SAN FRANCISCO—After a year of significant disruption at Novo Nordisk, the company’s R&D chief has told Fierce Biotech that the deal-hungry Danish pharma is largely sticking to its metabolic roots as it seeks out new innovation.
In the wake of an obesity market upheaval last year, the Danish pharma lost its prior CEO, announced significant layoffs and wound down a range of early-stage programs in liver disease, oncology and stem cells as part of an ambitious restructuring program.
Part of that restructure saw Martin Holst Lange, M.D., Ph.D., step up to the position of chief scientific officer. On the sidelines of the J.P. Morgan Healthcare Conference in San Francisco, Fierce Biotech caught up with Lange to learn more about Novo’s more streamlined approach.
“Historically, we’ve been a reasonably narrow, focused company,” Lange said. “Starting out with diabetes, we’ve done that for 100 years.”
From diabetes came the pharma’s weight loss franchise, anchored by Wegovy, and Novo now seeks to strengthen its obesity offerings while pursuing other indications that intersect with metabolic disease. This included a welcome win for Wegovy last month, when it beat rival Eli Lilly to become the first oral GLP-1 obesity drug to secure FDA approval.
Under new CEO Maziar Mike Doustdar, Novo has made no secret that it is looking to refill its obesity pipeline. Last fall, this ambition led to a high-profile, but ultimately unsuccessful, attempt to tempt Metsera Therapeutics away from Pfizer.
Novo has more than 200 meetings lined up for this year’s JPM, Lange told Fierce, with an eye on picking up new drug candidates and even entire platforms.
“It’s a wide array of early-, late-stage, big and small, different flavors,” he explained. “If you’re lucky, and I’ve been lucky a couple of times today, you get inspired from different pieces that you can then bring together into something that may add more synergistic value at the end of the day.”
Novo is casting a wide net in the hunt for these new “flavors,” taking an agnostic approach as to the innovation’s country of origin. China, of course, is on the menu, but Lange pointed out that other countries in Asia and Europe—like Japan and Germany—are becoming more appetizing.
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The pharma’s next-gen obesity pipeline is currently led by CagriSema, a once-weekly injection of Wegovy’s ingredient semaglutide in combination with an amylin analog called cagrilintide. Novo submitted the combo for FDA approval in December, though analysts have been unimpressed by the candidate’s weight loss numbers.
The company is also pursuing a pair of triple-acting agonists, one of which Lange thinks is unique to Novo.
“There are some competitors, both in the early and in the later stage, that have the combination of a GLP-1, a GIP and a glucagon” agonist, Lange explained. Novo pocketed such a molecule in a $2 billion deal with Chinese biotech United Laboratories in March 2024, while Lilly’s retatrutide has been tied to 28.7% weight loss at 68 weeks.
Novo’s pipeline also lists a triple agonist of GLP-1, GIP and amylin. Lange said he’s “not aware of many [companies] who also have a triple with an amylin biology in there.”
While Novo’s broad collection of obesity candidates is important to Lange, a particular point of pride for the R&D leader is the pharma’s upcoming “high risk, high reward” phase 3 readout in cardiovascular disease. Novo’s Zeus trial is testing ziltivekimab’s ability to reduce the risk of heart attacks, strokes and other cardiovascular events in patients with atherosclerotic cardiovascular disease, chronic kidney disease and inflammation.
In an earlier phase 2 study, the anti-IL-6 antibody slashed levels of C-reactive protein, a key cardio risk biomarker, by as much as 92%, without known possible side effects like neutrophilia and infections.
That the baseline rate of cardiovascular events in the study is more than 5%, Lange said, “means that it’s quite severe to have inflammation” for those patients. “To be able to reduce that in a meaningful way would be very impactful.”
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Lange is also not opposed to some more moonshot attempts for semaglutide, even though two phase 3 trials of the blockbuster in Alzheimer’s disease recently failed. After the “very disappointing” result, the neurodegenerative disease is “not within our core” strategy, he said.
But Lange thinks an attempt at using GLP-1 drugs to target another neurological condition—addiction—is in the cards.
“We do hear anecdotally that GLP-1 therapy does actually help people who have addiction challenges,” he said. “We would see an obligation to investigate that, so you’ll probably see us do that.”
A focus on metabolic diseases allows Lange a lot of room to think about new therapeutic areas, because metabolism intersects with essentially every part of the body, from the kidneys and the brain to the heart and liver.
“We identify unmet needs, and then we try to address them with the scientific knowledge that we have,” Lange said. “We want to be a company that actually makes a difference.”
