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HM15211 is a novel long-acting GLP-1/GIP/Glucagon triple-receptor co-agonist with extended half-life through reduced renal clearance and through FcRn mediated vascular endothelial recycling. HM15211 has shown therapeutic potential in animal models of NASH and dyslipidemia. This study was a randomized, double‐blind, placebo‐controlled First-In-Human trial designed to assess safety, pharmacokinetics, and pharmacodynamics of a single subcutaneous dose of HM15211 in obese but otherwise healthy adult subjects (Total 41 subjects were randomized, the mean age was 45.7 years, 51.2% were males, and the mean BMI was 33.6 kg/m2). Subjects were randomized to one of 5 sequential ascending doses of either HM15211 or matching placebo. HM15211 was safe and well-tolerated in this population with no significant changes in heart rate, blood pressure, ECG, physical exams, and clinical laboratory tests. There was no subject who discontinued the study and there were no serious adverse events due to study medication. Compared to placebo, HM15211 suppressed corresponding endogenous incretins and reduced circulating amino acids levels in a dose dependent manner, which may be related to the mode of action of HM15211. Plasma concentration of HM15211 reached its peak level (Tmax) in 31.20 to 68.08 hours. Plasma AUC0-inf and Cmax increased in a dose-proportional manner and the terminal half-life (t1/2) was 72.09 to 142.10 hours.
In conclusion, single doses of HM15211 were well tolerated, showed PK profiles suitable for weekly administration, and initial evidence in support of the hypothesized mode of action. Clinical studies in patients with obesity with NAFLD/NASH will follow.