Novo Nordisk has been on the hunt for differentiated obesity drugs that could complement its blockbuster GLP-1 agonist, Wegovy. It’s found a contender with preclinical data indicating it can lead to greater weight loss as part of a drug combination and also prevent weight regain after treatment with the GLP-1 medication is stopped.
The Danish pharmaceutical giant is licensing global rights to LX9851, a drug discovered and developed by Lexicon Pharmaceuticals, the companies announced Friday. LX9851 is an oral small molecule that blocks Acyl-CoA Synthetase 5 (ACSL5), an enzyme that plays a key role in a metabolic pathway regulating fat accumulation and energy balance. According to Lexicon, this molecule may also activate the ileal brake, a feedback mechanism that slows movement of food through the gastrointestinal system and promotes feelings of satiety.
The Woodlands, Texas-based Lexicon has been studying this LX9851 as a standalone therapy and in combination with GLP-1 agonists such as semaglutide, the main ingredient in Novo Nordisk’s Wegovy. At the Obesity Week 2024 conference last November, Lexicon presented preclinical results from a test of LX9851 in combination with semaglutide. Lexicon said this drug pairing led to significant reduction in weight, food intake, and fat mass compared to semaglutide alone. Additional results showed that after dosing of semaglutide was stopped, the Lexicon drug mitigated weight regain and had positive effects on the liver.
According to the terms of the license agreement, Lexicon is still responsible for completing the preclinical research that can support an investigational new drug (IND) application for the ACLS5 inhibitor. Novo Nordisk will take on responsibility for that IND filing as well as further development, manufacturing, and commercialization of the drug.
The deal gives the pharma giant global rights to LX9851 for all indications. Novo Nordisk has committed to pay up to $75 million in upfront and near-term milestone payments. Achieving additional milestones could bring the financial outlay to $1 billion. If the research results in a commercialized product, Lexicon will receive royalties from Novo Nordisk’s sales of the drug.
To Leerink Partners, the deal validates Lexicon’s obesity platform while providing the biotech with financial flexibility to focus on its other cardiometabolic drugs. In a note sent to investors, analyst Roanna Ruiz said the ACLS5 inhibition offered by LX9851 complements GLP-1 agonism, with preclinical results showing about 20% greater weight loss when added to semaglutide compared to semaglutide alone. Ruiz added that the molecule’s ability to prevent the weight regain after discontinuing GLP-1 use was particularly compelling because regaining weight continues to be a major hurdle in obesity management.
“Big picture, the deal aligns with Novo’s strategy to maintain dominance in the obesity space by adding complementary mechanisms to pair with their GLP-1 franchise, and we look forward to more updates from the collaboration going forward,” Ruiz said.
The LX9851 licensing agreement is the latest in a string of deals struck by Novo Nordisk to expand its metabolic medicines pipeline. Earlier this week, the pharma giant agreed to pay United Biotechnology $200 million up front for rights to an early clinical peptide drug engineered to activate three targets to prompt weight loss.
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