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.
There are over 1.2 million heart attacks annually in the US. In spite of advances made in thrombolytic therapy and angioplasty, up to 25% of men and 38% of women die within one year following a heart attack. A significant factor in high morbidity and mortality is due to the damage caused to the cardiac tissues by acute inflammation at the site of ischemia and reperfusion. The goal of the project is to develop a therapeutic compound that will inhibit the acute inflammation that occurs at the site of ischemia in patients following a myocardial infarction, minimizing the amount of microvascular damage and protecting viable cardiac cells in the infarct zone. Specifically, we will humanize our murine monoclonal antibody and confirm protection in a swine model of acute myocardial infarction.
| Sihag, Smita; Haas, Michael S; Kim, Karen M et al. (2016) Natural IgM Blockade Limits Infarct Expansion and Left Ventricular Dysfunction in a Swine Myocardial Infarct Model. Circ Cardiovasc Interv 9:e002547 |
| Tang, Kechun; Xia, Feng Cheng; Wagner, Peter D et al. (2010) Exercise-induced VEGF transcriptional activation in brain, lung and skeletal muscle. Respir Physiol Neurobiol 170:16-22 |
| Haas, Michael S; Alicot, Elisabeth M; Schuerpf, Franziska et al. (2010) Blockade of self-reactive IgM significantly reduces injury in a murine model of acute myocardial infarction. Cardiovasc Res 87:618-27 |
