Pipeline for Rare and Common Diseases Across All Ages

CAP-002: Capsida’s Program for STXBP1-DEE

STXBP1-DEE is a devastating developmental epileptic encephalopathy estimated to affect up to one in 26,000 births globally. STXBP1 is a protein involved in the release of neurotransmitters and neuropeptides, which are responsible for communication across neurons in the brain and throughout the central nervous system. STXBP1-DEE is characterized by early onset seizures and a risk of sudden unexpected death in epilepsy (SUDEP), severe developmental delay, intellectual disability and motor disorders. There are no disease-modifying therapies for STXBP1-DEE. Current treatments are supportive only, and include anti-seizure medication, and physical, occupational, and speech therapy.

CAP-002 is a wholly owned investigational gene therapy that is designed to stably supplement STXBP1 protein throughout the brain after a single intravenous infusion. Studies in relevant preclinical models have shown substantial detargeting of peripheral organs such as liver and dorsal root ganglia (DRG) and potential to lower dose compared to traditional gene therapy approaches. This potential disease modifying therapy aims to correct the underlying disease pathology to alleviate disease manifestations for patients with STXBP1-DEE.

CAP-002 received FDA IND clearance. The FDA has granted Fast Track and Orphan Drug Designation to CAP-002 for the potential treatment of STXBP1-DEE.

Capsida has an exclusive license agreement and research collaboration with Baylor College of Medicine and Associate Professor of Neuroscience Mingshan Xue, Ph.D., who has developed STXBP1 mouse models and AAV gene therapy approaches, in support of preclinical development of this program.

López-Rivera et al, 2020, Abramov et al, 2020, Stamberger et al, 2016, Saitsu et al., 2008; Stamberger et al., 2016

CAP-003: Capsida’s Program for PD-GBA

PD is the second most common neurodegenerative disorder, with an estimated prevalence of more than 10 million adults worldwide and nearly one million in the United States. Current evidence suggests up to 15% of PD patients have GBA1 mutations, making this the most common genetic risk factor for PD. PD involves the progressive loss of dopaminergic neurons in a part of the brain called the substantia nigra, and development and spread of aggregated protein inclusions called Lewy bodies in the brain. Patients with PD typically experience motor and non-motor symptoms, including tremor, rigidity, slowness of movement, cognitive decline, psychiatric symptoms, and sleep disturbances. PD GBA can be associated with an earlier onset and more severe disease course compared to idiopathic PD. Currently, there are no approved disease modifying treatments for any form of PD, including PD-GBA. Though standard of care is available for treatment of motor symptoms, motor fluctuations and dyskinesias (abnormal involuntary movements) develop in many patients, and non-motor symptoms will frequently persist, all of which can be debilitating in and of themselves.

CAP-003 is a next-generation systemically delivered gene therapy with potential for the treatment of PD-GBA. This investigational gene therapy is designed to supplement GCase enzyme with a single intravenous infusion, enabling potential long-term disease modification and substantial slowing of disease progression with limited treatment burden. CAP-003 has potential for delivering GCase enzyme to critical cortical and sub-cortical areas of the brain associated with PD-GBA, such as the substantia nigra, caudate nucleus, putamen, cortex, and thalamus. Studies in relevant preclinical models have shown substantial detargeting of peripheral organs such as liver and DRG and potential to lower dose compared to traditional gene therapy approaches.

CAP-003 has received FDA IND clearance.

Smith and Schapira 2022

CAP-004: Capsida’s Program for FA

FA is a rare, hereditary, form of ataxia causing progressive neurodegeneration, decline in gait and limb control, cardiac dysfunction, and sensory deterioration. The prevalence of FA is approximately 1 in every 50,000 people, affecting approximately 5,000 patients in the US and approximately 15,000 worldwide. The average life expectancy for FA patients is 37 years of age, with death typically precipitated by cardiac dysfunction. FA is caused by an intronic triplicate repeat expansion that diminishes the expression of the frataxin (FXN) protein. FXN protein plays a critical role in cellular respiration, and in its absence, there is deficient iron-sulfur clustering in the mitochondria leading to impaired cellular respiration, oxidative stress, and cell death. Owing to eventual cell death, the impact to functions controlled by non-regenerative cell types (e.g., neurons, cardiomyocytes) is most pronounced. Currently, there are limited treatment options for FA.

CAP-004 is a wholly-owned, next generation, IV-delivered gene therapy in IND-enabling studies comprising a novel capsid designed to deliver a functional FXN gene to neurons in the CNS, cardiomyocytes, and sensory regions, thereby providing a permanent source of FXN protein allowing for restoration of cellular respiration and prevention of cell death. CAP-004 offers the potential to stably replace wild type FXN protein in disease-relevant cell types across CNS, cardiac tissues, and sensory regions with a single IV infusion. Capsida’s aim is to enable long-term disease modification across multiple organ systems and tissues impacted by the disease with limited treatment burden and provide a superior safety profile compared to traditional gene therapy. Based on CNS, cardiac and sensory targeting combined with substantial detargeting to the liver and potential for lower dosing, CAP-004 has the potential to address significant unmet needs in FA patients.