Developmentof Petrelintide: a Potent, Stable, Long-ActingHuman Amylin Analogue

Abstract The past few years have seen the approval of several medications for weight management, but there is an increasing need for new therapies that target different pathways of energy balance. Owing to its role as a physiological satiety signal released after nutrient intake, amylin is an attractive pharmacological target for weight management in individuals living with obesity. Furthermore, combinations of peptide drugs for weight management may be more effective than individual peptide drugs. Thus, there is a need for peptide drugs that potentially also can be used as combination therapies, to enable coformulation with currently marketed drugs. Herein, we report the development of petrelintide, a potent, stable, long-acting analogue of human amylin that can be formulated at about neutral pH. This was enabled through optimization of chemical stability while retaining in vitro and in vivo potency. Petrelintide is in clinical development as a potential treatment for weight management.