Strongly associated with the epidemics of obesity and type 2 diabetes that are testing healthcare systems worldwide, Non-Alcoholic Fatty Liver Disease (NAFLD) is an increasingly common cause of advanced liver disease that is characterized by substantial inter-patient variability in severity and rate of progression. It is currently assessed by liver biopsy, an invasive, costly and risky procedure. The lack of noninvasive biomarkers has hampered patient care and impeded drug development by complicating conduct of clinical trials.The overarching aim of LITMUS is to develop, robustly validate and advance towards regulatory qualification biomarkers that diagnose, risk stratify and/or monitor NAFLD/NASH progression and fibrosis stage. This will be achieved through a goal-oriented, tri-partite collaboration delivering a definitive and impartial evaluation platform for biomarkers, bringing together: (i) End-users of biomarker technologies (clinicians with expertise in NAFLD and the pharmaceutical industry)? (ii) Independent academics with expertise in the evaluation of medical test/biomarker performance? and (iii) Biomarker researchers and developers (academic or commercial). LITMUS has the demonstrable capability to fulfil the IMI call remit. Built upon foundations laid by the EU-funded FLIP/EPoS projects and long-established, successful scientific collaborations amongst many of Europe’s leading clinical-academic centres, LITMUS is at a unique advantage due to its existing large-scale patient cohorts, bioresources and multi-omics datasets. Consortium members are internationally recognised experts with substantial relevant expertise supporting the program’s clear focus on biomarker identification, validation and accelerating EMA/FDA qualification. Thus, LITMUS is powered to provide clarity on biomarker validity for NAFLD at scale and pace: supporting drug development and the targeting of medical care and limited healthcare resources to those at greatest need.

The main aim of NEURONET is to set up an efficient platform to boost synergy and collaboration across the IMI projects of the Neurodegenerative Disorders (ND) portfolio, assisting in identifying gaps, multiplying its impact, enhancing its visibility and facilitating dovetailing with related initiatives in Europe and worldwide. This will be achieved through the following specific objectives: 1) creation of an overall platform for efficient collaboration, communication and operational synergies among present and future IMI ND projects; 2) designing systems to map and analyse information regarding actions, initiatives and partnerships, assessing impact of the individual projects, remaining gaps and global value of the programme for stakeholders; 3) supporting the management of the programme (timelines, dependencies, synergies and key results across projects); 4) proactively detecting needs, opportunities and transferable best practices of projects and to connect them; 5) providing support to the projects by organising tools, services, expert advice and guidelines/recommendations on common issues; 6) promoting enhancement and coordination of communication across the IMI neurodegeneration projects, increasing programme visibility, outreaching to key stakeholders and establishing relationships with initiatives in the field; and 7) preparing and securing the long-term sustainability of NEURONET itself. Achievement of these objectives will necessarily rely on buy-in from existing and future projects in the IMI ND portfolio, and effective connections with other programmes and initiatives in Europe and beyond, including stakeholder representation. For this, the Consortium has been constituted by very active partners in a variety of IMI ND projects and related initiatives with specialists in areas like complex/project management, data sharing & re-use, drug development, patient engagement, communication, sustainability and regulatory/HTA interactions.

Major current hurdles for wide clinical use of AAV vectors are attributable primarily to: (i) host elimination by both immune and non-immune sequestering mechanisms – such neutralization by host antibody responses critically limits the possibility of repeated AAV delivery; (ii) AAVs are prevalent in the environment and hence a large proportion of the population carry AAV antibodies (up to 80%)– this pre-existing immunity renders AAV unable to infect target cells forcing substantial patient cohorts to be excluded from clinical trials. The current proposal is founded on compelling track record in the field and brings together a ‘best-with-best’ multidisciplinary team of international leading academic and EFPIA partners with complimentary expertise in gene therapy, immunology, chemistry, engineering, biotechnology, drug safety, viral vector production, regulatory and clinical trials. The overall goal is to analyse the currently available clinical data and then design preclinical and clinical studies to fill the knowledge gaps in advanced therapies development. Our main aims are to: 1) Develop improved model systems for predicting product immunogenicity in humans. This will be achieved by generating human and NHP 3D hepatic models; 2) Enhance our understanding of gene/cell therapy drug metabolism inside a host of cell types. The plan is to define metabolism of the therapeutic vector genome in different cell types to understand whether rates of degradation, episomal maintenance, or integration, and metabolic stress induced by AAV vector transgene expression vary from cell to cell. We will then adopt strategies to mitigate the loss of vector genomes and improve persistence; 3) Use diverse clinical expertise to establish the clinical factors around pre-existing immunity limiting patient access to advanced therapies therapy; 4) Engage regulators to ensure that the concepts and the data generated through this IMI programme will fill the gaps and support furture trials.

ConcePTION partners have united around a shared vision that we have a societal obligation to radically and rapidly reduce uncertainty about the safety of medication use in pregnancy and lactation. What do we deliver? ConcePTION aims to create a paradigm shift in how we study medication safety in pregnancy. We will establish (1) a successful, sustainable open-science based EU non-proprietary ecosystem of public and private stakeholders, pregnant women and researchers to generate and disseminate timely and reliable evidence on drugs across maternal, neonatal and long term outcomes of medication exposure in pregnancy and breastfeeding (2) a catalogue with fully characterized data sources for rapid selection of suitable data sources; 3) operational, business, network, information and data governance models, (4) quality assured and tested methodological approaches, analytical tools and data platforms allowing for distributed analyses, (5) procedures and tools for collection of digital data and samples directly from pregnant women, (6) In vitro, in silico and in vivo models for prediction of drug transfer in human milk, (7) a biobank and analytical network for quantification of drug in human milk, (8) best practice documents endorsed by regulators and health authorities and (9) a web-based drug information knowledge bank. How do we deliver? (1) Experienced leaders, able to manage challenging networks and public-public or public-private partnerships. (2) Defragmentation by connecting all key stakeholders and EU networks in this area. (3) Re-use of data, tools and foreground from prior European commission funded projects. (4) Connecting to leaders of similar initiatives in the USA, Canada, Asia and other parts of the world. (5) Systematic consensus & endorsement building. (6) Quality throughout as a precondition to trust the results and information by all users.

The GetReal Initiative brings together partners from the IMI GetReal project to drive the adoption of tools, methodologies and best practices from IMI GetReal and increase the quality of real-world evidence (RWE) generation in medicines development and regulatory/HTA processes across Europe. We will establish, in Work Package (WP) 1, a Think Tank, a number of Task Forces and a RWE Research Community. The Think Tank will consist of international thought leaders and will discuss, assesses and give recommendations on the opportunities and barriers to the generation, use and acceptability of RWE. They will act as ambassadors for the use of RWE during the project and beyond, enagaging with key stakeholder groups to drive policy debate and facilitate the uptake of the outputs of IMI GetReal and the GetReal Initiative. The GetReal Taskforces will drive the focused development of tangible solutions to the key challenges identified in IMI GetReal and the Think Tank. The initial three task forces will be: (i) Pragmatic Trials (design, operational feasibility and analysis/the GetReal PragMagic tool), (ii) network meta-analysis and benefit risk assessment (incl. the GetReal ADDIS tool) and (iii) Statistical Approaches for enriching RCTs with real-world data. The GetReal Research Community will consist of researchers and organisations active in the field of RWE generation, regulators, HTAs, physicians and patients. The Community will review and comment on any GetReal Initiative guidelines, recommendations or white papers ahead of their finalisation, will have access to all the GetReal tools and outputs, receive regular newsletters and receive invitations to attend stakeholder events. The project will also invest in long term sustainability of the GetReal Initiative and the tools on a not-for-profit basis (WP2). The project is supported by professional experienced consortium management (WP3) and an ethics work package (WP4).