Capsida Biotherapeutics to Present Preclinical Data on GBA-Linked Parkinson's Disease Showing High GCase Enzyme Levels Post-IV Administration

Capsida Biotherapeutics, based in Thousand Oaks, California, has unveiled promising preclinical results for its innovative gene therapy candidate, CAP-003. This next-generation therapy is designed to treat Parkinson's disease (PD) associated with GBA mutations, known as PD-GBA, and will be administered intravenously (IV). These findings strongly support the potential of CAP-003 to be a best-in-class treatment, with the company planning to begin clinical trials in the first half of 2025.

GBA mutations, which affect the gene responsible for producing the GCase enzyme, are the most common genetic risk factor for PD. Current treatments for PD-GBA face significant hurdles, primarily their inability to cross the blood-brain barrier effectively and supplement sufficient GCase enzyme activity to impact the disease positively. Traditional methods, involving invasive direct brain or cerebrospinal fluid administration, have yielded limited success and impose a significant burden on patients.

CAP-003 represents a novel approach by Capsida, aiming to provide long-term disease modification through a single IV infusion. This method has the potential to significantly slow the progression of PD-GBA. In preclinical studies involving non-human primates (NHPs), CAP-003 was able to transduce a majority of neurons, including those in critical sub-cortical regions. This led to GCase enzyme activity levels that surpass the threshold required to restore GCase function in PD-GBA patients. Furthermore, CAP-003 demonstrated a significant reduction in liver targeting compared to AAV9, with no observed clinical pathology, immunogenicity, or histopathology findings, including in dorsal root ganglia (DRGs).

These promising results will be highlighted in an oral presentation at the American Society of Gene & Cell Therapy (ASGCT) 2024 Annual Meeting, held in Baltimore, Maryland, from May 7-11, 2024. Capsida's co-founder and Chief Research and Innovation Officer, Dr. Nicholas Flytzanis, will present the data under the title "Systemic AAV Gene Therapy with CNS-Targeted Engineered Capsids Achieves Significant GCase Activity Increases in the Primate Brain to Support the Potential Treatment of GBA-PD."

Capsida's CEO, Peter Anastasiou, expressed optimism regarding the potential of CAP-003 to offer a long-term reduction in disease progression with just a single IV infusion. He emphasized the company's commitment to advancing this promising therapy into clinical development by mid-2025, aiming to provide a vital treatment option for individuals affected by this debilitating condition.

Parkinson's disease is the second most common neurodegenerative disorder globally, affecting over 10 million adults worldwide and nearly one million in the United States. Approximately 15% of PD cases are associated with GBA mutations, making it the most prevalent genetic risk factor for the disease. Mutations in the GBA gene lead to decreased GCase enzyme activity and lysosomal dysfunction, contributing to the symptoms of PD-GBA. There are currently no approved disease-modifying treatments for PD, including PD-GBA.

CAP-003 is part of Capsida's broader initiative to develop gene therapies for central nervous system (CNS) diseases. The company, founded in 2019, leverages proprietary engineered capsids to achieve high transduction levels in targeted tissues and cells while minimizing impact on non-target organs like the liver. Capsida's pipeline includes treatments for genetic epilepsy due to STXBP1 mutations and PD-GBA, both in the preclinical development stage. Beyond its proprietary programs, Capsida has partnerships with leading pharmaceutical companies, including AbbVie, Lilly, and CRISPR Therapeutics, to further validate its CNS-focused therapies.