PN-477

PN-477 is a novel triple agonist peptide engineered to activate the glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon receptor (GCGR). The compound is being developed by Protagonist Therapeutics as both a once-daily oral formulation (PN-477o) and a once-weekly subcutaneous injection (PN-477sc) for the treatment of obesity. It is designed to maximize total body weight loss, improve gastrointestinal tolerability, and enhance the fat to lean mass ratio. Preclinical studies have demonstrated strong activation of all three targeted receptors in vitro, along with robust efficacy in multiple animal models of obesity and glycemic control. IND-enabling studies are underway, with Phase 1 clinical trials expected to start in the second quarter of 2026[1][2][4][5][7][8][9].