Aclaris Therapeutics Updates ATI-052 Phase 1 Data, Picks ATI-2138 for Phase 2b in Lichen Planus

Key Points

• ATI-052 Phase I‑A SAD/MAD showed dose‑proportional PK with an estimated ~45‑day half‑life that could support dosing as infrequently as once every three months, plus robust PD (100% inhibition of TSLP‑stimulated CCL17 through 20 weeks at 480 mg) and no safety signals or ADA impact.
• Aclaris has launched randomized, placebo‑controlled Phase I‑B proof‑of‑concept trials of ATI-052 in atopic dermatitis and asthma (actively enrolling), with top‑line readouts expected in H2 2026 and plans to initiate an asthma Phase IIb in Q4 2026.
• The company selected oral ATI-2138 for Phase IIb in lichen planus, highlighting its dual ITK (TCR) and JAK3 inhibition as a "bispecific‑like" approach; a basket Phase IIb will start with erosive mucosal and cutaneous LP testing 10 mg and 20 mg twice daily, targeting a U.S. market opportunity the company estimates at >$1 billion.

Aclaris Therapeutics NASDAQ: ACRS provided a clinical program update on Tuesday, highlighting full top-line results from its phase I-A single-ascending dose (SAD) and multiple-ascending dose (MAD) study of ATI-052 and outlining plans to advance oral candidate ATI-2138 into a phase IIb program in lichen planus.

ATI-052: Full phase I-A SAD/MAD results

CEO Neal Walker said the full results for ATI-052, the company’s lead bispecific antibody, “confirm and build upon” interim pharmacokinetic (PK), pharmacodynamic (PD), and tolerability data shared in January. ATI-052 is designed to bind thymic stromal lymphopoietin (TSLP) upstream and immune cells downstream in the TH2 cascade via IL-4 receptor (IL-4R), which is shared by IL-4 and IL-13.

President and COO Doug Davis described ATI-052’s construct and its intended advantages, including YTE and AQQ mutations that are designed to extend half-life and reduce off-target binding. Davis also compared the anti-TSLP binding region used in ATI-052 to the company’s anti-TSLP monoclonal antibody bosakitug, saying both have “over 400 hours” of residence time on TSLP and that this is “about 25-30 times” longer than tezepelumab, based on the company’s characterization discussed on the call.

Davis reviewed the phase I-A design in healthy volunteers:

• SAD: Four cohorts (n=8 each), randomized 3-to-1 to ATI-052 or placebo at 30 mg, 120 mg, 360 mg, or 720 mg (single dose).
• MAD: Two cohorts (n=8 each), randomized 3-to-1 to ATI-052 or placebo at 240 mg or 480 mg, administered as five doses every seven days.

On PK, Davis said ATI-052 showed dose-proportional increases in Cmax and AUC across SAD and MAD levels, with an estimated half-life of approximately 45 days based on an accumulation-ratio analysis. He said the data support the company’s expectation that ATI-052 could be dosed as infrequently as once every three months.

Pharmacodynamic assay shows sustained inhibition

Aclaris emphasized PD results from a whole-blood assay measuring inhibition of CCL17 (TARC) after stimulation with TSLP and IL-4. Davis said the company used “up to 500-fold” above endogenous levels in healthy volunteers—and at points referenced “even up to 1,000 times” higher than expected in disease settings—to create a stringent test of inhibitory activity.

In the 480 mg MAD cohort, Davis reported 100% inhibition of TSLP-stimulated CCL17 through the final sampling time point at 20 weeks, which he noted was four months beyond the last dose. He said the 240 mg cohort showed “nearly 100% inhibition” out to 20 weeks as well. For IL-4-stimulated CCL17, he said the 480 mg cohort showed 100% inhibition for at least three months, and management suggested near-complete inhibition would be expected through week 14 based on drug concentration, though PK was not measured at week 14.

Safety and next ATI-052 trials

On safety, Davis said no safety signals were observed in the phase I-A study and noted “no conjunctivitis was seen.” He added that no impact of anti-drug antibodies (ADA) on PK or PD was observed.

Chief Medical Officer Jesse Hall said Aclaris has initiated two randomized, double-blind, placebo-controlled phase I-B proof-of-concept trials intended to establish translational clarity on PK, target engagement, and biomarkers in disease populations:

• Atopic dermatitis (AD): Initiated in January in approximately 12 patients (EASI > 21) using 480 mg with five weekly doses over four weeks, with clinical endpoints at week 8 and follow-up extending 12 more weeks. Hall said PK/PD collection includes lesional and non-lesional tape strips.
• Asthma: Initiated in February as a 3-to-1 placebo-controlled single-dose trial in approximately 16 patients on GINA step 2–4 therapy, with top-line readout expected at day 29 and about six weeks of follow-up. Endpoints include FeNO, eosinophils, and FEV1.

Hall said both studies are actively enrolling, with top-line data expected in the second half of 2026. He also said the company is advancing phase IIb planning in both asthma and AD, aiming to initiate the asthma phase IIb in the fourth quarter of 2026.

In Q&A, management said the single-dose asthma design was intended to mimic a typical FeNO-focused study, while the AD regimen uses loading doses to drive skin exposure and provide an exposure-response profile. Walker said the company would like to see “a 10% bump” in efficacy measures and highlighted interest in rapid onset in AD.

ATI-2138: Lichen planus selected for phase IIb development

Walker said Aclaris completed an indication down-selection for ATI-2138 and selected lichen planus (LP) for phase IIb development. Chief Scientific Officer Roland Kolbeck described LP as a chronic inflammatory, CD8 cytotoxic T-cell driven interface dermatitis with multiple subtypes, and said there are currently no FDA-approved therapies. He cited estimates that 0.1% to 1% of the U.S. population is affected and said up to 40% of patients currently seek treatment despite the lack of targeted options.

Kolbeck said ATI-2138 is an investigational oral inhibitor that interrupts T cell receptor signaling via ITK inhibition and blocks common gamma chain cytokine signaling via JAK3 inhibition. He described it as “the first and only known JAK-based therapy that also inhibits the TCR,” and said this dual activity could provide a “bispecific-like effect” in LP.

Management described plans for a phase IIb “basket” study beginning with erosive mucosal and cutaneous LP (part A) and later adding lichen planopilaris (part B). In Q&A, Walker said the company plans to test 10 mg twice daily and 20 mg twice daily, and suggested the approach could be adaptive, selecting a “winning dose” before expanding. He also said the company sees orphan designation opportunities within the category and characterized the development plan as capital efficient.

Walker stated the company believes LP represents a “white space opportunity,” and said the company estimates U.S. market potential exceeding $1 billion, with an opportunity “up to nearly $4 billion.”

Separately, Aclaris also noted during Q&A that its ITK-selective program remains “on track” for an IND submission in the second half of 2026, which management said would bring the company to four clinical-stage assets.

About Aclaris Therapeutics NASDAQ: ACRS

Aclaris Therapeutics, Inc NASDAQ: ACRS is a clinical‐stage biopharmaceutical company focused on discovering, developing and commercializing novel small‐molecule therapies for dermatologic diseases and related rare disorders. The company's pipeline includes several product candidates designed to address chronic inflammatory skin conditions and non‐melanoma skin lesions. Lead programs include ATI‐50002, a topical agent in late‐stage development for molluscum contagiosum removal; ATI‐50003 for common wart resolution; ATI‐1501, an oral JAK1/2 inhibitor targeting pruritic disorders; and ATI‐450, an oral MK2 inhibitor for inflammatory indications.

Founded in 2016 and headquartered in Malvern, Pennsylvania, Aclaris leverages proprietary chemistry platforms and translational research capabilities to advance multiple clinical and preclinical candidates.

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