Terns Pharmaceuticals, Inc. announced that the first participant has been dosed in the Phase 1 clinical trial of TERN-601, the Company?s oral small-molecule glucagon-like peptide-1 receptor, or GLP-1R, agonist for the treatment of obesity. Phase 1 Trial Design: The Phase 1 trial is a randomized, double-blind, placebo-controlled single and multiple-ascending dose (SAD and MAD) trial to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of TERN-601 in healthy adults with obesity or overweight. The trial will consist of two parts.

Part 1 (SAD) is a single ascending dose study that will evaluate up to six once-daily TERN-601 dose levels in approximately 40 healthy participants with a Body Mass Index (BMI) of = 25 kg/m2 and < 40 kg/m2. The starting TERN-601 dose is 30 mg, with subsequent dose levels based on review of emerging safety and PK data from prior cohorts. In Part 2 (MAD) of the trial, obese and overweight healthy adults will be enrolled in cohorts that will include titration of TERN-601 administered for 28-days at doses to be selected based on data from Part 1 (SAD).

Part 2 will include approximately 72 healthy participants with a BMI of = 27 kg/m2 to < 40 kg/m2. The primary endpoint of the trial is safety and tolerability. Secondary endpoints include PK, efficacy as measured by body weight loss following 28-days of treatment with TERN-601, and other exploratory markers.

Top-line, proof of concept 28-day weight loss data from Part 2 (MAD) are expected in the second half of 2024. About TERN-601: TERN-601 is an oral, small-molecule glucagon-like peptide-1 receptor, or GLP-1R, agonist program for obesity. Obesity is a chronic disease that is increasing in prevalence in adults, adolescents and children and is often defined by having an elevated BMI of 30 or greater.

GLP-1 agonism offers multiple benefits including improved glucose control, slowing of gastric emptying and increases in satiety. Terns? lead GLP-1R agonist, TERN-601, was designed through internal structure-based drug discovery efforts employing proprietary three-dimensional QSAR model of the receptor, which was used to identify new GLP-1R agonist candidates.

The ligands were further optimized based on in vitro activity, metabolic stability, and pharmacokinetic parameters. Through this process, company discovered TERN-601, a potent GLP-1R agonist biased towards cAMP generation. A Phase 1, first-in-human clinical trial for obesity is underway with top-line data expected in the second half of 2024.

TERN-601?s potential as a treatment for obesity is supported by preclinical data that were presented at the American Diabetes Association?s 83rd Annual Scientific Session in June 2023.