ATI-052 Shows Rapid Improvements in Atopic Dermatitis

Aclaris Therapeutics announced positive phase 1b proof-of-concept results for ATI-052, an investigational bispecific antibody targeting thymic stromal lymphopoietin (TSLP) and interleukin-4 receptor α (IL-4Rα), demonstrating rapid improvements in disease severity and pruritus among patients with severe atopic dermatitis (AD).¹

The randomized, double-blind, placebo-controlled phase 1b trial included 14 patients with severe AD who were randomized 3:1 to receive 5 weekly doses of ATI-052 480 mg or placebo from weeks 0 through 4. Primary analysis end points were assessed at day 57. Four patients were excluded from the prespecified per-protocol analysis for reasons established before unblinding. Among patients in the active treatment arm included in the per-protocol analysis, 78% had severe disease at baseline, defined as a Validated Investigator’s Global Assessment (vIGA) score of 4.¹

Improvements in EASI and Itch

At day 57, ATI-052-treated patients experienced a 45% placebo-adjusted mean improvement from baseline in Eczema Area and Severity Index (EASI) score. The absolute mean improvement was 58% in the ATI-052 group compared with 13% in the placebo group.¹

ATI-052 also produced a 78% placebo-adjusted EASI 50 response at day 57. All patients with a baseline vIGA score of 3 achieved placebo-adjusted EASI 50 compared with 71% of those with a baseline vIGA score of 4. According to Aclaris, responses remained durable among the subset of patients with available data at week 16, with follow-up ongoing.¹

Improvements in pruritus emerged during the first week of treatment and continued to deepen through week 10 among patients with available data. At week 4, ATI-052-treated patients experienced a 40% placebo-adjusted mean improvement from baseline in Peak Pruritus Numerical Rating Scale (PP-NRS) scores.¹

By day 57, the placebo-adjusted mean improvement in PP-NRS was 43%, with a 38% absolute improvement in the ATI-052 arm compared with a 5% worsening in the placebo arm. A placebo-adjusted 33% of patients achieved a clinically meaningful improvement of at least 4 points on PP-NRS at day 57.¹

“These ATI-052 data in AD are very noteworthy, not only in strength of response at day 57 but also in rapidity and durability of response,” Michael Cameron, MD, FAAD, CEO of Equity Medical and assistant clinical professor in the Department of Dermatology at Mount Sinai in New York, and an investigator in the trial, said in a news release.¹

Cameron noted that the mechanism of ATI-052 could support both rapid and sustained responses by blocking IL-4 and IL-13 signaling through IL-4Rα while simultaneously inhibiting TSLP.

Dual Targeting Produces Broad Biomarker Effects

ATI-052 is designed to simultaneously inhibit TSLP and IL-4Rα. TSLP functions upstream in the inflammatory cascade, while IL-4Rα blockade inhibits signaling from IL-4 and IL-13, key cytokines involved in type 2 inflammation.¹

Pharmacodynamic findings showed 95% normalization of the lesional skin proteome at week 8 among ATI-052-treated patients, with immune protein expression resembling that observed in nonlesional skin. Treatment broadly modulated inflammatory pathways associated with AD, including Th1, Th2, Th17/Th22, fibrosis and extracellular matrix remodeling, and itch-associated molecular pathways.¹

Aclaris also reported reductions in established dupilumab-associated biomarkers alongside suppression of Th1, Th17 innate, and myeloid pathways.

Emma Guttman, MD, PhD, Waldman Professor of Dermatology and Immunology and health system chair of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai, said the biomarker findings correlated with the observed efficacy results.

“Key immune proteins were significantly downregulated by ATI-052 compared to placebo, potentially highlighting the contribution of added benefit of blocking TSLP in this indication,” Guttman said.¹

Favorable Early Safety Profile

Across the AD and separate asthma phase 1b proof-of-concept trials, ATI-052 was generally well tolerated. Treatment-emergent adverse events were predominantly grade 1, with no grade 3 or 4 treatment-emergent adverse events and no adverse events resulting in study discontinuation.¹

Injection-site reactions were reported at a low frequency and were transient and almost exclusively grade 1. No cases of conjunctivitis were observed.¹

The company separately evaluated a single 480-mg dose of ATI-052 in 16 patients with mild to moderate asthma, reporting rapid improvements in airway inflammation and lung function. Together, Aclaris stated that the findings support further investigation of simultaneously targeting TSLP, IL-4, and IL-13 across inflammatory diseases.¹

Despite the positive AD findings, Aclaris plans to initially prioritize phase 2b development of ATI-052 in eosinophilic esophagitis (EoE), with a phase 2b trial expected to begin in early 2027. The company said it expects to provide an update on plans for a potential additional indication in the near term.¹

References

1. Aclaris Therapeutics, Inc. Aclaris Therapeutics announces positive phase 1b proof-of-concept primary analysis results for its anti-TSLP/IL-4Rα bispecific ATI-052 in atopic dermatitis (AD) and asthma. Published October 27, 2026. Accessed October 27, 2026. Aclaris TherapeuticsAclaris Therapeutics, Inc.
2. Zhou J, Fiedler J, Guttman-Yassky E. Beyond T helper 2 cells: integrating immune, barrier, microbial, and neuroimmune pathways in atopic dermatitis pathogenesis. J Am Acad Dermatol. 2026;94(5S):S14-S20. doi:10.1016/j.jaad.2026.01.076. PubMed