IPM Take
The next phase of cardiometabolic competition may not be about putting another injectable drug into a tablet.
Novo’s new partnership with Orbis Medicines points toward a more fundamental wager: designing an entirely different class of molecules that could reach biological targets traditionally associated with larger, injectable therapies, while remaining orally available.
Under the agreement, Orbis is eligible for up to $1.4 billion across upfront and potential development and commercial milestone payments, plus tiered royalties. Novo will also make a strategic investment in the company. The companies have not disclosed the cardiometabolic targets involved, and no clinical candidate has yet emerged from the partnership.
That makes this an early discovery signal, not a therapeutic breakthrough. But the direction is becoming harder to ignore. Oral delivery is becoming a competitive strategy in cardiometabolic medicine, while macrocycles are attracting major pharmaceutical investment as companies search for ways to reach targets that conventional small molecules struggle to address.
Executive Summary
Novo and Copenhagen-based Orbis Medicines have entered a strategic collaboration and licensing agreement to discover and develop orally bioavailable macrocycle candidates against multiple cardiometabolic targets. Orbis will use its nGen discovery platform, which combines generative AI, automated chemistry, high-throughput synthesis and experimental datasets to design synthetic macrocycles called nCycles.
The financial package is worth up to $1.4 billion, rather than $1.4 billion paid upfront. It comprises upfront and potential future milestone payments, with additional tiered royalties if products reach the market. Novo is also taking an undisclosed strategic investment in Orbis.
Orbis’ underlying technology remains preclinical. A proof-of-concept study published in Nature Chemical Biology showed that researchers could design cyclic peptides with nanomolar target affinity and oral bioavailability of up to 18% in rats. That work provides biological plausibility for the platform, but it does not establish clinical efficacy, safety or oral bioavailability in humans.
Why it matters
- HTA bodies: There is no immediate assessment implication because the collaboration remains at discovery stage. If oral macrocycles eventually reproduce the effects of injectable biologics, future assessments may need to account for differences in administration burden, adherence, delivery infrastructure and patient preference rather than efficacy alone.
- Payers: Oral therapy can reduce some administration costs and access barriers, but easier delivery could also expand treatment uptake. For high-prevalence cardiometabolic diseases, convenience can change budget impact as much as price.
- Industry / innovation partners: The deal adds another large pharmaceutical company to the macrocycle race. Platform capability, oral bioavailability and access to difficult targets are becoming strategic assets as cardiometabolic R&D expands beyond conventional peptides and small molecules.
The success of injectable biologics has created a problem pharmaceutical companies increasingly want chemistry to solve.
Powerful medicines can reach highly specific biological targets, but many large molecules and peptides perform poorly when swallowed. They can be degraded in the gastrointestinal tract, absorbed inefficiently or fail to cross biological membranes.
Orbis Medicines is trying to design around those limitations.
Its nGen platform combines generative AI with automated synthesis and experimental screening to produce synthetic macrocycles, which the company calls nCycles. Unlike conventional linear peptides, macrocycles have ring-shaped structures that can offer high target affinity while potentially being engineered for greater stability and membrane permeability.
Novo is now placing a significant financial bet on that proposition.
The companies announced on 17 September that they would work together on multiple undisclosed cardiometabolic targets. Orbis could receive up to $1.4 billion through upfront and milestone payments, plus royalties, while Novo will make a strategic equity investment.
The size of the headline number needs context. It is a maximum potential deal value, dependent on future research, development and commercial milestones. Neither company has identified the targets involved, announced a development candidate or disclosed human data from the programme.
That distinction matters because the technology remains early.
The scientific foundation is nevertheless more than theoretical. Research led by Orbis scientific founder Christian Heinis and colleagues developed a library of 8,448 cyclic peptides against thrombin, ultimately identifying compounds with nanomolar affinity and oral bioavailability as high as 18% in rats. The study was published in Nature Chemical Biology in 2024.
The leap from a rat pharmacokinetic experiment to a successful cardiometabolic medicine is substantial. Human bioavailability, dosing, safety, manufacturability and clinical benefit all remain to be demonstrated.
But Novo’s investment matters because it sits inside a wider strategic pattern.
In 2025, Novo entered a separate collaboration with Septerna worth approximately $2.2 billion to pursue oral small-molecule therapies against cardiometabolic GPCR targets including GLP-1, GIP and glucagon receptors.
And Novo is not alone in pursuing macrocycles. Earlier in 2026, Novartis agreed to a potential $1.7 billion collaboration with Unnatural Products around macrocyclic peptide therapeutics for cardiovascular disease.
Taken together, these deals suggest that the cardiometabolic pipeline is widening beyond the current GLP-1 competition.
The question is no longer simply whether injectable medicines can be reformulated for oral use.
It is whether a new generation of chemistry can make previously injection-dependent or difficult-to-drug biology accessible in a pill.
That answer is still years away. The money is moving before the clinical evidence.
