Data for First-in-Class IV-Administered Gene Therapy to Treat Epilepsy Presented at ASGCT 2024

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The company is presenting preclinical data at the American Society of Gene & Cell Therapy annual meeting that supports the potential of the company’s CAP-002 gene therapy for correcting neurological phenotypes associated with genetic epilepsy due to syntaxin-binding protein 1 (STXBP1) mutations.

Capsida Biotherapeutics presented new preclinical evidence for its first-in-class IV administered gene therapy, CAP-002, on May 7, 2024 at the American Society of Gene & Cell Therapy (ASGCT) annual meeting in Baltimore. The presented data support the potential of CAP-002 to achieve levels of gene supplementation that corrects neurological phenotypes associated with genetic epilepsy due to syntaxin-binding protein 1 (STXBP1) mutations. 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” (1). The program is in investigational new drug-enabling studies and the company expects the therapy to enter the clinic in the first half of 2025.

Mutations in the syntaxin-binding protein 1 (STXBP1) gene cause genetic epilepsy, which impacts an estimated one in 30,000 children born each year globally. 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.

According to the company, earlier-generation adeno-associated viruses (AAVs) or wild-type AAVs could not achieve the level of widespread neuronal transduction that would be needed to modify the disease. Gene therapy for genetic epilepsy due to STXBP1 mutations, therefore, has not been previously possible.

The first presentation at the ASGCT event, “AAV Gene Therapy Corrects Neurological Phenotypes with Clinically Relevant Doses in a Mouse Model of STXBP1-Related Developmental and Epileptic Encephalopathy,” is co-authored with Mingshan Xue, PhD, 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.

The study showed 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” (1). The dose-dependent rescue of neurological phenotypes (i.e., epileptic seizures, motor deficits, and cognitive impairments) was observed to be dependent on “supplementation of STXBP1 in neurons throughout the brain and at levels not achievable by wild-type serotypes, such as AAV9.”


“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,” said Xue.

On May 8, 2024, Capsida will present additional data in a poster presentation that show “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” (1).

“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, PhD. “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.”


1. Capsida. Capsida Biotherapeutics Presents New Preclinical Evidence Indicating Novel First-in-Class IV-Administered Gene Therapy Effectively Treats Genetic Epilepsy Due to STXBP1 Mutations. Press Release. May 7, 2024.