MBX-2982

About MBX-2982 for Hypoglycemia

MBX-2982, a potent, selective, orally-active G protein-coupled receptor 119 (GPR119) agonist, is being evaluated in a Phase 2 clinical trial for the prevention of hypoglycemia in patients with type 1 diabetes (T1D). GPR119 is a receptor that interacts with bioactive lipids known to stimulate glucose-dependent insulin secretion, and emerging science supports its role in glucagon regulation. Glucagon is a hormone secreted by the pancreas that naturally reverses hypoglycemia by signaling the body to release stored glucose. Glucagon secretion is dysregulated in individuals with diabetes and can result in hypoglycemia.

In patients with diabetes, hypoglycemia is a significant limiting factor in achieving the desired glucose control and is the cause of significant morbidity. If left uncorrected, hypoglycemia can lead to unconsciousness or death. Preventing episodes of hypoglycemia in people with diabetes is an unmet medical need. According to the 2016 global HAT study of 27,000 people, 4 out of 5 individuals with T1D reported hypoglycemia, with a rate of severe hypoglycemia (requiring assistance of another person) of approximately five events per patient-year. It is estimated that 3 million individuals in the United States and EU are at risk for T1D-associated hypoglycemia. Today there are no therapies approved for the prevention of hypoglycemia in patients with T1D, and affected individuals must rely on rescue therapy to correct hypoglycemia once it has occurred.

Preclinical data indicate that MBX-2982 functions through a unique dual mechanism of action that acts directly on the beta cell to increase insulin secretion and stimulates release of the incretin GLP-1 from the gut. In recent preclinical studies, GPR119 agonists were shown to enhance glucagon secretion in response to low glucose levels and were able to prevent hypoglycemia in animal models and human islet cells.1 Additionally, data from clinical studies of MBX-2982 as a potential treatment for type 2 diabetes demonstrated that MBX-2982 treatment was generally safe and well tolerated.

MBX-2982 Development Status

The AdventHealth Translational Research Institute (TRI) in Orlando, FL is leading a Phase 2a proof-of-pharmacology study to determine whether MBX-2982 can enhance glucagon secretion during insulin-induced hypoglycemia in subjects with T1D (NCT04432090). The study is funded by The Leona M. and Harry B. Helmsley Charitable Trust. We expect to report data from this study in 2023.

1. Li NX, et al. Diabetes. 2018;67:1401-1413

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