Novo’s race to rejuvenate its cardiometabolic portfolio has seen the rebranded Danish pharma pen a $1.4 billion biobucks pact with oral macrocycle drug start-up Orbis Medicines.
The deal will focus on developing next-generation orally bioavailable macrocycle therapies aimed at “high-value” targets for cardiometabolic diseases, the companies explained in a Sept. 17 release. The precise number or nature of the targets was not disclosed.
The partners didn’t offer a breakdown of the financials, but did say that the upfront payment and milestone payouts potentially coming Orbis’ way could total $1.4 billion. Novo—which rebranded from Novo Nordisk on Monday—will also make a strategic investment in Orbis, which is likewise headquartered in the Danish capital of Copenhagen.
The agreement marks the first Big Pharma pact for Orbis. The biotech was founded by Novo Holding, an investment firm that is also Novo’s controlling majority shareholder. Orbis has raised 116 million euros ($134 million) since 2024 through a combination of seed financing and a series A backed by Eli Lilly’s VC arm.
The biotech’s stated aim has been to pioneer a “new era for oral macrocycle drug discovery.” Macrocycles are ring-shaped molecules that can alter protein interactions. While small molecules usually contain rings of five to seven atoms and are relatively inflexible, macrocycles normally contain 12 or more atoms.
Among the dozens of approved macrocycles are certain radiopharmaceuticals like Novartis’ Lutathera, cyclic peptide drugs like Rhythm Pharmaceuticals’ Imcivree and Pfizer’s tyrosine kinase inhibitor Lorbrena for lung cancer.
In recent years, macrocycles have been of particular interest in the cardiometabolic space. In February, Novartis agreed $100 million in near-term payments to work with Unnatural Products on macrocycles for cardiovascular disease, while Japan’s PeptiDream demonstrated last year that its oral macrocyclic peptides preserved lean muscle mass in mice given Novo’s Wegovy.
Orbis has been using its AI-enabled nGen platform to create oral macrocycle drug candidates, dubbed nCycles, which are suitable for both intra- and extracellular targets.
“Our nGen platform continuously learns from data generated by our high-throughput chemistry and screening platform to design orally bioavailable macrocycles with the potential to replace injectable medicines,” Orbis CEO Morten Graugaard said in the release. “Together with Novo, we have an opportunity to unlock a new generation of oral medicines for cardiometabolic diseases and demonstrate the transformative potential of AI-enabled macrocycle drug discovery.”
Novo has made no secret of the fact that it's still on the hunt to fill gaps in its cardiometabolic pipeline after a series of setbacks. The Wegovy-maker abandoned another attempt to develop a monthly GLP-1 drug on Monday. Last week the company gave up on two more phase 3 trials of ziltivekimab, further eroding the prospects for a molecule that analysts had once tipped as a potential inflammation blockbuster.
“We believe this collaboration has the potential to unlock innovative oral treatment options for patients with cardiometabolic diseases while expanding the possibilities of macrocycle therapeutics,” Brian Vandahl, Senior Vice President, Therapeutics Discovery, Novo, said in the release.