Orbis lands $1.4B macrocycle partnership with Novo

Why it matters: The deal is another big pharma endorsement of macrocycles as a way to combine some of the target-binding properties of biologics with the convenience of oral drugs. It also gives Orbis its first Big Pharma partnership, less than two years after the company emerged from stealth.

By the numbers: Orbis is eligible for upfront, development and commercial milestone payments totaling up to $1.4 billion, plus tiered royalties on future sales. The companies did not disclose the upfront payment, the size of Novo’s equity investment or how many targets are covered by the collaboration.

How it works: Orbis’ nGen platform combines high-throughput chemistry, experimental screening and generative AI to design synthetic macrocycles, which the company calls nCycles.

• Macrocycles are relatively large, ring-shaped molecules that occupy chemical space between traditional small molecules and biologics. Their size and shape can help them engage difficult targets, including protein-protein interactions, while newer discovery approaches are increasingly producing compounds that can be taken orally.
• Orbis CEO Morten Graugaard told Reuters that its compounds have achieved oral bioavailability of up to 18% in preclinical studies, while first-generation macrocycles like MSD’s Lipfendra (enlicitide) and J&J’s Icotyde (icotrokinra) have oral bioavailability of approximately 1%.

What they’re saying: “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,” Graugaard said in the announcement.

Backstory: Orbis was founded in Copenhagen in 2021 around research from Christian Heinis and Sevan Habeshian at EPFL. The biotech raised a €26 million seed round in 2024 followed by a €90 million Series A in January 2025. Its investors include Novo Holdings, Forbion, NEA and Lilly Ventures. Graugaard is himself a former partner at Novo Holdings.

Big picture: The agreement follows another billion-dollar macrocycle partnership this year. In February, Novartis struck a deal with California-based Unnatural Products to develop macrocyclic peptide drugs in cardiovascular disease, offering up to $100 million in upfront and pre-IND payments and another $1.7 billion in later milestones.

• That agreement, along with Orbis’ deal with Novo, reinforces a trend we highlighted in our recent deep dive into macrocycles: advances in automated chemistry, large experimental datasets and machine learning are turning a drug class once considered difficult to design into a serious platform opportunity for pharma.

What to watch: Neither Orbis nor Novo has disclosed the individual targets, so the next important milestone will be whether the collaboration produces development candidates that can deliver biologic-like pharmacology in a genuinely convenient oral format.