Novo Signs Up to $1.4 Billion Drug-Discovery Deal With Orbis Medicines for Oral Cardiometabolic Drugs

Novo has signed a multi-target drug discovery and licensing agreement with Orbis Medicines worth up to $1.4 billion, deepening the Danish pharmaceutical giant’s push into oral treatments for cardiometabolic diseases that have traditionally required injections. The deal, announced Thursday, pairs Novo with a Copenhagen-based biotech specializing in AI-designed macrocycle molecules, and comes just one day after Novo separately announced a drug-discovery partnership with Anthropic, underscoring how aggressively the company is now stacking external collaborations to reinforce its pipeline.

What the Deal Actually Covers

Under the agreement, Orbis Medicines is eligible to receive up to $1.4 billion in upfront and potential development and commercial milestone payments, plus tiered royalties on any resulting product sales. Novo will also make a strategic equity investment in the privately held company, though neither party disclosed the size of that investment or how the headline $1.4 billion figure splits between near-term cash and contingent future milestones. The collaboration targets multiple undisclosed cardiometabolic disease targets, with Orbis using its in-house discovery platform to generate macrocycle drug candidates against each one.

As with most discovery-stage pharma alliances of this size, it’s worth reading the headline number carefully: the overwhelming majority of a deal structured this way typically consists of milestone payments tied to preclinical, clinical, regulatory, and sales progress that only materialize if individual drug candidates actually succeed, rather than cash Orbis receives upfront.

What Are Macrocycles, and Why They Matter

Macrocycles are large, ring-shaped molecules that occupy a middle ground between conventional small-molecule drugs and larger biologic therapies like antibodies. Their ring structure gives them larger binding surfaces than typical small molecules, allowing them to potentially reach disease targets that have historically been considered difficult or “undruggable” using conventional chemistry, while still retaining a chance at oral bioavailability, something large biologic drugs like antibody therapies generally can’t achieve since they break down in the digestive system if swallowed.

“Together with Novo, we have an opportunity to unlock a new generation of oral medicines for cardiometabolic diseases.”

— Morten Graugaard, CEO, Orbis Medicines

That oral bioavailability question is the central technical challenge the Novo-Orbis partnership is built around. Graugaard said the company’s synthetic macrocycles have already achieved up to 18 percent oral bioavailability, a measure of how much of a swallowed drug actually reaches the bloodstream, in preclinical studies, a meaningful signal given how difficult oral delivery has historically been for this class of molecule.

Inside Orbis’s AI-Driven Discovery Platform

The collaboration will run on Orbis’s proprietary nGen platform, which combines generative AI with high-throughput automated chemistry and screening. The system designs candidate macrocycles, which Orbis calls nCycles, through a multi-parameter optimization engine that continuously improves using one of the industry’s larger experimental macrocycle datasets, generated in real time through what the company describes as a “lab-in-the-loop” process, meaning each round of laboratory testing feeds directly back into refining the AI model’s next set of molecular designs, rather than AI and wet-lab chemistry operating as separate, sequential steps.

Novo’s Track Record With Oral Peptides

Novo isn’t approaching this space as a newcomer. The company has already demonstrated it can bring oral versions of traditionally injectable drugs to market, having launched the world’s first oral GLP-1 medicines for type 2 diabetes and weight loss using its SNAC absorption-enhancing technology. That track record gives Novo direct commercial and regulatory experience turning peptide science into pill form, expertise it’s now aiming to extend into the structurally different, and in some ways more technically demanding, world of macrocycle chemistry.

A Deal Born Partly From Recent Setbacks

The timing of the Orbis deal isn’t incidental. Novo has had a rough stretch recently: the company abandoned an attempt to develop a monthly GLP-1 drug earlier this week, and scrapped two additional Phase 3 trials of ziltivekimab, a molecule analysts had once viewed as a potential blockbuster anti-inflammatory drug, just last week. Pairing those setbacks with a steady stream of new external collaborations, macrocycles with Orbis, AI drug discovery with Anthropic, and an earlier oral peptide and protein therapeutics deal worth up to $2.1 billion with Vivtex in February, suggests Novo is actively working to refill its pipeline through partnerships as some of its internal programs stumble. That pattern of leaning on outside AI and biotech partnerships to accelerate drug discovery lines up closely with Novo’s own stated rationale for its Anthropic partnership announced just one day earlier, and reflects a broader industry shift toward AI-accelerated pharmaceutical research more generally.

Part of a Broader Oral-Drug Arms Race

Novo isn’t alone in chasing macrocycle chemistry. Novartis struck its own macrocycle-focused alliance in February, partnering with peptide maker Unnatural Products in a deal worth up to $1.7 billion for cardiovascular disease targets. On the regulatory front, Johnson & Johnson won U.S. approval in March for Icotyde, an oral macrocyclic peptide for plaque psoriasis, and Merck secured approval in July for Lipfendra, an oral macrocyclic peptide that lowers cholesterol, evidence that oral macrocycle drugs are already reaching patients elsewhere in the industry rather than remaining a purely experimental concept.

An Interesting Wrinkle: Eli Lilly Is Also an Orbis Investor

One detail adds an unusual layer to the deal: Eli Lilly, Novo’s fiercest rival in the GLP-1 weight-loss and diabetes market, has been an Orbis investor since participating in the company’s €90 million Series A funding round in early 2025. That means both of the industry’s dominant weight-loss drugmakers now have a financial stake in the same macrocycle discovery platform, even as Novo’s new agreement gives it direct access to Orbis’s technology for its own drug candidates. Orbis has also recently strengthened its scientific credibility by appointing Mikael Dolsten, Pfizer’s former chief scientific officer and head of R&D, as chairperson of its board.

What Comes Next

For now, the Novo-Orbis collaboration remains firmly in the discovery stage, with no specific drug candidates or disease targets publicly named. Whether it produces an actual approved oral macrocycle medicine will likely take years to determine, and success is far from guaranteed given how much of the deal’s value depends on milestones that may never be reached. What’s clearer in the near term is the pattern: Novo is placing multiple, simultaneous bets across AI-driven drug discovery platforms, hoping that at least some of them translate into the kind of pipeline renewal the company badly needs after a difficult few weeks of internal setbacks.