Executives from Aclaris Therapeutics (NASDAQ:ACRS) outlined the company’s clinical-stage pipeline and upcoming catalysts during a presentation at Oppenheimer’s Annual Healthcare Conference, emphasizing programs in inflammatory and immunological diseases spanning monoclonal antibodies, a bispecific antibody, and small-molecule kinase inhibitors.
Company overview and pipeline cadence
Aclaris described itself as a clinical-stage biotechnology company focused on discovering and developing both large- and small-molecule therapeutics for major unmet needs in inflammation and immunology. Management highlighted the team’s prior drug development experience across companies including MedImmune/AstraZeneca, Centocor/J&J, GSK, and Pfizer, noting experience taking programs “from discovery through to the market.”
Bosakitug: anti-TSLP antibody in atopic dermatitis
The company’s most advanced disclosed program is bosakitug, an anti-TSLP monoclonal antibody being studied in atopic dermatitis (AD). Management said bosakitug has what it believes is “best-in-class potential” based on binding characteristics, specifically citing a ~400-hour retention time on TSLP, compared with “about 20 hours or less” for tezepelumab, with other antibodies described as having even shorter retention times.
Aclaris previously completed a Phase 2a proof-of-concept study in AD. In discussing that earlier study, management reported over 90% EASI-75 response and over 80% responders in “IJ01”, while also noting the study was open-label. Those results supported advancement into a larger Phase II AD study, which management said is expected to read out top-line data in the second half of this year.
On dosing, management said bosakitug has a natural 23-day half-life and suggested that retention time and Phase 2a observations support the possibility of dosing every two to three months. They noted that in the proof-of-concept study the EASI-75 response after the last dose extended through three months. However, the company is using a two-week dosing schedule in the Phase II trial, describing this as a rigorous test designed to maximize exposure and evaluate TSLP as a standalone target in AD while attempting to minimize placebo response through enrollment measures such as using photographs.
When asked about expanding bosakitug beyond AD, management said Aclaris is not pursuing additional indications directly. They referenced a separate company, CTTQ, described as having a previous relationship with Biohaven, that is investigating respiratory indications with bosakitug, including a Phase III trial in severe asthma, a Phase III in chronic rhinosinusitis with nasal polyps, and a Phase II in COPD in China. Aclaris said it has focused on AD and would consider partnering if results are strong.
ATI-052: bispecific targeting TSLP and IL-4R
Aclaris also discussed ATI-052, a bispecific antibody combining the TSLP-binding component used in bosakitug with an anti-IL-4 receptor component. Management highlighted Phase I healthy volunteer results, focusing on pharmacokinetics, pharmacodynamics, and safety.
In the healthy volunteer study, the company said it engineered ATI-052 with a YTE mutation to help offset target-mediated drug disposition related to IL-4 receptor binding. Management reported a 26-day half-life for ATI-052 and contrasted that to dupilumab, which they described as having a shorter half-life, as well as to a Sanofi competitor candidate (lunsekimig) described as having an eight- to nine-day half-life. They said the observed half-life could potentially support dosing intervals of eight to 12 weeks, depending on dose.
Management also described preclinical and ex vivo data, stating that ATI-052 showed four times greater potency in a PBMC assay compared with a combination of tezepelumab plus dupilumab in inhibiting a TSLP/IL-4–activated TARC response. In pharmacodynamic testing using whole blood from healthy volunteers, management said ATI-052 demonstrated up to six weeks of 100% inhibition of the TSLP response at a 360 mg dose, and for the IL-4–activated response showed “up to about three weeks of 100% inhibition” with near-complete inhibition through six weeks.
On safety, management said ATI-052’s safety profile in healthy volunteers was “great,” reporting no safety findings attributed to the molecule, no conjunctivitis, and adverse events described as grade 1.
Phase 1b studies in AD and asthma; small-molecule ITK programs
The company said it has initiated two Phase 1b studies for ATI-052: one in AD (announced in January) and one in asthma (announced earlier this week). For the AD Phase 1b, management said the trial enrolls 12 subjects with a 3:1 randomization (nine active, three placebo) and a baseline EASI score of 21, describing the population as more severe than the bosakitug AD study. Dosing is 480 mg administered weekly for five total doses over 28 days, followed by assessment at day 57. Endpoints include EASI, BSA, and IGA, and the company plans extensive PD work including tape strips, with follow-up extended to day 141.
For the asthma Phase 1b, management said the study plans to enroll 16 moderate asthma patients (GINA step 2 to 4) with a 3:1 randomization (12 active, four placebo). Patients will receive a single 480 mg dose at baseline, with the primary endpoint assessed at day 28 and focused on FeNO reduction and FEV1 improvement. The initial population is described as TH2-high with a FeNO cutoff greater than 35, with TH2-low exploration expected in later studies.
Management said data from both Phase 1b studies are expected in the second half of this year, potentially before the bosakitug Phase II AD readout. Executives argued ATI-052 could offer advantages versus approved therapies by combining TSLP and IL-4 pathway inhibition, potentially expanding reach to broader asthma populations (including T2-low) and offering a less frequent dosing interval relative to dupilumab, while also opening an AD opportunity.
On the small-molecule side, Aclaris discussed ATI-2138, described as a potent ITK/JAK3 dual inhibitor. Management said the company believes ITK and JAK3 expression is limited to the immune system and argued this could support a better safety profile than other JAK inhibitors, citing its chronic toxicology studies and clinical data. For indication selection, the company said it is considering areas with mechanistic fit and “white space,” identifying alopecia as a potential lead indication and referencing preclinical work in a severe alopecia model in collaboration with Angela Christiano at Columbia University. Management said it expects to select a lead indication for ATI-2138 by the end of this quarter.
Aclaris also highlighted a next-generation ITK-selective effort aimed at reducing JAK3 cross-reactivity. Management identified ATI-9494 as an ITK/TXK inhibitor and said the compound is currently in IND-enabling toxicology studies, with an IND targeted by the end of this year. The company summarized its approach as seeking “JAK-like activity with a better safety profile.”
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.
