AMRI (NASDAQ: AMRI) announced the selection of a compound from its proprietary research program for the treatment of irritable bowel syndrome (IBS) for advanced preclinical testing, with the goal of submitting an Investigational New Drug Application (IND) with the U.S. Food and Drug Administration (FDA) in 2011.
“We are pleased to announce another significant achievement emerging from our R&D efforts, this on the heels of the news that an AMRI anti-obesity compound was entered into Phase 1 testing in July”
AMRI‘s drug candidate is a 5-HT3 receptor partial agonist shown to moderate but not completely block the function of 5-HT3 receptors, an approach that could be particularly beneficial in treatment of the non-constipation forms of IBS. This approach is differentiated from the existing class of 5-HT3 receptor antagonists that completely block receptor function.
Pending favorable results in toxicity and safety pharmacology testing, AMRI estimates that it will submit an IND (or equivalent regulatory filing) for this compound in the first half of 2011. Subject to regulatory review, the submission would allow subsequent initiation of Phase I human clinical trials.
“We are pleased to announce another significant achievement emerging from our R&D efforts, this on the heels of the news that an AMRI anti-obesity compound was entered into Phase 1 testing in July,” said Chairman, CEO and President Thomas E. D’Ambra, Ph.D. “AMRI is proud and excited about the continued success of its R&D organization. The quantity and quality of developments achieved by this team since its inception only six years ago exemplifies the high level of scientific talent, expertise and persistence that AMRI can offer customers desiring a strong partner for the advancement of their drug discovery programs.”
AMRI has filed a series of patent applications to protect the intellectual property associated with this program, and plans to ultimately seek a licensee to commercialize the technology.
Today’s announcement marks the seventh AMRI compound transitioned into an early stage preclinical candidate. Four of these candidates have moved into Phase I clinical testing: two compounds from AMRI’s biogenic amines program being studied for the treatment of central nervous system (CNS) disorders by Bristol-Myers Squibb Company (NYSE: BMY) as part of a licensing arrangement; one from AMRI’s independent tubulin inhibitor program, currently in Phase I testing in cancer patients; and most recently, one from AMRI’s proprietary MCH1 program for the treatment of obesity entered into Phase I testing as of July 2010.
About the Preclinical Candidate
AMRI’s 5-HT3 partial agonist represents a novel approach to the treatment of IBS, a disease-complex for which there are few currently available therapies but which is estimated to affect 10-20% of adults.
Full blockade of the 5-HT3 receptor is an established and effective approach to treating diarrhea predominant IBS (IBS-D) by way of positive effects on visceral sensitivity, colonic transit and secretion resulting in improvements in abdominal discomfort and stool consistency in patients. However, the first generation agents that completely block this receptor were associated with significant side-effects, including severe constipation and ischemic colitis in some patients. AMRI’s low intrinsic activity partial agonist approach is designed to provide sufficient receptor blockade to alleviate the disease symptoms while retaining a level of stimulation to maintain adequate tone. This unique dual action of AMRI’s partial agonist is anticipated to normalize gastroenteric function but avoid severe constipation or bowel ischemia.
In cell-based testing, AMRI’s first preclinical candidate from this approach shows excellent affinity and selectivity for the 5-HT3 receptor with a low intrinsic activity partial agonist profile. This profile is confirmed in animal models, which also demonstrate potent oral activity.