Aclaris Therapeutics Announces Positive Top-Line Results from Open-Label Phase 2a Trial of ATI-2138, a Potent and Selective Investigational Inhibitor of ITK and JAK3; Trial Achieves Primary and Key Secondary Endpoints

Core Insights - Aclaris Therapeutics announced positive top-line results from its Phase 2a trial of ATI-2138, indicating a favorable tolerability profile and comparable efficacy to approved therapies for moderate-to-severe atopic dermatitis [1][2][13] Group 1: Trial Overview - The Phase 2a trial was an open-label, single-arm study involving 14 patients with moderate-to-severe atopic dermatitis, focusing on safety, tolerability, pharmacokinetics, efficacy, and pharmacodynamics of ATI-2138 administered at 10mg BID for 12 weeks [14] - The trial confirmed the strong tolerability profile of ATI-2138, with no severe adverse events reported and most adverse events being mild [6][12] Group 2: Efficacy Results - The mean improvement in Eczema Area and Severity Index (EASI) score at week 12 was 60.5%, with a median improvement of 76.8% among patients receiving ATI-2138 [12] - At week 12, 62.5% of patients experienced a clinically meaningful ≥4-point improvement in Peak Pruritus Numerical Rating Scale (PP-NRS) [9] - Improvements in EASI scores were observed as early as week 1, with significant reductions noted at weeks 4, 8, and 12 [12] Group 3: Pharmacodynamic Results - Pharmacodynamic analyses demonstrated strong downregulation of key inflammatory markers associated with ITK, including Th2 and Th1/Th17-related markers, indicating the therapeutic potential of ITK inhibition [3][10] - Near complete and sustained ITK target occupancy was observed, with reductions in multiple inflammatory pathways linked to ITK [10] Group 4: Future Development Plans - Aclaris plans to further develop ATI-2138 for alopecia areata and explore other indications relevant to its mechanism of action, with ongoing preclinical work for next-generation ITK inhibitors expected to lead to new INDs starting in 2026 [13][16]