Aclaris Therapeutics (ACRS) Study result summary

ATI-052 profile and study design

• Investigational bispecific antibody targeting TSLP and IL-4Rα to inhibit downstream IL-4/IL-13 signaling; multiparatopic binding and a YTE mutation were designed for potent, durable activity and less frequent dosing.

• Phase 1b proof-of-concept trials evaluated ATI-052 in atopic dermatitis (AD) and mild-to-moderate asthma; pharmacodynamic findings supported potential additive or synergistic effects of dual targeting.

• The 14-patient AD study used five weekly 480 mg doses through Week 4, with primary analysis at Day 57 and follow-up through Week 16; 78% had severe disease at baseline.

• The 16-patient asthma study randomized participants 3:1 to one 480 mg dose or placebo, with primary analysis through Day 29.

Atopic dermatitis results

• At Day 57, mean EASI reduction was 58% with ATI-052 vs 13% with placebo, a 45% placebo-adjusted improvement; 78% of active-arm patients achieved EASI-50.

• Skin improvement persisted through Week 16, 12 weeks after the final dose; EASI-50 was achieved by 89% of ATI-052 patients at some point during the study.

• Itch improvement began by Week 1; at Week 8, placebo-adjusted PP-NRS improvement was 43%, and 33% achieved a PP-NRS4 response.

Atopic dermatitis pharmacodynamics

• At Week 8, lesional skin proteome showed 95% improvement in the lesional-to-non-lesional relationship, vs 27% with placebo; published dupilumab data showed 66% improvement at Week 16.

• Skin analyses showed downregulation across Th1, Th2, Th17/22, myeloid, fibrosis and itch-related pathways, alongside reductions in AD biomarkers including CCL17 and IL-5.

• Biomarker findings, including suppression across inflammatory endotypes and near-normalization of lesional skin, supported biological activity from dual TSLP and IL-4Rα targeting.