Novo Nordisk signs oral macrocycle discovery deal with Orbis Medicines worth up to $1.4 billion

Novo Nordisk has signed a multi-target drug discovery partnership with Orbis Medicines, a Copenhagen startup working on pills built from ring-shaped molecules called macrocycles. Under the deal announced September 17, 2026, Orbis is eligible for up to $1.4 billion in upfront and potential development and commercial milestone payments, plus tiered royalties on any future product sales ^[1].

Novo will also make a strategic investment in Orbis ^[1][5]. The companies did not break down the financials, and they did not say how many drugs they will work on or which specific diseases they will target, only that the programs will aim at unnamed "high-value" cardiometabolic targets ^[2][3].

What macrocycles are

Macrocycles are ring-shaped molecules that can change how proteins interact with each other. Conventional small-molecule drugs usually contain rings of five to seven atoms and are relatively rigid; macrocycles typically contain 12 or more atoms ^[3]. Dozens are already approved, including Novartis' radiopharmaceutical Lutathera, Rhythm Pharmaceuticals' cyclic peptide Imcivree and Pfizer's lung cancer drug Lorbrena ^[3]. Merck brought a macrocyclic cholesterol-lowering pill, Lipfendra, to market earlier this year ^[2].

Orbis uses a platform it calls nGen, which pairs generative AI with high-throughput chemistry to design and test thousands of synthetic macrocycles — it calls them nCycles — in weeks ^[1]. The company's stated goal is to solve the long-standing problem that macrocycles are hard to absorb when swallowed ^[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 CEO Morten Graugaard said ^[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].

Why it matters for patients

The practical problem this research is chasing is familiar to anyone who has looked at oral semaglutide. Peptide drugs get broken down in the digestive tract before much of the medicine reaches the bloodstream. The highest dose of Novo's Wegovy pill contains 20 times the amount of drug in the highest injectable dose, because only a small share survives the trip ^[2]. Macrocycles are one route drugmakers hope will get around that inefficiency ^[2].

That said, nothing here is close to a prescription. The partnership is a discovery-stage deal with no named targets, no disclosed candidate molecules and no stated timeline ^[2][3]. Deal values like "$1.4 billion" are contingent: most of that money is paid only if programs hit development and commercial milestones that may never arrive ^[1][3].

The deal also shows where competition in obesity and cardiometabolic medicine is heading. Novo currently leads the oral market with its Wegovy pill, while Eli Lilly is gaining ground with Foundayo, its orforglipron pill ^[4]. Lilly's venture arm is also an Orbis investor ^[1][4][5]. Rivals are betting on the same chemistry: Novartis agreed in February to a deal with Unnatural Products worth $100 million in near-term payments and up to $1.7 billion overall for cardiovascular macrocycles ^[3][4]; Biogen signed with Dayra Therapeutics for $50 million upfront in immunology; and Boehringer Ingelheim partnered with Circle Pharma in 2024 on cancer macrocycles in a deal worth up to $607 million ^[4]. Japan's PeptiDream reported last year that its oral macrocyclic peptides preserved lean muscle mass in mice given Wegovy ^[3].

Context at Novo

The agreement lands during a difficult stretch for Novo. The company has swapped CEOs, cut staff and reshuffled its board after losing its lead in obesity and diabetes drugs to Lilly ^[2]. On Monday of the same week it dropped "Nordisk" from its everyday name ^[2][3][5], and it also walked away from a $285 million pact with Ascendis to develop a monthly GLP-1 ^[3]. The week before, it scrapped two more Phase 3 trials of ziltivekimab ^[3]. Novo separately announced an AI drug discovery alliance with Anthropic ^[2][5].

What happens next

No milestone dates, candidate nominations or trial start times have been disclosed ^[2][3]. Orbis, which emerged from stealth in February 2024 with $28.1 million in seed funding and has raised 116 million euros in total ^[1][4], says this is its first Big Pharma partnership ^[3].