Aclaris Therapeutics announced positive primary analysis results on October 27 from its Phase 1b proof of concept trials of ATI-052, a bispecific antibody that targets both TSLP and the IL-4 receptor alpha chain, in atopic dermatitis and asthma. The company said both trials demonstrated strong proof of concept with rapid and broad responses, with rapid and durable improvement in skin and itch in a severe atopic dermatitis population, and with a single dose rapidly improving airway inflammation and lung function in a diverse asthma population. Pharmacodynamic results, the company said, support additive or synergistic effects from blocking TSLP alongside the IL-4 and IL-13 pathways. The trials achieved their primary objective on safety and tolerability, including no observations of conjunctivitis, an eye side effect associated with IL-4 pathway drugs such as Dupixent.
The strategic decision in the release is sequencing. Rather than taking ATI-052 into Phase 2b first in dermatitis or asthma, the two indications just tested, Aclaris said it intends to prioritize Phase 2b development initially in eosinophilic esophagitis, a smaller indication where it believes a focused program fits its development strategy and disciplined capital management. The company hosted a conference call on the morning of October 27 to present the data, with slides published alongside the release.
The release gives direction and pharmacology rather than headline efficacy percentages, so the strength of the proof of concept claim cannot be scored from the announcement alone. What is verifiable is the design logic: TSLP blockade is the mechanism of AstraZeneca and Amgen’s Tezspire, and IL-4R alpha blockade is the mechanism of Sanofi and Regeneron’s Dupixent, and no approved drug combines them. Whether combining them in one antibody beats sequencing the two drug classes is the question the Phase 2b program now has to answer, starting in the indication Aclaris can afford to run properly.