Novo Nordisk is making yet another bet on obesity, offering Septerna more than $200 million in upfront and near-term payments for rights to preclinical oral small molecules that hit targets including GLP-1.
Eli Lilly, Novo’s main rival for the obesity market, shared phase 3 data on a small-molecule GLP-1 in April. The readout suggested Lilly’s orforglipron can provide Ozempic-like efficacy in Type 2 diabetes. Lilly is now racing toward phase 3 obesity readouts that could position it to file for approval in weight loss this year. The drugmaker is planning submissions in Type 2 diabetes in 2026.
Septerna’s discovery-stage programs are years behind Lilly, but the biotech has made the case that it has a unique feature that sets its molecules apart from the competition. Now, Septerna has the validation of a deal with Novo that is worth up to $2.2 billion across an upfront payment and milestones.
The biotech’s belief it can come from behind to make a mark on the obesity and diabetes markets rests on the discovery of a binding pocket. Because the pocket has similarity across GLP-1, GIP and glucagon, Septerna believes it can hit multiple incretin receptors using a single small molecule. Septerna’s binding site has 80% to 90% sequence similarity across the three receptors, versus 40% to 60% for rival assets.
Talking at the J.P. Morgan Healthcare Conference in January, Septerna CEO Jeffrey Finer, M.D., Ph.D., said the company was studying a single-target GIP receptor agonist and a dual-action molecule that hits GIP and glucagon. The biotech had also “started to get some traction” on a triple-action molecule that could activate GLP-1, GIP and glucagon simultaneously.
Septerna has shared (PDF) mouse data on the GIP receptor agonist. Mice lost a little weight after taking the small molecule as a monotherapy, but the combination data are more compelling. Septerna studied a combination of its GIP receptor agonist and semaglutide, the GLP-1 drug in Novo’s Ozempic and Wegovy. Mice on the combination lost 33% of their body weight in 14 days, compared to 24% for semaglutide.
Weight loss on the combination mirrored data on mice that received tirzepatide, the active ingredient in Lilly’s Mounjaro and Zepbound. Whereas semaglutide only hits GLP-1, tirzepatide acts on both GLP-1 and GIP. People lose more weight on tirzepatide than semaglutide, giving Lilly an edge in a booming market. Septerna’s data suggest adding an oral GIP agonist to semaglutide provides tirzepatide-like efficacy.
Novo and Septerna will initially work on four development programs for small molecules aimed at one or more targets, including GLP-1, GIP and glucagon. The partners will collaborate jointly in the early stages of the programs. Novo will take sole responsibility starting at IND-enabling activities. The agreement gives Septerna an option to take a share of the profits on one program instead of milestones.