IMU-856 is an orally available and systemically acting small molecule modulator that aims to regenerate the gut wall and barrier function by a new innovative targeted mechanism.

IMU-856 is an orally available and systemically acting small molecule modulator that targets Sirtuin 6, or SIRT6, a protein which serves as a transcriptional regulator of intestinal barrier function and regeneration of bowel epithelium. Based on preclinical data, the compound may represent a unique treatment approach, as the mechanism of action targets the restoration of the intestinal barrier function and bowel wall architecture in patients suffering from gastrointestinal diseases such as celiac disease, inflammatory bowel disease, short bowel syndrome, irritable bowel syndrome with diarrhea and other intestinal barrier function associated diseases. Immunic believes that, because IMU-856 has been shown in preclinical investigations to avoid suppression of immune cells, it may therefore have the potential to maintain immune surveillance for patients during therapy, which would be an important advantage versus immunosuppressive medications.

Impaired intestinal barrier function is suspected to be involved in the initiation of many chronic inflammatory or autoimmune conditions, and microbial translocation through the damaged gut mucosa has been associated with many diseases, not only of the bowel but of the whole body. To date, there are no adequate treatment strategies to ameliorate impaired barrier function.

A double-blind, randomized, placebo-controlled phase 1/1b clinical trial of IMU-856 comprised of three parts was completed.

In September 2022, Immunic announced positive results from Part A (single ascending doses, or SAD) and Part B (multiple ascending doses, or MAD) of the trial in healthy human subjects. The data revealed a favorable safety, tolerability and pharmacokinetic profile for IMU‑856 in single and 14-day multiple dosing. No maximum tolerated dose was reached and the investigated doses are expected to exceed the required therapeutic dosing of IMU-856.

In May 2023, Immunic announced positive results from the Part C portion of the trial in patients with celiac disease. IMU-856 demonstrated positive results in four key dimensions of the disease’s pathophysiology: histology, disease symptoms, biomarkers and nutrient absorption. IMU-856 was also observed to be safe and well-tolerated in this trial. Immunic believes that this data set provided initial clinical proof-of-concept for an entirely new therapeutic approach to gastrointestinal disorders by promoting regeneration of bowel architecture.

Immunic is currently preparing clinical phase 2 testing of IMU-856 in patients with ongoing active celiac disease despite gluten-free diet, while also considering further potential clinical applications in other gastrointestinal disorders.