Novo Nordisk and Orbis Medicines announced a $1.4 billion multitarget collaboration to discover oral cardiometabolic therapies using synthetic macrocycles designed for oral bioavailability. Orbis could receive upfront and milestone payments totaling as much as $1.4 billion, plus tiered royalties. The companies highlighted Orbis’ “nGen” platform and “nCycles,” which model and design macrocycles intended to overcome absorption limitations that have historically constrained oral peptide delivery. Novo also plans a strategic investment in Orbis, tightening the relationship between platform validation and therapeutic execution. The deal broadens Novo’s efforts after recent internal shifts and adds to a competitive push for oral alternatives to injectables in obesity, diabetes, and cardiovascular disease. It also reinforces how AI-enabled experimental pipelines are being used to generate chemistry datasets for macrocycle optimization.