WAYNE, PA — Aclaris Therapeutics Inc. (Nasdaq: ACRS) plans to advance its experimental antibody ATI-052 into a Phase 2b trial for eosinophilic esophagitis in early 2027, concentrating development spending on the inflammatory disease after preliminary studies showed improvements in patients with eczema and asthma.
The decision follows Phase 1b trials involving 30 patients across the two conditions, where the drug demonstrated early evidence of biological activity and was generally well tolerated.
The Wayne-based biotechnology company is prioritizing eosinophilic esophagitis, or EoE, as part of a strategy to focus its clinical development resources while evaluating the drug’s potential in other inflammatory diseases.
Aclaris also expects to provide an update on plans for a possible additional indication in the near term.
ATI-052 is a bispecific antibody designed to inhibit thymic stromal lymphopoietin, or TSLP, and the interleukin-4 receptor alpha, known as IL-4Rα. The approach targets inflammatory signaling involving TSLP, IL-4 and IL-13 through a single therapeutic agent.
The early-stage studies examined whether simultaneously blocking those pathways could produce clinical responses across diseases with different inflammatory characteristics.
In the atopic dermatitis trial, 14 patients with severe eczema were randomized in a 3-to-1 ratio to receive ATI-052 or placebo.
Participants received five weekly doses of 480 milligrams, with the primary analysis conducted on day 57.
Four patients were excluded from the prespecified per-protocol analysis for reasons established before the treatment assignments were revealed. Two ATI-052 recipients had received only two doses or failed to meet eligibility requirements, while two placebo recipients began rescue medication early.
Among patients included in the active-treatment per-protocol analysis, 78% had the highest severity rating on the five-point Validated Investigator’s Global Assessment scale at baseline.
Patients receiving ATI-052 experienced an average 58% reduction in Eczema Area and Severity Index scores by day 57, compared with a 13% reduction in the placebo group.
The resulting placebo-adjusted improvement was 45 percentage points.
The company also reported a 78-percentage-point placebo-adjusted difference in the proportion of patients achieving at least a 50% improvement in eczema severity, known as EASI-50.
Responses were observed across baseline severity categories, with available follow-up data suggesting that improvements persisted through week 16 in some patients. Follow-up remains ongoing.
The treatment also reduced itching, with improvements beginning during the first week.
By week four, ATI-052 recipients experienced an average 40% reduction in itch severity. At day 57, itching had improved by 38% from baseline in the active-treatment group, compared with a 5% worsening among placebo recipients.
That represented a 43-percentage-point placebo-adjusted difference.
The company reported a 33-percentage-point placebo-adjusted difference in the proportion of patients achieving at least a four-point improvement on the Peak Pruritus Numerical Rating Scale.
Michael Cameron, a dermatologist and investigator in the study, described the speed and persistence of the responses as noteworthy.
“Given the mechanism of ATI-052, one would expect reductions in EASI and itch from baseline to be rapid and sustained due to blockade of IL-4 and IL-13 via their shared receptor IL-4Rα, and durable through blockade of the TSLP alarmin,” Cameron stated.
Laboratory analyses provided additional evidence that the treatment affected inflammatory pathways.
At week eight, Aclaris reported 95% normalization of the protein-expression profile in affected skin, with measurements resembling those found in non-lesional skin.
The drug affected several inflammatory pathways associated with atopic dermatitis, including Th1, Th2 and Th17/Th22 signaling, tissue remodeling and itch-related processes.
The findings also showed reductions in biomarkers associated with dupilumab treatment, alongside effects on additional immune pathways.
Emma Guttman, professor of dermatology and immunology at the Icahn School of Medicine at Mount Sinai, indicated that the molecular findings were consistent with the clinical improvements observed in the trial.
The separate asthma study enrolled 16 patients with mild-to-moderate disease and elevated fractional exhaled nitric oxide, or FeNO, a marker of airway inflammation.
Participants were randomized to receive a single 480-milligram dose of ATI-052 or placebo, with assessments continuing through day 29.
Fifteen days after treatment, patients receiving ATI-052 experienced an average 59% reduction in FeNO, equivalent to 45 parts per billion, compared with a 15% reduction in the placebo group.
At day 29, the reduction in the ATI-052 group was 40%.
Approximately 58% of treated patients achieved FeNO levels of 25 parts per billion or lower by day 15, meeting the study’s threshold for normalization.
Lung function also improved.
Patients receiving ATI-052 experienced an average 200-milliliter increase in forced expiratory volume in one second, or FEV1, by day 15, representing both the absolute and placebo-adjusted mean improvement reported for the overall population.
In a post hoc analysis of patients with baseline FEV1 below 80% of predicted values and reversible airflow limitation, the average improvement reached 350 milliliters.
The corresponding placebo subgroup experienced an average decline of 140 milliliters.
Because the subgroup analysis was conducted after the study design was established, those findings are exploratory and require confirmation in larger trials.
Across both studies, treatment-emergent adverse events were predominantly Grade 1, the least severe classification.
No Grade 3 or Grade 4 treatment-emergent adverse events occurred, and no adverse events resulted in study discontinuation.
Injection-site reactions were infrequent, transient and almost exclusively Grade 1. No cases of conjunctivitis were observed.
The safety findings are preliminary, given the small patient populations and limited treatment exposure.
Neal Walker, Aclaris’ chief executive officer, identified the drug’s activity across different inflammatory conditions as supporting its broader development potential.
“Consistent with our development strategy, we intend to prioritize initiating a Phase 2b trial in EoE early next year and provide an update on plans for a potential additional indication in the near term,” Walker stated.
The results provide early evidence that ATI-052 can affect multiple inflammatory pathways, but the studies were primarily designed to assess safety and tolerability rather than establish definitive treatment efficacy.
Aclaris’ next development stage will focus on testing the antibody in eosinophilic esophagitis, a disease distinct from the eczema and asthma populations evaluated in these initial trials.
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