Aclaris Therapeutics (NASDAQ:ACRS) outlined development priorities and upcoming milestones for its biologics and oral small-molecule pipeline during a fireside chat at Guggenheim’s Emerging Outlook Biotech Summit. Company leaders described a two-pronged strategy spanning a TSLP-targeted antibody platform and an ITK-focused kinase inhibition franchise, with multiple clinical readouts anticipated in the back half of 2026.
Pipeline focus: biologics and oral small molecules
Chief Executive Officer and Board Chair Neal Walker said the company is advancing both large-molecule and small-molecule therapeutics. On the biologics side, Aclaris is developing a TSLP monoclonal antibody in a 90-patient study in moderate-to-severe atopic dermatitis (AD), with results expected in late 2026. The company is also developing a bispecific antibody built from the same TSLP monoclonal antibody paired with an IL-4 receptor (IL-4R) construct.
TSLP monoclonal antibody: clinical rationale and trial design
President and CEO Hugh Davis discussed the company’s TSLP monoclonal antibody, referred to in the discussion as “bosakitug,” describing a 20–23 day half-life and a long “residence time” on TSLP of more than 400 hours. Davis said the company benchmarked the molecule against “a number of clinical candidates, as well as Tezspire,” and stated the antibody was “70 times more potent than Tezspire” in those tests.
Davis also pointed to results from an earlier Phase IIa open-label study (conducted while he was at Biogen), saying that after six months of therapy the program showed an EASI score reduction characterized as “94% EASI-75,” along with an Investigator’s Global Assessment (IGA) 0/1 rate of 88%. He said these results helped motivate the move into a randomized Phase II study at Aclaris.
For the ongoing Phase II program in AD, Davis said the study includes 90 subjects, is powered on EASI reduction, and uses a 2-to-1 randomization against placebo. The trial is monotherapy and runs for 24 weeks. He added that the company expects the molecule could potentially support a dosing interval of two to three months, noting that in the earlier IIa study, EASI-75 responses persisted 12 weeks after the last dose at week 24.
Bispecific ATI-052: PK/PD, safety observations, and Phase 1b plans
Turning to the bispecific antibody ATI-052, Davis said a key development goal was to improve half-life given potential target-mediated drug disposition associated with IL-4R targeting. He said the molecule includes a YTE mutation and that the company observed a 26-day half-life in the dataset it recently reported from the first three single-ascending dose (SAD) cohorts. Davis also said the bispecific retains the TSLP antibody’s long residence time and showed strong target engagement in healthy volunteers, describing “both sides of the molecule working very effectively.” Additional data from the rest of the study are expected in the coming months, management said.
On tolerability, Davis said injection site reactions were the most common adverse event in the healthy volunteer study but described them as not dose-related or injection-related, mostly Grade 1, and resolving within a day or two without medication.
Management said two Phase 1b studies are planned for ATI-052:
- Severe atopic dermatitis: a placebo-controlled study already underway, enrolling severe patients only (9 active, 3 placebo). Davis said the regimen includes five weekly doses and is intended to assess population pharmacokinetics, target engagement on both TSLP and IL-4R, and early efficacy signals including EASI metrics.
- Moderate asthma: described as similar to a Sanofi study design referenced in the discussion, expected to start “imminently.” The company plans to enroll a higher T2 population (FeNO > 35 and eosinophils > 150) in a single-dose study, looking at FEV1 and FeNO reduction.
Oral ITK strategy: ATI-2138 results and next-generation selectivity
Chief Scientific Officer Roland Kolbeck framed ITK as a long-standing but challenging target for the industry, noting that reversible ATP-competitive approaches have historically struggled. He said Aclaris has focused on covalent inhibitors that target a cysteine in the kinase pocket, describing this as a key differentiator.
Kolbeck described ATI-2138 as a first-generation covalent inhibitor with “high single-digit nanomolar potency” for ITK as well as JAK3, which also contains a targetable cysteine. He emphasized that, mechanistically, ATI-2138 is designed to hit JAK3 without cross-reacting to other JAK family members, and noted JAK3’s expression is limited to immune cells.
In an open-label study in moderate-to-severe AD, Kolbeck said Aclaris tested a single dose level of 10 mg BID over 12 weeks and observed about a 70% reduction in EASI and about a 63% reduction in pruritus (a four-point drop in itch score). He also said the study included biomarker work (tape strips and biopsies) that showed reductions in ITK pathway biomarkers, along with target occupancy data showing ITK occupancy of roughly 60–70% at trough to over 90% at Cmax; JAK3 occupancy ranged from about 20–30% to 80%. He characterized the dataset as safe and well tolerated.
Asked about differentiation in a competitive JAK landscape, Kolbeck cited ritlecitinib as a close comparator in terms of JAK3 inhibition and said Aclaris believes ATI-2138 is more potent on JAK3 and “way more potent on ITK.” He said the company is considering indications including alopecia and lichen planus and is in the process of selecting a lead indication.
Walker added that the company has reviewed head-to-head data generated in Angela Christiano’s lab comparing ATI-2138 to ritlecitinib in alopecia, and said the lab described it as showing “the most robust and quickest effect” they had seen among JAK inhibitors, which Walker attributed to ITK activity.
Finally, management said it has engineered newer compounds that “dialed out” JAK3 while maintaining ITK potency and improving metabolic stability to support once-daily dosing. Kolbeck said the company can also “dial in and dial out” activity against the related kinase TXK, positioning one program as highly ITK-selective and another as ITK/TXK cross-reactive. Walker said adding TXK could potentially broaden biology beyond Th2-driven disease, and later stated the company believes it is about 12 months behind a competitor in the ITK space but is focused on accelerating development and pursuing best-in-class positioning.
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.
