TB-222-023

TB-222-023 is a potent, long-acting monoclonal antibody antagonist of the glucagon-like peptide 1 receptor (GLP-1R). Developed by Twist Bioscience in collaboration with the Children's Hospital of Philadelphia (CHOP) and the University of Pennsylvania, it is designed for the treatment of congenital hyperinsulinism (CHI), a rare genetic disorder characterized by excessive insulin secretion and severe hypoglycemia. TB-222-023 was optimized from an earlier candidate, TB-001-003, using Twist's synthetic antibody library and optimization technology. It demonstrates significantly higher potency and a longer half-life compared to the peptide antagonist exendin-(9-39) (avexitide). By blocking GLP-1R on pancreatic beta cells, TB-222-023 reduces insulin secretion, thereby increasing blood glucose levels and preventing hypoglycemia-induced brain damage.