Future transport and mobility will be disrupted by innovations in Connected Automated Vehicles (CAVs), in which safety will be of the highest priority. SAFE-UP aims to proactively address the upcoming safety challenges by developing innovative technologies, testing and assessment methods. SAFE-UP is based on 3 key pillars: i) future safety-critical scenarios, ii) new safety technologies, and iii) novel safety assessment methodologies. Future safety-critical scenarios will be designed and analysed in a highly automated and mixed traffic environment in a traffic simulation platform. Based on these scenarios, new safety technologies for active and passive systems will be developed, resulting in 4 Demos. The passive safety system of Demo 1 will include restraint and occupant monitoring technologies for new seating positions. Three active safety system prototypes (all on-vehicle, one of them also including on-user and infrastructure) will be developed. Demo 2 will enhance the interaction between vehicles and VRUs under bad weather conditions while Demo 3 will integrate advanced intervention functions to avoid critical events. Demo 4 will consist of a safety solution based on C-ITS to enable timely warning provisions. To prove the overall benefits, new safety assessment methodologies will be thoroughly designed. The SAFE-UP consortium is another major asset, consisting of key players in mobility across the entire value chain: advanced OEMs, leading suppliers & industry, and academia. The new technologies will reduce fatalities by covering pedestrians, cyclists and Powered Two Wheelers in urban areas through active safety systems and cars in non-urban through passive safety technologies, which will impact 64% of all road fatalities. SAFE-UP will also develop targeted education and training schemes for fostering the implementation of automated driving functions, while also focusing on raising awareness of future road safety challenges.