XyloCor Therapeutics' XC001 Shows Positive Phase 2 Data at SCAI 2024

XyloCor Therapeutics, Inc., a clinical-stage biopharmaceutical company, has announced promising results from the Phase 2 portion of its Phase 1/2 clinical trial, EXACT, testing its innovative gene therapy candidate, XC001 (encoberminogene rezmadenovec), for the treatment of refractory angina. These findings were presented at the Society for Cardiovascular Angiography & Interventions (SCAI) 2024 Scientific Sessions in Long Beach, California, and published in Circulation: Cardiovascular Interventions.

Refractory angina, a chronic and debilitating condition affecting over a million Americans, lacks sufficient treatment options. XC001 aims to address this unmet medical need by reducing ischemic burden through the creation of new blood vessels in the heart. This process is facilitated by the local expression of multiple vascular endothelial growth factor (VEGF) isoforms. In the Phase 2 EXACT trial, 32 patients with class II-IV angina were administered the maximal dose of XC001 via minimally-invasive transepicardial delivery directly to the heart.

Dr. Thomas Povsic of Duke University School of Medicine and Dr. Kenta Nakamura of the University of Washington, lead authors of the EXACT study, emphasized the potential of XC001 to improve cardiovascular outcomes for patients with refractory angina who lack other treatment options. They highlighted the significant need for novel therapies for this severe condition and expressed hope that the promising results from the EXACT trial will drive further development of this innovative gene therapy.

The Phase 2 results verified XC001’s potential to transform disease management by reducing ischemia and improving the quality of life for cardiac patients without remaining treatment options. Key outcomes included increased exercise duration, decreased ischemic burden as measured by PET imaging, and a reduction in the frequency of angina episodes. Remarkably, 93% of patients initially experienced severe chest pain that limited daily activities, but six months post-treatment, 43% reported no chest pain during ordinary activities. Furthermore, the VEGF gene therapy was well tolerated, with no serious adverse events directly related to the drug.

Al Gianchetti, President and CEO of XyloCor, noted that the EXACT trial’s results mark a significant advancement for patients suffering from refractory angina and the broader cardiovascular community. He stated that XyloCor is preparing for the next clinical trial phase to further explore XC001’s medical potential and benefits for patients and their families.

XC001 is engineered to promote the development of new blood vessels in the heart, bypassing diseased vessels and enhancing blood flow. This improvement can reduce chest pain and potentially allow patients to resume normal physical activities without discomfort. The gene therapy’s one-time, localized administration strategy aims to avoid the toxicity issues associated with other gene therapies, achieving higher gene expression in the heart while minimizing systemic side effects.

The EXACT study, formally known as the Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment clinical trial, was a Phase 1/2 multicenter, open-label, single-arm trial. The trial involved 12 subjects in ascending dose groups, followed by an expansion phase where additional subjects received the highest tolerated dose. XC001 was administered directly to the heart muscle via a mini-thoracotomy performed by a cardiac surgeon.

Chronic refractory angina remains a significant healthcare challenge in the United States, where coronary artery disease is a leading cause of death and disability. Patients with chronic angina who do not respond to optimal medical therapy and are ineligible for mechanical interventions like PCI or CABG often experience severe symptoms that drastically affect their quality of life.

XyloCor Therapeutics is committed to developing gene therapies to transform outcomes for cardiovascular patients. Besides XC001, the company is also working on XC002, a preclinical investigational product aimed at treating cardiac tissue damage from heart attacks.