Terns Pharma Presents TERN-501 Preclinical Data with GLP-1R Agonist for Obesity at ADA's 84th Sessions and Upcoming Conferences

Terns Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company, has revealed preclinical data indicating that TERN-501, a highly selective thyroid hormone receptor beta (THR-β) agonist, can significantly improve the efficacy of GLP-1 receptor agonists in combating obesity. This data will be featured at the American Diabetes Association's (ADA) 84th Scientific Sessions in Orlando, Florida, between June 21 and 24, 2024.

Emil Kuriakose, M.D., Chief Medical Officer at Terns, explained that while GLP-1 receptor agonists aid in weight reduction by decreasing food intake, their effectiveness can be limited by metabolic adaptation. This adaptation is a compensatory process where the body reduces energy expenditure in response to weight loss. THR-β agonists like TERN-501 work through a different mechanism, which helps normalize energy expenditure, thereby enhancing the weight loss effects of GLP-1 therapies. This approach not only promotes greater weight loss but also preserves relative lean mass. Dr. Kuriakose emphasized that TERN-501 could provide broader metabolic benefits, making it an ideal partner for both injectable and oral GLP-1 agonists used in treating obesity and other metabolic disorders.

In the preclinical study, obese mice subjected to a high-fat diet for 24 weeks were treated daily for six weeks with either a vehicle, TERN-501, semaglutide, a combination of TERN-501 and semaglutide, or tirzepatide. The results demonstrated that the TERN-501 and semaglutide combination significantly outperformed semaglutide alone in promoting weight loss. Moreover, this combination led to a higher proportion of fat mass loss relative to lean mass, suggesting an improvement in the quality of weight loss.

The study also examined the impact of metabolic adaptation, which typically limits the extent and sustainability of weight loss by decreasing energy expenditure. Mice treated with semaglutide and tirzepatide exhibited significant weight loss correlated with reduced energy expenditure. However, when TERN-501 was added to semaglutide, it prevented the reduction in energy expenditure typically induced by weight loss. Additionally, there was an increase in the thermogenesis marker UCP-1 in subcutaneous adipose tissue, indicating enhanced metabolic activity. Thus, TERN-501 appears to counteract metabolic adaptation and normalize energy expenditure, potentially amplifying the weight loss effects of GLP-1 therapies.

Terns Pharmaceuticals also announced its participation in a fireside chat at the Piper Sandler Virtual Obesity Day on June 26, 2024. The event will provide further insights and discussions on the burgeoning field of obesity treatments.

TERN-501 is characterized by high metabolic stability, increased liver distribution, and greater selectivity for THR-β compared to other THR-β agonists in development. Positive results from the Phase 2a DUET trial in August 2023 indicated significant MRI-PDFF reductions and a best-in-class safety and tolerability profile for TERN-501 in treating MASH. Although Terns has deprioritized MASH development due to current regulatory and clinical development requirements, the company continues to explore opportunities for TERN-501 in other metabolic diseases, particularly in combination regimens for obesity.

Terns Pharmaceuticals, Inc. is dedicated to developing small molecule product candidates to address severe conditions such as oncology and obesity. The company's pipeline includes three clinical-stage development programs: an allosteric BCR-ABL inhibitor, a small molecule GLP-1 receptor agonist, and a THR-β agonist. They are also working on a preclinical GIPR modulator.

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