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Terns Pharmaceuticals announced new preclinical data supporting their compound TERN-501 in combination with a GLP-1 receptor agonist for treating obesity. The data was presented at the ADA’s 84th Annual Scientific Sessions. TERN-501, a highly selective THR-β receptor agonist, was shown to enhance weight loss efficacy when used with a GLP-1 receptor agonist, specifically semaglutide, in obese mice. This combination resulted in increased fat mass loss and preserved lean mass, potentially overcoming metabolic adaptation that limits the effectiveness of GLP-1 therapies alone. The results suggest TERN-501 could be a promising adjunct to GLP-1 therapies for obesity and other metabolic disorders. Additionally, Terns will participate in the Piper Sandler Virtual Obesity Day on June 26, 2024.
Positive
- TERN-501 combined with semaglutide showed significantly enhanced weight loss in preclinical studies.
- Combination treatment resulted in greater fat mass loss while preserving lean mass, indicating improved quality of weight loss.
- TERN-501 potentially overcomes metabolic adaptation, enhancing GLP-1 therapy efficacy.
- Increases in thermogenesis marker UCP-1 were observed, suggesting improved metabolic outcomes.
The preclinical data on TERN-501 combined with a GLP-1 receptor agonist, such as semaglutide, shows promise in obesity treatment. The combination led to significantly greater weight loss, increased fat mass reduction and preservation of lean mass compared to semaglutide alone. This points to a potential breakthrough in managing metabolic adaptation, a key challenge in obesity therapies. Metabolic adaptation refers to the body’s counter-regulatory mechanisms that reduce energy expenditure during weight loss, making sustained weight loss difficult. By preventing this reduction through TERN-501’s action, the combination could offer a more effective and sustained weight loss solution. If these preclinical findings translate into clinical success, TERN-501 could become a valuable adjunct to GLP-1 therapies, potentially transforming the obesity treatment landscape.
This development could significantly impact the market for obesity treatments. GLP-1 receptor agonists, like semaglutide, are already well-established in the market and their combination with TERN-501 might enhance their efficacy, making the treatment more attractive to healthcare providers and patients. The obesity market is substantial, with a rising prevalence of the condition worldwide. Introducing a combination therapy that offers improved weight loss and lean mass preservation can lead to a larger market share for Terns Pharmaceuticals. Moreover, this improvement could position Terns as a key player in the obesity treatment market, potentially driving up their stock value significantly.
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 Title: | 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.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements about the Company within the meaning of the federal securities laws, including those related to expectations, timing and potential results of the clinical trials and other development activities of the Company and its partners; the potential indications to be targeted by the Company with its small molecule product candidates; the therapeutic potential of the Company’s small molecule product candidates, including when used in combination with another product or product candidate; the potential for the mechanisms of action of the Company’s product candidates to be therapeutic targets for their targeted indications; the potential utility and progress of the Company’s product candidates in their targeted indications, including the clinical utility of the data from and the endpoints used in the Company’s clinical trials; the Company’s clinical development plans and activities, the Company’s expectations regarding the profile of its product candidates, including efficacy, tolerability, safety, metabolic stability and pharmacokinetic profile and potential differentiation as compared to other products or product candidates; and the Company’s plans for and ability to continue to execute on its current development strategy, including potential combinations involving multiple product candidates. All statements other than statements of historical facts contained in this press release, including statements regarding the Company’s strategy, future financial condition, future operations, future trial results, projected costs, prospects, plans, objectives of management and expected market growth, are forward-looking statements. In some cases, you can identify forward-looking statements by terminology such as “aim,” “anticipate,” “assume,” “believe,” “contemplate,” “continue,” “could,” “design,” “due,” “estimate,” “expect,” “goal,” “intend,” “may,” “objective,” “plan,” “positioned,” “potential,” “predict,” “seek,” “should,” “target,” “will,” “would” and other similar expressions that are predictions of or indicate future events and future trends, or the negative of these terms or other comparable terminology. The Company has based these forward-looking statements largely on its current expectations, estimates, forecasts and projections about future events and financial trends that it believes may affect its financial condition, results of operations, business strategy and financial needs. In light of the significant uncertainties in these forward-looking statements, you should not rely upon forward-looking statements as predictions of future events. These statements are subject to risks and uncertainties that could cause the actual results and the implementation of the Company’s plans to vary materially, including the risks associated with the initiation, cost, timing, progress, results and utility of the Company’s current and future research and development activities and preclinical studies and clinical trials. These risks are not exhaustive. For a detailed discussion of the risk factors that could affect the Company’s actual results, please refer to the risk factors identified in the Company’s SEC reports, including but not limited to its Annual Report on Form 10-K for the year ended December 31, 2023. Except as required by law, the Company undertakes no obligation to update publicly any forward-looking statements for any reason.
Contacts for Terns
Investors
Justin Ng
investors@ternspharma.com
Media
Jenna Urban
Berry & Company Public Relations
media@ternspharma.com
FAQ
What is TERN-501?
TERN-501 is a highly selective thyroid hormone receptor beta (THR-β) receptor agonist developed by Terns Pharmaceuticals.
What are the benefits of combining TERN-501 with a GLP-1 receptor agonist?
Combining TERN-501 with a GLP-1 receptor agonist enhances weight loss efficacy, increases fat mass loss, preserves lean mass, and potentially overcomes metabolic adaptation.
When and where was the new data on TERN-501 presented?
The new preclinical data on TERN-501 was presented at the American Diabetes Association’s 84th Annual Scientific Sessions from June 21-24, 2024, in Orlando, FL.
What were the key findings of the TERN-501 preclinical study?
The study found that TERN-501 significantly enhanced weight loss when combined with semaglutide, increased fat mass loss, preserved lean mass, and improved metabolic outcomes.
When will Terns Pharmaceuticals participate in the Piper Sandler Virtual Obesity Day?
Terns Pharmaceuticals will participate in the Piper Sandler Virtual Obesity Day on June 26, 2024.
