Immunic, Inc. (Nasdaq: IMUX) has announced the publication of data from its Phase 1/1b clinical trial of IMU-856 in The Lancet Gastroenterology & Hepatology, showcasing promising results in patients with celiac disease. The study, led by Dr. A. James Daveson, indicates that IMU-856, an orally available small molecule modulator targeting SIRT6, may offer a novel approach to treating celiac disease by improving the integrity and function of the intestinal barrier.
IMU-856: A Novel Approach to Celiac Disease
Celiac disease, affecting approximately 1.4% of the global population, currently has limited treatment options, primarily a strict gluten-free diet. This diet poses significant challenges due to dietary restrictions and the risk of cross-contamination, leading to persistent intestinal inflammation and villous atrophy in many patients. IMU-856's mechanism of action focuses on restoring the intestinal barrier function and bowel wall architecture, potentially offering a significant advantage over existing treatments.
Phase 1/1b Trial Results
The Phase 1/1b trial included both healthy human subjects and patients with celiac disease. The trial consisted of three parts: single ascending dose (Part A), multiple ascending dose (Part B), and a double-blind, randomized, placebo-controlled trial in patients with celiac disease (Part C).
Parts A and B of the trial, involving 71 healthy subjects, established that IMU-856 was safe and well-tolerated across single and multiple ascending doses, with no IMP-related serious adverse events. Part C involved 43 celiac disease patients in Australia and New Zealand, who were administered either 80 mg or 160 mg of IMU-856 or a placebo once daily for 28 days, during both a gluten-free period and a 15-day gluten challenge (6g of gluten daily).
The results from Part C demonstrated positive effects of IMU-856 compared to placebo in several key areas: protection of gut architecture, improvement of patient symptoms, biomarker response, and enhancement of nutrient absorption. Specifically, the trial showed statistically significant histologic protection, even with a small patient sample. Functional improvements, such as increased vitamin B12 uptake despite gluten exposure, highlight its unique mode of action and rapid onset of efficacy.
Clinical and Commercial Implications
According to Daniel Vitt, Ph.D., CEO of Immunic, the publication in a prestigious peer-reviewed journal validates IMU-856's novel mechanism of modulating SIRT6. The Phase 1b trial demonstrated initial clinical signals of IMU-856's potential to restore a healthy gut by renewing the gut wall, showing meaningful improvements over placebo in histology, disease symptoms, biomarkers, and nutrient absorption. This, combined with a favorable safety profile, positions IMU-856 as a potential first-in-class oral therapy for celiac disease.
Immunic is currently preparing for Phase 2 clinical testing of IMU-856. The company believes that the data provides initial clinical proof-of-concept for a potentially new, oral therapeutic approach to a range of gastrointestinal diseases with high unmet needs, beyond celiac disease. Immunic aims to establish itself at the forefront of both gastrointestinal and neuroinflammatory diseases. Collaborations and strategic partnerships will likely play a key role in expanding the drug’s applications.
Safety and Tolerability
The Phase 1/1b trial also confirmed that IMU-856 is safe and well-tolerated in patients with celiac disease. There were no IMP-related serious or severe treatment-emergent adverse events, and the rates of treatment-emergent adverse events in non-disease-related parameters were comparable between the active treatment groups and placebo. Chronic toxicology studies have also confirmed its potential for long-term use across various gastrointestinal disorders. The favorable safety profile allows for flexible dosing strategies, with the 160 mg dose already showing strong efficacy. Future studies may explore slight adjustments in dosage to optimize treatment.
