Humanized EMAP II mAb as a Novel Therapy for Viral-Associated Lung Injury

Summary Abstract The ultimate goal of this project is the validation of a humanized endothelial monocyteactivating protein IIEMAP IIneutralizing monoclonal antibodymAbfor progression to clinical evaluation as a novel treatment for patients with influenza associated lung injuryInfection with influenza virusIAVremains a major world wide health threat to high risk populations including the young and elderlypregnant womenand people with weakened immune systemsAccording to CDC datainfluenza accounts for more thandeaths in US annually due to underlying respiratory and circulatory causesThe efficiency of influenza vaccination and antiviral drugs is compromised by the constant change in circulating viruses and the development of resistance in influenza virus strainsAllinaire TherapeuticsLLC is developing a first in class therapy which will not depend on the suppression of virus replicationand will be independent of the circulating influenza strainRatherthe EMAP II mAb will target the pathogenic components of lung injuryincluding vascular endothelium apoptosis and leakageWe hypothesize that EMAP II is a key underlying factor in IAV induced lung injuryand that a humanized EMAP II mAb will attenuate the development and serious consequences of lung damage produced by IAVHere we present preliminary data demonstrating that IAV induced pathologies are associated with dramatic increases in levels of EMAP II in the lungand that administration of a rodent EMAP II mAb to influenza AIAVinfected mice ameliorates lung injuryImportantlywe have competed the creation of a fully humanized version of the EMAP II mAba crucial step towards targeting EMAP II clinically and creating a novel medicineTo evaluate our hypothesis and meet our drug discovery milestoneswe plan to validate our humanized EMAP II mAb candidates in vitro in human lung cells exposed to IAV and recombinant EMAP IIAimand select the most potent and efficacious mAb to be tested in vivo in our established murine model of IAV induced lung injuryAimNarrative The goal of this project is the validation of a fully humanized EMAP II antibody for progression to clinical evaluation as a first in class treatment for patients with influenza associated lung injuryAn EMAP II targeted therapy will directly protect the lung from injury regardless of viral strain and represents a paradigm shift in the treatment of viral respiratory infections