Aclaris Therapeutics ATI-052 Posts Early Eczema, Asthma Signals in Phase 1b

Key Points

• ATI-052 showed early efficacy signals in atopic dermatitis: In a small Phase 1b study, 78% of treated patients achieved EASI-50 at week eight, with improvements in eczema severity and itch maintained through week 16.
• Asthma and biomarker results supported dual-pathway activity: A single dose reduced FeNO by 59% and improved FEV1, while skin analyses indicated broad inflammatory-pathway modulation. The treatment was generally well tolerated, with no serious adverse events reported across the studies.
• Aclaris plans to advance ATI-052 into eosinophilic esophagitis: The company expects to start a seamless Phase 2b/3 program early next year and raised $50 million to fund the program, other pipeline efforts and extend its cash runway into mid-2029.

Aclaris Therapeutics NASDAQ: ACRS reported Phase 1b proof-of-concept results for ATI-052, its bispecific antibody designed to inhibit thymic stromal lymphopoietin (TSLP) and IL-4 receptor alpha, in small studies of atopic dermatitis and asthma. The company said the treatment was well tolerated and produced early clinical and biomarker signals in both indications.

ATI-052 is designed to block TSLP, an upstream inflammatory signal, as well as IL-4 and IL-13 signaling through IL-4 receptor alpha. Chief Executive Officer Neal Walker said the results support the potential for additive or synergistic activity from targeting both pathways in one molecule.

Atopic Dermatitis Results

The atopic dermatitis trial enrolled 14 patients, who were randomized approximately 3:1 to receive five weekly 480 mg doses of ATI-052 or placebo over 29 days. The primary endpoint was safety and tolerability, while exploratory efficacy measures included the Eczema Area and Severity Index, or EASI, and Peak Pruritus Numerical Rating Scale, or PP-NRS.

Chief Medical Officer Jesse Hall said the trial enrolled a difficult-to-treat population with substantial baseline disease severity. He said 82% of enrolled patients had an Investigator’s Global Assessment score of 4, representing severe disease, and the study included Black, African American and Asian patients.

In the per-protocol efficacy analysis, ATI-052 produced a 45% placebo-adjusted improvement from baseline in EASI at week eight, according to Hall. The company reported that 78% of ATI-052-treated patients achieved EASI-50, defined as at least a 50% improvement in EASI, at week eight. Hall said responses were maintained through week 16, or 12 weeks after the final loading dose, although the study follow-up remains ongoing.

For itch, the company reported a reduction beginning as early as week one. At week eight, ATI-052 showed a 43% placebo-adjusted mean improvement from baseline in PP-NRS. One-third of treated patients achieved at least a four-point improvement in itch scores at week eight.

All 14 patients were included in the safety analysis. Hall said there were no serious adverse events, no Grade 3 or 4 adverse events and no treatment discontinuations due to adverse events. The company reported three transient injection-site reactions and no cases of conjunctivitis in the study or in its other ATI-052 clinical studies to date.

Biomarker Findings and Asthma Data

Chief Scientific Officer Roland Kolbeck said analyses of skin tape strips showed broad modulation of inflammatory pathways associated with Th1, Th2, Th17 and Th22 biology, as well as itch. The company said ATI-052 resulted in a 95% improvement in the relationship between lesional and non-lesional skin proteomes at week eight.

Kolbeck also cited reductions in IL-5 and peripheral eosinophils, which Aclaris said were consistent with TSLP pathway inhibition. The company characterized these findings as supporting engagement of both targets of ATI-052.

In a separate asthma trial, 16 patients were randomized 3:1 to receive a single 480 mg dose of ATI-052 or placebo. Patients were followed for 10 weeks, with safety as the primary endpoint and changes in fractional exhaled nitric oxide, or FeNO, and forced expiratory volume in one second, or FEV1, among exploratory assessments.

Hall said a single ATI-052 dose reduced FeNO by 59% from baseline, representing an absolute reduction of 45 parts per billion. At day 15, FeNO declined by 58% among patients with eosinophil counts below 300 cells per microliter and by 60% among those at or above that threshold.

The company reported a placebo-adjusted FEV1 improvement of 200 mL at day 15, increasing to 260 mL at day 29. In a post-hoc subset of ATI-052 patients with baseline FEV1 below 80% of predicted, Aclaris reported an absolute 350 mL improvement at day 15, compared with a 140 mL decline among placebo patients. The asthma study also reported no serious adverse events and one mild treatment-related injection-site reaction.

Next Development Steps

Aclaris plans to prioritize eosinophilic esophagitis, or EoE, for ATI-052’s next Phase 2b program. Walker said the company expects to begin the study early next year and intends to structure it as a seamless Phase 2b/3 program, beginning with dose ranging before potentially moving into a Phase 3 portion.

Walker said the company is evaluating an additional indication for ATI-052 and expects to provide an update later. He also said Aclaris announced a $50 million financing intended to fully fund the EoE program, potentially support a second bispecific indication, fund its lichen planus and ITK inhibitor programs, and extend its cash runway from the end of 2028 to mid-2029.

About Aclaris Therapeutics (NASDAQ:ACRS)

Aclaris Therapeutics, Inc NASDAQ: ACRS is a clinical-stage biopharmaceutical company focused on developing therapies for immune-inflammatory diseases. The company's research programs are designed to address conditions in areas such as rheumatology, dermatology and other inflammatory disorders.

Aclaris' lead investigational product is zunsemetinib (ATI-450), an oral small-molecule therapy being evaluated for inflammatory diseases. The company has also developed additional investigational programs, including selective kinase inhibitors intended for potential use in dermatologic and immune-mediated conditions.

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