Vivreon Biosciences – RFA-19-019 Investigation of Microglial CRAC Channels as a Novel Drug Target for Opioid Use Disorder Project Summary Vivreon Biosciences is pleased to apply for NIDA RFA-19-019. Vivreon Biosciences is an innovative life sciences company that is developing novel small molecule, Ca2+ channel inhibitors for the treatment of opioid use disorder (OUD). Our candidate therapeutics target brain microglial cells by an entirely new mechanism – inhibition of Ca2+ release-activated Ca2+ (CRAC) channels to block microgliosis. Vivreon seeks NIDA funding to perform preclinical proof of concept studies to test its preclinical lead, VV7063, in an animal model of opioid use disorder (OUD) and validate the CRAC channel as a therapeutic target for opioid withdrawal. Upon successful completion of this grant, Vivreon will identify a novel, non-opioid target for OUD. Future funding will be aimed at improving drug- like properties of Vivreon’s preclinical lead to identify the first ever CRAC-targeted clinical candidate for opioid withdrawal, providing an entirely new tool in the battle against OUD. Vivreon’s preclinical lead, VV7063, represents a novel chemotype with promising early drug-like properties and has no deleterious effect on autonomic or motor function, suggesting CRAC channels are a safe CNS drug target. It inhibits microgliosis by blocking CRAC channel activity with nM potency, suppressing M1-like NF-kB activity, while enhancing M2-like phagocytosis and a homeostatic transcriptional signature. We will now determine the pharmacokinetic (PK) profile of VV7063 in rats followed by testing of VV7063 in a rat model of OUD. The final milestone will be validation of the CRAC channel as a therapeutic target for OUD.

Vivreon Biosciences – RFA-19-019 Investigation of Microglial CRAC Channels as a Novel Drug Target for Opioid Use Disorder Project Narrative While opioid use disorder (OUD) is associated with pathologic changes throughout the brain, current OUD therapies are mostly targeted to neurons, leaving brain microglial cells as an untapped ripe therapeutic target for the next generation of OUD therapies. Vivreon seeks NIDA support to test its novel non-opioid, microglial- targeted preclinical Ca2+ release-activated Ca2+ (CRAC) channel inhibitor in an animal model of OUD to validate the CRAC channel as a therapeutic target for OUD.