First Tracks' ANB033 hits goals in coeliac gluten challenge

First Tracks Biotherapeutics has reported positive top-line results from Cohort 1 of its Phase 1b trial of ANB033 in coeliac disease, saying the investigational CD122 antagonist met key histological and symptom endpoints in a 14-day gluten-challenge study. The NASDAQ-listed company plans to advance ANB033 into late-stage development in 2027, following a Fast Track designation already granted by the US FDA.

The trial enrolled 32 evaluable patients, with 17 receiving ANB033 and 15 placebo. Participants underwent three subcutaneous loading doses over six weeks before consuming six grams of gluten daily, roughly equivalent to two slices of bread, for a fortnight. At Week 6, the least-squares mean change in villus height-to-crypt depth (Vh:Cd) ratio was -0.17 on ANB033 versus -0.66 on placebo, a placebo-adjusted delta of +0.49 (p=0.009). Intraepithelial lymphocyte density fell by 1.20 on ANB033 while rising by 18.83 on placebo, a statistically significant difference (p less than 0.001). Symptom scores, assessed daily using the validated Celiac Disease Symptom Diary, were significantly lower on ANB033 from the first day of the challenge through day seven, with only 6% of ANB033 patients taking rescue medication for gastrointestinal symptoms compared with 47% in the placebo group.

Clinical significance

Daniel Faga, president and chief executive, said ANB033 achieved a statistically significant and clinically meaningful protective effect against gluten-induced intestinal damage and symptoms while maintaining a favourable safety profile. No serious adverse events, no severe adverse events, and no discontinuations due to adverse events were recorded in the ANB033 arm. Injection-site erythema was the most common treatment-emergent event in that group, reported in around 28% of participants, a typical finding for subcutaneously administered biologics.

Benjamin Lebwohl, professor of Medicine and Epidemiology at NY-Presbyterian/Columbia University Irving Medical Center and director of Clinical Research at the Celiac Disease Center at Columbia University, described the concurrent prevention of symptoms and Vh:Cd benefit in a single study as notable, adding that ANB033's dual blockade of IL-15 and IL-2 signalling targets two recognised drivers of intestinal inflammation in the condition.

Market context and competitive landscape

Coeliac disease affects an estimated one in a hundred people globally and remains the largest autoimmune indication without an approved pharmacological therapy beyond dietary management. The space has attracted growing interest from both large pharma and specialist biotechs, with several programmes targeting IL-15 or the downstream effector cells it activates. ANB033's CD122 mechanism simultaneously blunts both IL-15 and IL-2 signalling, a differentiation the company argues could translate to broader mucosal protection and symptom control than single-cytokine approaches.

Cohort 2 of the same Phase 1b trial, assessing mucosal healing over twelve weeks in patients with a wider range of histological and symptom severity, is close to completing enrolment, with top-line data expected in the first quarter of 2027. First Tracks is also running a Phase 1b cohort of ANB033 in eosinophilic oesophagitis, with data anticipated in the third quarter of 2027, and intends to initiate Phase 2 studies in vitiligo and one additional, as yet unnamed, indication in the first half of 2027. Full Cohort 1 findings are expected to be presented at the International Coeliac Disease Symposium in Melbourne in November.