AGILE will design, develop, and apply a holistic methodological framework and practical tools for understanding, assessing, managing, and communicating HILPs events with a systemic risk and resilience perspective. The project will combine and integrate a wide range of established and innovative methodologies into a novel and replicable multi-sectoral risk and resilience stress testing methodology to better: UNDERSTAND (Systems theory, Lateral thinking, Strategic Foresight, Machine Learning) ANTICIPATE (Scenario Building & table-top exercises, Multi-Criteria Decision Analysis, Machine Learning) and MANAGE (Resilience assessment, capability development strategic training) These approaches and services will be co-created within a unique transdisciplinary consortium of research organisations, NGOs, SMEs, first responders, and local and regional authorities. The scalable and replicable methods will enable for the identification of common points of failure of critical societal functions in response to compounding low probability high impact threats as well as provide recommendations for both risk-informed system hardening and threat-agnostic systemic recovery. The project will ultimately improve the strategic and operational risk management capacities and capabilities of DRM stakeholders on local, regional and national level and thus strengthening the societal resilience to new and emerging risks in Europe and beyond. The project provides the means and the methodology to ensure a wide ranging impact of its results to not only improve the understanding, anticipation and management of HILP risks and events, but the direct and wide-ranging contribution to key European and international policy priorities and global challenges such as the EU disaster risk management policies (in particular UCPM), the European Green Deal priorities (EU Climate Adaptation Strategy), as well as the EU Security Union Strategy.

HyCoFlex is aiming at the development of a retrofitable decarbonisation package for cogeneration of power and industrial heat with 100%-fired gas turbines. The solution will be integrated and fully demonstrated at an industrial site in Saillat-sur-Vienne in France. HyCoFlex will leverage on and further advance the infrastructure of a power-to-hydrogen-to-power industrial scale plant which was developed and demonstrated within the HYFLEXPOWER project. The project will develop operational flexibility capabilities and protocols to satisfy the typical operating profiles experienced by industrial cogeneration plants. By doing so, HyCoFlex will elaborate credible pathways for upscaling and replicating the retrofit package, ultimately accelerating the achievement of industrial and energy sector decarbonisation. In order to meet the global objective, within the HyCoFlex project, the HYFLEXPOWER plant concept and infrastructure will be implemented for 100% H2-fuelled cogeneration. In the framework of the project a Siemens Energy SGT-400 gas turbine will be upgraded with an advanced dry low-emission (DLE) H2 combustion system to operate with different natural gas / H2 fuel mixtures. The retrofitted demonstrator plant will be validated for flexible operation under various natural gas/hydrogen mixtures and loads, while aiming at overcoming state-of-the-art efficiencies with decreased NOx emissions. Finally, HyCoFlex will explore pathways for upscaling and commercialization of decarbonised power generation from gas turbines within a circular-economy framework.

Every year, 1.3 million Europeans have a stroke and one million ultimately die of stroke. One third of stroke patients remain dependent on the help of others. The annual costs for stroke care in Europe are estimated at € 64.1 billion. Stroke incidence increases almost exponentially with age, and the personal, societal, and economic burden of stroke is therefore largely driven by its frequent occurrence in the elderly. The elderly have been strongly underrepresented in previous stroke trials and treatment guidelines have no recommendations specific to this important group. Elderly patients are at the highest risk of complications after stroke, such as infections, fever, and dysphagia. These complications are strongly and independently associated with a higher risk of death or dependency. We will perform a pragmatic, randomised, open clinical trial with blinded outcome assessment in 3800 patients with acute stroke aged 66 years or older, to assess whether pharmacological prevention of infections and fever, and early management of dysphagia, will reduce the risk of death, poor functional outcome, and poor quality of life, and lead to reductions in the costs of stroke care throughout Europe. Patients will be randomised using a factorial design to preventive treatment for 4 days with ceftriaxone, paracetamol, and/or metoclopramide, or to ‘standard care’ alone. The primary outcome is functional outcome at 3 months, assessed with the modified Rankin Scale (mRS), and analysed with ordinal logistic regression. The study will have 90% power to detect a statistically significant shift towards a favourable outcome, assuming a 5% absolute increase in the proportion of patients with a good outcome (mRS 0 to 2) in the intervention group, compared with controls. This simple, safe, and generally available treatment strategy has the potential to lead to an annual reduction of over 25 000 elderly Europeans being dead or dependent as a result of stroke, at very low costs.

OPTIMA is a multi-stakeholder-led consortium with the vision that each and every patient should have access to the most up-to-date individualised treatments and to innovative therapies. In that perspective, we will design, develop and deliver the first interoperable and GDPR compliant European real-world oncology data and evidence generation platform, along with decision support toolsets for prostate, lung and breast cancer. By designing this platform from the onset based on the needs of the clinicians and patients in an inclusive and sustainable way, OPTIMA aims to strengthen shared decision-making based on innovative data and AI-driven technology and tools. To achieve our vision, we have united the key partners from other data-driven European wide oncology initiatives (PIONEER, EHDEN, HARMONY) in our project along with Europes leading clinicians in the fields of breast, prostate and lung cancer that all have leading roles in medical societies such as ERS, ESMO, and EAU. At the core of the OPTIMA project are the major guideline offices of the three indications, whilst the project is further strengthened by patient advocacy groups, well-known academic partners and 6 SMEs as partners covering the needed expertise to implement OPTIMA successfully. The platform will build on existing open source solutions such as the OMOP-CDM, tranSMART and OHDSI ATLAS whilst developing novel AI models based on federated learning to facilitate knowledge discovery. At the start of the project, we will already have access to datasets covering over 200M people in Europe, along with data from high quality patient cohorts for AI model building. Moreover, the platform will be hosted in-kind on existing infrastructure provided by Helmholtz Institute in Germany. Finally, OPTIMA envisions sustainability of its platform through a value-based approach with various business models for commercial users.

CARAMBA is proposing to use the revolutionary CAR-T cell technology to tackle multiple myeloma, a rare and incurable hematologic malignancy. Myeloma is associated with a substantial socioeconomic burden and there is a strong demand by patients, their families and caregivers for a curative myeloma treatment. The CARAMBA investigators will conduct a phase I/II clinical trial of immunotherapy with patient-derived T cells that are engineered to express a synthetic chimeric antigen receptor (CAR) specific for the myeloma antigen SLAMF7. SLAMF7 is uniformly expressed on all myeloma cells in every patient, and SLAMF7 CAR-T cells will be equally effective in women and men. The efficacy and safety of SLAMF7 CAR-T cells has been validated by the coordinator in comprehensive pre-clinical testing which highlighted their unprecedented curative potential. SLAMF7 CAR-T cells have received an orphan designation for the indication multiple myeloma by the EC. The successful conduct, rapid and complete recruitment into the clinical trial is ensured by participation of 4 clinical myeloma centres of excellence in 4 EU member states, and the largest myeloma patient advocacy group in Europe, MPE. The SME partners in CARAMBA are prepared to develop the SLAMF7 CAR product all the way to market authorization. CAR-T cell therapy has been recognized as a ‘Breakthrough Therapy’ and clinical proof-of-concept obtained with CD19 CAR-T cells in leukemia and lymphoma. CARAMBA is building on novel and proprietary, cutting-edge CAR technologies including virus-free Sleeping Beauty CAR gene-transfer from DNA minicircles which substantially reduces the cost of CAR-T cell manufacturing, making it an economically viable and sustainable medicinal product. We are confident, that if funded, CARAMBA will accomplish its objective to establish the role of CAR-T cell therapy as a therapeutically effective, commercially attractive and socioeconomically desirable treatment in myeloma and other rare diseases.