The public-private partnership, READI, seeks to help clinical studies (CS) to finally serve the complete general population, and therefore more patients. To date CS have struggled to recruit and retain participants from diverse backgrounds and communities, such as marginalized or disadvantaged groups (e.g., sexual, gender, age, cultural, and socioeconomic cohorts). The resulting knowledge gaps entrench or increase health disparities. The READI consortium strives to tackle these challenges by fostering a more cohesive and integrated CS ecosystem for underserved (US) and underrepresented (UR) communities. It will actively connect all key stakeholders who can facilitate access to a wide range of patient populations. It will provide these stakeholders with the necessary tools, training programs, and approaches essential for the recruitment and retention of US/UR patients in CS. In addition, it will design, build and implement a digital platform which is patient-centred, sustainable, open and innovative. This will foster improved access to CS information and READI tools, while also supporting patient connections with the created communities. Finally, at least 4 CS will be used for testing the effectiveness of the developed tools and approaches. READI has a three-fold objective: to help US/UR communities overcome CS participation barriers (e.g., lack of information/awareness, mistrust, poor communication, geographic limitations, prejudice), which in turn will improve research of many diseases and conditions, preventative care and treatment effectiveness in different demographic groups, and better serve society. READI’s success will draw from its interdisciplinary, multi-stakeholder, consortium composition of 73 organizations from 18 countries, with key expertise in drug development and CS (design and operations), engagement strategies for US/UR populations, digital platform development, training and capability building initiatives, effective communication and dissemination, long-term sustainability, ethics and regulatory affairs.

Preclinical type 1 diabetes (T1D) research has made important advances in recent years, but less progress has been made in translating findings from in vitro and animal models into effective clinical interventions. INNODIA aims to achieve a breakthrough in the way in which we study T1D to enable us to move closer towards prevention and cure of T1D. To this end, INNODIA joins together the leading European experts from the fields of basic and clinical T1D research, four leading pharmaceutical companies with strong expertise in the discovery and development of diabetes medicines and the two leading public organizations involved in T1D research into one comprehensive collaborative consortium. The clinicians in INNODIA oversee T1D registries and have access to large populations of children and adults with T1D and family members at increased risk of developing the disease. The basic science researchers are experts in beta-cell pathophysiology, immunology, biomarker discovery, bioinformatics, systems biology and clinical trial design. INNODIA will accelerate understanding of T1D through coordinated studies of unique clinical samples and translation-oriented preclinical models. This should deliver novel biomarkers and interventions for testing in appropriately designed trials, to be developed in active collaboration with regulators and patients. INNODIA provides access to unique historical biorepositories and will create the Clinical Sample Network, a clinical EU infrastructure to recruit T1D subjects at diagnosis and at-risk relatives. These individuals will be deep-phenotyped and will provide biosamples, allowing the establishment of a ‘living biobank’ of subjects consented for recall. They will be characterized using standardized clinical, genetic and metabolic phenotyping procedures, including prospective, longitudinal sample collection to facilitate novel biomarker discovery. Diverse biological samples (blood, plasma, serum, urine, stools, etc.) will be collected at

Building on the strong foundations of INNODIA, with its unique, Europe-wide clinical and basic research network for the study of type 1 diabetes (T1D), we propose in INNODIA HARVEST an ambitious program which aims to prevent and arrest T1D via focused objectives targeting consolidation and innovation. First, we will consolidate the INNODIA clinical network as the reference point for conducting studies to prevent or arrest T1D. We will transform our standardized clinical and bioresource platforms into a high-performance clinical trial network, running academic and industry-driven trials alongside small, mechanism-centric, biomarker-rich intervention trials to examine pathobiological pathways to T1D. INNODIA HARVEST will conduct two large studies to arrest T1D at its onset, one academia-driven, beta-cell focused (VER-A-T1D, verapamil) and one industry-driven, immune-focused (Iscalimab-study). We will exploit our original INNODIA Master Protocol allowing novel adaptive trial design to introduce combination therapies that build on complementary mechanisms. Second, we will extend our study design strategy by introducing novel biomarkers, both clinical (continuous glucose monitoring) and experimental (microbiome analysis) to deconvolute disease heterogeneity and identify new endpoints to accelerate identification of effective therapeutics. Third, we will use ‘disruptors’ in small mechanistic studies to channel innovation from clinic to basic research through a reverse immunology and reverse beta-cell biology approach. Finally, we will implement new discovery pipelines for future therapeutics, exploiting tools such as iPSC-derived islet-like cells to promote next generation target identification and drug development. As in INNODIA, the voice of people living with T1D and their families will hold a central place in INNODIA HARVEST to drive implementation of new, patient-proximal outcomes, shape our clinical trials, and bring about a meaningful change in disease perspective. A major objective of INNODIA Harvest is the execution of at least two new phase 2 trials (studying Verapamil (VER-A-T1D) or Iscalimab (CCFZ533X2207)). Considering the expected time to first patient-in as preparations for trial start can only be initiated after the start of the Action and possible fluctuating recruiting rates, due to the intercurrent COVID epidemic, there is a risk that INNODIA HARVEST will not be able to completely finalize the clinical trials, fully analyse the biomarkers collected and publish the results in the initially proposed 24 months duration. To ensure the finalization of the clinical trials and corresponding full execution of the given budget including eligibility of EFPIA in-kind contribution we propose to extend the duration of the Action from 24 to 36 months.

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.

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.