Lead Optimization of CRAC Channel Inhibitors for the Treatment of Alzheimer's Disease

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Vivreon Biosciences, LLC 4940 Carroll Canyon Rd. Suite 110 San Diego, CA 92121 milton@vivreonbiosciences.com Vivreon Biosciences – NIA SBIR # PA-20-272: AG055205 Project Summary Vivreon Biosciences is pleased to apply for NIA SBIR Supplement #PA-20-272 to address medicinal chemistry optimization issues in our currently funded SBIR AG055205, “Lead Optimization of CRAC Channel Inhibitors for the Treatment of Alzheimer's Disease”. Supplemental funding is urgently required to de-risk our program prior to advancing to development studies. Vivreon Biosciences 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 models of Alzheimer’s disease. The lead series inhibits microgliosis by blocking CRAC channel activity with nM potency; suppressing M1-like NF-κB activity, while enhancing M2-like phagocytosis. Supplemental funding is required to de-risk our program prior to advancing to development studies. Several promising compounds are hampered from further development due to certain properties and further lead optimization is required to remove liabilities prior to selection of a development compound.