BenevolentAI announced top-line results from its Phase IIa, randomised, double-blind, placebo-controlled study of BEN-2293, a topical pan-Trk inhibitor. BEN-2293 is a selective inhibitor of the three tropomyosin-related kinases (Trk) receptors (TrkA, TrkB and TrkC) formulated to be administered topically in patients with mild-to-moderate AD. The study's primary endpoint was safety and tolerability, while secondary endpoints of the study were also specifically powered to show the fraction of patients achieving an improvement in the Eczema Area and Severity Index (EASI) and the fraction of patients achieving an improve in the pruritus Numerical Rating Scale (NRS).

In this Phase IIa study, 91 patients aged between 18-65 years with mild-to-moderateAD were randomised to receive either 1% BEN-2293 (n=49) or placebo (n=42) twice daily for 28 days on affected skin up to a maximum of 30% body surface area (BSA). BEN-2293 was shown to be safe and well-tolerated but did not demonstrate a statistically significant effect on NRS or EASI endpoints across the Intention-To-Treat (ITT) population. However, initial analysis of percentage BSA affected by AD showed an EASI treatment effect for BEN-2293 in patients with greater extent of disease at baseline, with magnitude of treatment effect growing over time (p=0.0296).

This result was also observed in the Per-Protocol population (p=0.0427) with the data at 28 days showing an interaction between treatment effect and disease burden (p=0.0237) such that a significant treatment effect for BEN-22 93 over placebo is expected for subjects with BSA affected of 20% or greater. This initial analysis suggests a new avenue for further clinical investigation. Although the top-line efficacy findings are not conclusive, the significant relationship of EASI efficacy with affected BSA requires further investigation and supports the hypothesis of utilising a PanTrk inhibitor in AD.