1. Lexicon announces preclinical data supporting ACSL5 as an obesity therapy target. 2. LX9851 shows potential as a first-in-class treatment for obesity management. 3. Exclusive licensing agreement with Novo Nordisk strengthens LX9851's market position. 4. Knockout mice exhibited reduced body fat and improved metabolic characteristics. 5. Lexicon aims to innovate obesity treatment beyond incretin-based therapies.
FAQ
Why Bullish?
The validation of ACSL5 opens market opportunities for LX9851, potentially increasing investor confidence.
How important is it?
The article showcases significant advancements in LX9851's efficacy and market strategy, influencing LXRX's market perception.
Why Long Term?
Successful clinical advancement and commercialization may take time, akin to similar biopharmaceutical product launches.
Lexicon Pharmaceuticals Publishes Groundbreaking Preclinical Data on ACSL5 in Obesity Treatment
THE WOODLANDS, Texas, Dec. 10, 2025 – Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) announced the publication of new preclinical data confirming Acyl-CoA Synthetase 5 (ACSL5) as a promising target for obesity and weight management. The study, featured in the Journal of the Endocrine Society, outlines how ACSL5 plays a critical role in lipid metabolism and underscores the potential of Lexicon's investigational drug, LX9851.
Key Findings on ACSL5 and LX9851
The publication titled “Acyl-CoA Synthetase 5 knockout and inhibitors protect against diet-induced obesity in mice by activating the ileal brake” details significant findings from animal studies. Mice genetically modified to lack the ACSL5 gene exhibited several metabolic advantages, including:
- Reduced body fat and triglycerides
- Lower total cholesterol and blood glucose levels
- Preservation of lean body mass
In addition, these knockout mice demonstrated a decrease in body weight when on a high-fat diet, which provides a strong scientific rationale for targeting ACSL5 with the oral small molecule drug, LX9851.
Partnership with Novo Nordisk and Future Implications
In March 2025, Lexicon established a worldwide licensing agreement for LX9851 with Novo Nordisk, further emphasizing the strategic importance of this therapy in the evolving obesity treatment landscape. According to Dr. Craig Granowitz, Lexicon’s senior vice president and chief medical officer:
“These preclinical findings validate our strategy of targeting ACSL5 for the development of new therapeutic options for people in need of obesity and weight management treatment and support the clinical advancement of LX9851.”
Dr. Granowitz also noted the potential of LX9851 to complement existing incretin-based therapies, enhancing its position in the market.
Mechanistic Insights from Preclinical Research
Lexicon’s research team observed that the activation of the ileal brake mechanism was responsible for the observed metabolic benefits in ACSL5 knockout mice. This mechanism delays gastric emptying, resulting in decreased food intake. The research also demonstrated that potent, small molecule ACSL5 inhibitors contributed similarly in mice with obesity induced by diet.
Overview of LX9851 and Its Potential
LX9851 is distinguished as a first-in-class, non-incretin, oral small molecule inhibitor specifically targeting ACSL5. This innovative approach is anticipated to treat not only obesity but also related cardiometabolic disorders. Lexicon's investigations have included studies on LX9851 both as a monotherapy and in combination with GLP-1 agonists like semaglutide.
About Lexicon Pharmaceuticals
Lexicon Pharmaceuticals is dedicated to pioneering therapeutics that can transform the lives of patients. Through the Genome5000™ program, Lexicon has engaged in extensive genetic target discovery, identifying over 100 protein targets with significant healing potential across various diseases. With multiple medicines already in market and a promising pipeline spanning conditions like heart failure, obesity, and diabetes, Lexicon is committed to advancing science and improving patient outcomes.
Safe Harbor Statement
This release contains forward-looking statements that involve risks and uncertainties, including those regarding Lexicon's growth, future operating results, and the potential therapeutic use of LX9851. Refer to the company’s most recent annual report on Form 10-K for a discussion of important risk factors.