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— 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

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