OM #1

Patients with end-stage heart failure (ESHF) have a 2-year survival rate of 50% with conventional medical therapy. This dismal survival rate (largely unknown to the medical community and lay public) is actually significantly worse than patients with AIDS, liver cirrhosis, stroke, and other debilitating diseases. Stem cell therapy may be a promising strategy for inducing myocardial regeneration via paracrine activation, prevention of cardiac apoptosis, and other mechanisms. The proposed cell product is generated from the federally approved human embryonic stem cell (hESC) line WA07. The hESC-CMs are then produced in a good manufacturing practice (GMP)-compliant process using a combination of small molecules and suspension culture at City of Hope. The hESC-CMs are cryopreserved at harvest and thawed for subsequent immediate use. The overall dose of hESC-CMs in our phase 1 safety clinical trial is expected to be between 100 million and 300 million cells; the percentage of cardiomyocytes in the cell product is ≥ 80%, as assessed by flow cytometry for cardiomyocyte-specific protein expression. Over the last six months, we were engaged in conversations with FDA reviewers regarding our revised pre-IND enabling studies package. Based on their recommendations and internal discussions, we reached an agreement regarding our preclinical studies being proposed in our final Pre-IND package. Over the last 3 months, our partner COH has procured most of the required cells and have them ready to be transferred to the CRO upon initiation of our small animal studies (efficacy and tumorigenicity) and for the large animal studies (safety & feasibility).