Novo signs deal worth up to $1.4 billion with Orbis for oral macrocycle drugs

Novo Nordisk will pay up to $1.4 billion to Orbis Medicines to discover oral drugs for cardiovascular and metabolic diseases, the companies said September 17 ^[1][5]. The partnership centers on macrocycles, ring-shaped molecules the partners hope can be swallowed rather than injected ^[1][3].

The $1.4 billion figure covers an upfront payment plus potential development and commercial milestone payments, and Orbis is also eligible for tiered royalties on future product sales ^[1]. Novo will make a separate strategic investment in Orbis; the size was not disclosed ^[1]. Neither company said how many drug programs the partnership covers or which biological targets it will pursue, describing them only as "high-value" targets for cardiometabolic disease ^[1][2][3].

Orbis is headquartered in Copenhagen, Denmark, with a second site in Lausanne, Switzerland ^[1]. Novo has backed the company since its seed rounds and took part in a 90 million euro ($93.2 million at the time) Series A round in early 2025. That round was led by NEA and included Eli Lilly's venture arm, Cormorant, EIFO, Forbion and Novo Holdings ^[1][4]. Orbis says it has raised 116 million euros ($134 million) in venture funding to date ^[1][3]. The Novo agreement is the first partnership the biotech has signed with a large drugmaker ^[3].

Orbis designs its molecules with a platform it calls nGen, which combines generative artificial intelligence with high-throughput chemical synthesis. The company says the system can design, make and analyze thousands of distinct synthetic macrocycles in weeks, learning from its own experimental data, and that it is aimed at oral bioavailability, the property that has historically held back this molecule class ^[1].

"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 chief executive Morten Graugaard said in a statement ^[1]. Brian Vandahl, Novo's senior vice president of therapeutics discovery, said the collaboration "has the potential to unlock innovative oral treatment options for patients with cardiometabolic diseases" ^[1].

Macrocycles are rings that normally contain 12 or more atoms, compared with the five to seven atoms typical of small-molecule drugs, and they can alter protein interactions in ways other molecules cannot ^[3]. Approved examples include certain radiopharmaceuticals, peptide drugs and a lung cancer treatment ^[3].

Absorption is the central problem the field is trying to solve. The highest dose of Novo's Wegovy pill contains 20 times the highest injectable dose, because most of the active ingredient is broken down before it reaches the bloodstream ^[2]. Biologics like peptides and antibodies have long been difficult to give by mouth without delivery technology that keeps them from degrading in the gut ^[4].

Other large drugmakers are pursuing the same chemistry. Novartis agreed in February to pay $100 million in near-term payments to Unnatural Products in a cardiovascular macrocycle deal worth up to $1.7 billion ^[3][4]. Biogen paid $50 million upfront in a collaboration with Dayra Therapeutics, and Boehringer Ingelheim entered a 2024 research partnership with Circle Pharma worth up to $607 million ^[4]. PeptiDream reported last year that its oral macrocyclic peptides preserved lean muscle mass in mice given Wegovy ^[3].

The deal is one of several recent moves at Novo, which this week said it would drop "Nordisk" from its name in day-to-day use ^[2][3]. On Monday it abandoned a monthly GLP-1 program, and last week it ended two more Phase 3 trials of the inflammation drug ziltivekimab ^[3].

Why it matters for patients

Nothing from this partnership is available to patients, and no drug candidate has been named ^[1][3]. The work is at the discovery stage, and no timeline for human testing has been disclosed. That means it does not change what is prescribed today.

The practical question the deal targets is absorption. Pills for GLP-1 drugs already exist — Novo sells an oral Wegovy and Eli Lilly sells Foundayo (orforglipron) — but oral versions have needed far larger amounts of drug to get enough into the blood ^[2][4]. If macrocycles can be absorbed more efficiently, they could open the door to pills for targets that currently require injections. Whether that works in people has not been established.

Both of the biggest obesity drugmakers now hold financial stakes in Orbis: Novo through its investment arm and this partnership, and Lilly through its venture arm ^[4][5].

What happens next

No dates have been set for selecting a drug candidate, starting human trials or seeking approval; the milestone payments depend on development and commercial progress that has not yet occurred ^[1]. The number and identity of the targets remain undisclosed ^[2][3].