Project Grant R43DA060646

INVESTIGATION OF A NOVEL PDE4B INHIBITOR FOR STIMULANT USE DISORDER - PROJECT SUMMARY FANNIN PARTNERS IS DEVELOPING A DRUG, 11H, FOR THE MANAGEMENT OF STIMULANT USE DISORDERS (STUD), AN AREA OF MAJOR UNMET MEDICAL NEED. OUR KEY INNOVATION IS SELECTIVE INHIBITION OF A KEY INFLAMMATORY PATHWAY IN THE BRAIN WHILE REDUCING THE ADVERSE EVENTS ASSOCIATED WITH CURRENTLY AVAILABLE NON-SELECTIVE INHIBITORS. STUDS HAVE INCREASED RAPIDLY IN THE LAST DECADE WITH STIMULANTS NOW THE 2ND MOST COMMONLY USED ILLICIT SUBSTANCE (AFTER CANNABIS PRODUCTS), RELATED TO 75% OF FEDERAL DRUG-RELATED OFFENSES. METHAMPHETAMINE (MA) IS A STIMULANT WITH HIGH ABUSE POTENTIAL AND HAS BECOME ONE OF THE MOST WIDELY AVAILABLE AND ILLICITLY-USED SUBSTANCES. DESPITE THE LACK OF SPECIFIC THERAPEUTICS APPROVED FOR STUD, INPATIENT TREATMENT COSTS ARE ESTIMATED AT ~$2.15 BILLION. THUS, NEW TREATMENT OPTIONS ARE URGENTLY NEEDED - IDEALLY ORALLY AVAILABLE AND WITH NEW MECHANISMS. 11H IS ORALLY BIOAVAILABLE AND SHOWS PROMISING EFFICACY IN MULTIPLE ANIMAL MODELS OF SUBSTANCE USE DISORDERS, INCLUDING WITH COCAINE, AS WELL AS ANTI-INFLAMMATORY ACTIVITY. 11H APPEARED WELL TOLERATED IN A VARIETY OF TOXICOLOGY MODELS. 11H ALSO DEMONSTRATED A FAVORABLE PHARMACOKINETIC PROFILE IN ANIMALS WITH ORAL BIOAVAILABILITY AND STRONG BRAIN PENETRATION. HERE, WE PROPOSE TO FURTHER DEVELOP THE DRUG THROUGH EARLY PRE-IND EFFICACY AND TOXICOLOGY STUDIES. OUR EXPERIENCED MANAGEMENT TEAM AND KEY COLLABORATORS PROVIDE THE ENVIRONMENTS REQUIRED TO SUCCESSFULLY ACHIEVE OUR PROPOSED AIMS. WE TRULY BELIEVE THAT THIS NOVEL DRUG COULD POTENTIALLY PLAY A CRUCIAL ROLE IN SAVING LIVES AND REDUCING THE CURRENT HEALTH CRISIS.