Announcement • Apr 30
Aclaris Therapeutics Announces Positive Full Top Line First-In-Human Results from Phase 1A Healthy Volunteer Clinical Trial of ATI-052 and Lichen Planus as Lead Indication for ATI-2138
Aclaris Therapeutics, Inc. provided a clinical update on its biologic and oral inhibitor compounds including positive full top line results from the first-in-human Phase 1a single (SAD) and multiple ascending dose (MAD) trial of its anti-TSLP/IL-4Ra bispecific antibody ATI-052 and the selection of lichen planus (LP) as the lead indication for its selective ITK/JAK3 inhibitor ATI-2138. Positive full results from Phase 1a trial of anti-TSLP/IL-4Ra bispecific antibody ATI-052 exceed Aclaris’ target profile, validating potential best-in-class potency advantage and opportunity for extended dosing. Estimated half-life of approximately 45 days; unlocks opportunity for up to three-month dosing interval. Complete and sustained inhibition of TSLP-induced and IL-4 induced CCL17 (TARC) provides potential to raise efficacy ceiling in Th2-driven diseases. Enrollment and dosing ongoing in Phase 1b trials in asthma and atopic dermatitis (AD) with top line results expected in the second half of 2026. Lichen planus selected as lead indication for ATI-2138; potential to be first mechanistically complete therapeutic candidate designed to address root inflammation and symptoms. ATI-052 is an investigational anti-TSLP and anti-IL-4Ra bispecific antibody that exhibits high binding affinity to, and dual blockade of, both the TSLP receptor signal transduction and downstream IL-4Ra activation thereby inhibiting this central proinflammatory pathway. By addressing the shared receptor IL-4Ra, ATI-052 blocks IL-4 and IL-13 biological activity, key cytokines driving Th2 inflammation. ATI-052 exhibited a potential best-in-class pharmacokinetic (PK) profile, including an estimated half-life of approximately 45 days. Dose proportional PK was observed across the pharmacologic dose range, including dose proportional increases in Cmax (maximum peak concentration) and AUC (area under the curve; a measure representing total systemic exposure). Pharmacodynamic (PD) results validate the potency of ATI-052, including robust target engagement and near complete target occupancy. ATI-052 demonstrated complete and sustained inhibition through at least week 20 (four months post last dose) of ex vivo TSLP stimulated CCL17/TARC and at least week 12 (two months post last dose) of ex vivo IL-4 stimulated CCL17/TARC in the 480 mg MAD cohort. The combination of the strong and sustained PK duration and PD effect supports the potential for up to every three-month dosing. No impact of anti-drug antibodies (ADA) on PK or PD has been observed in this trial. ATI-052 was well tolerated and demonstrated a favorable safety profile across all SAD and MAD cohorts, consistent with the interim results; no safety signals including conjunctivitis were observed. The randomized, blinded, placebo-controlled Phase 1a portion of the first-in-human study was designed to evaluate the safety, tolerability, PK, and PD of subcutaneously administered ATI-052 in healthy adults receiving SAD and MAD doses. In the SAD portion, four cohorts of 8 healthy volunteers each were randomized 3:1 to receive a single dose of ATI-052 (30, 120, 360, or 720 mg) or placebo. In the MAD portion, two cohorts of 8 healthy volunteers each were randomized 3:1 to receive five doses of two dose levels of ATI-052 (240 or 480 mg) or placebo administered every 7 days. Participants were followed for safety for approximately 16 weeks for the SAD cohorts and 20 weeks for the MAD cohorts. In January 2026, Aclaris announced the initiation of a Phase 1b proof-of-concept (POC) trial in patients with atopic dermatitis (EASI >21). In February 2026, the Company initiated a Phase 1b POC trial in patients with asthma on GINA (Global Initiative for Asthma) steps 2-4 treatment prior to screening. Enrollment is ongoing in both trials, and top line results from both are expected in the second half of 2026. Given the results observed to date and its mechanism of action targeting TSLP as well as effects of IL-4 and IL-13 through blockade of the shared receptor IL-4Ra, the Company announced its intent to initiate a Phase 2b program with ATI-052, initially targeting asthma, in the fourth quarter of 2026. ATI-2138 is a highly potent and selective novel investigational pharmacologic agent that acts as a dual inhibitor of interleukin-2-inducible T cell kinase (ITK) and Janus kinase 3 (JAK3); the dual mechanism enables deep suppression of pathogenic T-cells via inhibition of TCR signaling and effector cytokine activation. Aclaris intends to initiate a phased multi-part Phase 2b basket study of ATI-2138 in lichen planus (LP), an unaddressed chronic, inflammatory, CD8+/Th1-driven interface dermatitis impacting approximately 0.1% to 1.0% of the population. The trial is expected to comprise the three most common LP subtypes: erosive mucosal, cutaneous, and lichen planopilaris (LPP), a rare form of LP that causes permanent hair loss. The most common symptoms of LP include sores, pain, difficulty eating, severe itch, scales/plaques, hair loss, and fatigue; quality of life is also affected in most patients, including due to anxiety and depression. There is also the potential for malignancy in certain subtypes. Disease management has focused on immunosuppression and symptom control; there are currently no FDA-approved therapies. Despite the lack of therapeutic options, approximately 40% of patients seek treatment. An oral agent like ATI-2138 has the potential to provide rapid symptom and itch relief and address multi-site (cutaneous, oral, and scalp) disease involvement. The Company estimates that the potential market opportunity in the U.S. for an oral therapeutic for LP exceeds $1.0 billion with opportunity up to $4.0 billion. Aclaris expects to initiate Part A (erosive mucosal; cutaneous) of this trial in the second half of 2026 and intends to move into Part B (LPP) soon thereafter. ATI-052 is an investigational humanized anti-TSLP and anti-IL-4Ra bispecific antibody that exhibits high binding affinity to and dual blockade of both the upstream thymic stromal lymphopoietin (TSLP) receptor signal transduction and downstream interleukin-4 receptor (IL-4R) activation thereby inhibiting this central proinflammatory pathway. ATI-052 targets TSLP, which sits at the top of the inflammatory cascade; by targeting IL-4Ra, it blocks both downstream IL-4 and IL-13, which are key cytokines involved in Th2-mediated inflammation and allergic diseases. ATI-052 exhibits potential best-in-class potency and utilizes the same TSLP antigen-binding fragment (Fab) region as bosakitug (ATI-045), retaining the dissociation kinetics, long residence time, and high potency advantages over comparator antibodies, but is engineered to bind more tightly to the neonatal Fc receptor (FcRn), potentially extending its half-life.