CAP-002 Gene Therapy Receives FDA Orphan Drug Designation for STXBP1 Disorder
Key Insights
Capsida Biotherapeutics (search)' CAP-002, a novel gene therapy, has been granted Orphan Drug Designation by the FDA for STXBP1 disorder (search).
CAP-002 aims to address the underlying genetic cause of STXBP1 (search)-DEE by supplementing STXBP1 protein throughout the brain via a single infusion.
Preclinical studies have demonstrated the potential of CAP-002 to reverse neurological symptoms in animal models of STXBP1 disorder (search).
Capsida Biotherapeutics (search) has received Orphan Drug Designation from the FDA for CAP-002, a gene therapy being developed for STXBP1 disorder (search), a severe developmental and epileptic encephalopathy. The designation aims to accelerate the development of this potential first-in-class treatment, which has shown promise in preclinical studies. STXBP1 disorder affects an estimated 1 in 26,000 children globally, leading to intellectual disability, motor issues, and treatment-resistant epilepsies.
Addressing an Unmet Need in STXBP1 Disorder
Currently, there are no approved disease-modifying therapies for STXBP1 (search) developmental and epileptic encephalopathy (STXBP1-DEE). Existing treatments primarily focus on managing symptoms, often with limited success. Anti-seizure medications (ASMs) such as phenobarbital, valproic acid, and vigabatrin are commonly used, but approximately 25% of individuals with the disease are refractory to ASM therapy. CAP-002 represents a potential breakthrough by targeting the underlying genetic cause of the disorder.
CAP-002: A Novel Gene Therapy Approach
CAP-002 is an intravenously administered gene therapy designed to stably supplement STXBP1 (search) protein throughout the brain after a single infusion. The STXBP1 protein is crucial for normal neurotransmission, and mutations in the STXBP1 gene lead to a deficiency in this protein, resulting in the characteristic symptoms of the disorder. Capsida's approach utilizes an engineered adeno-associated virus (AAV) capsid to achieve widespread expression of STXBP1 protein in the brain, while minimizing off-target effects on other organs.
Preclinical Evidence and Future Development
Preclinical studies, conducted in collaboration with Dr. Mingshan Xue at Texas Children’s Duncan Neurological Research Institute, have demonstrated the potential of gene supplementation to treat and even fully correct STXBP1 disorder (search). These studies utilized a proprietary mouse model that replicates the disorder and showed that rescuing neurological symptoms depends on delivering STXBP1 (search) to neurons throughout the brain at levels beyond those achievable by standard AAV serotypes. Capsida plans to file an Investigational New Drug (IND) application with the FDA in the first half of 2025, which, if accepted, would allow them to initiate clinical trials.
Capsida's Broader Pipeline
In addition to CAP-002, Capsida is developing a pipeline of gene-based treatment strategies for other neurological disorders. This includes CAP-003, an IV-delivered agent for patients with Parkinson's disease associated with GBA (search) mutations (PD-GBA). Preclinical data presented at the Society for Neuroscience annual meeting showed that CAP-003 achieved brainwide RNA expression that was more than 200-fold greater than IV administered AAV9, along with substantial increases in GCase protein and enzyme activity compared with untreated animals. At a dose of 5.5E13 vg/kg, CAP-003 produced a 488% increase in GCase brain protein level, which were 8-24 times higher than ICM AAV9 reported in a previous non-human primate study.