NeoKera, LLC — Department of Health and Human Services SBIR Phase II: 103

Description

PROJECT SUMMARY Pain management is a significant unmet medical needPalmitoylethanolamidePEAis an endogenous analgesic substance that plays crucial roles in the peripheral control of pain and inflammationIts biological actions are terminated by the cysteine hydrolaseN acylethanolamine acid amidaseNAAADuring the Phaseof the present SBIRapplicationwe have developed the first class of potentselective and orally available NAAA inhibitorsThe lead compound in this classa benzothiazole piperazine derivative called ARNexerts profound analgesic effects in animal models of acute and chronic painsuggesting that NAAA inhibition may offer a transformative approach to pain therapyWork done during the Phaseof the present application has demonstrated that ARNiis a potent and reversible inhibitor of mouse and human NAAAiidisplays a high degree of target selectivity when assayed on a panel ofreceptorsion channelsenzymes and membrane transportersor toward other cysteine hydrolasesiiiis systemically active andunlike previous NAAA inhibitorshas excellent oral bioavailabilityandivsuppresses pain with high efficacy and prolonged duration of action in four distinct animal modelsBased on these propertieswe selected ARNas candidate for preclinical developmentThe objective of present proposal is to complete all key activities needed to enable the filing of an Investigational New DrugINDfor ARNin postoperative paina market that is now served by addictive opioid drugs or opioid NSAID combinationsOur specific aims areAimDetermine the metabolism and pharmacokinetics properties of ARNWe will collect the DM PK data necessary to support the IND filing of ARNAimDetermine the nonclinical toxicology properties of ARNWe will collect the toxicology data necessary to support the IND filing of ARNAimDetermine the nonclinical pharmacodynamics of ARNTo facilitate the clinical development of ARNwe will develop a circulating biomarker for NAAA inhibition and enhancement of PEA mediated signalingThe studies will be directed by an experienced team of scientists and pharmaceutical professionalswhich include NeoKera s cofoundersDrEdward MonaghanPIand Professor Daniele Piomellico PIalong with independent consultants DrWilliam Schmidta clinical pharmacology consultant specialized in pain therapyDrFred Renoa consultant in toxicologyDrGeorge Mooneya consultant in ChemistryManufacturing and ControlsDrEdwardNedWhittamorea consultant in regulatory affairsNancy Levineconsultant for pharmacokineticsand DrJoe RinehartVice Chair for Research at UCI s Department of Anesthesiologyas pro bono clinical consultantThe proposed studies will provide the necessary data in support of an IND filing for ARNas a treatment for general acute pain PROJECT NARRATIVE Opioid painkillers work well in only one quarter of patients and are at the core of an abuse epidemic that has claimed the lives of more thanAmericans fromtoIt is clear that we need better ways to control painOur lab has discovered a new class of chemicalscalledNAAA inhibitorswhich produce powerful pain suppression in animals through a novel non addictive mechanismhere we propose studies that will enable clinical testing of the first member of this new class of medicines