Roche struck multi‑hundred‑million‑dollar research terms with Manifold Bio to develop new ‘brain‑shuttle’ platforms and paid an initial $55 million to access Manifold’s AI‑driven discovery stack. The collaboration—structured with potential milestones and rights to novel blood‑brain‑barrier (BBB) shuttle approaches—aims to accelerate delivery of biologics and other modalities into the central nervous system. Roche is already running Phase 3 studies for a Brainshuttle‑enabled Alzheimer’s candidate and is now expanding its portfolio of delivery technologies. Manifold’s computational design tools will be used to discover shuttle scaffolds and engineer CNS‑penetrant conjugates. The upfront payment and potential multibillion‑dollar upside reflect high commercial value placed on reliable BBB delivery. For neurotherapeutics, linking AI discovery engines to validated delivery scaffolds could shorten lead selection cycles; regulatory and translational hurdles remain around brain exposure metrics and safety of shuttle constructs.