Novo Nordisk struck a wide-ranging cardiometabolic research deal with Orbis Medicines, paying Orbis undisclosed upfront amounts that could total $1.4 billion in development and commercial milestones plus royalties. The agreement centers on using Orbis’s AI-enabled macrocycle platform to engineer oral alternatives to injectable cardiometabolic biologics. Orbis’s nGen platform designs synthetic macrocycles (nCycles) optimized for oral bioavailability—an approach aimed at overcoming long-standing challenges for taking peptides and other biologics orally. Novo’s internal strategy also reflects its ongoing restructuring after leadership changes and shifting competitive dynamics in obesity and diabetes. Orbis initially targets validated cardiometabolic targets associated with injectable blockbuster biologics, while Novo also plans a strategic investment in Orbis to deepen the collaboration. The deal extends Novo’s broader investment posture in AI-driven drug R&D. For Orbis, the partnership reinforces prior venture momentum and builds on its reported progress toward orally delivered GLP-1 medicines, with macrocycles positioned as a pathway to increase patient convenience and potentially broaden access.