluorescence were visualized in retinal ganglion cells of cynomolgus monkeys treated with the ASO. Cumulatively, these data support the progression of STK-002 toward the clinic as the first potential disease-modifying treatment for ADOA.

项与 STK-002 相关的新闻（医药）

2024-11-05

·Business Wire

Stoke Therapeutics Reports Third Quarter Financial Results and Provides Business Updates

BEDFORD, Mass.--( BUSINESS WIRE )-- Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine, today reported financial results for the third quarter of 2024 and provided business updates including those related to zorevunersen, the Company’s proprietary antisense oligonucleotide (ASO) which is in development by Stoke as the first potential medicine to address the genetic cause of Dravet syndrome. “We are headed into a busy year-end as we prepare to share new data which is representative of our proposed Phase 3 dosing regimen and complete our regulatory discussions toward alignment on that study design,” said Edward M. Kaye, M.D., Chief Executive Officer of Stoke Therapeutics. “Key to our regulatory discussions are the assessments of behavior and cognition in patients with Dravet syndrome. In our studies of zorevunersen, we have demonstrated substantial and sustained effects across multiple measures of disease, starting within the first year of treatment. These data give us confidence in our Phase 3 planning and the potential for zorevunersen to go beyond seizure management by addressing the root cause of the disease.” The Company announced today that it has submitted abstracts for presentation at the American Epilepsy Society meeting taking place December 6-10, in Los Angeles, California. Included among these planned presentations are new data from all patients treated in the clinical studies with initial 70mg doses followed by 45mg maintenance dosing in studies of zorevunersen. A Phase 3 regimen of two or three loading doses of 70mg followed by maintenance doses of 45mg is currently under discussion with global regulatory agencies. As the Company continues to focus on zorevunersen as its lead program, it will delay the start of the Phase 1 study of STK-002, its clinical candidate for the treatment of autosomal dominant optic atrophy (ADOA). Recent Program Highlights and Upcoming Milestones In August, the Company announced that the U.S. Food and Drug Administration (FDA) has removed the Partial Clinical Hold on zorevunersen. In September, the Company shared data from the Phase 1/2a and open-label extension (OLE) studies of zorevunersen in children and adolescents with Dravet syndrome at the 15 th European Epilepsy Congress (EEC). Company management will present at the Jefferies London Healthcare Conference on Wednesday, November 20, at 6:30am EST (11:30am GMT). A live webcast of the presentation will be available on the Investors & News section of Stoke’s website. The Company expects to present data at the American Epilepsy Society (AES) 2024 Annual Meeting, pending acceptance of the abstracts. The Company plans to provide an update on Phase 3 registrational plans for zorevunersen by year-end. Third Quarter 2024 Financial Results As of September 30, 2024, the Company had $269.2 million in cash, cash equivalents, and marketable securities. Revenue recognized for upfront license fees and services provided from the License and Collaboration Agreement with Acadia Pharmaceuticals for the three months ended September 30, 2024 was $4.9 million, compared to $3.3 million for the same period in 2023. Net loss for the three months ended September 30, 2024 was $26.4 million, or $0.47 per share, compared to $24.5 million, or $0.55 per share, for the same period in 2023. Research and development expenses for the three months ended September 30, 2024 were $22.2 million, compared to $20.3 million for the same period in 2023. General and administrative expenses for the three months ended September 30, 2024 were $12.7 million, compared to $10.3 million for the same period in 2023. Year-to-Date 2024 Financial Results Revenue recognized for upfront license fees and services provided from the License and Collaboration Agreement with Acadia Pharmaceuticals for the nine months ended September 30, 2024 was $13.9 million, compared to $6.0 million for the same period in 2023. Net loss for the nine months ended September 30, 2024 was $78.5 million, or $1.48 per share, compared to $77.7 million, or $1.78 per share, for the same period in 2023. Research and development expenses for the nine months ended September 30, 2024 were $65.7 million, compared to $60.5 million for the same period in 2023. General and administrative expenses for the nine months ended September 30, 2024 were $36.0 million, compared to $30.7 million for the same period in 2023. The increase in operating expenses for the three and nine month periods ending September 30, 2024 over the same periods in 2023 primarily relates to increases in costs associated with personnel, third party contracts, consulting, facilities and other costs associated with development activities for zorevunersen and STK-002, research on additional therapeutics and growing a public corporation. 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 Zorevunersen (STK-001) Zorevunersen is an investigational new medicine for the treatment of Dravet syndrome currently being evaluated in ongoing clinical trials. Stoke believes that zorevunersen, a proprietary antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. Zorevunersen is designed to upregulate Na v 1.1 protein expression by leveraging the non-mutant (wild-type) copy of the SCN1A gene to restore physiological Na v 1.1 levels, thereby reducing both occurrence of seizures and significant non-seizure comorbidities. Zorevunersen 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 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 protein levels. Stoke’s first compound, zorevunersen (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/ . 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 Company’s current or future financial position and liquidity; the ability of zorevunersen (STK-001) to treat the underlying causes of Dravet syndrome and reduce seizures or show improvements in behavior and cognition at the indicated dosing levels or at all; and the timing and expected progress of clinical trials, data readouts, regulatory meetings, regulatory decisions and other presentations. Statements including words such as “expect,” “plan,” “will,” “continue,” 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 prove incorrect or do not fully materialize, could cause our results to differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, risks and uncertainties related to: the Company’s ability to advance, obtain regulatory approval of, and ultimately commercialize its product candidates, including zorevunersen; the timing of data readouts and interim and final results of preclinical and clinical trials; the receipt and timing of potential regulatory decisions; 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; the Company’s ability to fund development activities and achieve development goals, including expectations regarding its collaboration with Acadia Pharmaceuticals; the Company’s ability to protect its intellectual property; the direct or indirect impact of global business, political and macroeconomic conditions, including inflation, interest rate volatility, cybersecurity events, uncertainty with respect to the federal budget, instability in the global banking system and volatile market conditions, and global events, including public health crises, and ongoing geopolitical conflicts, such as the conflicts in Ukraine and the Middle East; and other risks and uncertainties described under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023, its quarterly reports on Form 10-Q, and the other documents it files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and the Company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof. Financial Tables Follow Stoke Therapeutics, Inc. and subsidiary Consolidated balance sheets (in thousands, except share and per share amounts) (unaudited) September 30, December 31, 2024 2023 Assets Current assets: Cash and cash equivalents $ 150,016 $ 191,442 Marketable securities - current 89,184 9,952 Prepaid expenses 9,837 11,320 Restricted cash - current 75 — Interest receivable 691 64 Other current assets 3,809 2,561 Total current assets $ 253,612 $ 215,339 Marketable securities - long-term 29,952 — Restricted cash - long-term 494 569 Operating lease right-of-use assets 4,928 6,611 Property and equipment, net 4,333 5,823 Total assets $ 293,319 $ 228,342 Liabilities and stockholders’ equity Current liabilities: Accounts payable $ 2,485 $ 1,695 Accrued and other current liabilities 15,768 13,815 Deferred revenue - current portion 31,612 15,309 Total current liabilities $ 49,865 $ 30,819 Deferred revenue - net of current portion 8,291 33,074 Other long term liabilities 3,050 4,884 Total long term liabilities 11,341 37,958 Total liabilities $ 61,206 $ 68,777 Stockholders’ equity Common stock, par value of $0.0001 per share; 300,000,000 shares authorized, 52,941,191 and 45,918,233 shares issued and outstanding as of September 30, 2024 and December 31, 2023, respectively 5 5 Additional paid-in capital 712,290 561,433 Accumulated other comprehensive income (loss) 166 (24 ) Accumulated deficit (480,348 ) (401,849 ) Total stockholders’ equity $ 232,113 $ 159,565 Total liabilities and stockholders’ equity $ 293,319 $ 228,342 Stoke Therapeutics, Inc. and subsidiary Consolidated statements of operations and comprehensive loss (in thousands, except share and per share amounts) (unaudited) Three Months Ended September 30, Nine Months Ended September 30, 2024 2023 2024 2023 Revenue $ 4,894 $ 3,308 $ 13,941 $ 5,978 Operating expenses: Research and development 22,205 20,271 65,710 60,453 General and administrative 12,692 10,271 35,950 30,712 Total operating expenses 34,897 30,542 101,660 91,165 Loss from operations (30,003 ) (27,234 ) (87,719 ) (85,187 ) Other income (expense): Interest income (expense), net 3,545 2,651 9,668 7,321 Other income (expense), net 28 41 (448 ) 125 Total other income (expense) 3,573 2,692 9,220 7,446 Net loss $ (26,430 ) $ (24,542 ) $ (78,499 ) $ (77,741 ) Net loss per share, basic and diluted $ (0.47 ) $ (0.55 ) $ (1.48 ) $ (1.78 ) Weighted-average common shares outstanding, basic and diluted 56,341,074 44,266,017 52,991,015 43,669,987 Comprehensive loss: Net loss $ (26,430 ) $ (24,542 ) $ (78,499 ) $ (77,741 ) Other comprehensive gain: Unrealized gain on marketable securities 181 232 190 1,028 Total other comprehensive gain $ 181 $ 232 $ 190 $ 1,028 Comprehensive loss $ (26,249 ) $ (24,310 ) $ (78,309 ) $ (76,713 )

财报临床3期寡核苷酸孤儿药临床结果

2024-09-10

·PipelineReview

Stoke Therapeutics Presents Zorevunersen Data Showing Substantial Reductions in Seizures and Improvements in Multiple Measures of Cognition and Behavior That Support the Potential for Disease Modification in Dravet Syndrome

– New data showed improvements in cognition and behavior during the first year of treatment with additional increases demonstrated as treatment continued – – Clinical effects observed across the Phase 1/2a and open-label extension studies (OLEs) of zorevunersen are a first in the treatment of Dravet syndrome and support plans for the Company’s Phase 3 registrational study – – Zorevunersen generally well-tolerated across the studies – – Data presented for the first time at the 15th European Epilepsy Congress (EEC) – BEDFORD, MA, USA I September 10, 2024 I Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine, today announced highlights from presentations at the 15th European Epilepsy Congress (EEC) related to the Company’s work to develop the first disease-modifying medicine for Dravet syndrome. Zorevunersen (STK-001) data showing substantial and sustained reductions in seizures and meaningful improvements in multiple measures of cognition and behavior were presented for the first time in a scientific forum. New data from an analysis of patients treated in the Phase 1/2a ADMIRAL study showed improvements in cognition and behavior during the first year of treatment with additional increases demonstrated as treatment continued. In addition, data from a two-year natural history study presented at the meeting showed that despite treatment with standard-of-care antiseizure medications, patients with Dravet syndrome continued to have high seizure rates and plateaued in their neurodevelopment, resulting in a widening gap in development compared to their neurotypical peers. 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. There are no approved disease-modifying therapies for people living with Dravet syndrome, which occurs in one out of 16,000 babies. “The profound reductions in seizures and improvements in cognition and behavior seen in these studies open the door to a new era in the treatment of Dravet syndrome and provide convincing evidence of the potential for zorevunersen as the first disease-modifying medicine,” said Helen Cross, MB ChB, Ph.D., Professor, 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, and the ADMIRAL study lead investigator. “We are very encouraged by the data from the Phase 1/2a ADMIRAL study that showed substantial reductions in seizures and meaningful improvements in cognition and behavior within the first year of treatment. As patients continue treatment in the open-label extension study we see even greater improvements in their cognition and behavior, which is remarkable.” “The two-year natural history data provide clear evidence that current anti-seizure medicines are insufficient because even with the best available medicines patients still suffer from continued high rates of seizures and, as these children age, their development falls further behind their neurotypical peers,” said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “Data from our clinical studies of zorevunersen provide a glimpse into the future of treatment for patients with Dravet syndrome. The data from our studies suggest that by restoring protein expression with zorevunersen, we may be able to substantially reduce seizures beyond any benefit patients are currently receiving from anti-seizure medicines. Even more promising is the potential to improve cognition and behavior, which has never before been demonstrated in a clinical study of Dravet syndrome. These data provide confidence in our plans for a Phase 3 registrational study, including the dose regimen and clinical endpoints.” Highlights from the Company’s presentations at the meeting include: All presentations are available for download on the Stoke Therapeutics website under the Investors & News tab. 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 Zorevunersen (STK-001) Zorevunersen is an investigational new medicine for the treatment of Dravet syndrome currently being evaluated in ongoing clinical trials. Stoke believes that zorevunersen, a proprietary antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. Zorevunersen 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. Zorevunersen 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 the U.S. Studies: MONARCH (Phase 1/2a) and SWALLOWTAIL (OLE) The MONARCH study was 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 were to assess the safety and tolerability of zorevunersen (STK-001), as well as to determine the pharmacokinetics in plasma and exposure in cerebrospinal fluid. A secondary objective was to assess the efficacy as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency. Following completion of MONARCH, patients who met study entry criteria were 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 zorevunersen. The study is also evaluating the long-term effects of zorevunersen on convulsive seizure frequency and on behavior, cognition and overall quality of life. Dosing in SWALLOWTAIL is ongoing. About the UK Studies: ADMIRAL (Phase 1/2a) and LONGWING (OLE) The ADMIRAL study was 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 were to assess the safety and tolerability of multiple doses of zorevunersen (STK-001), as well as to determine the pharmacokinetics in plasma and exposure in cerebrospinal fluid. A secondary objective was to assess the effect of multiple doses of zorevunersen as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency. Overall clinical status and quality of life were secondary endpoints of ADMIRAL. Following completion of ADMIRAL, patients who met study entry criteria were 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 zorevunersen. The study is also evaluating the long-term effects of zorevunersen on convulsive seizure frequency and on behavior, cognition and overall quality of life. Dosing in LONGWING is ongoing. About the BUTTERFLY Observational Study The BUTTERFLY study was a multicenter, longitudinal, prospective, observational study of children and adolescents ages 2 to 18 who have been diagnosed with Dravet syndrome as a result of an SCN1A gene mutation. This study was designed to evaluate neurodevelopmental status and change from baseline to 24 months. Secondary and exploratory endpoints in the study evaluated changes in other disease measures, including seizures and additional non-seizure comorbidities. No investigational medications or other treatments were provided. Participants continued to receive their usual care, including anti-seizure medications, and were observed for up to two years. The study was conducted at approximately 20 sites in the United States. Two-year results were presented at the American Epilepsy Society Annual Meeting in December 2023 and showed that, on average, patients experienced no meaningful improvement in convulsive seizure frequency and exhibited widening gaps in cognition and behavior compared to neurotypical peers, despite treatment with the best available anti-seizure medicines. 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 protein levels. Stoke’s first compound, zorevunersen (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/ . SOURCE: Stoke Therapeutics

临床结果临床3期孤儿药

2024-09-03

·Business Wire

Stoke Therapeutics to Present Encore Data at the 15th European Epilepsy Congress that Demonstrate the Potential for Zorevunersen to be the First Disease-Modifying Medicine for the Treatment of Dravet Syndrome

BEDFORD, Mass.--( BUSINESS WIRE )-- Stoke Therapeutics, Inc. (Nasdaq: STOK), a biotechnology company dedicated to restoring protein expression by harnessing the body’s potential with RNA medicine, today announced it will present data from its Dravet syndrome clinical program at the 15th European Epilepsy Congress (EEC) taking place September 7 – 11, in Rome, Italy. The Company is advancing zorevunersen (STK-001), a proprietary antisense oligonucleotide (ASO), as the first potential medicine to address the genetic cause of Dravet syndrome. Presentations include a platform session as well as two poster presentations showcasing a comprehensive dataset from the Company’s Dravet syndrome studies. “Our natural history study makes a compelling case that current treatments are insufficient to address the needs of patients with Dravet syndrome because patients still have high seizure rates and plateau in their neurodevelopment,” said Barry Ticho, M.D., Ph.D., Chief Medical Officer of Stoke Therapeutics. “In this context, and based on the data we have seen from our clinical studies of zorevunersen, we believe we have the potential to change the way this disease is treated by addressing the root cause of the disease, not just the symptoms. We look forward to continuing to work with Dravet syndrome leaders around the world to prepare for a Phase 3 registrational study of zorevunersen.” Details for the Company’s presentations at EEC are as follows: Title: MONARCH and ADMIRAL: Open-label, Phase 1/2a studies in USA and UK investigating safety, drug exposure, and clinical effect of zorevunersen, an antisense oligonucleotide (ASO), in children and adolescents with Dravet syndrome Session: Platform Session – Paediatric Epileptology Event Type: Platform Session Presentation Date & Time: Tuesday, September 10, 12:22 – 12:30 PM CEST 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 Title: 24-month analysis of BUTTERFLY: A prospective, observational study to investigate seizures and comorbidities in children and adolescents with Dravet syndrome (DS) Event Type: In-Person Posters Presentation Date & Time: Sunday, September 8, 2:30 PM - 2:33 PM CEST 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: P788 Title: SWALLOWTAIL and LONGWING: Open-Label Extension (OLE) studies for children and adolescents with Dravet syndrome who previously participated in a study of Antisense Oligonucleotide zorevunersen Event Type: In-Person Posters Presentation Date & Time: Sunday, September 8 - Tuesday, September 10; Q&A from 1:30 - 3:00 PM CEST each day Presenter: Andreas Brunklaus, MD, 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 Poster Number: P875 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 Zorevunersen (STK-001) Zorevunersen is an investigational new medicine for the treatment of Dravet syndrome currently being evaluated in ongoing clinical trials. Stoke believes that zorevunersen, a proprietary antisense oligonucleotide (ASO), has the potential to be the first disease-modifying therapy to address the genetic cause of Dravet syndrome. Zorevunersen 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. Zorevunersen 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 the U.S. Studies: MONARCH (Phase 1/2a) and SWALLOWTAIL (OLE) The MONARCH study was 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 were to assess the safety and tolerability of zorevunersen (STK-001), as well as to determine the pharmacokinetics in plasma and exposure in cerebrospinal fluid. A secondary objective was to assess the efficacy as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency. Following completion of MONARCH, patients who met study entry criteria were 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 zorevunersen. The study is also evaluating the long-term effects of zorevunersen on convulsive seizure frequency and on behavior, cognition and overall quality of life. Dosing in SWALLOWTAIL is ongoing. About the UK Studies: ADMIRAL (Phase 1/2a) and LONGWING (OLE) The ADMIRAL study was 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 were to assess the safety and tolerability of multiple doses of zorevunersen (STK-001), as well as to determine the pharmacokinetics in plasma and exposure in cerebrospinal fluid. A secondary objective was to assess the effect of multiple doses of zorevunersen as an adjunctive antiepileptic treatment with respect to the percentage change from baseline in convulsive seizure frequency. Overall clinical status and quality of life were secondary endpoints of ADMIRAL. Following completion of ADMIRAL, patients who met study entry criteria were 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 zorevunersen. The study is also evaluating the long-term effects of zorevunersen on convulsive seizure frequency and on behavior, cognition and overall quality of life. Dosing in LONGWING is ongoing. About the BUTTERFLY Observational Study The BUTTERFLY study was a multicenter, longitudinal, prospective, observational study of children and adolescents ages 2 to 18 who have been diagnosed with Dravet syndrome as a result of an SCN1A gene mutation. This study was designed to evaluate neurodevelopmental status and change from baseline to 24 months. Secondary and exploratory endpoints in the study evaluated changes in other disease measures, including seizures and additional non-seizure comorbidities. No investigational medications or other treatments were provided. Participants continued to receive their usual care, including anti-seizure medications, and were observed for up to two years. The study was conducted at approximately 20 sites in the United States. Two-year results were presented at the American Epilepsy Society in December 2023 and showed that, on average, patients experienced no meaningful improvement in convulsive seizure frequency and exhibited widening gaps in cognition and behavior compared to neurotypical peers, despite treatment with the best available anti-seizure medicines. 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 protein levels. Stoke’s first compound, zorevunersen (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/ . 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 zorevunersen to treat the underlying causes of Dravet syndrome and reduce seizures or show improvements in non-seizure comorbidities, the timing and expected progress of clinical trials, regulatory meetings and regulatory decisions, and the participation of scientists associated with the Company making presentations at EEC and the presentation of data at EEC. Statements including words such as “expect,” “plan,” “will,” “continue,” 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 prove incorrect or do not fully materialize, could cause our results to differ materially from those expressed or implied by such forward-looking statements, including, but not limited to, risks and uncertainties related to: the Company’s ability to advance, obtain regulatory approval of, and ultimately commercialize its product candidates, including zorevunersen; the timing of data readouts and interim and final results of preclinical and clinical trials; the receipt and timing of potential regulatory decisions; 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; the Company’s ability to fund development activities and achieve development goals; the Company’s ability to protect its intellectual property; the direct or indirect impact of global business, political and macroeconomic conditions, including inflation, interest rate volatility, cybersecurity events, uncertainty with respect to the federal budget, instability in the global banking system and volatile market conditions, and global events, including public health crises, and ongoing geopolitical conflicts, such as the conflicts in Ukraine and the Middle East; and other risks and uncertainties described under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023, its quarterly reports on Form 10-Q, and the other documents it files from time to time with the Securities and Exchange Commission. These forward-looking statements speak only as of the date of this press release, and the Company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date hereof.

临床研究临床结果孤儿药寡核苷酸

100 项与 STK-002 相关的药物交易

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