Aclaris Reports Positive ATI-052 Topline Results; Sets Sights on Lichen Planus with ATI-2138

Aclaris Therapeutics has reported positive full topline results from the first-in-human phase 1a study of ATI-052, while also outlining development plans for ATI-2138 in lichen planus.¹ Today’s update positions ATI-052 as a potential differentiated entrant in Th2-driven inflammatory disease and introduces lichen planus as a strategic lead indication for ATI-2138, an oral investigational therapy targeting pathogenic T-cell signaling.

Clinical Trial of ATI-052

The phase 1a single- and multiple-ascending dose trial evaluated ATI-052, a novel bispecific antibody designed to simultaneously inhibit thymic stromal lymphopoietin (TSLP) and IL-4 receptor alpha, thereby blocking upstream and downstream mediators of type 2 inflammation. Investigators emphasized the dual-pathway inhibition as a potentially important differentiator, with the ability to simultaneously target TSLP at the top of the inflammatory cascade while also suppressing IL-4 and IL-13 signaling through IL-4Rα blockade. This approach may have implications for raising efficacy ceilings in diseases driven by type 2 inflammation, including atopic dermatitis and asthma.

Among the most notable findings was an estimated half-life of approximately 45 days, a profile that may support dosing as infrequently as once every 3 months. Dose-proportional pharmacokinetics were observed across evaluated doses, while pharmacodynamic analyses showed sustained inhibition of TSLP- and IL-4-induced CCL17/TARC responses, biomarkers linked to Th2 inflammatory signaling. In the highest multiple-ascending dose cohort, inhibition of TSLP-driven signaling was maintained through at least 20 weeks, while IL-4 pathway suppression persisted through at least 12 weeks after the last dose, suggesting durable biologic activity beyond active dosing.

Safety findings were also favorable in the randomized, placebo-controlled single- and multiple-dose cohorts. ATI-052 was reported to be well tolerated among the adult patients, with no significant safety signals identified, including no observed conjunctivitis. Anti-drug antibodies did not appear to affect pharmacokinetic or pharmacodynamic performance in the study.

“These results validate that ATI-052 is a highly potent and well-tolerated bispecific antibody that has the potential to be highly effective in a variety of inflammatory and immunological disorders,” Neal Walker, MD, Chief Executive Officer of Aclaris, said in the press release. “Based on the strong safety and tolerability profile and dose-proportional pharmacokinetic and pharmacodynamic profiles that support the potential for an extended dosing schedule of up to every three months and the potential for synergistic efficacy resulting from its dual inhibition of TSLP and IL-4Rα, we are rapidly progressing this molecule through two proof-of-concept studies and plan to initiate a Phase 2b program in the fourth quarter of 2026.”¹

ATI-2138's Role in Lichen Planus Treatment

Alongside the ATI-052 update, Aclaris announced lichen planus as the lead indication for ATI-2138, a selective dual ITK/JAK3 inhibitor that the company believes may offer a mechanistically differentiated approach for interface dermatitis disorders driven by pathogenic T cells. Despite a substantial disease burden, there are no FDA-approved therapies available for lichen planus.

ATI-2138 is designed to inhibit both T-cell receptor signaling through ITK and cytokine-driven activation through JAK3, a dual mechanism intended to more comprehensively suppress pathogenic T-cell activity. The company is planning a phase 2b basket study for the second half of 2026, beginning with erosive mucosal and cutaneous lichen planus, followed by expansion into lichen planopilaris.

“We also intend to initiate a phased multi-part phase 2b basket study in lichen planus with ATI-2138 later this year,” Walker added. “ATI-2138 is the only known drug that hits pathogenic T cells, the key drivers of interface dermatitis disorders like LP, by inhibiting both TCR and effector cytokine mediated activation - and as such, we believe it is an ideal mechanistic fit for this indication. LP causes debilitating symptoms and significant impacts to quality of life across the spectrum of subtypes.”¹

The selection of lichen planus as a lead indication also reflects growing industry attention to diseases historically underserved in inflammatory dermatology. Investigators suggested the oral agent may hold promise for multi-site disease involvement while potentially addressing both symptoms and underlying inflammatory drivers. According to the company, approximately 40% of patients with lichen planus seek treatment, making the potential market opportunity in the US for an oral therapeutic for LP exceed $1.0 billion.

“Lichen planus remains a challenging, immune-mediated disease with significant patient burden, and there is a clear need for additional therapies that can more effectively address both its symptoms and underlying pathology,” Johann Gudjonsson, MD, PhD, Arthur C. Curtis Professor of Skin Molecular Immunology at the University of Michigan Skin Research Center, said in a statement.¹

Reference

1. Aclaris Therapeutics Announces Positive Full Top Line First-in-Human Results from Phase 1a Healthy Volunteer Clinical Trial of ATI-052, a Novel Potential First-in-Class Anti-TSLP/IL-4Rα Bispecific Antibody, and Announces Lichen Planus as Lead Indication for ATI-2138, an Oral ITK/JAK3 Inhibitor. News release. Globe Newswire. Published April 28, 2026. Accessed April 28, 2026. https://www.globenewswire.com/news-release/2026/04/28/3282383/37216/en/aclaris-therapeutics-announces-positive-full-top-line-first-in-human-results-from-phase-1a-healthy-volunteer-clinical-trial-of-ati-052-a-novel-potential-first-in-class-anti-tslp-il.html