JACC Associate Editor Khurram Nasir, MBBS, FACC, speaks with author Michael J. Koren, MD, FACC, on his Featured Clinical Research study published in JACC and presented at ACC.25. This randomized, multicenter, double-blind, placebo-controlled, dose-ranging phase 2 study assessed efficacy, safety, and tolerability of AZD0780, a small molecule PCSK9 inhibitor. The study randomized 428 patients (426 started treatment) with hypercholesterolemia on standard-of-care statin therapy to daily oral administrations of AZD0780 1, 3, 10 or 30 mg, or matching placebo for 12 weeks. AZD0780 significantly reduced LDL-C levels versus placebo at all doses (from 35.3% to 50.7%) and demonstrated a safety and tolerability profile similar to placebo. These findings support further development of AZD0780 as part of a simple, oral regimen for lowering LDL-C beyond that achieved with statin therapy.