New Data Demonstrate Substantial Therapeutic Potential of Capsida's IV Gene Therapy for Parkinson's Disease Associated with GBA Mutations

CAP-003 achieved best-in-class GCase increases in NHPs exceeding levels needed for normalizing activity in patients

Brainwide RNA expression greater than 200-fold higher than AAV9, with significant detargeting of liver and DRGs with proprietary engineered capsid

Company on track to file IND in first half of 2025

THOUSAND OAKS, Calif., Oct. 7, 2024 /PRNewswire/ -- Capsida Biotherapeutics ("Capsida") presented new IND-enabling data on its intravenously (IV) delivered gene therapy for Parkinson's disease associated with GBA mutations (PD-GBA), CAP-003, that demonstrate its substantial therapeutic potential. Capsida's next-generation therapy, using a proprietary engineered capsid, demonstrates best-in-class potential to effectively and safely treat PD-GBA. CAP-003 achieves unprecedented levels of GCase protein and activity while simultaneously detargeting the liver and dorsal root ganglion (DRGs). These data were presented in a late-breaking poster presentation at the Society for Neuroscience "Neuroscience 2024" annual meeting being held October 5-9, 2024 in Chicago, IL.

Mutations in GBA, the gene expressing the GCase enzyme, affect up to 15% of PD patients and are the most common genetic risk factor for PD. Post-mortem studies demonstrate an approximate 30% GCase activity deficit in patients¹. Other potential treatments for PD-GBA have been limited by their inability to cross the blood-brain barrier and supplement GCase enzyme activity in sufficient quantities to overcome the deficit in patients and impact the disease. In an attempt to overcome these challenges, they have utilized invasive direct brain or cerebrospinal fluid administration, with limited results, but significant burden for patients.

Results from Capsida's IND-enabling non-human primate (NHP) studies show brainwide RNA expression more than 200-fold greater than IV administered AAV9 and substantial increases in GCase protein and enzyme activity compared to untreated animals. A single IV infusion of CAP-003 resulted in up to six-fold increase in GCase protein compared to untreated animals in relevant brain regions. Across doses and brain regions, including the substantia nigra, the levels of GCase activity following infusion of CAP-003 was increased by up to approximately 250% compared to untreated animals. These data support the potential for meaningful clinical benefit in patients. Increases of 30% are expected to normalize GCase activity in patients with PD-GBA. NHPs dosed with CAP-003 IV have 19- and 17-fold less biodistribution to the liver and DRG, respectively, compared to IV administered wild-type AAV9. CAP-003 is well tolerated with no notable safety findings in NHPs.

"Capsida's wholly owned novel gene therapy offers the potential to normalize GCase activity in patients with a single IV infusion safely, enabling the potential for long-term disease modification and substantial slowing of disease progression," said Peter Anastasiou, Capsida's Chief Executive Officer. "These data give us confidence that we are on track to enter the clinic with CAP-003 in the first half of 2025."

Capsida to Present at Cell & Gene Meeting on the Mesa
In addition, Capsida will present these data as part of a corporate presentation at the Cell & Gene Meeting on the Mesa taking place October 7-9, 2024, in Phoenix, AZ. Mr. Anastasiou will present a corporate update on Tuesday, October 8, 2024 at 3:45 PM local time.

The Capsida corporate presentation can be accessed by visiting the News section of the Company's website at www.capsida.com. 

About Capsida Biotherapeutics
Capsida Biotherapeutics is a fully integrated gene therapy company with a central nervous system (CNS) pipeline consisting of disease modifying and potentially curative treatments for rare and more common diseases across all ages. Capsida's intravenously (IV) administered gene therapies utilize proprietary engineered capsids that enable high transduction levels to desired tissues and cells, while limiting tropism to non-target organs, such as the liver. Capsida has three wholly owned programs, including potential best-in-class treatments for genetic epilepsy due to STXBP1 mutations and Parkinson's disease associated with GBA mutations, both of which are in IND-enabling studies and on track to enter the clinic in the first half of 2025. In addition to its wholly owned programs, the Company has validating CNS partnerships with AbbVie, Lilly, CRISPR Therapeutics, and the AbbVie partnership was expanded to include ophthalmology disorders. Capsida was founded in 2019 by lead investors Versant Ventures and Westlake Village BioPartners and originated from groundbreaking research in the laboratory of Viviana Gradinaru, Ph.D., a neuroscience professor at Caltech. Visit us at www.capsida.com.

¹Gegg, M. E, et al (2012). Annals of neurology, 72(3), 455-463.

SOURCE Capsida Biotherapeutics