A phase 1 study evaluating the safety, tolerability, and pharmacokinetics of the porcupine inhibitor, AZD5055.

Excessive Wnt signaling contributes to the development of fibrotic diseases and cancer. Here, we report the findings of a phase 1 study evaluating AZD5055, an orally administered porcupine inhibitor, which inhibits Wnt signaling. The primary objective was to evaluate the safety and tolerability of AZD5055 in healthy volunteers. Secondary and exploratory objectives were the pharmacokinetics and pharmacodynamics of AZD5055, respectively. Sixty healthy volunteers were randomized to receive placebo or AZD5055 in single ascending doses of 7, 20, or 40 mg (part 1), or multiple ascending doses of 5, 15, or 20 mg once daily over 14 consecutive days of dosing (Part 2). AZD5055 was safe and well tolerated in both study parts. AZD5055 exposure increased dose-proportionally with a pharmacokinetic profile enabling once daily dosing. AZD5055 effectively inhibited Wnt signaling in skin, hair follicles, and serum samples. Thus, AZD5055 has therapeutic potential in Wnt-driven fibrotic diseases and cancers.