Capsida Biotherapeutics announced today that the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for CAP-002, a groundbreaking intravenously administered gene therapy for syntaxin-binding protein 1 developmental and epileptic encephalopathy (STXBP1-DEE). This milestone marks the first clinical-stage gene therapy utilizing an engineered capsid that can cross the blood-brain barrier while specifically avoiding off-target tissues such as the liver and dorsal root ganglia.
CAP-002 represents a significant technological advancement in the field of gene therapy, enabled by Capsida's proprietary engineered capsid technology and optimized genetic cargo. The therapy is manufactured in Capsida's state-of-the-art Good Manufacturing Practice (GMP) facility using the company's proprietary manufacturing process.
A Critical Unmet Need in Rare Pediatric Epilepsy
STXBP1-DEE affects approximately one in 26,000 births globally, translating to around 5,000 pediatric patients in the United States and Europe. The condition results from mutations in the STXBP1 gene, which encodes a protein essential for normal neurotransmission in every neuron. Patients with STXBP1-DEE experience devastating symptoms including early-onset seizures, severe developmental delays, intellectual disability, motor abnormalities, and risk of sudden unexpected death in epilepsy (SUDEP). Currently, there are no approved treatments that address the underlying cause of the disease.
"STXBP1-related disorders present devastating challenges in communication, development, motor function and seizures. We are in dire need of targeted therapies that can improve the lives and functioning of our children and families," said Charlene Son Rigby, STXBP1 Foundation President and Cofounder.
Overcoming Previous Gene Therapy Limitations
Traditional gene therapy approaches using wild-type adeno-associated viruses (AAVs) like AAV9 have been unable to achieve the widespread neuronal transduction necessary to effectively treat STXBP1-DEE. CAP-002 overcomes this limitation through its novel engineered capsid design.
In non-human primate studies, CAP-002 demonstrated remarkable efficacy, achieving transduction of more than 70% of neurons across critical brain areas while simultaneously avoiding off-target tissues. This brain-wide expression of STXBP1 has the potential to correct the multiple manifestations of the disease—including seizures, developmental disabilities, and motor abnormalities—after just a single intravenous infusion.
Safety data from Good Laboratory Practice (GLP) toxicology studies in non-human primates have shown a well-tolerated profile with no adverse histopathology, supporting the advancement to human clinical trials.
SYNRGY Clinical Trial Initiation
Following the FDA's IND clearance, Capsida is now initiating study start-up activities for the SYNRGY Phase 1/2a clinical trial. The company expects to dose the first patient in the third quarter of 2025. The FDA granted CAP-002 Orphan Drug Designation (ODD) in October 2024, recognizing the therapy's potential to address this rare pediatric condition.
"This is the first potentially disease-modifying treatment for STXBP1-DEE, and we are excited to be part of the SYNRGY clinical trial," said Ingo Helbig, M.D., Pediatric Neurologist and Clinical Director of Clinical Research at the Center for Epilepsy and Neurodevelopmental Disorders (ENDD) at Children's Hospital of Philadelphia (CHOP), and paid consultant to Capsida.
Swati Tole, M.D., Chief Medical Officer of Capsida, emphasized the significance of this milestone: "The FDA clearance of the CAP-002 IND is a significant milestone for Capsida, the STXBP1 community, and the field of genetic medicine. We look forward to initiating the SYNRGY clinical trial and dosing patients starting in the third quarter of this year with this potential first targeted therapy for STXBP1-DEE."
Broader Implications for CNS Gene Therapy
The advancement of CAP-002 into clinical trials represents not only hope for patients with STXBP1-DEE but also validates Capsida's platform technology for delivering gene therapies to the central nervous system (CNS). The company's pipeline includes additional CNS-targeted gene therapies, including treatments for Parkinson's disease associated with GBA mutations (PD-GBA) and Friedreich's ataxia (FA). The PD-GBA program is also expected to enter clinical development this quarter.
Founded in 2019 by Versant Ventures and Westlake Village BioPartners, Capsida originated from groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., a neuroscience professor at Caltech. The company has established partnerships with pharmaceutical leaders including AbbVie, Lilly, and CRISPR Therapeutics, further validating its innovative approach to genetic medicine.
As CAP-002 advances into clinical trials, it represents a potential paradigm shift in how gene therapies can be delivered to treat neurological disorders, potentially opening the door for more effective treatments for a range of currently untreatable CNS conditions.
