Health and human services (HHS) and the Biomedical Advanced Research and Development Authority (BARDA) have suggested a severe pandemic influenza outbreak is the greatest current threat to national andglobal security. The Center for Disease Control rates H7N9 as the most threatening of the Influenza A virusesas it, along with H5N1, have fatality rates of ~40% and ~60%, respectively. Models have predicted that anH7N9 pandemic could result in infection of one third of the world population and death of ~40% of thoseinfected, making it the deadliest virus in recorded history (the 1918 flu had a fatality rate of ~2.5%). There iscurrently no approved therapeutic for severe influenza infection, and in the case of H7N9 ~98% of thoseinfected develop severe infection and require hospitalization. This project seeks to provide some hope ofprotection in such an outbreak by advancing the most effective broad-spectrum human antibody therapeuticcurrently available, CM-IAV1. CM-IAV1 is a broadly neutralizing human monoclonal that is cross-reactive forgroup 1 and group 2 avian influenza. CM-IAV1 has already been shown to protect mice against lethal (non-laboratory strain) H7N9 and H5N1 when given in a single dose 72 hours post-infection. To leverage thisoutstanding preclinical data, we have assembled a world-class team that is focused on advancing CM-IAV1into the clinic. The experiments presented in this application will take a promising preclinical agent and,together with our continued and parallel investments, create a clinical asset with enormous potential to reducemorbidity and mortality associated influenza infection from the most relevant CDC- prioritized pandemicstrains. We believe that development of this antibody, at this time, and by this team represents the best hopeof offering meaningful lifesaving protection against the terrifying possibility of a global Influenza A outbreak.The overarching goal of this project is to advance a novel broad-spectrum, lifesaving therapeutic for pandemicinfluenza A infection from promising preclinical candidate through investigational new drug (IND)-enablingstudies to IND filing.
Public Health Relevance Statement: Project Narrative The threat of an H7N9 or H5N1 Avian Influenza pandemic expands constantly with virtually no current strategy to mitigate the enormous loss of life that such an outbreak would inflict. The human monoclonal antibody CM- IAV1 is a preclinical asset that we propose to develop into a well-characterized IND-ready drug, one ready to save lives when the most serious influenza outbreaks occur. CM-IAV1 targets the well-conserved hemagglutinin stalk region of group 1 and group 2 influenza and has been shown protect mice against H7N9 (group 2) and H5N1 (group 1) influenza A infections, even when given in a single dose 72 hours post-infection.
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