STXBP1

Wholly owned first-in-class program anticipated to enter clinical trials in first half of 2025 THOUSAND OAKS, Calif., Oct. 30, 2024 /PRNewswire/ -- Capsida Biotherapeutics ("Capsida") today announced the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to Capsida for CAP-002. CAP-002 is the company's lead investigational gene therapy for the treatment of developmental and epileptic encephalopathy (DEE) due to syntaxin-binding protein 1 (STXBP1) mutations. CAP-002 is a novel, first-in-class IV-administered gene therapy using one of Capsida's proprietary engineered capsids designed to achieve brain-wide neuronal expression of the STXBP1 protein while significantly detargeting the liver. CAP-002 is currently in IND-enabling studies. "FDA's granting Orphan Drug Designation signals the significant potential that CAP-002 demonstrates based upon our preclinical data," said Peter Anastasiou, Chief Executive Officer of Capsida Biotherapeutics. "There are no disease-modifying therapies available for STXBP1 developmental and epileptic encephalopathy and CAP-002 could be the first, bringing hope for patients and families affected by this devastating disorder." The STXBP1 protein is present in every neuron in the brain and is essential for normal neurotransmission. A mutation in the STXBP1 gene is associated with treatment-resistant seizures, severe developmental delay and intellectual disability, motor abnormalities, and sudden unexpected death in epilepsy (SUDEP). Preclinical pharmacology studies have established the potential to treat and even fully correct the disease through gene supplementation. These studies demonstrated rescue of these neurological phenotypes was dependent on supplementation of STXBP1 in neurons throughout the brain at levels not achievable by wild-type serotypes, such as AAV9. Capsida conducted these studies with a proprietary murine disease model in collaboration with Mingshan Xue, Ph.D., associate professor of neuroscience and molecular and human genetics at Baylor College of Medicine, as well as a member of the Cain Foundation Laboratories and the Duncan Neurological Research Institute at Texas Children's Hospital. "Receiving Orphan Drug Designation moves us one step closer to our goal of transforming the lives of people living with STXBP1 developmental and epileptic encephalopathy," said Swati Tole, M.D., Chief Medical Officer at Capsida. "We are committed to advancing CAP-002, with our IND filing in the first half of 2025, and bringing novel gene therapies to people with high unmet medical needs." The FDA's Orphan Drug Designation is intended to encourage the development of treatments for rare diseases, defined as those affecting fewer than 200,000 people in the United States. Orphan Drug Designation may shorten the clinical development path through closer FDA collaboration and potential qualification for expedited development programs. This designation also provides the company with certain benefits, including tax credits for qualified clinical trials, exemption from user fees, and potential seven-year market exclusivity upon FDA approval. About STXBP1 Developmental and Epileptic Encephalopathy Developmental and epileptic encephalopathy caused by STXBP1 mutations is estimated to affect up to one in 26,000 children globally. It is associated with treatment resistant seizures, severe developmental delay and intellectual disability, motor abnormalities, and sudden unexpected death in epilepsy (SUDEP). There are no approved treatments. About Capsida Biotherapeutics Capsida Biotherapeutics is a fully integrated gene therapy company with a central nervous system (CNS) pipeline consisting of disease modifying and potentially curative treatments for rare and more common diseases across all ages. Capsida's intravenously (IV) administered gene therapies utilize proprietary engineered capsids that enable high transduction levels to desired tissues and cells, while limiting tropism to non-target organs, such as the liver. Capsida has three wholly owned programs, including a potential -first-in-class treatment for STXBP1 developmental and epileptic encephalopathy and a best-in-class treatment Parkinson's disease associated with GBA mutations, both of which are in IND-enabling studies and on track to enter the clinic in the first half of 2025. In addition to its wholly owned programs, the Company has validating CNS partnerships with AbbVie, Lilly, CRISPR Therapeutics, and the AbbVie partnership was expanded to include ophthalmology disorders. Capsida was founded in 2019 by lead investors Versant Ventures and Westlake Village BioPartners and originated from groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., a neuroscience professor at Caltech. Visit us at . SOURCE Capsida Biotherapeutics WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

Findings offer new insights with potential to inform diagnosis and treatment PHILADELPHIA, Oct. 16, 2024 /PRNewswire/ -- Researchers at Children's Hospital of Philadelphia (CHOP) announced the results of a new study highlighting significant genetic links in speech and language disorders in children. The findings, published today in the journal Brain, mark the first time that researchers have studied the genetic basis of linguistic differences separately from other conditions. Genetic factors are known to play a role in speech and language disorders, and the researchers hoped their study would bridge a gap in knowledge to better understand this critical area impacting child development. The research was a collaboration between CHOP's Department of Speech-Language Pathology, the Division of Neurology and the Department of Biomedical and Health Informatics (DBHI). "Our findings highlight the intricate relationship between genes and speech and language development," said Jan Magielski, the study's first author and a data scientist within CHOP's Division of Neurology and Department of Biomedical and Health Informatics. "We hope that the novel connections between genetic causes and specific speech and language disorders reported in the study will offer new and innovative possibilities for earlier intervention and personalized treatment plans." In the study, researchers analyzed electronic medical records of more than 52,000 children treated at CHOP to identify and analyze 26 broad speech and language diagnoses. They found that genetic causes play a major role in speech and language disorders, which are diagnosed more frequently in children between the ages of two and five. While conditions like aphasia, characterized by difficulty speaking, and speech apraxia, or trouble making speech movements, were accurately identified, some speech and language disorders were found to be frequently undetected. Most importantly, stuttering is often underreported in medical records. Their innovative data analysis approach allowed researchers to make three crucial observations. First, they found significant variations in the frequency of speech diagnoses, with mixed receptive-expressive language disorder and developmental disorder of speech and language being the most common diagnosis. Second, the authors observed that speech and language disorders have considerable overlap with neurodevelopmental disorders, movement disorders, and epilepsy. Lastly, the researchers noted that distinct speech characteristics can be linked to specific genes and overlap with known neurodevelopmental conditions. The study connected the genes STXBP1, PTEN and CACNA1A with speech and language disorders. Certain variants of STXBP1 were associated with aphasia while variants of the gene MYO7A were linked with delays in speech and language due to hearing loss. Additionally, in a subset of 726 children with whole exome sequencing data, researchers identified rare genetic changes, linking associations of UQCRC1 and KIF17 with expressive aphasia, MROH8 and BCHE with poor speech, and USP37, SLC22A9, and UMODL1 with aphasia. "In the future, we anticipate more targeted studies that delve deeper into the genetic landscape of speech disorders," said Joe Donaher, PhD, CCC-SLP, a senior study author and the Research and Academic Program Director at CHOP's Center for Childhood Communication. "Our study results underscore the need for focused investigations, particularly in areas like stuttering, where genetic research has significantly lagged behind other fields." This study was supported by The Hartwell Foundation through an Individual Biomedical Research Award. This study received support from the National Institute for Neurological Disorders and Stroke, and intramural CHOP funds from the Epilepsy NeuroGenetics Initiative (ENGIN). Magielski, et. al. "The clinical and genetic spectrum of paediatric speech and language disorders." Brain. Online October 16, 2024. DOI: 10.1093/brain/awae264. About Children's Hospital of Philadelphia: A non-profit, charitable organization, Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as the Middleman Family Pavilion and its dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children's Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit . Contact: Kaila M. Revello Children's Hospital of Philadelphia 267-426-6054 [email protected] SOURCE Children's Hospital of Philadelphia WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

CAP-003 achieved best-in-class GCase increases in NHPs exceeding levels needed for normalizing activity in patients Brainwide RNA expression greater than 200-fold higher than AAV9, with significant detargeting of liver and DRGs with proprietary engineered capsid Company on track to file IND in first half of 2025 THOUSAND OAKS, CA, USA I October 7, 2024 I Capsida Biotherapeutics (“Capsida”) presented new IND-enabling data on its intravenously (IV) delivered gene therapy for Parkinson’s disease associated with GBA mutations (PD-GBA), CAP-003, that demonstrate its substantial therapeutic potential. Capsida’s next-generation therapy, using a proprietary engineered capsid, demonstrates best-in-class potential to effectively and safely treat PD-GBA. CAP-003 achieves unprecedented levels of GCase protein and activity while simultaneously detargeting the liver and dorsal root ganglion (DRGs). These data were presented in a late-breaking poster presentation at the Society for Neuroscience “Neuroscience 2024” annual meeting being held October 5-9, 2024 in Chicago, IL. Mutations in GBA, the gene expressing the GCase enzyme, affect up to 15% of PD patients and are the most common genetic risk factor for PD. Post-mortem studies demonstrate an approximate 30% GCase activity deficit in patients 1 . Other potential treatments for PD-GBA have been limited by their inability to cross the blood-brain barrier and supplement GCase enzyme activity in sufficient quantities to overcome the deficit in patients and impact the disease. In an attempt to overcome these challenges, they have utilized invasive direct brain or cerebrospinal fluid administration, with limited results, but significant burden for patients. Results from Capsida’s IND-enabling non-human primate (NHP) studies show brainwide RNA expression more than 200-fold greater than IV administered AAV9 and substantial increases in GCase protein and enzyme activity compared to untreated animals. A single IV infusion of CAP-003 resulted in up to six-fold increase in GCase protein compared to untreated animals in relevant brain regions. Across doses and brain regions, including the substantia nigra, the levels of GCase activity following infusion of CAP-003 was increased by up to approximately 250% compared to untreated animals. These data support the potential for meaningful clinical benefit in patients. Increases of 30% are expected to normalize GCase activity in patients with PD-GBA. NHPs dosed with CAP-003 IV have 19- and 17-fold less biodistribution to the liver and DRG, respectively, compared to IV administered wild-type AAV9. CAP-003 is well tolerated with no notable safety findings in NHPs. “Capsida’s wholly owned novel gene therapy offers the potential to normalize GCase activity in patients with a single IV infusion safely, enabling the potential for long-term disease modification and substantial slowing of disease progression,” said Peter Anastasiou, Capsida’s Chief Executive Officer. “These data give us confidence that we are on track to enter the clinic with CAP-003 in the first half of 2025.” Capsida to Present at Cell & Gene Meeting on the Mesa In addition, Capsida will present these data as part of a corporate presentation at the Cell & Gene Meeting on the Mesa taking place October 7-9, 2024, in Phoenix, AZ. Mr. Anastasiou will present a corporate update on Tuesday, October 8, 2024 at 3:45 PM local time. The Capsida corporate presentation can be accessed by visiting the News section of the Company’s website at www.capsida.com . About Capsida Biotherapeutics Capsida Biotherapeutics is a fully integrated gene therapy company with a central nervous system (CNS) pipeline consisting of disease modifying and potentially curative treatments for rare and more common diseases across all ages. Capsida’s intravenously (IV) administered gene therapies utilize proprietary engineered capsids that enable high transduction levels to desired tissues and cells, while limiting tropism to non-target organs, such as the liver. Capsida has three wholly owned programs, including potential best-in-class treatments for genetic epilepsy due to STXBP1 mutations and Parkinson’s disease associated with GBA mutations, both of which are in IND-enabling studies and on track to enter the clinic in the first half of 2025. In addition to its wholly owned programs, the Company has validating CNS partnerships with AbbVie, Lilly, CRISPR Therapeutics, and the AbbVie partnership was expanded to include ophthalmology disorders. Capsida was founded in 2019 by lead investors Versant Ventures and Westlake Village BioPartners and originated from groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., a neuroscience professor at Caltech. Visit us at www.capsida.com . 1 Gegg, M. E, et al (2012). Annals of neurology, 72(3), 455-463. SOURCE: Capsida Biotherapeutics