The vision of Immune Safety Avatar (imSAVAR) is to develop a platform for integrated nonclinical assessments of immunomodulatory therapy safety and efficacy. Existing nonclinical models do not adequately represent the complexity of the immune system and its interactions in both immunoncology and immunmediated diseases. They also do not accurately reflect the diversity of response to new therapies that is seen in clinical medicine. We will, thus, constantly refine existing and develop new nonclinical models with the final goal of validation aiming at: (i) understanding the value of nonclinical models for predicting efficacy and safety of immunomodulators incorporating cellular high throughput assays, complex organisms models and micro physiological systems, (ii) developing new endpoints and better monitoring approaches for immune function tests, and (iii) designing cellular and molecular biomarkers for early detection of adverse effects. The platform imSAVAR will be based upon case studies for prioritized therapeutic modalities and has been built around institutes of the Fraunhofer-Gesellschaft which has strong track records in applied science and in particular toxicology. The consortium will improve the prediction of the transferability of safety and efficacy of immunomodulators from pre-clinical models to first-in-human studies in collaboration with the private sector, pharma, regulators and technology providers. We will share experience on customized models that can be deployed (w.r.t. the 3Rs principles), establish the necessary infrastructure, conduct the analyses and provide wider disease domain expertise. This conjoint effort assures that the platform imSAVAR constantly benefits the field of immune safety evaluation, and will generate opportunities for European businesses. A guiding principle of this consortium is the meaningful engagement of multiple stakeholders including patients and regulators. A multi-stakeholder community will be established.

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.

Immune cells that are empowered by gene-engineering to seek and destroy cancer cells (engineered T cell therapy) constitute a transformative novel treatment that has the potential to cure cancer. Multiple new versions of this therapy are being developed for distinct types of cancer but their introduction into clinical practice is hampered by a lack of standardized and validated models to predict safety and efficacy, customized manufacturing and monitoring to scale up production and clinical use to industry standard, and strategies for optimal patient conditioning. The T2EVOLVE consortium unites scientists and physicians, regulators and policy makers, SMEs, and patient stakeholders to tackle these challenges in an orchestrated multi-disciplinary multi-stakeholder approach. A core feature of this approach will be the embedding of patient stakeholders as contributing members of the team across all levels of the R&D process. The overall aim is the development of an innovation ecosystem that will accelerate the process of developing engineered T cell therapy in the EU. The project will deliver novel tools for education and for improving the communication between healthcare providers and patients, optimized laboratory models that can help determine how safe and effective new therapies with engineered T cells are, standardized methods in which these therapies are produced and monitored during treatment. The consortium members are innovators and pioneers in this field that are dedicated to bringing the EU to the forefront of the global engineered T cell therapy movement. This effort will ensure that EU citizens will continue to have access to the most innovative and best-available medical care, provide guidance on how to implement this novel treatment into the EU health care system in a sustainable way, and secure a leading role for Europe in this emerging field in medicine and science, the economy and society.