Immunotherapies have emerged as effective treatments for immune system-related diseases, such as cancer and inflammatory diseases. Although immunotherapeutics are effective not all patients benefit and side effects vary greatly. Thus, there is an unmet need for a personalized approach. Blood and tissue biomarkers have played only a modest role up until now in assessing immune status in vivo and we believe that non-invasive whole body imaging will make a significant contribution in the future. Although the field of imaging (PET, MRI, Optical Imaging) is flourishing, its application to patient immune status measurement and monitoring has barely been explored. Within Immune-Image we aim to develop new immunotracers for imaging specific immune cell subsets, develop quantitative imaging workflows, validate the immunotracers pre-clinically in relevant disease models, produce the tracers in a Good Manufacturing Practice (GMP)-compliant way, and conduct smart clinical trials, including with novel tracers. To this end, insights will be gained into the optimal use of drugs and a more efficient development of immunotherapeutics. Moreover, the success rate of immunotherapy development will be enhanced since our molecular imaging platform will provide novel insights into patient immune status, which will support drug development and treatment decisions. To achieve our goals, we have assembled an experienced international multi-disciplinary consortium composed of chemists, biologists, immunologists, physicists, pharmacists, information technologists, and medical specialists with diverse and essential backgrounds who will join forces to design, synthesise, evaluate and validate immunotracers and create sustainable molecular imaging techniques that can be broadly applied in the assessment of the immune status and immune modulation of patients. There will be input from patients and regulators in order to assure optimal design and execution of immunotracer clinical trials.

1.Our consortium has broad, deep experience of drug development and imaging biomarker (IB) validation. We are internationally recognized experts in transporter biology, animal models of lung injury, toxicology, DCEMRI, compartmental modeling, 1H&129Xe lung MR, and labeling of biologicals with PET and fluorescence tags, together with physicians who care for relevant patients. We have an outstanding record of translating IBs: (a) into animals, (b) into man, (c) into tools which drug developers use with confidence in clinical trials of investigational agents, (d) into regulatory drug development and healthcare. We will develop and validate the required IBs and make them commercially available. 2.Building on our previous work with gadoxetate DCEMRI IBs we will develop and standardise, define sensitivity and specificity in rats, and show valid and comparable data multicentre in human volunteers and patients. 3.We believe the search for IBs of Drug Induced Interstitial Lung Disease (DIILD) should start in DIILD patients. Cancer and rheumatology patients receiving, in their standard care, drugs with DIILD liability, and whose physicians withdraw the drug due to suspected DIILD, will be imaged when symptomatic and followed up. From this we will derive IBs of DIILD which predict outcome. We will also develop IBs from 1H/129Xe MRI and PET to further characterise DIILD, and will back-translate and validate all these IBs in rat models. 4.To better assess biodistribution of biologics, we will thoroughly characterise two well-chosen exemplars in rats, pigs and humans: an antibody biologic and a peptide biologic. We will use 89Zr, 18F and 68Ga PET, fluorescence and MALDI imaging. 5.We will follow an imaging biomarker roadmap to establish (a) that the IBs can be deployed robustly in whatever centre they are needed, (b) the relationship of the IB to underlying biology, (c) how well the IB forecasts clinical outcome, and make appropriate arrangements for dissemination.

Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD), and its global incidence and prevalence have reached epidemic dimensions in recent years. Unfortunately, there are no effective means to prevent or cure DKD, the few existing treatments have limited effect and very few alternative therapies have emerged in the past years. Lack of new predictive and prognostic biomarkers for a more accurate patient stratification, limited access to kidney tissue from patients at various stages of DKD as well as novel model systems to better understand the pathogenesis of the disease, are likely reasons for the stagnating development of new treatments. The BEAt-DKD consortium combines outstanding basic and translational researchers in nephropathy, diabetes, kidney model systems, imaging techniques and systems biology, and includes leaders of diabetes and kidney disease-relevant IMI1, FP7 and US consortia, like SUMMIT, KIDNEYCONNECT, Syskid, CPROBE and C-Path, in an unprecedented search for new and better biomarkers for DKD, through a better understanding of the disease. Jointly, the partners have access to vast and very relevant clinical cohorts and trials, state-of-the-art analysis and imaging techniques, novel model systems and the long-standing experience and networks to make this collaboration a success. By involving regulatory agencies throughout the project, BEAt-DKD aims at making the introduction and acceptance of new tools as efficient as possible. The overall goals of BEAt-DKD are (1) to provide a holistic systems medicine view of the pathogenesis of DKD with the aim to identify targetable mechanisms and pathways underlying initiation and progression of DKD, applying a novel sub-classification of diabetes, and (2) to identify and validate biomarkers of disease progression and treatment responses representing first steps towards precision medicine in the management of DKD.

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.