Mitochondrial Biogenesis Modulator for Treatment of Inflammatory Bowel Disease

By 2029, in?ammatory bowel disease (IBD) will afflict 5.4 million globally with pharmaceutical sales of $23.8 billion(B). Biologic (monoclonal antibody) agents used to treat ulcerative colitis (UC) and Crohn’s disease (CD) will comprise 63% and 78% of the market share respectively. However, to date, no biologic can claim remission rates greater than 38%. Thus, there is an unmet need for a treatment that increases remission rates for IBD patients. The current drug invented at the University of Kentucky, oral AuPhos, targets a unique mechanism of action (MOA) that increases the energy source (mitochondria) and protective (anti-oxidant) properties of intestinal lining cells in IBD patients. Because of its unique MOA, we predict AuPhos-Glu will enhance therapeutic effects of biologic agents (anti-TNF, anti-integrin, anti-interleukins and JAK inhibitors). Thus, we are positioning this agent to serve as a monotherapy and/or complementary oral therapy to biologics. The current proposal requests $41,750 in support to pay for 1) a 14- day repeat dose toxicology studies of our lead AuPhos-Glu candidate in rats (based on preliminary 7-day toxicology in mice), and 2) pharmacokinetic (PK) studies. Upon reaching these milestones, we expect to attract funding via venture ?rms/angel investors or diluted small business grants to enable IND-enabling studies using GLP-grade AuPhos. We have assembled an outstanding team of experts including a physician-scientist (Dr. Terrance Barrett, Gastroentorologist), IBD molecular scientist (Dr. Neeraj Kapur), a PK/PD expert (Dr. Robert McCorkle) and medicinal chemist (Dr. Samuel Awuah) positioned to accomplish the goals of this project.