CAP-004

CAP-004 is a systemically administered next-generation gene therapy for the treatment of Friedreich’s ataxia. CAP-004 utilizes one of the company’s proprietary engineered capsids to target central nervous system (CNS), cardiac, and sensory manifestations of the disease while limiting effects in off-target tissues, especially the liver.

In the study conducted in non-human primates (NHPs), results showed that CAP-004 demonstrated:

• Brain-wide biodistribution, achieving more than 80% transduction in key cell types, such as Purkinje cells in the cerebellum, neurons in the dentate nucleus, and motor neurons in the cortex and spinal cord.
• 100 times higher RNA expression compared with AAV9 in the cerebellum, motor cortex, and spinal cord.
• Significant cardiac tissue transduction, covering nearly 30% of the left ventricle tissue area.
• Bulk hFXN protein levels in treated NHPs were up to 8.2 times higher than endogenous levels in the motor cortex and 1.7 times higher in the left ventricle, highlighting the therapeutic potential in both CNS and cardiac regions.
• Potential in treating sensory vision loss, with significant RNA expression detected in the retina.
• Significant detargeting of the liver and other non-target tissues contributed to the favorable safety profile characterized by no adverse immunogenicity, clinical pathology, and histopathology findings.

CAP-004 is in IND-enabling studies. Based on CNS, cardiac and sensory targeting combined with substantial de-targeting to the liver and potential for lower dosing burden, the company will assess what safety profile CAP-004 can provide compared to traditional gene therapy.