BackgroundTranslational research and medicines development refers to the translation of basic scientific discoveries into clinical applications such as new therapeutic, diagnostic or preventive products. Translational research and medicines development thus lays at the foundation of any improvement of human health and quality of life, and is a motor for growth and innovation. In order to be successful in this field, professionals need to be aware of all stages and research disciplines and also understand the various roles played by academia, industry and regulatory authorities. The multidisciplinary, multi-sectorial and transnational nature of translational medicines underlines the need for a defined set of skills and qualifications which learners and professionals can rely on to move freely between different labour markets and countries. ObjectivesThe objective of C-COMEND is to bring together players from different sectors and disciplines in order to develop curricula and provide a course aimed at PhD students and early Post-Docs, teaching the skills and competencies required to successfully contribute to translational research and medicines development. To ensure that the course indeed teaches the right skills and is relevant for the labour market, be it in academia, industry or the regulatory field, the course curriculum will be based on a competency profile developed during the project. The course will be delivered as a blended course, where the face-to-face course is preceded by e-learning to bring learners to the same level of understanding, thus allowing more in-depth discussion during the face-to-face course. The project aims at delivering the courses to a broad target group. The face-to-face course will therefore be offered twice during the project lifetime with 15 participants for each course from project partners and 15 from participants outside the consortium. The e-learning module will be made accessible to all biomedical students and professionals in Europe and worldwide.Participants: The consortium consists of 5 partners: 2 higher education institutes, 1 research institute, 1 research infrastructure and 1 e-learning provider and developer.ActivitiesThe methodology to develop the courses is the ADDIE principle. ADDIE stands for the steps needed to prepare an effective learning session and which will be implemented in this project accordingly: 1) During the Analysis phase, the project will develop a competency profile for students and professionals in translational research and medicines development. Competency provides a shared ‘currency’ applicable to learning of all types and at all career stages. The profile will include not only the scientific competencies but also competencies in transversal skills and entrepreneurship. The profile will be complemented by a competency portfolio where participants can document the new competencies plus the competencies they already acquired during previous formal, informal and non-formal learning, to support the recognition of their competencies. 2) During the Design Phase, the consortium will design and document the curricula for courses based on the competency profile. The curriculum will apply multi-competency training wherever possible. This will include student presentations of their projects, which will teach the latest scientific developments but also improve their presentation skills. 3) During the Development Phase, the course content will be designed including learning methods which promote the transfer of course content into observable competencies and cater for different learning styles. 4) The Implantation Phase will consist of the implementation of the e-learning module and the face-to-face courses. 5) The feedback of the Evaluation Phase will be used to optimise the 2nd delivery of the e-learning and face-to-face course.In addition to the curricula, courses, the competency profile and a scientific publication, the project will deliver a Business Plan describing how the face-to-face and e-learning courses can be maintained in a way that enables a broad participation and reduces the costs for participants. The envisaged impacts are• Enhanced quality and increasing labour market relevance of learning provision via the developed curricula based on a competency profile• Improving career opportunities of course participants• Fostering the interaction between research, education and innovation • Services available to a broad audience • Support of mobility (between countries and public & private sector)Longer term benefits• Delivery of competencies ensuring the European competitiveness of Medicines Development;• Sustainable contribution to strategic planning of professional development via a publically available competency profile• Increased number of scientific ideas turned into innovative products bringing growth and jobs to the European economy.• Improvements in public health due to better trained professionals

ContextAdvanced therapy medicinal products (ATMPs) is a class of innovative therapeutics which includes gene, cells and tissue engineered products. ATMPs offer unprecedented promise for the long-term management and even cure of diseases, especially in areas of high unmet medical need, such as cancers and haematological, ocular, neurodegenerative and genetic diseases. However, the translation from research into patient benefit faces many challenges and requires the involvement of many stakeholders (including academic start-ups, biotech industry, regulatory agencies). For ATMPs to fulfil their potential, specific skills and knowledge in four key areas need to be available in the workforce, which are currently lacking: manufacturing, clinical trials, regulatory approval and reimbursement.ObjectivesThe main objective of the project is to support early career researchers in developing currently missing scientific knowledge, transversal skills and competences to meet the key challenge areas existing in the ATMP development cycle. By establishing an innovative and focused learning programme, ADVANCE aims at establishing a strategic partnership between key players from education, research and industry that contribute to innovation of ATMPs to jointly develop curricula for early career biomedical professionals.ParticipantsThe “next generation of ATMP developers” – i.e. early career biomedical academics (PhDs, Postdocs), including doctors in training, clinician scientists and SME-based professionals, who are considered to be an important component of the labour market and the critical intermediaries of the ATMP development pipeline - are the core target group for the three-stage blended learning programme foreseen by ADVANCE. Activities and outputsThe three-stage blended learning programme consists of three complementary and interconnected modules all addressing key challenge areas in ATMP development : (1) online course (for teaching “basic” scientific knowledge); (2) webinars (for in-depth scientific knowledge and skills, combined with career coaching; and (3) face-to-face workshops (for training transversal skills and competences). Both the webinars and the online course will be free of charge and available to a broad audience. The three curricula (IO1-3) will be complemented by digital credentials (IO4) and a sustainability plan (IO5). MethodologyThe project methodology for developing the courses is based on the ADDIE principle – an instructional design model – consisting of 5 interrelated steps that will be implemented in the project accordingly: 1) Analysis; 2) Design; 3) Development; 4) Implementation; and 5) Evaluation.1. During the Analysis phase, learning objectives for the courses will be defined based on a previously established competency profile (within the Erasmus+ funded C-COMEND project) for scientists involved in medicine research and development, including ATMPs, to ensure matching with labour market needs.2. During the Design phase, the consortium will design the curricula of the courses based on the established learning objectives. The curricula will apply multi-competency training and Bloom’s taxonomy will be used to classify educational learning objectives into levels of complexity.3. During the Development phase, the content of the training activities will be designed, including interactive learning methods which promote the transfer of course content into observable competencies and cater for different learning styles. 4. The Implementation phase will consist of the delivery of the online course, the webinars and career coaching sessions as well as the workshop programme.5. In the Evaluation phase, the feedback obtained from participants as well as faculty, organisers and project partners will be used to optimise the second delivery of the online course and workshop cycle.Envisaged results and impact:• Outputs available to a broad audience (aim online course 500, webinars 700 and workshop 60 participants).• Enhanced quality and relevance of competencies and knowledge to the labour market in the biomedical sciences.• Improved course participants' career opportunities and employability in the field.• Fostered interaction between research, education and innovation.• Supported mobility between countries and between public & private sectors.Longer term benefits:• Increased European competitiveness of ATMP development.• Increased number of scientific ideas turned into innovative products bringing growth and jobs to the European economy.• Strengthened public-private strategic partnership and collaborations in the field of ATMPs.• Improvements in public health due to better trained professionals who will drive effective and accelerated ATMP development and offer safer and affordable treatments for patients with high unmet medical needs.

Sickle cell disease (SCD) is one of the most prevalent monogenic diseases in Europe. A single amino acid substitution in the beta-globin chain of the adult hemoglobin (Hb) drives red blood cell sickling and multi-organ damage. The clinical severity of SCD is alleviated by the co-inheritance of mutations causing expression of fetal gamma-globin in adult life ? a condition termed hereditary persistence of fetal hemoglobin (HPFH). Transplantation of autologous, genetically modified hematopoietic stem/progenitor cells (HSPCs) is an attractive therapeutic option for SCD patients. To this end, genome editing approaches based on the use of site-specific nucleases or, more recently, base editors have been explored by many groups, including teams in our consortium. These approaches either correct the single point mutation causing SCD or reactivate fetal gamma-globin expression by mimicking HPFH mutations. On the other hand, (pre)clinical data from SCD patients or SCD mouse models, as well as preliminary data from our labs suggest that SCD HSPCs are characterized by a high mutational burden, oxidative stress and expression of inflammatory genes. This can alter HSPC properties as well as their interactions within the bone marrow niche. In the context of gene therapy, it is essential to understand the mechanisms underlying SCD HSPC dysfunction and assess the impact of genome editing approaches on SCD HSPCs. In this proposal, we have assembled a multidisciplinary team to: (i) understand the molecular and cellular mechanisms underlying SCD HSPC autonomous and non-cell-autonomous dysfunctions and (ii) evaluate the impact of established and novel genome editing approaches on SCD HSPC properties and genome integrity. This study will lay the foundation of an improved gene therapy strategy to treat SCD and provide best practice tools and protocols for genome editing-based therapies in HSPCs.

HEAL will focus on general bottlenecks to induced pluripotent stem cell therapies with a particular focus on heart failure, which remains a major cause of morbidity and mortality with very few treatment options. HLA-homozygous cell line derived cardiomyocyte aggregates offer the prospect of a restorative heart therapy applicable to large patient populations and to overcome economic barriers associated with autologous approaches. By developing solutions for their mass-production and cryopreservation we will enable allogeneic treatment with minimum requirements for immunosuppression. Assays for assessment of immunogenicity will provide data for the development of an artificial intelligence powered algorithm to predict recipients's immune responses for personalised design of immunosuppression protocols. A potency assay to assure product effectiveness will be developed together with assays of tumorigenicity in vitro and in vivo that meet and exceed current regulatory requirements. A genetic integrity pipeline defining the most sensitive assays for rigorous assessment will be developed and a rescue tool in the form of a biallelic suicide gene for programmed cell death will add to the safety toolbox for the therapy. Optimisation of cell-product administration in terms of retention and engraftment, including catheter-based delivery as minimally invasive alternative to surgical application, and assessment of risks of graft-induced arrhythmia will be determined in a pig model. Early dialogues, via established links, to the regulatory authorities will ensure proper development according to GMP requirements. Freedom to operate and licensing strategies with a health technology and infrastructure assessment of European centres will set the scene for approval of the cell product and related assays and protocols for storage and distribution required to progress towards a first in man study of cell-based heart repair.