Aclaris’ TSLP/IL-4Rα Bispecific ATI-052 Shows Early Activity in Atopic Dermatitis and Asthma

Aclaris Therapeutics’ ATI-052, a bispecific antibody that blocks both thymic stromal lymphopoietin (TSLP) and the interleukin-4 receptor alpha (IL-4Rα), improved skin disease in atopic dermatitis (AD) and reduced airway inflammation in asthma in two phase 1b proof-of-concept trials.¹ The company plans to prioritize a phase 2b trial in eosinophilic esophagitis (EoE), with initiation expected early next year.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,” said Michael Cameron, MD, assistant clinical professor in the Department of Dermatology at Mount Sinai in New York and an investigator in the trial.¹

How does ATI-052 work?

ATI-052 is a humanized bispecific antibody that targets TSLP and blocks IL-4 and IL-13 signaling through their shared receptor, IL-4Rα.¹ TSLP is an epithelial cytokine that acts at the top of the inflammatory cascade, and it is the target of the approved monoclonal antibody tezepelumab (Tezspire) in severe asthma.² IL-4Rα blockade addresses the downstream type 2 inflammatory signals driven by IL-4 and IL-13.¹

The TSLP-binding arm of ATI-052 shares the same Fab as Aclaris’ anti-TSLP monoclonal antibody bosakitug (ATI-045), which the company said binds TSLP with very slow dissociation kinetics.¹ ATI-052 is also engineered to bind more tightly to the neonatal Fc receptor (FcRn) to extend its half-life.¹ In a Phase 1a trial in healthy volunteers, the estimated half-life was approximately 45 days, which Aclaris said could support dosing as infrequently as every three months.³

What did the AD trial show?

The randomized, double-blind, placebo-controlled trial enrolled 14 patients with severe AD who received 480 mg of ATI-052 or placebo weekly for five doses.¹ At Day 57, patients receiving ATI-052 had a 45% placebo-adjusted improvement in the Eczema Area and Severity Index (EASI), with a 58% reduction from baseline compared with 13% for placebo.¹ The placebo-adjusted EASI-50 response rate was 78%, and itch improved by 43% compared with placebo.¹ Four patients were excluded from the per-protocol analysis.¹

Proteomic analyses showed that ATI-052 downregulated key immune proteins compared with placebo. “These results, including ATI-052’s ability to modulate all three T helper cell related markers, are suggestive of early potent anti-inflammatory clinical activity,” said Emma Guttman, MD, PhD, Waldman Professor of Dermatology and Immunology at the Icahn School of Medicine at Mount Sinai.¹

What did the asthma trial show?

In 16 patients with mild-to-moderate asthma and elevated fractional exhaled nitric oxide (FeNO) of at least 35 ppb, a single 480-mg dose of ATI-052 reduced FeNO by 59% at Day 15, compared with 15% for placebo.¹ Lung function, measured by forced expiratory volume in one second (FEV1), improved by 200 mL vs placebo at Day 15.¹

Treatment-emergent adverse events across both trials were mostly Grade 1, with no Grade 3 or 4 events, no discontinuations due to adverse events, and no conjunctivitis.¹

Why target two pathways at once?

The rationale for dual blockade is that hitting complementary drivers of inflammation may produce deeper or longer-lasting responses than a single target. In a BioPharm International® interview at BIO 2026, Howard Berman, PhD, chief executive officer of ReAlta Life Sciences, described the value of a multitarget approach in inflammatory disease. “Being able to hit all these targets at once is so critically and verifiably important to ameliorate the disease,” Berman said.

What happens next?

Aclaris will prioritize a phase 2b trial of ATI-052 in EoE and said it will provide an update on a potential additional indication in the near term.¹ In April, the company had said it planned a phase 2b program initially targeting asthma.³

“Consistent with our development strategy, we intend to prioritize initiating a Phase 2b trial in EoE early next year,” said Neal Walker, DO, chief executive officer of Aclaris.¹

References

1. 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. News release. Aclaris Therapeutics. October 27, 2026. Accessed October 27, 2026.
2. Tezspire (tezepelumab) approved in the US for severe asthma. News release. AstraZeneca. December 17, 2021. Accessed October 27, 2026.
3. Aclaris Therapeutics reports full top-line Phase 1a results for ATI-052 and provides clinical development update. News release. Aclaris Therapeutics. April 28, 2026. Accessed October 27, 2026.