CAP-004
CAP-004 is a next generation, IV-delivered gene therapy comprising a novel capsid designed to deliver a functional FXN gene to neurons in the CNS, cardiomyocytes, and sensory regions with a single administration.
FA is a candidate for genetic therapy because it is caused by a mutation in a single gene, FXN. Mutations in FXN cause low production of a protein called frataxin, which leads to the symptoms of FA. Genetic therapies are treatment approaches that aim to address a disease at the DNA level. Gene addition is one type of genetic therapy that is designed to deliver working copies of the FXN gene to cells within the body. These delivered FXN genes would then produce frataxin protein.
Stages of Development for CAP-004
The drug development process can be thought of as a series of stages, and drugs must successfully pass through each stage to become available to patients. This treatment has been evaluated, and the program has been discontinued. Thus, it is not in the pipeline.
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.
This data was presented on a poster at ICAR 2024 in London.
CAP-004 is a next generation, IV-delivered gene therapy comprising a novel capsid designed to deliver a functional FXN gene to neurons in the CNS (brain and spinal cord), peripheral nervous system (PNS), as well as cardiomyocytes, with substantial detargeting to the liver and potential for lower dosing.