TERN-501 significantly improved the efficacy of a GLP-1 receptor agonist by normalizing energy expenditure, resulting in greater weight loss, increased fat mass loss and relative preservation of lean mass
FOSTER CITY, Calif., June 21, 2024 (GLOBE NEWSWIRE) -- Terns Pharmaceuticals, Inc. (Terns or the Company) (Nasdaq: TERN), a clinical-stage biopharmaceutical company developing a portfolio of small-molecule product candidates to address serious diseases, including oncology and obesity, today announced that preclinical data supporting TERN-501, a highly selective thyroid hormone receptor beta (THR-β) receptor agonist, in combination with a GLP-1 receptor agonist for obesity will be highlighted in a poster presentation at the American Diabetes Association (ADA) 84th Scientific Sessions, taking place June 21 “ 24, 2024 in Orlando, FL.
While GLP-1 receptor agonists facilitate weight loss by suppressing food intake, efficacy may be limited by metabolic adaptation, a counter regulatory process that lowers energy expenditure in response to weight loss. THR-β agonism, an orthogonal mechanism to GLP-1, appears to unlock additional efficacy of GLP-1 therapies by normalizing energy expenditure during weight loss, while preserving relative lean mass, said Emil Kuriakose, M.D., chief medical officer at Terns. These exciting results suggest that TERN-501 may be an ideal combination partner for injectable and oral GLP-1 agonists for use in obesity and other metabolic disorders by potentially offering broader metabolic benefits beyond additional weight loss.
The poster and viewing detail are listed below:
| Presentation | TERN-501 Enhances Weight Loss Efficacy of a GLP-1R Agonist in Obese Mice via Increased Fat Mass Loss without Additional Loss of Lean Mass | |
| Abstract Number: | 760 | |
| Presentation Date and Time: | Sunday, June 23, 2024 from 12:30 p.m. “ 1:30 p.m. ET | |
| Session: | Clinical Therapeutics”Incretin-Based Therapies | |
| Presenter: | Christopher Jones |
The presentation reports results from a preclinical study in mice fed a high fat diet for 24 weeks prior to study start. Obese mice were treated once daily with vehicle, TERN-501, semaglutide, TERN-501+semaglutide, or tirzepatide for six weeks. The combination of TERN-501+ semaglutide significantly enhanced weight loss compared to semaglutide alone. Additionally, the TERN-501+semaglutide combination showed proportionally greater loss of fat mass relative to lean mass compared to semaglutide alone, indicating improved quality of weight loss.
The study also explored metabolic adaptation, a counter regulatory process that decreases energy expenditure and limits the magnitude and sustainability of weight loss. Mice treated with semaglutide and tirzepatide showed significant weight loss that was associated with decreases in energy expenditure. When TERN-501 was combined with semaglutide, weight loss-induced lowering of energy expenditure was prevented and increases in the thermogenesis marker, UCP-1, were observed in subcutaneous adipose tissue. TERN-501 has potential to attenuate metabolic adaptation and normalize energy expenditure, which may enhance the weight loss efficacy of GLP-1 therapies.
The full poster is available on Terns' scientific publications website.
In addition, Terns announced that management will participate in a fireside chat at the Piper Sandler Virtual Obesity Day on June 26, 2024 at 12:30pm ET. The Piper Sandler event webcast link is available from Piper Sandler and will require registration.
About TERN-501
TERN-501 is a THR-β agonist with high metabolic stability, enhanced liver distribution and greater selectivity for THR-β compared to other THR-β agonists in development. The Phase 2a DUET trial (NCT05415722) produced positive top-line data in August 2023; showing compelling MRI-PDFF reductions and best-in-class safety and tolerability profile with TERN-501 in MASH. Terns has deprioritized development for MASH given the current regulatory and clinical development requirements for the indication. Terns continues to evaluate opportunities for TERN-501, including in other metabolic diseases, with a focus towards combination regimens for obesity.
About Terns Pharmaceuticals
Terns Pharmaceuticals, Inc. is a clinical stage biopharmaceutical company developing a portfolio of small molecule product candidates to address serious diseases, including oncology and obesity. Terns' pipeline contains 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 discovery effort, prioritizing a GIPR antagonist nomination candidate. For more information, please visit: www.ternspharma.com.
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