Immunic, Inc. announced positive results from the part C portion of its phase 1 clinical trial of IMU-856 in patients with celiac disease. The company believes that this data set provides initial clinical proof-of-concept for an entirely new therapeutic approach to gastrointestinal disorders by promoting regeneration of bowel architecture. Data from four key dimensions of celiac disease pathophysiology and outcomes are summarized as follows: Protection of gut architecture and reduction of gluten-induced intestinal damage: Over the course of the trial, the placebo group (N=11) experienced a 60.3 µm reduction in villous height in response to four weeks of treatment and two weeks of 6 g/day gluten challenge.

In contrast, this reduction was only 20.9 µm and 22.5 µm for the 80 mg (N=11) and 160 mg (N=13) IMU-856 groups, respectively (p=0.04). Villi are small finger-like projections found in the lumen of the small intestine, which play a key role in the absorption of digested nutrients necessary for health and growth. Decrease in villous height is a well-recognized measure of gluten-induced damage in celiac disease and a main reason for signs and symptoms of malabsorption.

Of particular interest, during the course of the trial, two IMU-856 treated patients demonstrated a 1-category improvement in Q-Marsh histology scores despite 15 consecutive days of exposure to gluten challenge. No analogous improvement was seen with placebo treatment. Improvement of patients' symptoms related to gluten exposure: On the first day of gluten challenge, the placebo group (N=12) experienced a marked average increase in symptoms, as assessed by the Celiac Disease Symptom Diary using a 5-point scale, of 0.8 for nausea, 0.8 for abdominal pain, and 0.8 diarrhea.

In contrast, among the pooled IMU-856 arms (N=26), these average increases were only 0.4 for nausea, 0.5 for abdominal pain and 0.6 for diarrhea. Continued treatment with IMU-856 during gluten challenge also resulted in improvement or reversal of disease-related symptoms, such as bloating and tiredness. Dose-dependent changes in biomarker responses: Following the initiation of gluten challenge on day 14, patients treated with IMU-856 exhibited a dose-dependent lessening of acute immune response, as measured by serum interleukin-2 (IL-2) release, compared with placebo.

IL-2 is a well-recognized biomarker of acute gluten exposure which has been correlated by independent third parties with timing and severity of symptoms after gluten exposure. In addition, average levels of citrulline, a biomarker for the proper function of gut wall cells, were increased in both active treatment arms while decreasing levels were observed in placebo-treated patients, reflecting a positive effect of IMU-856 on the function of gut lining cells. Enhancement of nutrient absorption: Over the course of the trial, the placebo group (N=11) experienced a 31.0 pmol/L reduction in levels of vitamin B12.

In contrast, the 80 mg (N=11) and 160 mg (N=13) IMU-856 groups experienced a 45.8 pmol/L and 74.2 pmol/L increase in vitamin B12 levels, respectively. Vitamin B12 is a nutrient essential for the formation of red blood cells, and the normal functioning of the brain and nervous system, whose absorption from the gastrointestinal tract is frequently impaired in patients with celiac disease. Similar responses to treatment were observed for zinc- and iron-related measures.

Immunic believes that this data provides first clinical evidence that IMU-856's ability, observed in preclinical studies, to re-establish proper gut cell renewal translates into clinical benefits for patients with celiac disease. Most importantly, the observed protection of intestinal villi from gluten-induced destruction, independent of targeting immune mechanisms involved specifically in celiac disease, appears to be unique among proposed therapeutic approaches and may be applicable to other gastrointestinal diseases. IMU-856 was observed to be safe and well-tolerated in this trial.

There were no investigational medicinal product-related serious or treatment-emergent adverse events nor was there any dose-dependency in adverse events. Moreover, the rates of treatment-emergent adverse events in non-disease-related parameters were comparable between the active treatment groups and placebo. Part C of the phase 1 clinical trial of IMU-856 was structured as a double-blind, randomized, placebo-controlled trial designed to assess the safety and tolerability of IMU-856 in patients with celiac disease during periods of gluten-free diet and gluten challenge.

The trial was conducted at sites in Australia and New Zealand. A total of 43 patients were enrolled in two consecutive cohorts with 80 mg or 160 mg of IMU-856 or placebo given once-daily over 28 days. Secondary objectives included pharmacokinetics as well as acute and chronic disease markers, including those evaluating gastrointestinal architecture and inflammation.