Terns Pharmaceuticals Announces First Participant Dosed in Phase 1 Clinical Trial of Oral GLP-1 Receptor Agonist for Obesity Treatment

Terns Pharmaceuticals, Inc. recently announced 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.

“We are excited to initiate this first-in-human study of our oral GLP-1R agonist, TERN-601, as we believe it represents a potentially meaningful alternative to the currently marketed injectable GLP-1R agonist treatments,” said Erin Quirk, MD, President and Head of Research and Development at Terns. “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. 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.”

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.

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 our 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, we 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 83^rd Annual Scientific Session in June 2023. The full poster is available on Terns’ scientific publications website.

Terns Pharmaceuticals, Inc. is a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology, obesity and NASH. Terns’ pipeline includes three clinical stage development programs including an allosteric BCR-ABL inhibitor, a small-molecule GLP-1 receptor agonist, a THR-β agonist and a preclinical GIPR modulator program. For more information, visit www.ternspharma.com.