Safety of Allogeneic Cardiosphere-Derived Cells for Acute Myocardial Infarction

DESCRIPTION (provided by applicant): Project Abstract: Capricor, Inc. has an allogeneic cell therapy product, CAP-1002, presently in clinical development. CAP-1002 consists of cardiosphere-derived cells (CDCs), grown from a donor unrelated to the recipient, using a proprietary process exclusively licensed to Capricor. Autologous CDCs have demonstrated their utility as a regenerative agent: able to reduce infarct size (a.k.a scar size), add viable tissue mass, and attenuate adverse left ventricular (LV) remodeling when administered to patients several months after a myocardial infarction (MI). The magnitude of benefit seen in CDC-treated patients could foreshadow a reduction in future adverse clinical events. Allogeneic CDCs are currently being tested in a similar post-MI population in a randomized, double-blinded, placebo-controlled, multi-center safety and efficacy study. The current proposal aims to test the safety of CAP-1002 administered in the acute MI setting, adjunctive to the gold-standard treatment(i.e. PCI [percutaneous coronary intervention]), rapidly after restoration of blood flow (or reperfusion), as a cardioprotective agent. Capricor has an approved IND (Investigational New Drug application) for the use of CAP-1002 in the treatment and/or prevention of LV dysfunction following MI, and the proposed clinical trial falls under the umbrella of this indication. Preclinial data support the safe use of CAP-1002 in acute MI and reveal the product's ability to limit infarct size and reduce acute myocardial damage. CAP-1002 is manufactured in an existing GMP (Good Manufacturing Practice compliant) facility and will be stored at the clinical site for immediate availability. CAP-1002 is formulated such that it can be prepared for use within minutes and administered within minutes. Patients will be treated open-label with CAP-1002 within hours of successful reperfusion. Safety endpoints will include assessments of blood flow in the coronary arteries and microvasculature, resolution of myocardial damage, immune reaction, arrhythmias, and MACE (major adverse cardiac events). Efficacy assessments will examine infarct size, LV volumes, and ejection fraction by MRI (magnetic resonance imaging). Funding for a follow-on trial that would demonstrate efficacy will bepursued concurrently. Capricor is well-positioned to secure financing for the next study, particularly with an ongoing multi-center study utilizing the same product in a complementary patient population. The company has a sound regulatory strategy and advisors in place to guide interactions with the FDA (Food and Drug Administration) as CAP-1002 is advanced toward approval. The current manufacturing scale and facility will suffice through early commercialization and plans to scale up are underway. Capricorhas identified several potential avenues by which to enter the public market and maintains active business development efforts. The company anticipates being revenue generating within a few years of project completion. The ongoing and proposed clinical trial series encompass nearly the full continuum of disease states following MI. CAP-1002 developed successfully for all MI patients would offer both a cardioprotective and regenerative therapy, to be administered as needed. PUBLIC HEALTH RELEVANCEPUBLIC HEALTH RELEVANCE: Project Narrative: Cardiovascular disease is the No. 1 cause of death in the United States and myocardial infarction (MI) affects more than 1 million Americans every year. Cardiosphere-derived cells (CDCs) will be tested as a safeand effective therapy when administered immediately after MI, in the hopes of limiting the amount of damage caused by the event, lowering the number of adverse clinical events experienced in the future, and reducing the population of Americans living withand dying from heart failure after MI.