Apelin receptor agonism shows promise in boosting metabolic health and offering cardiac benefits, with added advantages when used alongside incretin therapy.
Data supports development of next-generation APJ agonists for obesity and related health problems.
EMERYVILLE, Calif. – June 21, 2025 – BioAge Labs (BIOA), a clinical-stage biotech company, today unveiled compelling preclinical data highlighting the potential of apelin receptor (APJ) activation. The research signals a possible breakthrough in treating diabetic obesity and heart failure with preserved ejection fraction (HFpEF). The findings were presented at the American Diabetes Association’s 85th Scientific Sessions in Chicago, Illinois, held from June 20-23, 2025.
“Our preclinical work demonstrates that APJ activation can deliver significant benefits in models of diabetic obesity and heart failure while enhancing the effects of incretin therapy,” stated Dr. Kristen Fortney, BioAge’s CEO and co-founder. “We’re actively working on next-generation APJ agonists to turn this promising science into new therapies for obesity and its major complications.”
APJ is activated by apelin, an “exerkine” released during exercise. In preclinical studies, apelin mimics many of the positive effects of physical activity. BioAge’s discovery platform identified apelin signaling as a key therapeutic target. Analysis of human aging data revealed that higher apelin levels are linked to improved physical function and longevity. The company’s research in preclinical obesity trials shows that APJ agonism can nearly double the weight loss seen with GLP-1 receptor agonists while also restoring body composition and muscle function. This suggests that APJ agonists could serve as exercise mimetics, potentially boosting the efficacy of incretin therapies.
BioAge is pursuing multiple APJ agonist approaches, including oral small-molecule and long-acting injectable formulations, with an Investigational New Drug (IND) filing expected in 2026.
At the conference, Dr. Paul Rubin, BioAge’s CMO and EVP of Research, and scientist Dr. Shijun Yan, will unveil data from their research, demonstrating that in preclinical models of diabetic obesity and HFpEF, APJ agonist treatment showed potential as a standalone therapy and even greater benefit when combined with incretin treatments.
- Enhanced Glycemic Control in Diabetic Obesity – Dr. Rubin’s presentation reveals that in mouse models, APJ agonist monotherapy reduced HbA1c levels— a key marker of blood sugar control— to those seen in lean, healthy mice. It also improved glucose tolerance by 25%. When combined with an incretin, APJ agonism further improved glycemic control compared to the incretin alone. Currently, less than half of type 2 diabetes patients achieve optimal glycemic control with existing incretin therapies.
- Cardioprotective Effects in HFpEF – Dr. Yan’s poster will showcase that in a mouse model of obesity-related heart failure, APJ agonist monotherapy reduced cardiac hypertrophy and suppressed markers of cardiac injury. Combining APJ agonism with an incretin provided enhanced cardioprotective benefits and led to greater weight loss than either therapy alone. Over half of heart failure patients have preserved ejection fraction, and around two-thirds of these patients are also battling obesity. Existing treatment options for obesity-associated HFpEF remain limited.
Oral Presentation: Saturday June 21, 2025, 5:00 PM – 5:15 PM CDT
Title: An Oral Apelin Receptor Agonist Enhances Glycemic Control in Preclinical Models of Diabetic Obesity Both as Monotherapy and in Combination with Tirzepatide
Session: Early Phase, Post Hoc, and Subgroup Analyses from Clinical Trials Testing Incretin-Based Therapies—Take 1; W181 A-C
Presenter: Paul Rubin, MD, Chief Medical Officer and EVP-Research
Poster Presentation: Sunday Jun 22, 2025, 12:30 PM – 1:30 PM CDT
Title: The Apelin Receptor Agonist Azelaprag Shows Cardioprotective Effects as Monotherapy and Enhanced Benefits with Semaglutide in a Diet-Induced Obesity Model of Heart Failure with Preserved Ejection Fraction
Session: Poster Hall F1, Board No. 866
Presenter: Shijun Yan, PhD, MBA, Senior Scientist, In Vivo Biology
Visual materials from the presentations can be accessed on the BioAge investor relations website concurrently with the start of each session.
About BioAge Labs, Inc.
BioAge is a clinical-stage biotech company focused on developing potential treatments for metabolic diseases by targeting the underlying mechanisms of human aging. The company’s lead product candidate, BGE-102, is a potent, orally available, brain-penetrant small-molecule NLRP3 inhibitor being developed for obesity. In preclinical studies, BGE-102 has shown significant weight loss, both as a standalone treatment and in combination with GLP-1 receptor agonists. An IND submission and initiation of a Phase 1 SAD/MAD trial are scheduled for mid-2025, and initial data from the SAD trial is anticipated by the end of the year. BioAge is also developing long-acting injectable and oral small molecule APJ agonists for obesity. Further preclinical programs leverage insights from the company’s proprietary discovery platform, which has been built on human longevity data, and address key pathways involved in metabolic aging.
Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include but are not limited to the company’s plans to develop and commercialize its product candidates, BGE-102 and its APJ program, the timing and results of clinical trials, and the potential ability of these candidates to treat disease. These forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially from those projected, including risks related to the development and regulatory approval of the company’s product candidates.
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