Background & Objectives:
CD122 regulates immune cell activation and function through IL-15 and IL-2 signaling. ANB033, a novel CD122 antagonist monoclonal antibody binds with high affinity and potently inhibits IL-15 and IL-2 signaling, thereby targeting two key drivers of epithelial injury and immune activation in celiac disease (CeD). A two-part, randomized, double-blind, placebo-controlled Phase 1 study assesses the safety, clinical pharmacology, tolerability, and potential efficacy of ANB033.
Materials & Methods:
Part A was conducted in healthy volunteers (HV) and assessed sequential, escalating doses of ANB033 in 4 IV/3 SC single ascending dose cohorts and 3 SC multiple ascending dose cohorts (~6 active:2 placebo /cohort). Part B included participants with CeD on a gluten-free diet for > 1 year. Randomization was 1:1 (ANB033:Placebo). Participants received 3 SC doses of study treatment at Week 0, 2, and 4, with 2 endoscopies with biopsies; symptoms were assessed throughout the study. Part B consists of 2 cohorts. Participants with relatively preserved mucosa (Vh:Cd > 2.0) were assigned to Cohort 1 and received a 14-day gluten challenge (GC; 6 g/day)(efficacy analysis at Week 6). Participants with broad range of mucosal injury and symptom severity were assigned to Cohort 2 and did not receive GC (efficacy analysis at Week 12).
Results:
In Part A, 83 participants were randomized. ANB033 was well tolerated, with no dose-limiting toxicities and only mild or moderate adverse events reported. The half-life of ANB033 was ~3 weeks.
Part B Cohort 1 (~30 participants) is fully enrolled. Baseline characteristics, safety and tolerability, and histological changes (e.g., Vh:Cd, IEL density) will be presented. Cohort 2 is ongoing.
Conclusion:
In HV, ANB033 demonstrated favorable safety, tolerability, bioactivity, and pharmacokinetics including one dose level in Part B. Top-line data in CeD from Part B/Cohort 1 GC will be available for presentation at ICDS.