EU-PEARL has the ambition of transforming the current approach of conducting single-compound clinical trials into the use of cross-company Integrated Research Platforms (IRPs), taking into consideration both patients’ interests and the opportunities from novel molecules for addressing medical needs. Patient-centric data and knowledge sharing have the potential to accelerate the development of new treatments and reduce the operational costs of clinical trials. EU-PEARL will improve clinical effectiveness, patients’ satisfaction and societal access to timely and affordable medicines and it will shape the clinical trials of the future. This will change the industry paradigm from competition to cooperation in four disease areas and provide the framework for designing IRPs in other disease areas. The main objectives of EU-PEARL are: (1) To create a reusable, accessible and sustainable modular IRP for the design and execution of patient-centric, cross- company IRP in any disease area with unmet needs; (2) To set up the open, dynamic, patient inclusive IRP governance structure that will manage the appropriate regulatory, ethical, legal, statistical and data utilisation requirements of the IRP; (3) To disseminate and exploit the EU-PEARL paradigm through the provision of the necessary common tools, procedures, expertise and operational skills working to the highest scientific, regulatory and ethical standards and best practices, developed jointly by public and industry partners in a consensus-based approach; and (4) To create trial-ready IRP networks in the four disease areas of Major Depressive Disorder (MDD), Tuberculosis (TB), Non-Alcoholic Steatohepatitis (NASH) and Neurofibromatosis (NF).

There is a very high need for improving the management of pain. Acute and persistent pain of different origins represent a common medical, social, and economic burden, and its pharmacotherapy is often inadequate. To advance management of pain patients and support decision making in clinical practice, more predictive assessments of treatment success are needed. The development of analgesics is onerous because promising preclinical data often do not translate into the clinic. Improved pharmacodynamic biomarkers could define whether nociceptive signalling is adequately modulated by a new drug, so increasing the chance of successful translation and greatly reducing the risk in initiating clinical development. Further, the pathophysiology of chronic pelvic pain indications is poorly understood and no adequate preclinical models are available, precluding focused preclinical research and leaving affected patients with little hope of relief. IMI-PainCare aims at making advances in these three pain areas in a complementary manner. Three subprojects will address specific scientific challenges. Subproject PROMPT will identify Patient Reported Outcome Measures as tools to standardise assessments of treatment success of acute and chronic pain in Real World conditions and controlled trials, and so improve its management; subproject BioPain will validate the translatability of pharmacodynamic biomarkers and PK-PD modelling in pain pathways of healthy subjects and preclinical species, thereby offering tools to improve drug development; subprojectTRiPP will identify biomarkers and novel therapeutic pathways of clinical phenotypes of patients with chronic pelvic pain, which after back-translation, can improve how preclinical models reflecting human diseases. The goal of IMI-PainCare is to improve the care of patients with acute or chronic pain by providing a toolbox to streamline the development process for novel analgesic drugs and to improve treatment quality in clinical practice.

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.

Clinical trials increase in size, complexity and costs. This is fuelled with the need to demonstrate effects in more complex therapeutic areas, and to detect subgroups with different benefit and safety responses. Complexities, rigid clinical control, physical distance and (perceived) burden put patient engagement under pressure. (S)low recruitment and retention compromise efficiency, generalisability and validity of traditional, site-centred trials. Remote Decentralized Clinical Trials (RDCTs) and hybrid approaches address these challenges. RDCTs are an operational strategy for technology-enhanced clinical trials, which enable (semi-)continuous data collection and real-world evidence generation, increase patient recruitment and retention and decrease patient and investigator burden and costs. Trials brought to the home of patients. Paradigmatic changes in EU clinical trial design are required to fully benefit from the digital era. Yet, the feasibility of running RDCTs needs to be rigorously demonstrated toge

Mitochondrial dysfunction is implicated in Parkinson’s Disease (PD), but detailed understanding of the cause and effect in αSyn toxicity is lacking. Through provision of quantitative and systematic characterisation of mitochondrial dysfunction, PD-MitoQUANT will provide unprecedented understanding of the role of mitochondrial dysfunction in PD, identify and validate novel disease biomarkers, and propose innovative therapeutic targets that can be further progressed by the EFPIA partners. The consortium leverages multi-disciplinary expertise in the fields of αSyn biochemistry, iPSC-derived PD models, mitochondrial function and structural analysis, proteotoxicity, ER stress and UPR signaling, systems biology of mitochondrial function, and in vivo animal models. A key focus will be quantitative description and integrated analysis of mitochondrial function and its relation to proteotoxicity; representing a key panel of consortium partners Prehn [RCSI], Abramov [UCL], Corti [ICM] and Koopmann [RUMC] who also have assembled long–standing expertise in primary neuron culture, iPSC-derived neurons, PD in vivo models, proteostasis and ageing studies. These investigations will be supported by expert teams in iPSC-derived in vitro PD models and in vivo PD models from the academic partners (Hunot [ICM], Melki [CNRS], Di Monte [DZNE], Broccoli [CNR], SME [Mimetas] and EFPIA partners [Teva], [Lundbeck] and [UCB]. Through integrated in vitro, in silico and in vivo approaches, and supported computationally by SME [GENEXPLAIN], PD-MitoQUANT will perform thorough and unprecedented investigations of mitochondrial dysfunction. Finally, the consortium will initiate a European research platform of excellence investigating mitochondrial dysfunction in PD continuing beyond the project, further supported by [PUK]’s PD human tissue biobank. This will provide long-term and sustainable progress in the understanding of mitochondrial dysfunction in PD and towards clinical application.