IMU-838, Immunic Therapeutics‘ lead therapy candidate for the treatment of ulcerative colitis (UC) and relapsing-remitting multiple sclerosis (RRMS), shows strong activity in cellular and animal models of disease, preclinical studies show.

New unpublished data was shared by Hella Kohlhof, PhD, chief scientific officer of Immunic, during an oral presentation titled, “IMU-838 in Clinical Phase 2 – New Selective Oral Treatment for IBD,” at the GI Inflammatory Diseases Summit (GIIDS), held June 24-25 in Boston.

An oral, next-generation elective immune modulator, IMU-838 works by blocking the activity of dihydroorotate dehydrogenase (DHODH), an enzyme involved in the metabolism of activated immune cells. It reduces immune system overactivation and inflammation.

The compound has been designed to work specifically on overactive T- and B-cells, and spare other “resting” immune cells. This ensures the immune system remains functional during treatment.

Both immune cells, T-cells are responsible for destroying microbes or other harmful pathogens, while B-cells produce antibodies against threats perceived by the immune system.

IMU-838 is currently being tested in two Phase 2 trials — CALDOSE-1 (NCT03341962) for UC patients, and EMPhASIS (NCT03846219) for people with RRMS. Both trials are still recruiting participants. For the CALDSOSE-1 trial, go here for more information; for EMPhASIS, go here.

New preclinical data presented at the meeting showed that:

• IMU-838 specifically targets activated T-cells that are producing and releasing high amounts of pro-inflammatory cytokines. Cytokines, molecules involved in immune and inflammatory responses, include interferon-gamma (IFNγ) and interleukin-17 (IL-17).
• In cell assays, IMU-838 can successfully work together with the tumor necrosis factor (TNF) inhibitor Remicade (infliximab), which reduces inflammation.
• The compound showed strong activity not only in animal models of inflammatory bowel disease (IBD), but also in a mouse model of UC. In the UC model, IMU-838 mitigated diarrhea and decreased the levels of TNF-alpha, which subsequently reduced inflammation in the animals’ gut.

During the presentation, Kohlhof also highlighted some of the advantages IMU-838 has over other available therapies. These include:

• IMU-838 does not fully suppress the immune system, avoiding reactivation of latent (dormant) viral infections. This is one of the most serious side effects of other immunosuppressants.
• Unlike other DHODH inhibitors, IMU-838 does not target kinases, which are enzymes that add phosphate groups to other molecules. This avoids additional treatment side effects, including diarrhea, alopecia (hair loss), and neutropenia (low white blood cell count).
• IMU-838 has a half-life of approximately 30 hours in the blood and is suited for a once-a-day method of administration.
• In a Phase 2a study involving patients with UC and Crohn’s disease (CD) who were taking steroids to control their symptoms, most participants gradually succeeded weaning off of the steroids after being treated with IMU-838. The total response rate was 88.5%.

“The data we have generated thus far for IMU-838 remains encouraging and supports our thesis that it may represent a potential new, best-in-class, oral treatment for patients with UC, RRMS and other underserved immunologic diseases,” Kohlhof said in a press release. “In particular, we are pleased to report previously unpublished data confirming the drug’s activity in key preclinical models, as well as evidence of its potency on high producer T cells and ability to work in a symbiotic fashion with today’s anti-TNFa antibodies such as infliximab [Remicade].”

The company is planning to start a Phase 2 trial for patients with Crohn’s disease later in 2019.