STXBP1-related epileptic encephalopathy

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

Dose-dependent rescue of neurological phenotypes, including epileptic seizures, motor deficits, and cognitive impairments, with long-lasting effects in adult mice Capsida poster will also show new data with its next-generation gene therapy showing significant brain-wide expression of STXBP1 protein and liver detargeting after a single IV infusion Wholly owned program is first in class and currently in IND-enabling studies to support initiation of clinical trials in first half of 2025 THOUSAND OAKS, Calif., May 7, 2024 /PRNewswire/ -- Capsida Biotherapeutics ("Capsida") today announced new preclinical data supporting the potential of Capsida's gene therapy candidate, CAP-002, to achieve levels of gene supplementation necessary to correct neurological phenotypes associated with genetic epilepsy due to syntaxin-binding protein 1 (STXBP1) mutations. Gene therapy for genetic epilepsy due to STXBP1 mutations has not been previously possible because earlier generation adeno-associated viruses (AAVs) or wild-type AAVs could not achieve the level of widespread neuronal transduction required to modify the disease. CAP-002 is a first-in-class next-generation intravenous (IV)-administered gene therapy that achieves brain-wide neuronal expression while simultaneously detargeting the liver. Capsida's wholly owned program is currently in IND-enabling studies and is expected to enter the clinic in the first half of 2025. The first presentation, co-authored with Mingshan Xue, Ph.D., Associate Professor, Department of Neuroscience, Department of Molecular and Human Genetics at Baylor College of Medicine and the Cain Foundation Laboratories, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital is entitled, "AAV Gene Therapy Corrects Neurological Phenotypes with Clinically Relevant Doses in a Mouse Model of STXBP1-Related Developmental and Epileptic Encephalopathy." The study found that IV administration of the gene encoding STXBP1 in adult mice lacking one functional copy of the STXBP1 gene rescues key phenotypic defects in a dose-dependent manner and does so with long-lasting effects. Capsida and Baylor observed that the dose-dependent rescue of neurological phenotypes, including epileptic seizures, motor deficits, and cognitive impairments, was dependent on supplementation of STXBP1 in neurons throughout the brain and at levels not achievable by wild-type serotypes, such as AAV9. These data will be featured in an oral presentation today at the American Society of Gene & Cell Therapy (ASGCT) 2024 Annual Meeting, taking place May 7-11, 2024 in Baltimore, MD and virtually. Wu Chen, Ph.D., Instructor, Department of Neuroscience, Baylor College of Medicine, will deliver the oral presentation (abstract 38) at 3:00-3:15 PM ET as part of the Neurologic Diseases I Session (location: Ballroom 4, Baltimore Convention Center). Dr. Xue commented, "This study built upon our previous proof-of-concept study and represents a significant advancement in our understanding of the therapeutic potential of engineered AAV gene supplementation therapy in the treatment of genetic epilepsy and developmental disorders due to STXBP1 mutations. These data are encouraging and emphasize the potential for CAP-002 to meaningfully improve outcomes in patients with this disease." On Wednesday, May 8, 2024, Capsida will also present new data in a poster presentation entitled, "CAP-002: Systemic AAV Gene Therapy with Next Generation Capsids for Treatment of STXBP1 Encephalopathy" (abstract 504). The data show that a single IV infusion of CAP-002 results in brain-wide STXBP1 gene expression and is capable of transducing up to 70% of neurons at therapeutically relevant doses in non-human primates (NHPs). This level of gene expression raises neuronal STXBP1 protein to levels comparable to those that reversed disease phenotype in the mouse model. CAP-002 had no clinical pathology, histopathology, or immunogenicity findings. "These data demonstrate that our STXBP1 program effectively crosses the blood-brain barrier in NHPs following IV delivery and achieves breakthrough levels of widespread brain transduction and STXBP1 protein expression needed to achieve disease-modifying impact as demonstrated in the mouse model data," said Capsida's Chief Scientific Officer Susan Catalano, Ph.D. "Coupled with significant detargeting of the liver compared to AAV9, CAP-002 holds the promise of effectively reversing disease and does so via less-invasive IV administration. We look forward to advancing our STXBP1 program into clinical development in the first half of 2025, so that we can bring this disease-modifying treatment option to people suffering from this devastating disease." About Genetic Epilepsy Due to STXBP1 Mutations Genetic epilepsy caused by mutations in the syntaxin-binding protein 1 (STXBP1) gene is a devastating developmental and epileptic encephalopathy estimated to affect one in 30,000 children born each year globally. It is associated with severe developmental delay and intellectual disability, treatment-resistant seizures, and sudden unexpected death in epilepsy (SUDEP). The STXBP1 protein is present in every neuron in the brain and is essential for normal neurotransmission. There are no disease-modifying therapies for this disorder. About CAP-002: Capsida's Program for Genetic Epilepsy Due to STXBP1 Mutations CAP-002 is a wholly owned first-in-class next-generation intravenous (IV)-administered gene therapy that achieves brain-wide neuronal expression of the syntaxin-binding protein 1 (STXBP1) protein after a single infusion, with significant liver detargeting. Capsida is developing CAP-002 for the treatment of genetic epilepsy caused by mutations in the STXBP1 gene. CAP-002 is currently in IND-enabling studies and is expected to enter the clinic in the first half of 2025. 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. 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

Four presentations highlight expansion of the company’s CNS pipeline and vector engineering platform Preclinical data presented supports potential to advance programs in Angelman Syndrome and Lennox-Gastaut Syndrome Proof-of-concept data demonstrating knock-down of neuropathic pain (SCN9A) and Alzheimer’s disease (MAPT) targets showcase advancements in the company’s vector engineering platform SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Encoded Therapeutics Inc., a biotechnology company developing genetic medicines for severe central nervous system (CNS) disorders, today highlights oral and poster presentations on the Company’s preclinical gene therapy programs and vector engineering platform at the 27th ASGCT Annual Meeting being held May 7 – 11, 2024 in Baltimore, MD. “We are thrilled to share multiple advancements across our portfolio of precision genetic medicines, showcasing substantial progress across various fronts. These data underscore our platform’s potential to deliver precision therapies for a range of CNS diseases,” said Stephanie Tagliatela, Chief Scientific Officer at Encoded. “Alongside clinical advancement of our lead program, ETX101 for SCN1A+ Dravet syndrome, we are poised to nominate multiple programs to development in 2025, marking yet another significant milestone.” Oral Presentation Title: GABA Selective AAV-mediated Gene Therapy Provides Durable Seizure Protection in Multiple Refractory Epilepsy Models (Abstract #19) Session: AAV Vectors - Preclinical and Proof-of-Concept: Therapy Focus Date & Time: Tuesday, May 7, 1:45–2:00 p.m. ET Location: Ballroom 2 Epilepsy affects approximately 1% of the population, with nearly one third of cases failing to respond to first- and second-line treatments. Encoded’s vector engineering platform has enabled the development of GABA-selective AAV-mediated gene therapies designed to potentiate GABAergic neurotransmission and modulate the circuit dysfunction underlying refractory epilepsies. Our lead candidate reduced seizure incidence and severity in two biologically distinct seizure assays with no adverse impact on body weight, motor function or locomotion. Furthermore, the top candidate is well-tolerated in non-human primates (NHP) even at high doses. These data support further development of our candidate gene therapy for the treatment for refractory epilepsies. Poster Presentations Title: Advancing Gene Therapy for STXBP1-related Disorders Through Targeted Vector Engineering: Efficacy and Safety Results in Mice and Non-Human Primates (Abstract #508) Date & Time: Wednesday, May 8, 5:30–7:00 p.m. ET Location: Exhibit Hall STXBP1-related disorders (STXBP1-RD) result from loss-of-function variants in STXBP1, causing severe developmental delay and treatment-resistant epilepsy. Encoded has engineered AAV9 vectors that drive potent expression within CNS tissue while reducing off-target expression in dorsal root ganglia (DRG) and non-neuronal tissues. These engineered AAV9-STXBP1 vectors achieved robust, dose-dependent improvements in seizure, cognitive, and motor phenotypes in Stxbp1+/- mice, with no observed dose-limiting toxicity. In NHPs, the engineered vectors showed strong CNS expression and were well-tolerated. Furthermore, the inclusion of a DRG de-targeting element reduced expression within the DRG and spinal cord by >10-fold, ameliorating microscopic DRG-related findings. These findings establish proof-of-concept for an AAV9-based gene therapy for STXBP1-RD and support the use of modular regulatory element engineering to drive desired expression profiles within the CNS. Title: A Vectorized miRNA-based Approach to Unsilence UBE3A in Angelman Syndrome (Abstract #1125) Date & Time: Thursday, May 9, 5:30–7:00 p.m. ET Location: Exhibit Hall Angelman syndrome (AS) is a severe neurodevelopmental disorder characterized by intellectual disability, ataxia, and seizures. AS is caused by loss-of-function of the maternally-inherited UBE3A gene. Unsilencing of the paternal copy of UBE3A has the potential address the underlying cause of the disease while mitigating the risk of UBE3A overexpression-related toxicity. We demonstrated that an AAV-based miRNA vector was capable of upregulating paternal UBE3A and correcting multiple phenotypes in the AS mouse model. Encoded’s lead miRNA candidate was well-tolerated in NHPs and demonstrated potent unsilencing of paternal UBE3A in critical brain regions. Collectively, these data support further development an AAV-based miRNA treatment approach for Angelman Syndrome. Title: Identification of Potent and Selective AAV-miRNA Candidates to Knockdown Non-Monogenic Neurological Targets SCN9A (Pain) and MAPT (Tauopathies) (Abstract #1601) Date & Time: Friday, May 10, 5:30–7:00 p.m. ET Location: Exhibit Hall Encoded's innovative AAV-mediated miRNA platform offers a promising strategy for long-term knockdown of target genes in the central and peripheral nervous systems. We identified potent and target-specific miRNA candidates to effectively knock down two clinically relevant, non-monogenic neuronal targets: SCN9A and MAPT. SCN9A encodes the NaV1.7 sodium channel, which is associated with pain sensation, while MAPT encodes the microtubule protein, Tau, which is implicated in Alzheimer's disease neuropathology. Encoded's miRNA candidates demonstrated potent, dose-dependent, and selective knockdown of SCN9A in human iPSC sensory neurons and in mouse dorsal root ganglion sensory neurons, establishing proof-of-concept for miRNA-based inhibition of NaV1.7. Similarly, MAPT candidates significantly reduced Tau protein levels in vitro and in vivo. These findings support advancement of SCN9A and MAPT candidates to NHP studies and showcase the potential of vectorized miRNA knockdown as a promising treatment avenue for various neurological disorders. About Encoded Therapeutics Encoded Therapeutics is a clinical-stage genetic medicines company developing potentially disease-modifying therapies to improve the lives of people with severe CNS disorders. Our proprietary vector engineering approach combines novel regulatory elements and payloads with AAV vectors to unlock innovative solutions for debilitating, intractable CNS conditions. At the forefront is our flagship clinical program, ETX101 for Dravet syndrome, which targets the underlying cause of the disorder to enable highly selective upregulation of SCN1A for potentially long-lasting benefit. In parallel, we are advancing a pipeline of potentially best-in-class programs to address significant unmet needs across both monogenic and prevalent CNS conditions. For more information, please visit . View source version on businesswire.com: Contacts Jennifer Gorzelany communications@encoded.com 650-515-9695 Source: Encoded Therapeutics Inc. View this news release online at: