Periodic Reporting for period 2 - ERACoSysMed (ERACoSysMed - Collaboration on systems medicine funding to promote the implementation of systems biology approaches in clinical research and medical practice) Reporting period: 2015-11-01 to 2020-06-30 Summary of the context and overall objectives of the project Systems medicine is an approach, which integrates biological and medical data with mathematical and computational modelling in order to understand the underlying mechanisms of disease and to develop new strategies for individualised diagnosis, treatment and prevention. Moreover, systems medicine can fill the gap between experimental data produced by modern technologies and medical knowledge. In consequence, systems medicine provides a new tool to clinicians that will change the capabilities of the clinician to diagnose and treat patients faster and more effectively – a tool, which has the potential to become a generic prerequisite for personalised medicine. ERACoSysMed was an ERA-Net funded under the ERA-NET Cofund scheme in the H2020 programme from January 2015 to June 2020. It comprised 15 funding and management organisations from 13 countries. The overarching aim of ERACoSysMed was to enhance the implementation of systems biol-ogy approaches in medical concepts, research and practice by structuring, coordinating and integrating national efforts. Guided by the CASyM roadmap the main objectives have been:• To implement systems medicine on long-term across Europe by supporting the systems medi-cine community in fostering inter- and multidisciplinary collaborations.• To establish a network of funding bodies for systems medicine to sustainably implement sys-tems medicine across Europe. • To implement joint transnational calls for research proposals with the aim to push forward the desired paradigm shift towards personalised medicine. • To provide a platform for the implementation of the actions guided by the systems medicine implementation strategy recommended by the CASyM roadmap. In the project duration ERACoSysMed organised and implemented three joint calls for transnational research projects on systems medicine. In the 1st joint transnational call (JTC-1) in 2015, co-funded by the European Union, nine research projects demonstrating the social and economic benefit of the sys-tems medicine approach were selected with a total budget of approximately 12.7 Mio €. The 2nd joint transnational call (JTC-2) was implemented in 2017 and focused on research projects improving cur-rent knowledge of health and disease. Five projects were funded with a total budget of approximately 6.1 Mio €. The 3rd joint transnational call (JTC-3) was implemented in 2019 having the focus on the val-idation of existing predictive computational models using biomedical data to expand the knowledge about human diseases and their treatment. Six projects were selected with a total budget of approxi-mately 5.6 Mio €. In sum, twenty transnational research projects were funded comprising over 100 re-search groups from 15 countries with a budget of approximately 24.4 Mio €.ERACoSysMed further organised six awareness events in different participating partner countries to enhance the awareness of systems medicine and its feasibility and benefits in the clinic and beyond. In addition, two dedicated workshops demonstrating and discussing on how to implement systems medicine in the education of medical schools and on how to integrate systems medicine into clinical prac-tice and research were held.Overall, ERACoSysMed made a substantial contribution in strengthening the European Research Area in the field of systems medicine and its implementation. This supported the European policy for personalised medicine. Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far During its project duration ERACoSysMed organised and implemented three joint transnational calls (JTC-1, JTC-2, and JTC-3) in the field of systems medicine. In the preparation phase of these joint transnational calls workshops were organised to define call topics and procedures reflecting on les-sons learnt from the former calls. In order to facilitate the monitoring of the co-funded JTC-1 projects, a midterm and a final status sem-inar were organised, which took place in 2018 and 2019 in France. In addition, a workshop was held in 2019 to identify potential impact of the funded JTC-1 and JTC-2 projects on clinical practice discussing bottlenecks, challenges and needs to achieve significant impact. For dissemination, the outcome was summarised in a 5 min video and a short recommendation letter. To strengthen networks and the systems medicine community in Europe, six awareness events were held. Each awareness event brought together key players from various disciplines and provided a for-ward-looking forum to demonstrate state of the art, discuss challenges and reflect about the future perspective of systems medicine. Moreover, the events raised awareness not only of systems medi-cine as a way to set up and organise clinical research in a systematic way, but also of the ERA-NET in-strument and activities in ERACoSysMed. In addition, two dedicated workshops were organised re-garding implementation of systems medicine education in medical schools and integration of systems medicine into clinical practice and research in Ljubljana in Slovenia. These workshops and awareness events contributed to the dissemination activities of ERACoSysMed. To further raise awareness, a factsheet and a short animation movie for laymen about systems medi-cine have been produced. Furthermore, a movie demonstrating the impact of systems medicine ap-proaches in cardiovascular diseases was produced as well as flyers of projects with success stories. Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far) ERACoSysMed was devoted to address a societal challenge and to build a socio-economic impact with the measures taken. In line with the CASyM road map, research projects have been selected for fund-ing, which had a clear clinically derived origin and a strong translational aspect with a high societal and economic impact potential. Through the transnational character of the research consortia inter- and multidisciplinary collaborations have been fostered on the European level helping and the improve-ment in Europe's research performance in the field of systems medicine and the development of a critical mass of expertise. The assessment of the short-term impact of the co-funded JTC-1 projects performed indicated as an important outcome a better overall understanding of disease processes and underlying mechanisms improving clinical decision making. Furthermore, their results constitute possible health care interven-tions and and contribute to the public understanding of systems medicine. Importantly, ties to the in-dustry were established and business opportunities arose. Moreover, improvement of existing health policy standards was foreseen. Overall, ERACoSysMed had an impact in the field of system medicine at both European and national levels and on the research community. Future developments within this area will accelerate the un-derstanding of diseases, and hence, changing the medical landscape by moving towards prevention or early treatment of diseases in clinical practice. This will build a real, lasting benefit for personalised medicine, and consequently the patients and the health care system. Further socio-economic impact is thus expected beyond the project duration of ERACoSysMed due to the substantial contribution of sys-tems medicine approaches in personalised medicine.