Project Summary/Abstract Acute myocardial infarction (AMI) affects over 1 million US individuals a year and at the present there are no preventive therapeutics other than direct percutaneous coronary intervention. DecImmune's long-term goal is to develop therapeutics to reduce the severe lethal reperfusion injury that follows removal of coronary artery blockage. This goal is based on our identification of a novel pathway that is activated during reperfusion of ischemic tissues and development of a peptide mimetope (N2) and monoclonal antibodies that block inflammation. The current application is a re-submission of our Phase IIB application of 2012. Our studies from Phase I demonstrated that the novel pathway we identified in rodents is conserved in humans. In Phase II, we showed that both the peptide (N2) and our murine monoclonal antibody against N2 (21G6) were protective during acute myocardial infarction and that a therapeutic candidate monoclonal antibody has been humanized and manufacturing efforts have begun. Therefore, in order to move the potential therapeutics to clinical trials, we propose to start non-GLP and GLP safety studies, manufacture clinical trial material, complete a normal volunteer human Phase 1 safety and tolerability study and initiate Phase 2 clinical trials in heart attack patients.