VasaPlex-based biologics for treatment of reperfusion injury after myocardial infarction

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PROJECT SUMMARY Coronary heart disease leading to acute myocardial infarction (MI; heart attack) is a principal cause of mortality worldwide. Cornerstone treatments for MI are designed to restore blood flow (i.e. to “reperfuse”) blocked coronary arteries. Despite reduced times to intervention, and successful stent placement, 30-50% of primary Percutaneous Coronary Intervention (PCI) patients exhibit low- or “no-reflow”, a phenomenon linked to poor outcomes, increased probability of heart failure, and death. Low/no-reflow occurs when macroscopic vessels are opened by stenting or thrombolysis, but distal myocardial perfusion remains compromised. “VasaPlex” (HGF:IgG complex) and “VasaPlex-F2” (FGF2:HGF:IgG complex) are vaso- and cardioprotective biologic drugs we designed to increase vascular integrity and preserve cardiac tissue jeopardized by reperfusion injury and low/no-re-flow. In a large animal (pig) model of acute MI with reperfusion, intracoronary infusion of VasaPlex preserved 48 ± 12% of myocardial tissue at risk. We propose the following Specific Aims: 1. Determine effects of intracoronary treatment with VasaPlex or VasaPlex-F2 on cardiac structure and function 1 month after MI and PCI. Milestone: Obtain data for circulating biomarkers of cardiac injury, tissue histology, and echocardiographic measures of cardiac function that demonstrate significant long-term benefit conferred by VasaPlex and/or VasaPlex-F2-treatment in a pre-clinical, large animal model of MI with reperfusion. 2. Develop standardized conditions to form and maintain VasaPlex-based products. Milestone: Obtain basic, foundational data for dissociation/association kinetics of our drug components and the effects of IgG Fc domain glycosylation; these data will help us to generate our products more efficiently, improve product safety, and support IND filing and product commercialization. Deliverables: In alignment with the goals of the NIH STTR program, Samba BioLogics, Inc., will provide new, innovative and effective products that improve patient survival, outcomes and quality of life after MI.