Ascletis Pharma-B (01672) announced positive results from a randomized, double-blind, placebo-controlled 28-day proof-of-concept clinical trial of ASC50 in patients with mild to moderate plaque psoriasis in the United States.

The Phase I study was designed to evaluate the safety, efficacy, and pharmacokinetics of once-daily 200 mg ASC50 in patients with mild to moderate plaque psoriasis after 28 days of treatment (NCT07024602).

Key findings:

In patients with mild to moderate plaque psoriasis who received 28 days of once-daily 200 mg treatment, the placebo-corrected reduction in Psoriasis Area and Severity Index (PASI) score reached 48.9%.

The steady-state elimination half-life in patients after 28 days of treatment was 6.5 days, potentially supporting once-weekly oral dosing.

On Day 6 and Day 15 after the last dose (the 28th dose), the placebo-corrected PASI score reductions increased to 60.7% and 65.9%, respectively. These data potentially support once-weekly oral dosing.

The PASI score reduction with once-daily 200 mg dosing is comparable to published secukinumab data (non-head-to-head study). Secukinumab is a marketed interleukin-17A (IL-17A) antibody drug.

Significant target engagement was demonstrated after 28 days of dosing, as evidenced by elevated plasma IL-17A levels.

The 28-day once-daily 200 mg treatment was safe and well tolerated. All adverse events (AEs) were mild (Grade 1) and of short duration. No serious adverse events (SAEs) were reported, and no subjects withdrew from the study. No elevations in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) were observed. No liver safety signals were detected.

"The strong efficacy along with the encouraging safety and pharmacokinetic data demonstrated in this proof-of-concept clinical trial support ASC50's potential to become a first-in-class and best-in-class oral small molecule IL-17A inhibitor, offering patients a non-injectable dosing option as an alternative to injectable antibody therapies. The novel scaffold of ASC50 demonstrated a 6.5-day steady-state elimination half-life in patients, potentially supporting once-weekly oral dosing," said Dr. Wu Jinzi, Founder, Chairman of the Board, and Chief Executive Officer of Ascletis. "Compared with injectable antibody therapies, ASC50 has the potential to become a differentiated oral alternative therapy and to benefit patients through once-weekly oral dosing."

ASC50 is an IL-17A-targeting oral small molecule inhibitor independently developed by Ascletis. IL-17A has been well biologically validated in multiple autoimmune and inflammatory diseases including psoriasis, and possesses established commercial value. ASC50 is a new chemical entity (NCE) with a novel scaffold.