WAYNE, PA — Aclaris Therapeutics, Inc. (Nasdaq: ACRS) reported striking preclinical results for its experimental oral drug ATI-2138, showing rapid, near-complete, and sustained hair regrowth in a severe mouse model of alopecia areata, a difficult-to-treat autoimmune form of hair loss.
The results, generated in a murine model conducted by Dr. Angela Christiano at Columbia University, showed ATI-2138 outperforming ritlecitinib, a JAK inhibitor used as a comparator, with faster onset and greater overall hair regrowth. Alopecia areata affects millions worldwide and, in its most severe forms, has limited effective treatment options.
ATI-2138 is a potent and highly selective inhibitor of both interleukin-2–inducible T cell kinase (ITK) and Janus kinase 3 (JAK3), giving it a dual mechanism that targets immune pathways involved in inflammation, fibrosis, and itch. According to the company, this pharmacologic profile positions the drug as a potential therapy across a range of inflammatory and autoimmune diseases, including multiple forms of alopecia.
“ATI-2138 is a potent and selective inhibitor of ITK and JAK3 with dual pharmacology that has been demonstrated to downregulate Th1, Th2, Th17, TCR (ITK) and fibrosis pathway markers, and reduce itch,” said Roland Kolbeck, Aclaris’ chief scientific officer. He noted that the mice used in the study were older and more difficult to treat than those typically evaluated, yet still showed accelerated and durable regrowth.
Kolbeck said near-complete hair regrowth was observed after just four weeks of treatment and was sustained through the end of the study, adding that ATI-2138 consistently outperformed ritlecitinib.
The murine model used in the study represents alopecia universalis, the most severe phenotype of alopecia areata, and is widely regarded as predictive of clinical responses in humans treated with JAK inhibitors. Kolbeck said the rapid regrowth observed with ATI-2138 is particularly compelling because the drug is differentiated from other JAK inhibitors by its dual targeting of ITK and JAK3.
In the study, mice with established hair loss were randomized to receive control chow, ATI-2138 at two dose levels, or ritlecitinib. By week two, mice receiving the higher ATI-2138 dose showed a mean hair regrowth of 37%, compared with 25% in the ritlecitinib group. By week four, regrowth reached 87% with ATI-2138 versus 48% with ritlecitinib. At week six, ATI-2138-treated mice achieved a mean regrowth of 93%, compared with 78% for ritlecitinib, while control animals showed no improvement.
ATI-2138 works by interrupting T cell receptor signaling upstream and downstream, regulating immune cell expansion and activation through inhibition of ITK and JAK3. The compound is more than 1,000-fold selective against other JAK isoforms, a level of specificity the company believes could translate into a potent anti-inflammatory effect.
Based on the results, Aclaris said it is evaluating additional indications for ATI-2138 and expects to initiate a Phase 2b clinical trial in the first half of 2026, including studies focused on alopecias and related immune-mediated diseases.
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