Terns Pharmaceuticals has 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 (GLP-1R) agonist for the treatment of obesity.
The Phase 1 trial is a randomised, 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 BMI≥25 kg/m2 and <40kg/m2. The starting TERN-601 dose is 30mg, with subsequent dose levels based on review of emerging safety and PK data from prior cohorts.
In Part 2 (MAD) of the trial, healthy adults with obesity and overweight 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≥27kg/m2 to <40kg/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.
“TERN-601 represents our first internally discovered small molecule GLP-1R agonist, which is designed to be administered orally once daily with a competitive profile for weight loss, both as a monotherapy and as part of a potential all oral combination treatment for obesity,” said Dr Erin Quirk, president and head of research and development at Terns. “We are encouraged by the prospects for our obesity franchise and look forward to reporting initial 28-day weight loss proof of concept data from the Phase 1 trial of TERN-601, which is anticipated in the second half of 2024. We also have ongoing discovery efforts in obesity with our TERN-600 series of additional small molecule GLP-1R agonists and our TERN-800 series of small-molecule glucose-dependent insulinotropic polypeptide receptor (GIPR) modulators, which have the potential to be combined with GLP-1R agonists. These programs along with TERN-501, our highly selective THR-β agonist in development for the treatment of NASH, aim to meaningfully improve clinical outcomes for patients battling metabolic diseases, with better potential tolerability, accessibility and ease-of-use than currently available treatments.”