Capsida Gains FDA IND Approval for IV Gene Therapy for STXBP1 Encephalopathy

On May 12, 2025, Capsida Biotherapeutics announced that the U.S. Food and Drug Administration (FDA) has approved their Investigational New Drug (IND) application for CAP-002. This groundbreaking gene therapy is set to initiate clinical trials targeting syntaxin-binding protein 1 developmental and epileptic encephalopathy (STXBP1-DEE). CAP-002 represents a pioneering approach as it is the first IV-administered gene therapy designed to cross the blood-brain barrier while being detargeted from off-target tissues, such as the liver and dorsal root ganglia, marking a significant advancement in neurological treatment.

STXBP1-DEE is a severe condition impacting approximately one in 26,000 births worldwide, affecting around 5,000 children in the U.S. and Europe. The disorder is characterized by early-onset seizures, severe developmental delays, intellectual disabilities, motor abnormalities, and an increased risk of sudden unexpected death in epilepsy (SUDEP). Currently, there are no approved therapies to treat this condition. The STXBP1 protein is integral to normal neuron communication, and mutations in the STXBP1 gene result in the condition’s debilitating symptoms.

Charlene Son Rigby, President and Cofounder of the STXBP1 Foundation, emphasized the urgent need for targeted therapies for children and families affected by STXBP1-related disorders, which severely impact communication, development, and motor skills.

Gene therapy for STXBP1-DEE was previously unattainable due to the limited ability of wild-type adeno-associated viruses (AAVs) to achieve the necessary neuronal transduction levels to alter the disease. In preclinical studies involving non-human primates, CAP-002 demonstrated transduction of over 70% of neurons in crucial brain areas while avoiding non-target tissues like the liver and dorsal root ganglia. This comprehensive brain expression of STXBP1 could potentially rectify seizures, developmental issues, and motor dysfunctions with a single intravenous infusion. The product’s safety profile has been supported by a Good Laboratory Practice (GLP) toxicology study, showing no adverse histopathology. CAP-002 received Orphan Drug Designation (ODD) from the FDA in October 2024, and Capsida is gearing up for the SYNRGY Phase 1/2a clinical trial, aiming to dose the first patient in the third quarter of this year.

Dr. Ingo Helbig, a pediatric neurologist and clinical director at the Center for Epilepsy and Neurodevelopmental Disorders at Children’s Hospital of Philadelphia, expressed enthusiasm about participating in the SYNRGY clinical trial, highlighting CAP-002 as the first potentially disease-modifying treatment for STXBP1-DEE.

Dr. Swati Tole, Chief Medical Officer at Capsida, declared the FDA clearance of CAP-002 as a significant achievement for the company and the genetic medicine field. Capsida eagerly anticipates the commencement of the SYNRGY clinical trial and the opportunity to provide the first targeted therapy for STXBP1-DEE.

Capsida Biotherapeutics, founded in 2019, is a comprehensive genetic medicines company focusing on developing disease-modifying and potentially curative treatments for both rare and common neurological diseases across all age groups. Its pipeline includes therapies for STXBP1-DEE, Parkinson’s disease related to GBA mutations (PD-GBA), and Friedreich’s ataxia (FA). The company has collaborative partnerships with AbbVie, Lilly, and CRISPR Therapeutics, and originated from the innovative research at Caltech led by Dr. Viviana Gradinaru.