Aclaris Therapeutics (ACRS) H.C. Wainwright 4th Annual Inflammatory Skin Disease Virtual Conference summary

Lead candidate overview and scientific rationale

• ATI-052 is a bispecific antibody targeting TSLP and IL-4R, designed for inflammatory skin diseases like atopic dermatitis and asthma.

• Demonstrates best-in-class potency, with 70x greater activity than tezepelumab and 4x more potent than the combination of Dupixent and Tezepelumab.

• Achieves 100% inhibition of TSLP, IL-4, and IL-13 activity in healthy volunteers, suggesting strong synergy over monotherapies.

• Two phase 1b studies are ongoing in severe atopic dermatitis and asthma, with a phase 2b in asthma planned.

Clinical efficacy, dosing, and safety profile

• Anticipates improved efficacy on IGA and EASI endpoints, with expectations of higher response rates and durability compared to current standards.

• Phase I data show a half-life exceeding 40 days, supporting dosing intervals of up to three months, a significant improvement over biweekly regimens.

• No conjunctivitis observed in early studies, potentially due to the unique mechanism of action; ongoing studies will further assess safety.

• The molecule is being developed for convenient administration, including prefilled syringes and needle pens.

Competitive landscape and molecular advantages

• The bispecific construct offers four independent binding sites, providing higher potency and longer half-life than trispecific competitors.

• Functions effectively as a trispecific in terms of inhibitory activity, but with optimized binding and pharmacokinetics.

• Designed to outperform Pfizer's and Sanofi's multi-specific antibodies in both efficacy and dosing convenience.