A Novel Chemokine Receptor Antagonist to Block Opioid Reinforcement, Relapse and Physical Dependence

Project Summary Abstract This SBIR application is proposed in response to RFA DAthe HEAL Initiative on building technologies to stop the opioid crisisCreative Bio PeptidesIncis committed to providing effective and safe non opioid treatments for themillion Americans suffering daily pain and themillion who live with opioid dependency or addictionCurrent decades old addiction treatments like methadone are not up to the magnitude of this problemand themselves have abuse liability concernsChemokineshormones of the immune system that mediate innate immune inflammationenhance painreduce opioid analgesiaand promote drug seeking behavior and addictiongiving them a central role at the crossroads of chronic pain and the opioid crisisSoblocking chemokinesrather than opioid receptorsprovides an exciting and untested treatment opportunity for pain and opioid use disordersOUDOur chemokine antagonistblockerpeptide Rstops neuropathic pain and enhances the potency of morphine to relieve acute painRecent studies suggest that Rcould also become an effective treatment for OUDOther drugsthat block the same chemokine receptors targeted by Rlower the rewarding and reinforcing effects of drugs of abuseUsing rat behavioral studies that model human drug takingwe and others have reported that a CXCRantagonist AMDPlerixafora CCRantagonist MaravirocSelzentryand a CCRantagonist reduce the rewarding and locomotor effects of drugs of abuseHoweverthe only two approved treatments each block only one receptor target and have significant safety concernsneed to be injectedallergic risks and or liver toxicityRis a preferred treatmentas it blocks multiple chemokine receptorsCCRCCRCXCRis more potent and our prior clinical analogvery similar peptidehad no safety issues in humansWe propose to assessin animal self administration models that mimic human drug takingwhether Rreduces morphine intakeSuccess will be defined as a andgtreduction in the breakpoint difference scorea measure of motivation for drug takingPhysical dependence develops during chronic opioid exposure and upon discontinuation of opioid intakepresents as a withdrawal syndrome that triggers opioid relapseWe will further assess if Rwill prevent or blunt naloxone precipitated withdrawal signs in morphine dependent rats and stop relapseSuccess will be a andgtreduction in theWithdrawal Symptom Scoreof Rcompared to vehicleWe will also evaluate the safety of Rby determining a maximum tolerated doseSuccessful execution of this program will create new intellectual propertyde risk IND enabling studies of Rin Phase II developmentand will culminate with a pre IND meeting with the FDA to establish a regulatory approval plan for our subsequent human efficacy studies in OUDCreative Bio PeptidesInc has obtained two issued patents for Rthe composition of matterUSand the use in treating neuropathic painUSWe have ten pending applicationsincluding uses of Rto reduce morphine use in painand as a treatment for addictionsProject Narrative Creative Bio Peptides develops novel non opioid treatments for themillion Americans who experience daily pain and themillion who live with opioid dependency or addictionoften arising from prescription pain medications and their diversionWe create drugs that block the innate immune chemokine receptor systems that when activated promote painblock the action of opioids to stop painand promote drug seeking and use behaviorsThe global pain market is projected to reach $B byreflecting the large populations in need of better pain and addiction treatments which we hope to provideeither as a stand alone therapyor to reduce opioid need in pain management