WAYNE, PA — Aclaris Therapeutics, Inc. (NASDAQ: ACRS) has announced encouraging top-line results from a Phase 2a trial evaluating ATI-2138, its oral investigational treatment targeting moderate-to-severe atopic dermatitis (AD). The study demonstrated strong safety, promising efficacy, and pharmacodynamic outcomes, reinforcing the company’s plans to advance development of the compound for additional immune-mediated conditions, including alopecia areata.
ATI-2138 is a covalent inhibitor of interleukin-2-inducible T cell kinase (ITK) and Janus kinase 3 (JAK3). The open-label, single-arm trial involved 14 patients, with 12 completing the 12-week treatment. The primary goal was to assess safety and tolerability, while secondary endpoints focused on disease severity reduction and biomarker response.
Favorable Safety Profile
The trial met its primary endpoint with no serious or treatment-emergent adverse events. Mild side effects resolved on their own, and no patients discontinued treatment due to adverse reactions. One moderate case of myalgia was noted but was not accompanied by elevated creatine phosphokinase levels.
Lab monitoring, including blood chemistry, ECG, and vital signs, showed no emerging safety concerns throughout the treatment period.
Strong Efficacy Signals
Patients receiving 10mg of ATI-2138 twice daily showed notable improvements in disease severity scores. By week 12, average Eczema Area and Severity Index (EASI) scores had improved 60.5%, with a median gain of 76.8%. Excluding one patient identified as a molecular outlier with inconsistent compliance, the average improvement rose to 77.1%.
Efficacy was observed early, with substantial gains recorded at weeks 1, 4, and 8. Similarly, 62.5% of patients reported a clinically meaningful reduction (≥4-point drop) in itch severity on the Peak Pruritus Numerical Rating Scale by the end of treatment.
Pharmacodynamic Validation of ITK Targeting
Biomarker analysis showed high occupancy of the ITK target, with trough levels maintaining 60–70% inhibition. Lesional skin analyses revealed downregulation of Th2, Th17, and Th1 inflammatory markers, as well as antifibrotic effects—suggesting ATI-2138 could address a range of immune-mediated skin disorders.
These results support ITK as a viable therapeutic target and demonstrate ATI-2138’s potential to offer efficacy comparable to existing JAK and IL-4/13 inhibitors, but with fewer safety risks.
Future Development
Aclaris plans to expand development of ATI-2138 into alopecia areata and other ITK-relevant diseases. Additionally, the company is advancing a pipeline of next-generation ITK inhibitors with plans to file new investigational drug applications (INDs) beginning in 2026.
The company’s findings from this small but targeted study will help shape future dosing strategies and support broader clinical exploration of ITK modulation in dermatology and immunology.
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