PTG-100, a potential first-in-class oral peptide antagonist of α4β7 integrin, is being developed for the treatment of patients with ulcerative colitis and Crohn’s disease. Protagonist’s oral peptide technology platform was utilized to discover PTG-100 as a potent, selective, and orally stable peptide that alters trafficking of gut homing T cells in animal models of colitis. Target engagement was assessed in the peripheral blood of colitis and healthy mice, and translated to the demonstration of pharmacodynamic proof-of-concept in a Phase 1 trial with normal healthy volunteers. We initiated a Phase 2b clinical trial in patients with active ulcerative colitis. The discovery process and Phase 1 clinical results of PTG-100 will be discussed.