Aclaris Therapeutics Reports Positive Interim Phase 1a ATI-052 Data, Speeds Up Development Plans

Aclaris Therapeutics (NASDAQ:ACRS) hosted an investor conference call on January 6, 2026 to discuss positive interim results from its ongoing first-in-human Phase 1a single ascending dose (SAD) and multiple ascending dose (MAD) study of ATI-052, a bispecific antibody designed to bind both thymic stromal lymphopoietin (TSLP) and IL-4 receptor (IL-4R). Management said the interim data, as of December 31, 2025, support safety and tolerability in healthy volunteers, demonstrate a pharmacokinetic (PK) and pharmacodynamic (PD) profile consistent with extended dosing, and have led the company to accelerate clinical development plans.

ATI-052 rationale and design

Chief Executive Officer Neal Walker said ATI-052 is intended to inhibit TSLP “upstream” and immune cell signaling “downstream” in the TH2 cascade via IL-4R, thereby blocking signaling of TSLP, IL-4, and IL-13. President and COO Hugh Davis added that ATI-052 incorporates the same anti-TSLP ligand-binding regions as the company’s anti-TSLP monoclonal antibody (Bosacatug), while also including two IL-4R-binding single-chain variable fragments.

Davis said ATI-052 includes two Fc mutations: a YTE mutation intended to extend half-life through tighter FcRn binding, and an AQQ mutation intended to reduce off-target binding and potential toxicity. He emphasized the company’s view that ATI-052’s TSLP binding features translate into a potency advantage, highlighting slow dissociation kinetics and a reported residence time on TSLP of over 400 hours. As presented, ATI-052’s residence time was compared to Tezepelumab at 14.3 hours.

In addition to binding kinetics, Davis said ATI-052 can bind two molecules of TSLP and two molecules of IL-4R concurrently, with all four binding sites acting independently. He also cited in vitro work in which ATI-052 showed greater potency inhibiting CCL17 (TARC) production than the combined use of dupilumab and tezepelumab in a peripheral blood mononuclear cell assay, and described ATI-052 as exhibiting broad activity across TSLP, IL-4, and IL-13 pathways.

Phase 1a study design

Chief Medical Officer Jesse Hall outlined the Phase 1a SAD/MAD trial in healthy adults as randomized, blinded, and placebo-controlled, evaluating subcutaneous ATI-052 for safety, tolerability, PK, and PD.

• SAD: Four cohorts (n=8 each) randomized 3:1 to ATI-052 or placebo; single doses of 30, 120, 360, or 720 mg.
• MAD: Two cohorts (n=8 each) randomized 3:1 to ATI-052 or placebo; five doses of 240 or 480 mg administered every seven days.

Hall said baseline characteristics were generally balanced across cohorts and typical of a healthy volunteer population.

Safety and tolerability findings

Hall said ATI-052 was well tolerated with a “strong safety profile” across SAD and MAD cohorts up to 720 mg, with a low overall adverse event rate and predominantly Grade 1 events. The most common adverse event was injection-site redness, which he described as generally mild and self-resolving. The company reported no serious adverse events, no adverse events leading to discontinuation, and no Grade 3 drug-related adverse events.

Hall also highlighted that no conjunctivitis cases had been observed to date, noting that conjunctivitis has been a point of attention in the broader category. Management said the SAD cohorts were followed out to Day 113 and the MAD cohorts will be followed out to Day 141.

PK/PD profile and dosing implications

Davis described dose-proportional increases in PK (Cmax and AUC) across the 120–720 mg SAD dose range. He said linear PK was observed above a threshold concentration for target-mediated drug disposition (TMDD) related to IL-4R, which he described as approximately 1–2 micrograms per mL. As concentrations approach that threshold, he said, enhanced clearance can occur.

According to Davis, drug concentrations above the TMDD threshold were observed for six to eight weeks after a single dose and at least eight weeks after the lower MAD regimen (240 mg). He said the effective half-life in the study was at least 26 days and characterized this as roughly two and a half times that of dupilumab. Based on the PK profile and sustained PD effects, he said the company believes ATI-052 has the potential for up to a three-month maintenance dosing interval, which it plans to explore in Phase 2.

On PD, Davis said Aclaris adapted a CCL17/TARC assay to a human whole-blood format to better reflect endogenous cytokine conditions. Using ex vivo stimulation with either IL-4 or TSLP, the company evaluated inhibition of CCL17 secretion at multiple timepoints (Days 4, 8, 14, 22, 43, and 113 were referenced across the discussion). He said the 30 mg SAD cohort showed strong inhibition of IL-4-stimulated CCL17 despite being intended as a sub-pharmacologic dose, and that the 360 mg cohort showed strong inhibition out to at least Day 43, including complete inhibition for at least three weeks. For TSLP-stimulated CCL17, Davis said inhibition was “even more impressive,” citing greater than 50% inhibition at 30 mg and complete or near complete inhibition out to Day 43 in the 360 mg cohort, with partial inhibition beyond that.

During Q&A, management said TSLP inhibition appeared somewhat more pronounced than IL-4 inhibition, which Davis attributed to the design and potency of the TSLP-binding side of the molecule and the translation of Bosacatug’s potency attributes into ATI-052.

Next steps: Phase 1b POC studies and Phase 2 planning

Walker said the interim Phase 1a data prompted Aclaris to expedite ATI-052 development. The company expects to initiate a Phase 1b proof-of-concept (POC) study in atopic dermatitis “imminently,” followed by a second Phase 1b study in asthma later in the quarter. Management said it expects both studies to read out in the back half of 2026.

Hall provided additional design details in response to analyst questions:

• Atopic dermatitis Phase 1b: ATI-052 at 480 mg (the high-dose MAD cohort level), dosed five times over a 28-day interval; primary endpoint at Day 57.
• Asthma Phase 1b: ATI-052 at the same 480 mg dose administered once; primary endpoint at Day 28.

Management said the intent of using the same dose as the healthy volunteer MAD cohort in the atopic dermatitis study is to enable comparable PK/PD evaluation and inform subsequent Phase 2b dose selection, including population PK modeling work.

Walker also said planning is underway for a Phase 2b trial in the second half of 2026, with an emphasis on evaluating multiple doses and a longer dosing schedule supported by the Phase 1a interim results. In Q&A, management indicated the Phase 1b study would complete before the Phase 2 program begins, but said the company intends to advance preparatory work so the Phase 2 can begin promptly afterward.

On immunogenicity, management said anti-drug antibody (ADA) testing is being conducted with samples assessed at the end of the SAD and MAD cohorts using an in-study cut point, and said more information would follow once analyses are complete. Management also noted that work related to a future commercial presentation is “in flight,” without providing specifics.

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.