No Effect of Food or Proton Pump Inhibitor on the Pharmacokinetics of TERN-601, an Oral Small Molecule GLP-1 Receptor Agonist

Introduction and Objective: TERN-601 is a novel once-daily oral small molecule GLP-1 receptor agonist, in development for chronic weight management. This Phase 1 study was conducted to evaluate the effect of food and a proton pump inhibitor (PPI) on the pharmacokinetics (PK) of TERN-601. Methods: In Period 1, healthy participants (N=10) were randomized 1:1 to receive two single doses of TERN-601 (500 mg): in the fed (high-fat/calorie) or fasted state on Day 1, then in the opposite prandial state on Day 4. In Period 2, all received rabeprazole (20 mg QD) (PPI) on Days 1-4, then TERN-601 and rabeprazole on Day 5. PK samples were collected up to 48 hours after each TERN-601 dose. Safety assessments were performed throughout the study. Results: All participants completed the study without adverse events or clinically meaningful changes in vital signs, ECGs, or laboratory values. No change in t1/2 or Tmax. AUCinf increased 18% in the fed state and decreased 11% with a PPI compared to TERN-601 alone, fasted. TERN-601 Cmax decreased 18% in the fed state compared to the fasted state; no change when administered with a PPI. Conclusion: TERN-601 appeared safe and well-tolerated. Neither food nor a PPI had clinically meaningful effects on the PK of TERN-601, supporting the administration of TERN-601 without restriction of food or acid reducing agents. Disclosure: C.H. Nelson: Employee; TERNS Pharmaceuticals. Stock/Shareholder; TERNS Pharmaceuticals, Gilead Sciences, Inc. C. Jones: Employee; TERNS Pharmaceuticals. E. Kwan: Employee; TERNS Pharmaceuticals. E.N. Castelloe: Consultant; TERNS Pharmaceuticals, Ascendis Pharma A/S, Artelo Biosciences, Dianthus Therapeutics, Soleno Therapeutics, Plexium, Sustained Therapeutics, Virogenics, Nobias Therapeutics. T. Marmon: None. E.T. Kuriakose: Employee; TERNS Pharmaceuticals.