HOUSTON (Sept. 26, 2023) — Aviara Pharmaceuticals, Inc., through a research collaboration with The Texas Heart Institute® (THI), recently was awarded a two-year, $1.9 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to develop a safe and novel drug for inflammatory bowel disease (IBD).

IBD is characterized by chronic inflammation of the digestive tract (or gut). The two most common forms of IBD are Crohn’s disease and ulcerative colitis, which include symptoms such as diarrhea, nausea, fatigue, weight loss and rectal bleeding. Recent findings indicate that IBD is diagnosed in almost 1 in 100 Americans.

Unfortunately, IBD patients face lifelong treatments with no long-term cures — and select surgical interventions to repair the damaged intestinal wall often carry complications. Current first-line treatment may benefit only 50% of these patients, and aggressive steroids and immunosuppressants often are prescribed to the other half of patients who continue to suffer.

Drugs that target specific types of inflammatory cells and prevent these cells from getting to the gut have enhanced IBD treatment. These drugs target adhesion molecules, named integrins, on the surface of inflammatory cells. These drugs largely are biologics requiring monthly injections, and there currently are no small molecule drugs in the U.S. that can be taken as a once-a-day pill to prevent inflammatory cell recruitment to the gut.

The development of an effective integrin antagonist — specifically, a small molecule drug administered by mouth daily that is not an immunomodulatory biologic — would represent a significant improvement in treatment options for patients with IBD.

“The proposed orally available small molecule drug, taken once daily, would target gut inflammatory cells and could provide a safe and effective alternative to current IBD therapeutics associated with high levels of unresponsiveness,” said Darren G. Woodside, PhD, vice president for Research and senior investigator at The Texas Heart Institute. “If successful, this approach could provide substantial improvements to the care of IBD patients.”

In 2020, Aviara Pharmaceuticals, Inc. first collaborated with Dr. Woodside in a National Institutes of Health (NIH)-funded, Phase 1 Small Business Technology Transfer (STTR) grant. Taking advantage of small molecule inhibitors that target a cell-surface integrin involved in cardiovascular inflammation, and using it to address inflammation in the gut, the researchers sought to develop the aforementioned drug that would inhibit inflammatory cell trafficking to the gut. They successfully identified a class of small molecule compounds that have a profile consistent with a once-a-day orally administered drug.

In this current Phase II STTR award, Dr. Woodside and Ronald J. Beidiger, PhD — senior investigator and director of Medicinal Chemistry in THI’s Molecular Cardiology Research department — will work jointly with Aviara toward testing safety and efficacy of the small molecule compounds in IBD mouse models, followed by future preclinical development and clinical trials in patients with IBD. Adhering to U.S. Food and Drug Administration guidelines, they will identify and establish the potential clinical candidate’s pharmacologic properties and determine a safe dosage for its first-in-human studies.

The NIDDK has the mission to “conduct and support medical research and research training to disseminate science-based information on diabetes and other endocrine and metabolic diseases; digestive diseases, nutritional disorders, and obesity; and kidney, urologic, and hematologic diseases, to improve people’s health and quality of life.”

Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R42DK127869. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.