Aclaris Therapeutics Highlights Atopic Dermatitis Data Catalysts, ITK Progress at Leerink Conference

Aclaris Therapeutics (NASDAQ:ACRS) outlined multiple clinical and near-term development milestones across its large-molecule and small-molecule pipeline during a presentation at the Leerink Partners Global Healthcare Conference, with management emphasizing upcoming data readouts in atopic dermatitis and progress in its ITK inhibitor franchise.

Pipeline overview and near-term milestones

Chairman and CEO Neal Walker described Aclaris as a clinical-stage immunology and inflammation company with three clinical-stage assets and another program expected to enter the clinic following an IND filing in the second half of the year. He framed the company in two “buckets”:

• Large molecules: ATI-045 (TSLP monoclonal antibody) in a Phase 2 study in moderate-to-severe atopic dermatitis (AD), with results expected in the back part of the year; and ATI-052, a bispecific that combines the ATI-045 TSLP antibody with an IL-4 receptor component, currently in SAD/MAD with Phase 1b studies enrolling in moderate asthma and severe AD, with readouts targeted for the end of the year.
• Oral small molecules: ATI-2138, described as Phase 2-ready with a long-term toxicology package while the company selects a lead indication; and a “next-gen” ITK program engineered to remove a JAK component, with an IND planned for the back part of the year.

ATI-045: differentiation thesis and Phase 2 design

President and COO Hugh Davis said ATI-045 is differentiated by retention time and potency. He stated the antibody shows over 400 hours of binding to TSLP in internal testing, which he compared to approximately 20 hours for other clinical compounds tested and to tezepelumab. Davis said Aclaris believes retention time and potency are important for targeting an “alarmin” like TSLP, which he characterized as highly potent and present at picogram-per-milliliter concentrations.

Discussing prior clinical results, Davis highlighted Phase 2A open-label data that he said showed a 94% EASI response with EASI-75 and 88% of subjects achieving IGA 0/1 across seven U.S. sites. He noted the open-label dataset supported advancement into a larger, placebo-controlled trial.

Management said the ongoing Phase 2 study includes 96 subjects with a 2-to-1 randomization, is double-blind and placebo-controlled, and evaluates the endpoint at 24 weeks. On dosing, Davis said the study used 300 mg every two weeks to maximize the chance of success in establishing TSLP as a target in AD. He also cited a 23-day half-life for the “naked antibody” and said the Phase 2A suggested durability, with EASI-75 responses observed for 12 weeks after the last dose. Based on available data, he said the company believes a three-month dosing interval could be feasible longer term.

Walker and Davis also discussed steps designed to reduce placebo variability in AD trials. Walker said both he (as a board-certified dermatologist) and an independent medical reviewer are using patient photographs to confirm diagnosis and inclusion criteria, including whether baseline EASI assessments match visible disease severity.

ATI-052 bispecific: Phase 1 findings and upcoming updates

On ATI-052, Walker said the company presented initial Phase 1 data covering the first three SAD cohorts up to 360 mg, with additional SAD and MAD data expected in the early second quarter. He said upcoming cohorts include a 720 mg SAD dose and MAD cohorts at 240 mg and 480 mg.

Walker characterized the pharmacodynamic readout shown to date as “100% inhibition” and said the company expects higher doses to extend the duration of the PD effect. Davis added that the company calculated a 26-day half-life using available PK data and said this was longer than most receptor-targeting antibodies, comparing it to dupilumab as being “three times” longer. He said measurable PK has extended to eight weeks after the last dose so far in a 240 mg cohort, and he expects it could extend to three months at 480 mg, supporting the possibility of dosing every two to three months.

Asked about immunogenicity, management said the focus is on consequences rather than incidence. Walker said the company has not seen enhanced clearance or neutralization signals in the data reviewed so far and plans to complete analysis after the healthy volunteer study.

The team also discussed the rationale for pursuing asthma and AD in parallel. Walker said the first Phase 2b study “out of the gate” is planned in asthma, describing the thesis as combining the biologic profiles of tezepelumab and dupilumab. CSO Roland Kolbeck said tezepelumab has demonstrated activity in both T2-low and T2-high asthma populations, while dupilumab is effective in T2-high asthma, and that combining TSLP and IL-4 receptor biology could be suitable for a broad asthma population.

For the Phase 1b AD study, management said the primary endpoint is at eight weeks, with the last dose administered four weeks before that assessment, and that follow-up will include an additional 10 weeks to track PK, PD, and other measures, including clinical efficacy during follow-up to assess durability.

ITK franchise: ATI-2138 indication selection and next-gen ITK plans

Turning to small molecules, Walker said ATI-2138 is in an indication selection process and has a Phase 2-ready package, including six- and nine-month chronic toxicology that he described as clean, as well as a “very clean profile” in an AD clinical study. He also cited preclinical work from Angela Christiano’s lab in an alopecia model, describing the results as rapid and robust in a hard-to-treat mouse model and noting head-to-head testing versus ritlecitinib. Walker said selecting the lead indication is “forthcoming very soon” and framed the choice as either entering a more crowded market with approved drugs or pursuing a more niche strategy.

For the next-gen ITK program, Walker said Aclaris has nominated ATI-9494 and expects to file an IND in the second half of the year. He said internal testing versus a competitor’s molecule suggests improved potency by “orders of magnitude,” which he argued could reduce drug burden and provide dosing flexibility for a covalent drug. He also said the program was optimized for extended half-life, keeping once-daily dosing “on the table.”

Walker said Aclaris believes it is “probably 12 months behind” competitors in timing but said the focus is on achieving a superior molecule, including efficacy, dosing convenience, and safety profile. He also described efforts to tune selectivity, including removing the JAK3 component and evaluating potential modulation involving TXK, and said the company plans to run proof-of-concept studies to guide selection among candidates.

Cash runway

In closing, management said the company’s cash runway extends into Q4 2028. Walker said recently disclosed additional capital enables Aclaris to fund the milestones discussed, including adding a Phase 2b asthma study for the ATI-052 bispecific, and provides flexibility to expand development now that programs have been further de-risked.

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.