Novo Nordisk entered a major cardiometabolic deal with Orbis Medicines to develop oral alternatives to injectable therapies using AI-enabled macrocycle design. Orbis could receive undisclosed upfront payments plus milestones totaling up to $1.4 billion, along with tiered royalties, and Novo will also make a strategic investment in Orbis. The partnership centers on Orbis’ nGen/nGen platform and its nCycles synthetic macrocycle approach, which aims to improve oral bioavailability for peptide-like drug modalities that traditionally struggle with gastrointestinal absorption. Orbis’ platform is designed to optimize multi-parameter properties using a large experimental macrocycle dataset generated in real time. The deal reinforces Novo’s continued push into oral peptides and oral biologics as it seeks to rebuild growth after setbacks in obesity and diabetes leadership shifts. It also aligns with a broader industry interest in macrocycles as a way to overcome dosing and formulation limitations that force high injectable strength for current cardiometabolic standards. For biotech partners and competitors, the scale of the Novo-Orbis commitment signals that AI-enabled chemistry platforms are now being treated as strategic engines for next-generation route-of-administration platforms, not just discovery tooling.