GLP-1R, GIPR, GCGR Program

Incretin Programs – Oral Small Molecule Single- and Multi-Incretin Receptor Agonists for Metabolic Disorders Including Obesity and T2D

Obesity and diabetes are two of the most prevalent diseases in the world, affecting a combined total of more than 800 million people, and are associated with severe health complications, including cardiovascular disease and kidney failure, as well as an increased risk of death. Weight reduction is seen as an important treatment goal for patients with either condition. In recent years, several injectable peptide agonists targeting select metabolic hormone receptors, or incretin receptors, have been approved for the treatment of T2D and obesity.

Three incretins play significant roles in glucose metabolism and homeostasis: glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon. Approved injectable incretin peptide therapies have demonstrated substantial and sustained reductions in body weight, as well as the ability to improve blood glucose control. Despite these advancements in the treatment of obesity and T2D, a number of key limitations remain for the incretin therapeutic class, including tolerability, prolonged titration schemes, injection administration, and supply challenges.

Based on unique chemical and structural insights obtained with our Native Complex Platform^TM, we believe we have an opportunity to discover and develop novel, next-generation, oral small molecules as selective single- or multi-acting GLP-1, GIP, glucagon receptor agonists.