Lexicon’s LX9851 targets ACSL5, a liver enzyme involved in fat metabolism that helps moderate fat accumulation and slow down gastric emptying.
In its search for its next-generation obesity drug, Novo Nordisk on Friday put $1 billion on the line for Lexicon Pharmaceuticals’ non-incretin obesity drug.
Under the terms of the agreement, Novo will hand over up to $75 million in upfront and near-term milestone payments. Lexicon, meanwhile, will be eligible to receive additional development, regulatory and sales-based milestone payments, with the total deal value reaching $1 billion. The Texas-based biotech will also be able to claim tiered royalties on net sales, in the event of approval.
The star of Wednesday’s deal is Lexicon’s molecule called LX9851. Unlike Novo’s blockbuster product semaglutide—marketed as Ozempic for type 2 diabetes and Wegovy for chronic weight management—LX9851 is not an incretin drug.
Incretins exert their cardiometabolic effect through gut hormones that trigger the secretion of insulin and suppress blood sugar levels. Instead, LX9851 targets ACSL5, an enzyme primarily found in the liver that plays an important role in lipid metabolism, helping to regulate energy balance and fat accumulation. According to Lexicon’s news announcement, LX9851 could also help induce feelings of satiety by slowing down the emptying of the stomach.
In November 2024, Lexicon presented in vivo preclinical data for LX9851, showing that the drug candidate could lead to “significant” drops in food intake, fat mass and overall weight in mice. LX9851 also mitigated weight regain even after patients stopped semaglutide treatment and had positive effects on liver steatosis.
As per Friday’s agreement, Lexicon will usher LX9851 through IND-enabling activities, after which Novo will take charge. The Danish drugmaker will be responsible for filing the IND and all future clinical development of LX9851, as well as its manufacturing and commercialization.
Novo has not yet detailed its development plans for LX9851. In a prepared statement on Friday, Jacob Sten Petersen, senior vice president for Novo’s Diabetes, Obesity and MASH therapeutic areas, said the Lexicon deal will help the pharma cater to the “diverse needs of people living with obesity and other metabolic diseases.”
Novo is not new to non-incretin development. CagriSema, which the pharma had been positioning as the successor to its Ozempic and Wegovy, combines semaglutide with cagrilintide, a peptide mimic of the pancreatic hormone amylin. Many analysts and industry observers believe amylin to be the next hot target in the obesity market.
In December 2024, however, Novo’s Phase III readout for CagriSema underwhelmed investors, which had expected it to perform better than Eli Lilly’s incretin competitor Zepbound.
Novo’s search for a next-generation obesity drug also involved a potential $2 billion licensing pact with China’s United Laboratories International, which in turn will hand over UBT251, a so-called triple-G asset that activates the GLP-1, GIP and glucagon receptors.
