The development of new in vitro models (Biological Twins) for clusters of patients suffering from specific pathologies (3 different types of cancer, degenerative pathologies like multiple sclerosis, metabolic pathologies like diabetes) is the core business of Spoke 4 and perfectly matches with the evocative mission of developing “technology driven” innovative diagnostics and therapies in precision medicine envisaged by the NRPP. Indeed, besides providing a first level validation of the newly generated models (Digital Twin) developed in Spoke 2, Spoke 4 aims to provide further biological and patient-derived info and input to enquire for alternative scenarios (i.e. new therapy options) or to better tailor digital models with the definitive ambition to deliver a truly enabling technological platform for the healthcare system, granting clinical decision support and addressing improvements in diagnostics, therapy and rehabilitation. The expected results of Spoke 4, synergic with the previous complementary Spokes, will then comply with the NRPP target to strengthen the foundation for appropriate preclinical and clinical trial phases, allowing for patients to be stratified by associating them with new, better tailored and targeted therapeutic protocols to improve the complex clinical management.