Development of CM-IAV1 for Treatment of High-risk Pandemic Influenzas

Project Summary 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 and global security. The Center for Disease Control rates H7N9 as the most threatening of the Influenza A viruses as it, along with H5N1, have fatality rates of ~40% and ~60%, respectively. Models have predicted that an H7N9 pandemic could result in infection of one third of the world population and death of ~40% of those infected, making it the deadliest virus in recorded history (the 1918 flu had a fatality rate of ~2.5%). There is currently no approved therapeutic for severe influenza infection, and in the case of H7N9 ~98% of those infected develop severe infection and require hospitalization. This project seeks to provide some hope of protection in such an outbreak by advancing the most effective broad-spectrum human antibody therapeutic currently available, CM-IAV1. CM-IAV1 is a broadly neutralizing human monoclonal that is cross-reactive for group 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 this outstanding preclinical data, we have assembled a world-class team that is focused on advancing CM-IAV1 into 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 reduce morbidity and mortality associated influenza infection from the most relevant CDC- prioritized pandemic strains. We believe that development of this antibody, at this time, and by this team represents the best hope of 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 pandemic influenza A infection from promising preclinical candidate through investigational new drug (IND)-enabling studies to IND filing.