Vivreon Biosciences, LLC 7558 Trade St. San Diego, CA 92121 vivreonbiosciences@gmail.com Vivreon Biosciences – NIA SBIR # PA-18-187 Project Summary Vivreon Biosciences is pleased to apply for NIA SBIR Solicitation #PA-18-187. Vivreon Biosciences is an innovative life sciences company that is developing a series of novel small molecule, Ca2+ channel inhibitors for the treatment of Alzheimer's disease (AD). Our lead compound series achieves neuroprotection by an entirely new mechanism – inhibition of Ca2+ release-activated Ca2+ (CRAC) channels to block microgliosis. Vivreon seeks NIA funding to bridge the gap between discovery and development. We will perform chemistry and biology experiments to identify and validate a new clinical candidate therapeutic drug. Upon successful completion of the program, our clinical candidate will be the first to specifically target the CRAC pathway for neuroprotection in AD, thus comprising an entirely new tool in the battle against AD. Vivreon has discovered a lead compound series with oral bioavailability that penetrates into the central nervous system (CNS) very efficiently, shows no neurotoxicity in the Irwin test of central nervous system (CNS) integrity, and demonstrates neuroprotection in a mouse model of neurodegeneration. The lead series inhibits microgliosis by blocking CRAC channel activity with nM potency; suppressing M1-like NF-κB activity, while enhancing M2- like phagocytosis. We will now expand our library of small molecule CRAC channel inhibitors by synthetic chemistry followed by pharmacology assays designed to identify a candidate with properties appropriate for AD therapy. The candidate therapeutic will be validated in a new humanized animal model of AD (5x-MITRG). The final aim for this proposal is identification and validation of the first CRAC channel inhibitor for AD therapy.