Predevelopment of VV2003, a Novel CRAC Channel Inhibitor, to Improve Outcomes Associated with Checkpoint Inhibitor Immunotherapy

Vivreon BiosciencesNCI SBIRPAProject Summary Vivreon Biosciences is pleased to apply for NCI SBIR SolicitationPAVivreon Biosciences is an innovative life sciences company that is developing a novel small moleculeCachannel inhibitorVVto improve outcomes in persons undergoing checkpoint inhibitor immunotherapyCheckpoint inhibitors have improved overall survival in numerous cancersbut enterocolitis has emerged as the most frequent dose limiting toxicity associated with these therapiesCheckpoint inhibitor induced colitis is currently treated with immunosuppressive therapywhich blunts the tumor killing potential of the checkpoint inhibitor immunotherapyVVis an oral candidate therapeutic designed to selectively and safely block enterocolitis without systemic immunosuppression side effectsVivreon seeks NCI funding to bridge the gap between discovery and developmentWe will perform predevelopment genotoxicity and in vivo checkpoint inhibitor immunotherapy enterocolitis animal model efficacy studiesUpon successful completion of the programour preclinical candidate will be the first to specifically inhibit Carelease activated CaCRACchannels for immunosuppression targeted specifically to sites of enterocolitisLeukocyte CRAC channels facilitate Cainfluxa process that is upstream of numerous enterocolitis disease causing processes including immune infiltration and inflammatory cytokine secretionVVhas extremely low epithelial permeability and remains in the gut lumen following oral administrationThis permits VVto achieve colon restricted immunosuppressionavoiding unwanted systemic side effectsWe have developed several strategies to confirm that VVcan be used in combination with multiple checkpoint inhibitor immunotherapiesincluding in vitro and in vivo checkpoint inhibitor immunotherapy blockade assaysThe final aim for this proposal is characterization and testing of the first CRAC channel inhibitor to address enterocolitis associated with checkpoint immunotherapy Vivreon BiosciencesNCI SBIRPAProject Narrative Vivreon Biosciences is conducting predevelopment studies for VVa novel therapeutic to improve outcomes in persons undergoing checkpoint inhibitor immunotherapyCheckpoint inhibitors have improved overall survival in numerous cancersbut severe diarrhea and enterocolitis side effects limit the effectiveness of these drugsVVaddresses this urgent clinical need through colon specific immunosuppressionwithout systemic side effectsby selective blockade of gut resident inflammatory Carelease activated CaCRACchannels