28 July 2021 - - US-based biopharmaceutical company XyloCor Therapeutics has completed the Phase 1 dose-escalation component of its Phase 1/2 clinical trial (EXACT) of XC001 (encoberminogene rezmadenovec), its lead investigational gene therapy candidate for patients with refractory angina who have no further treatment options, the company said.

Following a review of clinical data from the Phase 1 dose escalation component of the study, the Independent Data Monitoring Committee authorized proceeding to the Phase 2 component of the study at the highest dose tested.

Since the IDMC authorization, three patients have been dosed in the Phase 2 expansion cohort.

This progress highlights the potential for gene therapy to go beyond rare diseases and to address larger patient populations with significant unmet needs, such as chronic cardiovascular diseases.

XyloCor also confirms that it plans to submit an additional Phase 2 clinical study to the US Food and Drug Administration for XC001 as adjunctive therapy to coronary artery bypass grafting in 2H21.

The company also plans other clinical studies in additional cardiovascular indications, including heart failure caused by ischemic heart disease and as adjunctive therapy to percutaneous coronary intervention.

XC001 (encoberminogene rezmadenovec) is a novel, investigational gene therapy designed to stimulate the growth of new blood vessels in the heart, in order to bypass diseased vessels and improve coronary blood flow.

XC001 delivers the gene for vascular endothelial growth factor, a naturally occurring protein, in targeted myocardial cells, thus stimulating the creation of new blood vessels via a process called angiogenesis. XC001 employs a proprietary multi-isoform VEGF expression cassette that has been optimized to maximize expression of VEGF.

XC001 has been granted Fast Track designation by the FDA for study in refractory angina. XyloCor commenced the EXACT Trial, a Phase 1/2 study of XC001 in chronic refractory angina, in 2020.

The Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment (EXACT) clinical trial is a Phase 1/2 multicenter, open-label, single-arm, dose-escalation trial. 12 subjects (n=3 per dose cohort) who have refractory angina were enrolled into four ascending dose groups, to be followed by an expansion phase of the trial with 21 additional subjects at the highest tolerated dose.

The trial is designed to assess the preliminary safety and efficacy of XC001. The investigational gene therapy is administered directly to the heart muscle through a mini-thoracotomy by an experienced cardiac surgeon.

The EXACT Trial is being conducted at top cardiovascular research sites across the United States.

In the United States, coronary artery disease is a leading cause of death and disability. Chronic angina pectoris occurs when the heart muscle does not receive sufficient oxygen resulting in chest pain.

This is usually due to atherosclerotic plaques that block the coronary arteries. Refractory angina is a growing problem that occurs in patients with chronic angina who are symptomatic despite optimal medical therapy and are no longer eligible for mechanical interventions like percutaneous coronary intervention and coronary artery bypass grafting.

These patients currently have no treatment options and are frequently highly symptomatic, which severely impacts their quality of life, and may exacerbate comorbidities and cause further deterioration of their health status. Refractory angina results in significant consumption of healthcare resources, including visits to the emergency department as a result of patients' chest pain.

An estimated one m people suffer from refractory angina in the United States.

XyloCor Therapeutics is a private, clinical-stage biopharmaceutical company developing potential best-in-class gene therapies to transform outcomes for patients with cardiovascular disease.

The company's lead product candidate, XC001, is in clinical development to investigate use for patients with refractory angina for which there are no treatment options.

XyloCor has a second preclinical investigational product, XC002, in discovery stage, being developed for the treatment of patients with cardiac tissue damage from heart attacks. The company, which was co-founded by Ronald Crystal, MD, and Todd Rosengart, MD, has an exclusive license from Cornell University.