PegBio Co., Ltd. (02565) announced that CR059, a next-generation GLP-1 receptor agonist developed with circular RNA protein replacement technology and an AI-assisted molecular design platform, has completed a single-dose administration in human subjects and obtained one-month clinical observations. This development is part of the phased strategy for the PB-2309 triple receptor (GLP-1/GIP/GCG) agonist program.

CR059 employs a lipid nanoparticle delivery system to provide long-acting metabolic intervention through sustained in vivo expression of GLP-1 receptor agonists. Preclinical studies in db/db mice showed superior metabolic intervention compared to semaglutide with a clear dose-response trend. In a spontaneous type 2 diabetes model of rhesus monkeys, monthly subcutaneous injections significantly improved fasting plasma glucose and reduced glycated hemoglobin levels, with continued improvement observed until Day 88. A single subcutaneous injection in healthy rhesus monkeys also supported low-frequency administration by achieving a weight loss of approximately 11.8% after five weeks.

The ongoing first-in-human study in type 2 diabetes mellitus aims to evaluate the safety, tolerability, and pharmacokinetic/pharmacodynamic profiles of CR059. Four weeks after a single administration, glycated hemoglobin and fasting blood glucose continued to improve. Continuous glucose monitoring data demonstrated an increased time in target range (4-10 mmol/L) and a notable decrease in mean blood glucose. These findings suggest a sustained metabolic improvement trend.

PegBio’s circular RNA platform optimizes the codon structure design and uses high-expression IRES elements for stable protein translation without a 5′cap or poly(A) tail, potentially supporting a long-term, low-frequency treatment model for chronic metabolic disorders. Nonetheless, there is no guarantee of ultimate successful development or marketing of CR059, and caution is advised when dealing in the company’s securities.