Terns Pharmaceuticals Reports Positive Phase 1 Results for TERN-601 Oral Obesity Treatment

Terns Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company, has announced promising top-line data from its Phase 1 clinical trial of TERN-601. The trial aimed to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of TERN-601, a small-molecule GLP-1R agonist, in healthy adults with obesity or overweight.

The study was structured as a randomized, double-blind, placebo-controlled trial, and included single and multiple-ascending dose evaluations. Results indicated that TERN-601 was well tolerated across all tested doses, with a statistically significant mean weight loss compared to placebo. In particular, the 28-day multiple-ascending dose study showed a maximum placebo-adjusted mean weight loss of 4.9% at the highest dose of 740 mg QD, with 67% of participants losing 5% or more of their baseline body weight.

CEO Amy Burroughs highlighted TERN-601’s potential to become a leading GLP-1R agonist due to its favorable efficacy, tolerability, and manufacturing scalability. She emphasized the drug’s promise as a treatment for obesity, either as a standalone therapy or in combination with other agents like TERN-501 or a GIPR modulator from the TERN-800 series. The company plans to advance TERN-601 into Phase 2 clinical trials in 2025.

Chief Medical Officer Emil Kuriakose also noted the significant GLP-1R agonism demonstrated by TERN-601. The drug’s properties allowed for sustained target engagement with once-daily dosing, even at high doses. He confirmed that the company has identified an optimal range of clinically active and well-tolerated doses for future studies, eliminating the need for further dose range exploration.

No treatment-related dose interruptions, reductions, or discontinuations were observed, even with rapid dose titration. Over 95% of treatment-emergent adverse events were mild, and all gastrointestinal events were mild to moderate, consistent with the GLP-1R agonist class. There were no significant changes in liver enzymes, vital signs, or electrocardiograms.

The unique properties of TERN-601 may offer advantages for oral GLP-1R agonists. Its low solubility and high gut permeability could result in prolonged absorption and sustained target coverage, contributing to a flat pharmacokinetic curve. Additionally, high drug levels in the gut wall may activate GLP-1 receptors, triggering satiety centers in the brain. The drug also has a low free fraction in circulation, which, combined with the flat PK curve, may enhance its tolerability at high doses.

Terns Pharmaceuticals plans to present the data from this clinical trial at an upcoming scientific conference. The Phase 1 trial consisted of two parts: a single ascending dose study (Part 1) and a multiple-ascending dose study (Part 2). Part 1 evaluated five dose levels of TERN-601 in healthy participants with a BMI of ≥ 25 kg/m² and < 40 kg/m², starting at 30 mg. Part 2 included obese and overweight healthy adults with a BMI of ≥ 27 kg/m² to < 40 kg/m², who received TERN-601 for 28 days at doses determined based on Part 1 data.

The primary goal of the trial was to evaluate the safety and tolerability of TERN-601 administered once-daily for 28 days. Secondary endpoints included pharmacokinetic parameters and efficacy, assessed by body weight loss after 28 days of treatment.

TERN-601 is a novel, orally administered GLP-1R agonist developed by Terns Pharmaceuticals for the treatment of obesity. The drug was discovered through the company’s proprietary three-dimensional QSAR model of the receptor, optimizing ligands for in vitro activity, metabolic stability, and pharmacokinetic properties. As a result, TERN-601 emerged as a potent GLP-1R agonist with a bias towards cAMP generation.

How to obtain the latest research advancements in the field of biopharmaceuticals?

In the Synapse database, you can keep abreast of the latest research and development advances in drugs, targets, indications, organizations, etc., anywhere and anytime, on a daily or weekly basis. Click on the image below to embark on a brand new journey of drug discovery!