ASCLETIS-B (01672) announced positive topline results from a randomized, double-blind, placebo-controlled Phase I clinical trial (NCT07024602) of ASC50 conducted in the US. The single ascending dose (SAD) study evaluated the safety, tolerability, pharmacokinetics, and peripheral interleukin-17A (IL-17A) target engagement in healthy subjects.
A total of 46 healthy participants received doses of 10 mg, 30 mg, 100 mg, 200 mg, 400 mg, or 600 mg ASC50 or matching placebo. Key findings include: - Elimination half-life after single oral doses of ASC50 ranged from 43 to 104 hours (10 mg to 600 mg), supporting potential once-daily or even once-weekly dosing. - ASC50 demonstrated significant target engagement, with elevated plasma IL-17A levels lasting up to 7 days post-dose at higher concentrations. - Pharmacokinetics showed dose proportionality across the 10 mg to 600 mg range. - In non-human primate head-to-head studies, ASC50 exhibited superior absolute oral bioavailability, drug exposure, half-life, and clearance compared to LY4100511 (DC-853), another oral small molecule IL-17 inhibitor currently in clinical development. - ASC50 was safe and well-tolerated in the SAD study. All adverse events (AEs) were mild (Grade 1) and transient, with no serious AEs, study discontinuations, or hepatic safety signals observed.
Based on these favorable results, ASC50 has advanced to the next clinical development stage—a multiple ascending dose study in mild-to-moderate plaque psoriasis patients.
ASC50 is ASCLETIS' internally developed oral small molecule IL-17 inhibitor targeting validated autoimmune and inflammatory diseases like psoriasis. As a new chemical entity (NCE), it holds US and global compound patent protection until 2043 (excluding potential extensions).
"These data demonstrate ASC50's excellent safety profile and differentiated, dose-dependent pharmacokinetics," said Dr. Jinzi Wu, Founder, Chairman, and CEO of ASCLETIS. "As our first immunology-focused oral small molecule candidate developed using AI-assisted structure-based drug discovery (AISBDD) technology, these results are highly encouraging. The findings underscore ASC50's potential as a best-in-class oral small molecule IL-17 inhibitor."