Type 1 diabetes (T1D) is an incurable disease, often starting in childhood, with a risk of devastating complications, premature mortality, and high social burden. It is caused by the autoimmune destruction of insulin-producing beta cells, yet the standard of care is insulin replacement, acting only at the symptom level. Thus, T1D is a disease with a high unmet need for innovative therapy. Ideally, such therapy shall suppress selectively the immune cells driving T1D without impairing protective immunity. Regulatory T cells (Tregs) are the guardians of human immune tolerance, and genetic defects in Tregs are associated with T1D. Tregs additionally possess tissue regenerative capacity, making them ideal to treat T1D in cell therapy. However, such therapy, performed with polyclonally expanded patient Tregs, showed limited efficacy in T1D. These expanded Tregs are however poor in relevant autoreactive Tregs to save insulin-producing cells. In fact, the identification and manufacturing of autoreactive Tregs remain fundamental technical challenges to successfully apply these cells in the clinic. ARTiDe aims at a breakthrough in antigen-specific Treg therapy in T1D by establishing the production of human Tregs genetically engineered to express an autoreactive T cell antigen receptor (TCR) ready for clinical use. To achieve this ambitious goal, ARTiDe combines the complementary expertise of 8 partners providing novel technologies for the systematic identification of autoantigen-specific Tregs in humans, the selection of optimal TCR to produce protective Tregs, and innovative humanized T1D pre-clinical models to test their efficacy and safety, as well as Treg supporting strategies, in vivo. World-leading biotechs for adoptive T cell therapy will establish novel GMP-compatible manufacturing of highly purified TCR-engineered Tregs. ARTiDe will deliver a Treg production process and regulatory certificates that will allow launching a phase 1 clinical trial just after the project.

Recent pandemics showed Europe how serious health threats can be to society. Proactive approaches are needed to ensure that medical countermeasures are available during pandemics. PROACT EU-Response’s overarching objective is to prepare Europe for future pandemics by strengthening upon existing networks of experts and civil society focused on clinical therapeutic platform trials within hospital inpatient settings across Europe. In case of an outbreak, this network will provide capacity to pivot rapidly to implement large, multi-country platform trials studying therapeutics and diagnostic-tool performance. Underpinned by strong community involvement and further strengthened by the inclusion of social and implementation scientists, PROACT EU-Response centres on six objectives: expand a solid network of clinical centres across Europe that will implement a clinical trial assessing a syndromic approach for respiratory viral infections; strengthen a laboratory network to identify pathogens and biomarkers of disease monitoring for routine surveillance; support a network of methodologists and trialists who will ensure the trials’ logistical and methodological aspects; initiate a network of professionals to work on preparedness tools to ensure a smooth pivot from inter-pandemic to the pandemic period in case of an outbreak; build a network of social science researchers who will provide nuanced understanding of the social contexts; and establish a community group to work on activities that will empower patients and citizens in Europe regarding their own health and educate them about science and health issues. By bringing together scientists, social science researchers, and civil society members, PROACT EU-Response will benefit the entire European population and beyond through decreased mortality and morbidity associated with emerging diseases, lower societal economic costs of morbidity, strengthened research and innovation expertise, human capacities, and know-how for combatting communicable diseases.

The evaluation of new medicines for rare diseases (RD) including rare paediatric RDs is challenging for several reasons, among which are the small patient sample sizes, heterogeneity of patients and diseases and heterogeneity in disease knowledge. Due to these difficulties, access to effective treatments and the number of treatment options are often limited in RDs. INVENTS aims to provide clinical trial trialists, researchers and regulators with a global framework encompassing methods, workflows and evidence assessment tools to be implemented in orphan and paediatric drug development. Our ambition is to significantly improve the evaluation of evidence and regulatory decision-making through the development and validation of: refined longitudinal model-based diseases trajectories and treatment effect, improved extrapolation models, in silico trials (e.g., virtual patient cohorts), optimised model-based clinical trial designs and evidence synthesis methods. These will be evaluated through simulation studies and tested on extensive data from a range of use cases provided by our industrial partners Roche and Novartis and Real World data (RWD) from RD registry. The INVENTS framework will improve consistency and efficiency of the drug evaluation process for RD by augmenting clinical evidence without compromising its scientific integrity and providing regulators assessment credibility criteria. At the end of this 5 years project, the European industry will be able to exploit novel and improved clinical trial designs, in silico trials and RWD analysis approaches supporting drug development in RD. The European Medicine Agency and European national regulators (including Health Technology Assessment bodies) will be supplied with a general framework allowing better informed decision-making. Most importantly, RD patients will benefit from an increased and faster access to efficacious and safe treatments.