Therapeutic D-peptide Inhibitor of HIV Entry

DESCRIPTION provided by applicant With million people living with HIV AIDS including million in the US and million AIDS related deaths annually HIV AIDS remains a formidable global epidemic UNAIDS CDC Modern HIV therapy combines drugs from different classes to form andquot cocktailandquot therapies that have significantly prolonged the lives of many HIV patients However side effects and drug resistance remain serious concerns Thus there is an enduring need for novel HIV inhibitors with new mechanisms of action and stronger barriers to resistance Navigen is a pharmaceutical development company targeting infectious diseases Through an innovative discovery and design process we have identified a novel HIV entry inhibitor protease resistant D peptide that targets HIVandapos s conserved entry machinery and overcomes the current limitations of this inhibitor class Our lead candidate chol PIE trimer inhibits diverse strains from all major subtypes of HIV with high potency and possesses an unprecedented barrier to resistance Further chol PIE trimer appears from our Phase I SBIR preclinical studies to possess pharmacokinetic PK and physicochemical properties that would support development of a once weekly and perhaps once monthly with depot formulation subcutaneous injectable In this three year grant application we propose the following specific aims to advance chol PIE trimer towards IND filing as well as continue to explore potential backup candidates including PIE trimer should problems with chol PIE trimer arise advance the manufacturing and formulation of chol PIE trimer investigate the ADME properties of chol PIE trimer hold a pre IND meeting with the FDA to discuss our nonclinical and early clinical plans evaluate the in vivo proof of concept efficacy of chol PIE trimer in a standard nonhuman primate NHP model of HIV infection and further characterize the safety of chol PIE trimer in toxicology and safety pharmacology studies in rats and NHPs These data will be used to select a final candidate for advancement to IND and ultimately to the clinic as a marketable entry inhibitor This proposal will also provide valuable toxicology data that will advance D peptides as a therapeutic platform against diverse viral infections and other diseases PUBLIC HEALTH RELEVANCE Navigen is developing a novel D peptide inhibitor of HIV entry with remarkable potency breadth and an unparalleled barrier to resistance The goal of this proposal is to establish the in vivo efficacy of our lead candidate chol PIE trimer and advance it towards IND filing and human clinical trials Chol PIE trimer has the potential to offer an exciting new therapeutic option to HIV AIDS patients