STXBP1-related epileptic encephalopathy

Preclinical data show IV administration of a next-generation gene therapy produced dose-dependent replacement of syntaxin-binding protein 1 (STXBP1) throughout the brain, with efficacy predictive of clinical relevance lasting at least 12 months post therapeutic intervention Data to be showcased in an oral presentation at Epilepsy Therapies & Diagnostics Development Symposium today THOUSAND OAKS, Calif., June 2, 2023 /PRNewswire/ -- Capsida Biotherapeutics ("Capsida") today announced it will present new preclinical data showing the potential for its engineered adeno-associated virus (AAV) therapeutics to treat genetic epilepsy caused by mutations in the syntaxin-binding protein 1 (STXBP1) gene. These preclinical data, generated in collaboration with Mingshan Xue, Ph.D., assistant professor of neuroscience, Baylor College of Medicine, demonstrated that intravenous (IV) administration of a next-generation capsid carrying STXBP1 cargo produced dose-dependent improvement across seizure, motor, and cognitive deficits in adult mice, lasting at least 12 months post therapeutic intervention. Furthermore, data on Capsida's most recent generation of engineered capsids showed significantly enhanced brain-wide distribution required for treatment of genetic epilepsy due to STXBP1 mutation, while simultaneously de-targeting the liver, in non-human primates. Capsida will present these data in an oral presentation at the Epilepsy Therapies & Diagnostics Development Symposium being held May 31 to June 2, 2023, in Aventura, FL. Nicholas Flytzanis, Ph.D., chief research and innovation officer at Capsida, will present on June 2 at 10 a.m. ET, in a talk entitled, "Next-Gen AAV Therapeutics for Treatment of Genetic Epilepsy Caused by Mutations in the STXBP1 Gene." "Treatment of this type of genetic epilepsy requires replacement of the STXBP1 gene throughout the brain in order to correct circuits associated with seizure, cognitive, and motor phenotypes," said Susan Catalano, Ph.D., chief scientific officer of Capsida. "These new preclinical data showed that using engineered AAVs capable of efficiently crossing the blood-brain barrier and globally replacing the affected gene, while de-targeting tissues like the liver allowing for lower efficacious dosing, may be the key to brain-wide correction of this devastating disease." "Capsida made the decision to focus our internal pipeline on diseases where there is high unmet need and the requirement to go beyond what is currently possible with wild type AAVs," said Peter Anastasiou, Capsida's chief executive officer. "We are excited to be presenting our preclinical results for what we believe is a first-in-class disease-modifying therapy for this significant genetic epilepsy disorder." About Genetic Epilepsy due to STXBP1 Mutations Genetic epilepsy caused by mutations in the syntaxin-binding protein 1 (STXBP1) gene is a devastating developmental epileptic encephalopathy affecting one in 30,000 children globally. It is associated with severe developmental delay, treatment-resistant seizures, and sudden unexpected death in epilepsy. STXBP1 genetic epilepsy is caused by mutations in the STXBP1 gene encoding a protein involved in the release of neurotransmitters and neuropeptides, which are responsible for communication across neurons in the brain and central nervous system. There are no disease-modifying therapies for STXBP1 genetic epilepsy. Current treatments are supportive only, and include anti-seizure medication, and physical, occupational, and speech therapy. About Capsida Biotherapeutics Capsida Biotherapeutics is a fully integrated next-generation gene therapy platform company. Capsida's approach unlocks the potential to treat both rare and common diseases across all ages. We create customized therapies that selectively target specific organ systems and simultaneously limit exposure to non-targeted organs. The company has wholly owned programs in central nervous system (CNS) and strategic collaborations with AbbVie (CNS and eye care), Lilly (CNS), and CRISPR Therapeutics (CNS), providing independent validation of Capsida's capabilities. Capsida is backed by Versant Ventures and Westlake Village BioPartners. Its platform originated from groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., a neuroscience professor at the California Institute of Technology. Visit us at to learn more.

PHILADELPHIA, Feb. 7, 2023 /PRNewswire/ -- A $25 million gift from an anonymous donor to Penn Medicine and Children's Hospital of Philadelphia (CHOP) will establish the Center for Epilepsy and Neurodevelopmental Disorders (ENDD), accelerating collaborative research in genetic therapies for neurodevelopmental disorders. This gift will bolster the efforts of an interdisciplinary group of clinicians and scientists at Penn and CHOP, led by director Benjamin Prosser, PhD and co-directors Beverly Davidson, PhD and Ingo Helbig, MD. Dr. Prosser is an associate professor of Physiology at the University of Pennsylvania's Perelman School of Medicine, who adjusted the focus of his research career when his own daughter, Lucy, was diagnosed shortly after birth in 2018 with a rare genetic neurodevelopmental disorder. Continue Reading Dr. Benjamin Prosser and his family. "ENDD offers hope to patients and families living with the many challenges of rare, genetic neurodevelopmental disorders," said J. Larry Jameson, MD, PhD, executive vice president of the University of Pennsylvania for the Health System and dean of the Perelman School of Medicine. "This important gift will accelerate the progress of an extraordinary partnership between Penn and CHOP that demonstrates the power of collaboration and a commitment to finding cures. We are incredibly grateful to this donor, whose dedication to the advancement of research in this area is sure to create the launch pad for a new outlook for those diagnosed with these conditions." The gift was made in honor of the late television executive Daniel B. Burke whose son Stephen B. Burke served on the board of trustees at CHOP. "We are extremely grateful for this visionary gift that supports our efforts to solve the unsolvable when it comes to rare diseases, improving our ability to translate new discoveries about potential therapies into clinical practice," said Madeline Bell, President and CEO of Children's Hospital of Philadelphia. "CHOP and Penn have systematically invested in integrated care programs for genetic epilepsies and neurodevelopmental disorders. This new center will fill the gap between the tremendous advances in early diagnosis and comprehensive clinical care and the development of new treatments for these patients." ENDD will initially focus on developing therapies for disorders related to mutations of the STXBP1 and SYNGAP1 genes – which are linked to abnormal brain function, intellectual disability, epilepsy, and motor and behavioral impairments – with the goal of expanding its efforts to other genetic neurodevelopmental disorders over time. ENDD strengthens an existing partnership between Dr. Prosser and Dr. Davidson, the Director of the Raymond G. Perelman Center for Cellular and Molecular Therapeutics and Chief Scientific Strategy Officer at CHOP and Professor of Pathology and Lab Medicine at Penn, and Dr. Helbig, a pediatric neurologist in the Department of Neurology at Penn and Division of Neurology at CHOP and the Director of Genomic Science at CHOP's Epilepsy NeuroGenetics Initiative (ENGIN). Their joint work in the Center will target the development of anti-sense oligonucleotide (ASO), gene therapy, and CRISPR-based strategies for the treatment of NDD. Dr. Prosser's daughter Lucy was diagnosed with a rare, genetic neurodevelopmental disorder caused by a mutation of the STXBP1 gene. STXBP1-related disorders cause a range of symptoms, including seizures, developmental delays, intellectual disabilities, and movement disorders. There is no known cure or effective treatment. Driven by a desire to help his daughter and the more than 5,000 children with STXBP1 disorders born each year worldwide, Prosser, an expert in cardiac molecular biology, launched a separate research arm in his lab focused on developing new therapies for STXBP1 and related disorders. He began collaborating with Davidson and Helbig, as well as other researchers and clinicians across Penn and CHOP, forming the ENDD Therapeutics Team. "As a scientist and as a parent, I am incredibly grateful for this gift, which will propel our work forward with the hope of changing the course of these disorders," Prosser said. "We have a rare opportunity with such a brilliant and dedicated team of scientists and clinicians at Penn and CHOP, who are motivated each day to make a difference for Lucy and children like her." Davidson, a world-renowned expert in gene therapy in neurological disorders, works to understand the molecular basis of childhood onset neurodegenerative diseases and the development of gene and small molecule therapies for treatment. Helbig, who serves as one of the directors of the Epilepsy Neurogenetics Initiative (ENGIN) at CHOP, has particular expertise in SYNGAP1 and STXBP1 and treats many children with these disorders, including Lucy Prosser. This unique combination of clinical knowledge, innovation in gene therapy, and the drive of a parent-scientist will accelerate the development of new therapies for neurodevelopmental disorders. SOURCE Children's Hospital of Philadelphia; University of Pennsylvania School of Medicine

– Researchers will now be able to access rich clinical data on patients with rare neurological disease – SAN FRANCISCO, Sept. 12, 2022 /PRNewswire/ -- Invitae ( NYSE: NVTA), a leading medical genetics company, today announced a collaboration with Simons Searchlight, an international research program with a goal of accelerating research and improving lives for people with rare genetic neurodevelopmental disorders. This partnership will connect two sets of data – the longitudinal clinical data extracted from medical records through Invitae's Ciitizen, a patient-consented, digital natural history data platform and patient reported outcomes and biospecimens collected by Simons Searchlight. The partnership breaks down data silos and provides a rich and deep dataset that will help accelerate research for rare neurodevelopmental diseases. "We are excited about this collaboration that will allow researchers to get deep, rich longitudinal data on rare disease patients," said Farid Vij, president and general manager of data for Invitae. "This is intended to help improve treatment, with a goal of ultimately finding a cure for these rare diseases." Rare disease patients and caregivers are often asked to participate in many different stand- alone studies to help advance research. Through the combined clinical and patient-reported data in these two datasets, researchers get a deeper understanding of the etiology and progression of disease, sparing additional time, effort and data collection from the patient. "Joining forces with Invitae is incredibly powerful for patients with rare diseases," said Jennifer Tjernagel, M.S., senior project manager at Simons Searchlight, Simons Foundation. "Our partnership and the resulting datasets will help improve understanding, diagnosis and treatment of neurodevelopmental disorders, such as STXBP1, SYNGAP1 and others. Having the support of Invitae's Ciitizen platform will help pair patient-reported data with clinical information for in depth data analysis." Charlene Son Rigby, president and co-founder of STXBP1 Foundation shared, "We are thrilled to partner with Invitae and Simons Searchlight on this initiative. We believe in the power of data and how important sharing that data can be in the journey to finding a cure for STXBP1 Disorder. Having this kind of collaboration in our toolkit is opening up an entirely new approach for our foundation and our patient community. The combination of Invitae's existing clinical data which will be transitioned into a readily usable format, and Simons' deep information from patients and caregivers, will provide doctors and scientists with an innovative way to accelerate understanding of natural history, while allowing patients and their loved ones to focus on what's most important - their health." Mike Graglia, Managing Director and Co-Founder of the SynGAP Research Fund stated, "Invitae's Ciitizen is a powerful digital natural history study data platform in the rare disease space. The technology, execution and clinical expertise behind it are exceptional. Simons Searchlight is the most established clinician-led registry in autism and related disorders. The accomplishment of connecting these two platforms is a testament to their collective focus on helping patients. Every single patient who has access to Invitae's Ciitizen platform and Searchlight should consent to join their profiles now." This agreement expands upon a partnership that was originally launched as a pilot for STXBP1 patients and the STXBP1 Foundation. The relationship allowed consenting patients to link their de-identified Invitae Ciitizen data with the Simons Searchlight database to accelerate understanding of patients with STXBP1 disorder. By expanding focus to additional rare neurological disorders, such as SYNGAP1, SCN2A, SLC6A1 and more, researchers are one step closer to finding the needle in the haystack for patients with these conditions. To learn more about Invitae's Ciitizen data platform and request access to the consented dataset for research, email [email protected] About Invitae Invitae Corporation ( NYSE: NVTA) is a leading medical genetics company, whose mission is to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time and lower prices. For more information, visit the company's website at invitae.com. About Simons Searchlight Simons Searchlight collects medical, developmental, and behavioral data on people living with rare developmental disorders. Participants and their families share this valuable information and experiences so that scientists around the world may increase understanding of these medical conditions and ultimately improve lives. For more information, visit simonssearchlight.org Safe Harbor Statement This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the availability, features and potential impact of the company's products; the company's belief that it is the first and only laboratory to offer this comprehensive suite of tests for neurodevelopmental disorders in an easily accessible format; the company's belief that its NDD package is affordable and fast; and the company's belief that its NDD package will inform care decisions and treatment plans for patients. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially, and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: the company's history of losses; the company's ability to compete; the company's failure to manage growth effectively; the company's need to scale its infrastructure in advance of demand for its tests and to increase demand for its tests; the company's ability to use rapidly changing genetic data to interpret test results accurately and consistently; security breaches, loss of data and other disruptions; laws and regulations applicable to the company's business; and the other risks set forth in the company's filings with the Securities and Exchange Commission, including the risks set forth in the company's Annual Report on Form 10-K for the year ended December 31, 2021. These forward-looking statements speak only as of the date hereof, and Invitae Corporation disclaims any obligation to update these forward-looking statements. Contact: Renee Kelley [email protected] (628) 213-3283 SOURCE Invitae Corporation