Nourexal® (Cyclocreatine Phosphate) is a Novel Bioenergetic/Anti-inflammatory Drug that Resuscitates Poorly Functioning Hearts and Protects Against Development of Heart Failure

There is a need for new therapies that can protect the myocardium against ischemic injury and abort ischemic effects that lead to cardiac dysfunction and the development of heart failure. To address this unmet need, Nour Heart developed and patented Nourexal® (cyclocreatine phosphate - CCrP) as a potent bioenergetic/anti-inflammatory drug to preserve high energy levels of cellular adenosine triphosphate (ATP) and enhances its stores during ischemia. Nourexal® was recently awarded by the FDA the Orphan Drug Status for the designation of “Prevention of Ischemic Injury to Enhance Cardiac Graft Recovery and Survival in Heart Transplantation” (DRU-2015-4951). Therefore, Nour Heart’s first clinical application of CCrP is for end-stage heart failure patients scheduled for heart transplantation.

Mechanistically, Nourexal® (CCrP) is a synthetic analogue of the naturally occurring creatine phosphate (CrP). CCrP is more stable and superior to CrP and continues to synthesize ATP under acidic/anaerobic conditions, while CrP stops working. As a potent high-energy phosphate donor, CCrP is taken up into cardiac tissue and can directly phosphorylate adenosine diphosphate (ADP) under conditions of limited O₂ supply, thereby generating adenosine triphosphate (ATP). Nourexal™ is water soluble compound and it is a safe drug when administered to rats daily for 14 days. Nour Heart is the only company producing Nourexal® using its issued chemical patent and a new pending process patent application. Because ATP is required for normal systolic and diastolic contractile performance, studies demonstrated that the failing heart is unable to meet the hemodynamic requirements of the body because there is not enough chemical energy available. Thus, maintaining a high ATP supply is critically important for preventing ischemic injury and restoring cardiac performance. Nour Heart demonstrated that Nourexal® is a novel bioenergetic/anti-inflammatory drug that enhances myocardial ATP stores during ischemia, prevents ischemic injury, blocks the downstream harmful events of ischemia, and development of heart failure.

Cyclocreatine Phosphate (CCrP): A Novel Therapy to Protect Hearts Against Ischemic Injury and Retore Cardiac Function.

The cardioprotective drug, Cyclocreatine Phosphate (CCrP) (Nourexal™) is an FDA Orphan Designated Drug for heart transplantation (DRU-2015-4951). It is a New Paradigm that restores cellular energy (adenosine triphosphate (ATP)) despite hypoxia/ischemia. As a bioenergetic drug, CCrP protects hearts against ischemic injury and restores cardiac function during reperfusion. Clinical applications include, end-stage heart failure patients scheduled for heart transplantation procedure, patients undergoing high-risk cardiac surgery and high-risk intervention cardiology.

CCrP: A Novel Bioenergetic Drug

Nour Heart, Inc. the first to patent Cyclocreatine Phosphate (CCrP) (Nourexal™) as a potent cardioprotective drug to:

• Prevent myocardial ischemic injury and restore strong cardiac function during early reperfusion,
• Block the harmful downstream events of ischemia that lead to cardiac dysfunction,
• Prevent the development of cardiac dysfunction and heart failure.

Unmet Need in Heart Transplantation:

In the U.S., approximately 6.2 million adults experience heart failure (HF) and this number has recently increased with COVID-19 infection. Although HF patients can be managed with medications or medical procedures, some HF patients, including COVID-19 patients, reach end-stage organ failure, where the only lifesaving solution is a heart transplant. Over 20,000 heart transplants are needed each year, but due to lack of progress in heart preservation since 1995, 6 hearts from every 10 organ donors are unutilized, fewer than 4,000 procedures are performed despite the availability of yearly 12,000 donors. The vast majority of hearts are rejected because current transport time is limited to 4 hours and due to poor cardiac function, defined as an ejection fraction (EF) of ≤40%. Poor cardiac function is primarily due to stress cardiomyopathy (demand ischemia) that arises from the exhaustion of the cellular high energy source, adenosine triphosphate (ATP). Hormonal support (thyroxine (T4) and triiodothyronine (T3)) to improve poor cardiac function in rejected hearts has not consistently reversed myocardial dysfunction, nor has it increased the number of transplanted hearts. Thus, there is an unmet need to salvage poorly functioning hearts (by preserving ATP) and extend transport time, which can potentially increase heart utilization and yearly transplant cases.

Nour Heart’s Strategy:

Nour Heart developed and patented CCrP as a bioenergetic drug that enhances myocardial ATP stores during ischemia, prevents ischemic injury, and maintains strong cardiac function in a variety of animal models. A single injection of CCrP to rat donors protected hearts during harvesting and allowed prolonged storage for 22 hours with full, persistent cardiac recovery over 3 days in recipient rats. Recipient rats did not receive the drug. CCrP could be used to increase donor heart utilization for transplantation.

Commercialization:

Nour Heart submitted a Pre-IND application to the FDA and received a response with FDA-recommended, IND-enabling CCrP preclinical safety assessment in rats and dogs for heart transplant indication.

Additional future clinical applications:

Predictable myocardial ischemia, where pretreatment with CCrP would likely protect against complications, improve outcomes and quality of life for patients who are undergoing:

• high-risk cardiopulmonary bypass
• high-risk transcatheter aortic valve implantation (TAVI) procedures
• high-risk percutaneous coronary intervention (PCI).