Lexicon Pharmaceuticals, Inc. (Nasdaq: LXRX) and Novo Nordisk A/S have taken a significant step forward in the fight against obesity and metabolic disorders. Today, the companies announced the initiation of a Phase 1 clinical trial for LX9851, a groundbreaking oral, non-incretin drug candidate. This milestone marks a pivotal moment in their collaboration, which began in March 2025.

Under the exclusive license agreement, Novo Nordisk gained worldwide rights to develop, manufacture, and commercialize LX9851 across all indications. As part of this partnership, Lexicon has already secured the second of three $10 million near-term milestone payments, following the successful initial dosing in the Phase 1 study. The company is also on track to earn a third $10 million milestone payment later this year. In total, Lexicon stands to receive up to $1 billion in upfront and milestone payments, along with tiered royalties on LX9851's net sales.

A Promising Start to Clinical Development

Mike Exton, CEO and director of Lexicon, expressed his enthusiasm for the progress made by Novo Nordisk. "We are thrilled to see the Novo Nordisk team advancing LX9851 into clinical development," he said. "Their swift action underscores the significant potential of this novel oral candidate to transform obesity treatment. We believe LX9851 could offer a differentiated approach in the next wave of therapies for obesity and metabolic diseases."

Novo Nordisk's Senior Vice President and Head of Global Research, Jacob Sten Petersen, echoed this optimism. "We're excited to bring LX9851 into clinical testing and explore its potential further," Petersen stated. "This candidate represents a novel approach to treating obesity and related metabolic conditions. It's a valuable addition to our pipeline as we strive to address the diverse needs of individuals living with obesity, diabetes, and associated comorbidities."

Details of the Phase 1 Study

The Phase 1 trial aims to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of LX9851. The study involves 96 participants with overweight or obesity and compares single and multiple ascending doses of the drug to a placebo. Completion of the trial is anticipated in the first quarter of 2027.

What Makes LX9851 Unique?

Discovered by Lexicon and now under development by Novo Nordisk, LX9851 is a potent and selective oral small molecule inhibitor of Acyl CoA Synthetase 5 (ACSL5). This enzyme plays a critical role in regulating fat accumulation and energy balance. Additionally, LX9851 may activate the ileal brake mechanism, which increases satiety by delaying gastric emptying and suppressing appetite.

Preclinical data presented at Obesity Week 2024 highlighted LX9851's potential. When combined with semaglutide, the drug significantly reduced weight, food intake, and fat mass compared to semaglutide alone. Furthermore, LX9851 demonstrated the ability to mitigate weight regain and improve liver steatosis when introduced after semaglutide discontinuation.

About the Companies

Lexicon Pharmaceuticals is dedicated to pioneering medicines that transform lives. With a robust pipeline targeting neuropathic pain, hypertrophic cardiomyopathy (HCM), obesity, and other cardiometabolic conditions, the company continues to push the boundaries of biopharmaceutical innovation. For more information, visit www.lexpharma.com.

Novo Nordisk, a global healthcare leader founded in 1923 and headquartered in Denmark, is committed to defeating serious chronic diseases. The company focuses on scientific breakthroughs, expanding access to medicines, and working toward disease prevention and cures.