Peripheral FAAH as a target for novel analgesics

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 2R42DA033683-02A1
Agency Tracking Number: R42DA033683
Amount: $1,100,244.00
Phase: Phase II
Program: STTR
Solicitation Topic Code: NIDA
Solicitation Number: PA14-072
Solicitation Year: 2014
Award Year: 2017
Award Start Date (Proposal Award Date): 2017-03-15
Award End Date (Contract End Date): 2019-11-30
Small Business Information
10575 ROSELLE ST, San Diego, CA, 92121-1505
DUNS: 078765734
HUBZone Owned: N
Woman Owned: N
Socially and Economically Disadvantaged: N
Principal Investigator
 (949) 824-7080
Business Contact
Phone: (858) 205-5904
Research Institution
IRVINE, CA, 92617-3213
 Nonprofit college or university
DESCRIPTION provided by applicant Pain management is a significant unmet medical need Anandamide is an endocannabinoid mediator that plays important roles in the regulation of pain Previous work has shown that endocannabinoid receptors located outside the central nervous system CNS exert a powerful regulatory control over pain initiation The biological actions of anandamide are stopped by the enzyme fatty acid amide hydrolase FAAH To explore the role of anandamide in the peripheral regulation of pain our lab has developed a novel class of FAAH inhibitors that do not enter the CNS The lead compound in this class called URB exerts profound analgesic effects in animal models suggesting that peripheral FAAH blockade may offer an innovative approach to pain therapy Work done during the Phase of the present application has demonstrated that URB a suppresses postoperative pain in mice more effectively than do currently used analgesics b does not cause side effects typical of those drugs i e sedation constipation gastric damage c shows a high degree of target selectivity d has excellent oral bioavailability in rats and e exerts no genotoxic effcts in the Amesandapos test and does not inhibit the human potassium hERG channel These results identify URB as a suitable candidate for preclinical development in postoperative pain an extremely common but still underserved pain condition The objective of present proposal is to complete all key activities needed to enable the filing of an Investigational New Drug IND for URB in postoperative pain Our specific aims are Aim Synthesis and physicochemical characterization of URB We will produce a large scale lot of URB for use in nonclinical pharmacokinetics and toxicology studies Aim Drug metabolism DM and pharmacokinetic PK properties of URB We will collect the DM PK data necessary to support the IND filing of URB Aim Nonclinical toxicology properties of URB We will collect the toxicology data necessary to support the IND filing of URB Aim Nonclinical pharmacodynamics of URB We will develop a circulating biomarker for peripheral FAAH inhibition which will be of great value during the clinical development of URB The proposed studies will be coordinated by an experienced team of scientists and pharmaceutical professionals which include Anteanaandapos s cofounders Professor Daniele Piomelli and Dr Miguel Garcia Guzman Professor Andrew Rice Imperial College London a world recognized leader in pain therapy along with and independent consultants Dr Edward Monaghan Soar Pharmaceutical Development Services preclinical development Dr Fred Reno toxicology Dr William Schmidt NorthStar Consulting health economics Dr Jason Brittain JNG Pharmaceutical Consulting Chemistry Manufacturing and Controls and Dr Richard Lowenthal Pacific Link Consulting regulatory affairs We expect that the successful completion of our studies will provide the data needed to file an IND for URB and allow us to raise the private capital necessary to bring this compound to clinical proof of concept PUBLIC HEALTH RELEVANCE Current painkillers work well in only about one quarter of the patients who take them and can cause a variety of negative effects for example sedation and addiction by acting on cells of the brain Our lab has recently discovered a new class of medications called `peripheral FAAH inhibitorsandapos which cannot enter the brain yet produce powerful pain suppression in experimental models Here we propose a series of studies that will enable the clinical testing of the lead compound in this class for the treatment of acute pain after surgery

* Information listed above is at the time of submission. *

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