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Mayo Clinic & ASU Investigator-Initiated Study Focusing on Investigational Product for Primary Sclerosing Cholangitis

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Mayo Clinic & ASU Investigator-Initiated Study Focusing on Investigational Product for Primary Sclerosing Cholangitis

An investigator-initiated study driven by Arizona State University and Mayo Clinic announced the first patient in a proof-of-concept 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).

The Problem: Primary Sclerosing Cholangitis

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. In PSC, the bile ducts of the liver become inflamed, narrow, and prevent bile from properly flowing. The exact cause of these mechanisms are not known but an autoimmune mechanism may play a role. It is associated with inflammatory bowel disease, ulcerative colitis and less commonly with Crohn’s disease. Estimated time from diagnosis to PSC to death or liver transplant is less than 15 years.

The Study

The proof-of-concept (POC) study 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 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 a change in serum ALP has been an accepted biomarker of disease progression in PSC patients. The investigational product maker, Immunic Inc. (IMUX), reports in a press release that they will supply the medication.

The study received clearance from the FDA (IND) and the IRB review at Mayo Clinic. The study will be conducted at Mayo Clinic in Arizona and Minnesota, both of which are tertiary care centers for PSC patients.

The Clinical Investigators

Keith Lindor, MD, 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, MD, Professor of Medicine, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic.

John E. Eaton, MD will conduct the study for Mayo in Minnesota.

What is IMU-838

Produced by IMUX, the investigational product is a small molecule (vidofludimus calcium) and oral tablet formulation for the treatment of relapsing-remitting multiple sclerosis (RRMS), inflammatory bowel disease (IBD), and other chronic inflammatory and autoimmune diseases.

The product inhibits dihydroorotate dehydrogenase (DHODH), a key enzyme of pyrimidine de novo biosynthesis, metabolically activated T and B immune cells experience metabolic stress, and the release of Th1 and Th17 key cytokines including IL-17A, IL17F and IFNg are inhibited, thereby reducing the inflammation associated with IBD for example.

In preclinical studies, vidofludimus, the active ingredient of IMU-838, apoptosis (or programmed cell death) was induced in activated T cells, which IMUX believes may also play a crucial role in the activity of the dug-in IBD by further dampening the inflammatory response.

IMUX believes a key differentiator for DHODH inhibition is that the sensitivity of specific immune cells to the DHODH inhibition correlates with their intracellular metabolic activation state, and therefore may not negatively impact normal bone marrow cells.

IMUX

IMUX is a clinical-stage biopharmaceutical company developing a pipeline of selective oral immunology therapies aimed at treating chronic inflammatory and autoimmune diseases, including relapsing-remitting multiple sclerosis, ulcerative colitis, Crohn’s disease, and psoriasis. The company is developing three small molecule products: IMU-838 is a selective immune modulator that inhibits the intracellular metabolism of activated immune cells by blocking the enzyme DHODH; IMU-935 is an inverse agonist of RORγt, and IMU-856 targets the restoration of the intestinal barrier function. Immunic’s lead development program, IMU-838, is in phase 2 clinical development for relapsing-remitting multiple sclerosis and ulcerative colitis, with an additional phase 2 trial in Crohn’s disease planned for the second half of 2019.

Financials

IMUX represents microcap equity. It operates at a loss of about $27 million and commands a market capitalization as of writing at $136.7 million ($13.55 per share). They hold about $36 million cash reserves and recently raised an additional $30 million from investors.

Pipeline

The IMUX pipeline includes investigational products IMU-838 (MS & UC & PSC Phase II; CD Phase I); IMU-935 (Psoriasis & Orphan AI disease preclinical); and IMU-856 (GI preclinical).

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