Robert Preti, PhD – Amorcyte, Inc.

Proposal Title: Bone Marrow Derived CD34+ Cells for Treatment of Acute
Myocardial Infarction

Acute myocardial infarction causes necrotic and apoptotic myocardial cell death resulting in ventricular remodeling, which leads to subsequent cardiac dysfunction, congestive heart failure and resulting cardiac related adverse events including death in a significant percentage of patients. In the United States alone, there are reported incidences of 1.1 million cases annually. AMR-001 is Amorcyte’s Phase I cell therapeutic, bone marrow derived autologous CD34+ cells, for the treatment of myocardial infarct-related coronary damage. In vitro and studies have demonstrated the ability of CD34+ cells that co-express both CXCR-4 and VEGF-2, to home and localize in areas of ischemia, including the peri-infarct zone, following a myocardial infarction. CD34+ cells are capable of differentiating into endothelial cells that effect neoangiogenesis and may support new cardiac muscle formation. Following submittal of Amorcyte’s initial safety assessments, the Food and Drug Administration (FDA) approved the testing of this product through a Phase I clinical trial, scheduled to commence enrollment of patients by the end of 2005. Our long term goal is to continue to develop this product to prepare it for Phase II, then Phase III clinical trials, and to submit for a Biological License Application (BLA) to allow for its commercial distribution. The proposed studies would provide a level of control in CD34+ cell product manufacturing which is logistically feasible and an understanding of its characteristics to ensure safety, stability and efficacy in clinical use. The specific aims are to: 1. optimize the manufacturing process, 2. assess the feasibility of attaining adequate doses for clinical use, 3. correlate the in vitro CD34+ cell functionality with clinical outcome, 4. understand the CD34+ cell product stability characteristics, 5. test the biocompatibility and safety of the balloon dilatation catheters that are used for cell product infusion to the myocardial infracted zone, and 6. conduct validation study for the entire cell product manufacturing, product storage, transportation and cell infusion through catheters.

Lay abstract: Amorcyte's AMR-001 is a therapeutic cell product intended to be used for treatment after heart attack. AMR-001 is prepared by isolating certain cells from the patient's own bone marrow. These therapeutic cells will then be delivered to the damage heart tissue through a catheter.