Immunic, Inc. (Nasdaq: IMUX), a clinical-stage biopharmaceutical company focused on developing potentially best-in-class, oral therapies for the treatment of chronic inflammatory and autoimmune diseases, today announced enrollment of the first patient in an investigator-sponsored proof-of-concept clinical trial of IMU-838 for the treatment of patients with primary sclerosing cholangitis (PSC). IMU-838 is an orally available, next-generation selective immune modulator that inhibits the intracellular metabolism of activated immune cells by blocking the enzyme dihydroorotate dehydrogenase (DHODH). PSC is a progressive disease of the liver with unknown cause and a prevalence of about 4.15 per 100,000 in the United States. Other than liver transplantation, there are currently no approved therapies that have been shown to improve survival in patients with PSC.
Keith Lindor, M.D., Senior Advisor to the Provost and Professor of Medicine, College of Health Solutions, Arizona State University, and Principal Investigator for the trial, was awarded a grant from the National Institutes of Health (NIH) for the study. The study will be sponsored by Elizabeth Carey, M.D., Professor of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic, who has received Investigational New Drug (IND) approval from the U.S. Food & Drug Administration (FDA) and has been granted Institutional Review Board (IRB) approval to conduct the study. The study will be conducted at Mayo Clinic in Arizona (Dr. Carey) and Minnesota (John E. Eaton, M.D.), both of which are tertiary care centers for PSC patients.
The proof-of-concept study, for which Immunic is providing the study medication, is a single-arm, open-label, exploratory study planning to enroll a total of 30 patients with PSC, aged 18 to 75 years, who will receive 30mg IMU-838 once daily for a period of six months. The trial’s primary endpoint is the change in serum alkaline phosphatase (ALP) at six months compared to baseline. In previous trials, a biochemical endpoint such as change in serum ALP has been an accepted biomarker of disease progression in PSC patients.
Dr. Keith Lindor commented, “Recent studies indicate that the proinflammatory cytokine interleukin 17, or IL-17, may play a central role in the pathogenesis of PSC, as well as ulcerative colitis. Significant increases in IL-17-expressing lymphocytes are found in the livers of PSC patients. These findings speak to the strong possibility of an overlap in therapeutic approaches to the two diseases. Our goal with this study is to examine the safety, tolerability, and efficacy of daily dosing of IMU-838, an orally available, small molecule inhibitor of DHODH, a target known for its effect on Th17 cells, in order to establish proof-of-concept that IMU-838 shows activity for the treatment of PSC. Establishing such a baseline should enable the design of more comprehensive clinical studies.”