Novo Nordisk Teams With Orbis Medicines on Oral Macrocycles in Deal Worth Up to $1.4 Billion

What happened

Novo Nordisk agreed on Sept. 17 to collaborate with Orbis Medicines, a Danish biotech, to discover multiple macrocyclic drugs. According to BioPharma Dive, Orbis could receive up to $1.4 billion in upfront and downstream payments, plus royalties on sales.

The companies did not disclose how many drugs the collaboration will pursue or which diseases they will target, saying only that the work will focus on unnamed cardiometabolic targets.

Deal and company details

• Value: Up to $1.4 billion in upfront and downstream payments, plus royalties. The split between upfront and milestone payments was not disclosed.
• Scope: Discovery of multiple macrocycles against cardiometabolic targets.
• Orbis: Launched in January 2025 with $93 million. It uses an AI-driven platform it calls nGen to design molecules that are orally bioavailable and can act on hard-to-reach targets inside and outside cells.

Orbis said the macrocycles have the “potential to replace injectable medicines.”

Why macrocycles

Macrocyclic peptides are ring-shaped molecules that are larger than conventional small-molecule drugs but smaller than antibodies. Their structure can make them more stable in the digestive tract and better able to bind complex targets. Standard peptides, by contrast, tend to be absorbed poorly when swallowed.

BioPharma Dive pointed to Novo’s own Wegovy pill as an example of the problem: its highest dose is about 20 times the highest injectable dose, because most of the active ingredient is broken down before reaching the bloodstream. A drug that is absorbed more efficiently could, in principle, require less active ingredient and be easier to manufacture at scale.

Interest in the approach has been building. Merck recently won approval for a macrocyclic cholesterol drug, and startups including Orbis, Unnatural Products and Dayra Therapeutics have each signed deals with larger drugmakers, according to BioPharma Dive.

Why it matters for the sector

Obesity and diabetes drugs have become the largest commercial battleground in pharma, and the next phase of competition is expected to center on oral options, longer-acting injections and combinations that preserve muscle or improve tolerability. Companies that can deliver peptide-like efficacy in a pill could reach patients who prefer not to inject and lower the cost of supply.

For Novo, the deal is part of a broader effort to recover momentum. BioPharma Dive reported that Novo has lost obesity and diabetes market leadership to Eli Lilly and has responded with a chief executive change, layoffs, board changes, a rebrand that drops Nordisk from the name in everyday use and investments in AI, including an alliance with Anthropic. Investing in oral biologics is one strand of that strategy.

The deal also reflects a pattern in which large drugmakers partner with platform startups early, paying modest amounts upfront in exchange for rights to future candidates. That gives the buyer exposure to new chemistry while the startup gains validation and non-dilutive funding.

For European biotech, a deal of this size for a company less than two years old is a notable vote of confidence in AI-enabled drug design, an area that has attracted large rounds from investors in 2026.

What to watch

• Disclosure of the upfront payment or first targets, which could come in either company’s future reporting.
• Progress of macrocycle programs at other companies, which will indicate whether the class can deliver on oral bioavailability claims.
• Further Novo deals in oral and next-generation obesity medicines.
• Whether Orbis raises additional capital or signs other pharma partnerships.

Sources: BioPharma Dive

Why Oral Delivery Is So Hard for Peptide Drugs

Many of today’s most important metabolic medicines are peptides, chains of amino acids similar to the body’s own hormones. They work well when injected, but swallowing them presents several obstacles:

1. Stomach acid. The acidic environment of the stomach can damage the molecule’s structure.
2. Digestive enzymes. The gut is designed to break proteins and peptides down into their building blocks for absorption as food.
3. The intestinal wall. Large molecules pass poorly through the cells lining the intestine into the bloodstream.
4. First-pass effects. What does get absorbed may be partly processed by the liver before reaching the rest of the body.

Formulation technologies such as absorption enhancers can help, but typically only a small fraction of the dose reaches circulation. That is why high oral doses are often needed relative to injections.

What Makes Macrocycles Different

A macrocycle is a molecule built around a large ring. Closing a peptide chain into a ring, and adding chemical modifications, can change how it behaves:

• Rigidity. A ring holds its shape more firmly, which can improve binding to a target and make the molecule harder for enzymes to cut.
• Surface binding. Macrocycles can cover larger areas of a target than small molecules, making them suited to interactions between proteins that small drugs struggle to block.
• Tunable properties. Medicinal chemists can adjust features that influence absorption, such as how the molecule hides or exposes water-loving groups.

Designing macrocycles that are both potent and orally absorbed has historically been slow and difficult, which is where computational design platforms aim to help by exploring many more candidate structures than could be made and tested by hand.

How Multi-Target Discovery Deals Are Usually Structured

Collaborations of this kind commonly follow a pattern. The biotech applies its platform to targets chosen by the pharma partner, generating candidate molecules. The partner then takes selected candidates into further development and clinical trials. Payments typically include an upfront amount, research funding, milestones for each program that reaches defined stages and royalties on sales. Because each target is a separate program, the headline value assumes several programs succeed, which rarely happens in full.

Questions Readers Ask

What does “cardiometabolic” cover?

Conditions linking the heart, blood vessels and metabolism, such as obesity, type 2 diabetes, high cholesterol and related cardiovascular disease.

Would an oral drug be as effective as an injection?

That depends on the molecule and must be shown in clinical trials. Patients should discuss treatment options with their own physicians.

Why does manufacturing cost come up so often with oral peptides?

If only a small share of a swallowed dose is absorbed, each pill must contain much more active ingredient than an injection. At the scale of global metabolic disease, that difference adds up to large quantities of drug substance, so better absorption can make supply easier and potentially less costly.

This article is for general information only and is not investment or medical advice.