Project Grant R44DA058467

DEVELOPMENT OF A NOVEL CALCIUM CHANNEL THERAPEUTIC FOR OPIOID USE DISORDER - VIVREON BIOSCIENCES, LLC 4940 CARROLL CANYON RD., STE. 110 SAN DIEGO, CA 92121 MILTON@VIVREONBIOSCIENCES.COM NIDA RFA-DA-23-021 PROJECT SUMMARY OPIOID USE DISORDER (OUD) IS THE CHRONIC USE OF OPIOIDS THAT CAUSES CLINICALLY SIGNIFICANT DISTRESS OR IMPAIRMENT. MOST HOSPITALIZED PATIENTS ADMITTED TO THE TRAUMA UNIT OR INTENSIVE CARE UNIT (ICU) RECEIVE OPIOIDS, COMMONLY AS PART OF ANALGESIA AND SEDATION REGIMENS. REPEATED OPIOID EXPOSURE PRODUCES BEHAVIORAL SENSITIZATION THAT CONTRIBUTES TO DRUG CRAVING, OPIOID-INDUCED HYPERALGESIA (OIH), AND WITHDRAWAL SYMPTOMS. OPIOID DEPENDENCE CAN BE EXPECTED IN HOSPITALIZED PATIENTS WHO HAVE RECEIVED LENGTHY OPIOID DOSE REGIMENS, AND PATIENTS ARE AT SIGNIFICANT RISK OF CONTINUING OPIOID USE FOLLOWING DISCHARGE. INPATIENT STAYS ARE OFTEN EXTENDED TO TAPER DOSAGES AND WEAN PATIENTS OFF OPIOIDS, YET THESE PATIENTS REMAIN AT INCREASED RISK OF OPIOID DEPENDENCE, WITHDRAWAL, AND OUD. THIS CYCLE OF OPIOID TREATMENT, OPIOID DEPENDENCE, OPIOID TAPERING, AND POTENTIAL FOR DEVELOPING OUD UPON DISCHARGE REPRESENTS AN URGENT UNMET MEDICAL NEED THAT CONTRIBUTES TO THE OPIOID PANDEMIC. A SMALL MOLECULE THERAPEUTIC THAT PREVENTS OPIOID DEPENDENCE WOULD REDUCE THE LENGTH OF HOSPITAL STAYS, IMPROVE PATIENT OUTCOMES, REDUCE THE RISK OF OUD, AND SIGNIFICANTLY REDUCE THE COST OF CARE. VIVREON BIOSCIENCES INTENDS TO ADDRESS THIS UNMET NEED BY DEVELOPING A NON-OPIOID NEW CHEMICAL ENTITY (NCE) FOR PREVENTION OF OPIOID DEPENDENCE TO COMBAT OUD. TISSUE DAMAGING MICROGLIOSIS, THE SHIFT OF QUIESCENT CNS MICROGLIA TOWARDS INFLAMMATORY BEHAVIORS IN RESPONSE TO SPECIFIC SIGNALS SUCH AS OPIOID RECEPTOR (OR) ACTIVATION, IS DOCUMENTED TO BE ASSOCIATED WITH OUD. THERAPEUTIC PREVENTION OF INFLAMMATORY MICROGLIOSIS IS AN INNOVATIVE APPROACH TO PREVENTING THE DEVELOPMENT OF OPIOID DEPENDENCE. CENTRAL NERVOUS SYSTEM MICROGLIAL CELLS ARE ACTIVATED BY ORS AND SUPPORT INFLAMMATORY MICROGLIAL POLARIZATION. WE HAVE DEMONSTRATED THAT OUR CANDIDATE THERAPEUTIC BLUNTS MULTIPLE DIMENSIONS OF MORPHINE-INDUCED BEHAVIORAL ADAPTATIONS. IN THIS FAST TRACK SBIR PROJECT VIVREON WILL BUILD A FULL PRECLINICAL DEVELOPMENT PROGRAM AROUND OUR LEAD VV MOLECULE TO TREAT OUD. IN PHASE I WE WILL DEVELOP DOSE-RESPONSE METRICS IN A MOUSE MODEL OF OPIOID DEPENDENCE WITH MULTIPLE READOUTS AND DOSE-RANGE FINDING STUDIES TO ESTABLISH THERAPEUTIC WINDOW INDICES FOR TWO THERAPEUTIC COMPOUNDS. THIS WILL ALLOW SELECTION OF THE MOST PROMISING LEAD COMPOUND FOR FURTHER DEVELOPMENT. SUCCESSFUL LEAD SELECTION WILL JUSTIFY ENTERING FULL DEVELOPMENT STUDIES IN PHASE II. THESE STUDIES WILL ENCOMPASS STANDARD SMALL MOLECULE INVESTIGATIONAL NEW DRUG (IND) EFFORTS INCLUDING ADME/PK, TOXICOLOGY AND MANUFACTURING STUDIES TO DE-RISK THE LEAD. SUCCESSFUL CONCLUSION OF THE PROJECT WILL YIELD AN ATTRACTIVE PACKAGE THAT IS ENTICING TO THIRD PARTY INVESTORS ABLE TO PROVIDE THE FINANCIAL SUPPORT REQUIRED FOR ADVANCEMENT OF THE LEAD INTO CLINICAL VALIDATION.