Novo Signs $1.4B Oral Macrocycle Peptide Deal With Orbis

Novo Nordisk agreed on Sept. 17 to pay Orbis Medicines up to $1.4 billion in upfront and milestone payments, plus tiered royalties, to co-develop oral macrocycle peptides for cardiometabolic disease — a bet that the next generation of pill-form peptide drugs will come from molecular design rather than delivery technology. The multi-target collaboration and license agreement covers molecules the Copenhagen-based biotech calls nCycles, designed with generative AI against targets “that have historically been reachable only through injectable biologics.”

What the deal covers

Under the terms, Orbis is eligible for up to USD 1.4 billion in upfront and potential development and commercial milestone payments, in addition to tiered royalties on future product sales. Novo will also make a strategic investment in Orbis. Neither company disclosed the size of that investment, and the announcement gives the $1.4 billion as a single figure rather than separating the upfront payment from the milestones — which means the money committed at signing cannot be sized from outside the negotiation.

Orbis’ board chair is Mikael Dolsten, Pfizer’s former chief scientific officer and president of R&D, who took the role in March 2025. Both Novo Holdings, the controlling shareholder of Novo Nordisk, and Lilly Ventures, the venture arm of Novo’s principal obesity competitor, appear on the company’s investor register. Orbis has raised EUR 116 million in venture funding to date, including a EUR 90 million Series A led by NEA with participation from Lilly Ventures, Cormorant, EIFO, Forbion and Novo Holdings.

Macrocycles are not GLP-1 analogues

Macrocycles are ring-shaped molecules large enough to reach targets that conventional small-molecule drugs cannot, but historically too large and too polar to survive the gut. That trade-off — biologic-like reach, pill-like convenience — is the problem Orbis says its platform solves.

The company’s nGen platform pairs generative AI with automated, high-throughput chemistry in what it describes as a “lab in a loop” system. It starts with hit-finding libraries of 100 billion compounds and target-specific libraries designed by generative AI, then synthesizes and analyzes up to 100,000 distinct synthetic macrocycles in weeks. Candidates are optimized for oral bioavailability and membrane permeability — the two properties that have limited macrocycle medicines to injectable and intravenous routes. Proof-of-concept work from the platform has been published in Nature Communications and Nature Chemical Biology.

“This collaboration reinforces that the future of oral biologic drug discovery lies at the intersection of AI, proprietary experimental macrocycle datasets and world-class automated chemistry,” said Morten Graugaard, chief executive officer of Orbis Medicines. “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.”

Novo’s discovery leadership framed the deal as capability, not a single asset. “Orbis Medicines has developed a differentiated platform for macrocycle drug discovery, combining deep expertise in macrocycle chemistry with AI-enabled molecular design,” said Brian Vandahl, senior vice president, Therapeutics Discovery, Novo Nordisk. “We believe this collaboration has the potential to unlock innovative oral treatment options for patients with cardiometabolic diseases while expanding the possibilities of macrocycle therapeutics.”

A pivot from formulation to molecular design

Most oral peptide progress to date has come from the delivery side: permeation enhancers, coated carriers and effervescent tablets engineered to push peptides across the intestinal wall before enzymes degrade them, the approach covered by BioLife’s U.S. oral peptide delivery patent earlier this month. Oral and injectable versions of the same molecule still differ on food rules, refrigeration and price, as our GLP-1 pill vs injection comparison sets out, and weekly prescription data continues to show how quickly prescribers shift when an oral option appears (Wegovy pill vs Foundayo).

Macrocycle design attacks the problem one step earlier, changing the molecule so that no delivery technology is required. If it works at scale, the pipeline of injectable-only peptide targets — the class of drugs that made Novo one of the largest healthcare companies in Europe — becomes addressable in tablet form. That is the strategic logic behind a deal priced at up to $1.4 billion for a company with no clinical-stage asset disclosed.

The compounding fight is a separate fight

Novo’s partnership is a prescription drug development story, and it is worth keeping distinct from the regulatory fight over unapproved peptides sold for compounding and gray-market use — a fight that has run in the opposite direction over the same period.

In July, the FDA’s Pharmacy Compounding Advisory Committee recommended six of the seven peptides it reviewed — BPC-157, TB-500, KPV, MOTS-c, epitalon and semax — for the 503A bulks list and declined to recommend emideltide (DSIP), according to the FDA’s posted meeting materials. Those votes were recommendations only; formal placement requires rulemaking and could take months or years, as our PCAC July 2026 tracker records. Enforcement has continued in parallel: the agency issued warning letters to five peptide vendors in late August over unapproved new-drug sales, and FDA maintains that certain bulk drug substances used in compounding may present significant safety risks. A Texas compounder’s glutathione recall has kept compounded-product safety in front of state and federal regulators.

The two tracks now run simultaneously: venture-scale investment in new prescription peptides, and tightening scrutiny of compounded and consumer peptides that never entered a trial.

Supply side moves on the same day

A day that produced a $1.4 billion peptide discovery deal also produced a supply-chain announcement. Medisca, which has supplied compounding pharmacies with pharmaceutical-grade ingredients since 1989, launched a dedicated global peptide division on Sept. 17, focused on API-grade peptides for compounding and personalized medicine markets.

“When I founded Medisca, I saw an opportunity to bring pharmaceutical compounding closer to the standards of traditional pharma by giving compounders better access to API-grade ingredients and holding those ingredients to a higher standard,” said Antonio Dos Santos, the company’s founder and chief executive officer. “Today, I see a similar opportunity with peptides. We are not entering this space to follow it. We intend to help shape it.”

Medisca said it will apply its existing manufacturer-qualification, testing, documentation and supply-chain oversight processes to the peptide APIs it distributes, and that it intends to advocate for “added guardrails, transparency, responsible access and appropriate quality standards” as regulation develops. The division will roll out across selected markets first, the company said.

What to watch

The disclosures to track are the ones the announcement withheld: the upfront-versus-milestone split, the size of Novo’s equity investment, and whether a development candidate emerges on a stated timeline. Orbis did not announce one.

For the wider category, the open question is whether oral macrocycles can be manufactured and dosed at the scale obesity and cardiometabolic markets demand — a chemistry problem that no licensing deal settles.

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