The European Regimen Accelerator for Tuberculosis (ERA4TB) has the explicit goal of developing a new combination therapy to treat all forms of TB starting from ~20 leads and drug candidates provided by EFPIA. Since details of these are as yet unavailable, we will implement an agile drug development algorithm that entails profiling and portfolio construction. Profiling involves characterisation and ranking molecules in preclinical studies comprising in vitro drug combination assays, hollow fiber and single cell analysis, innovative murine and non-human primate models, PK/PD studies, combined with biomarker discovery and non-invasive NIR or PET/CT imaging to monitor disease progression and response to treatment. Modelling, simulation and artificial intelligence tools will help progress compounds from early preclinical to clinical development and to predict drug exposure, human doses and the best combinations. After extensive preclinical profiling, selected compounds will enter portfolio development for first time in human tests and phase I clinical trials in order to ensure that they are safe, well-tolerated and bioavailable with negligible drug-drug interactions. If needed, formulation studies will be conducted to improve pharmacological properties. ERA4TB has assembled the best expertise and resources available in Europe, to build a highly effective and sustainable drug development consortium with a flexible and dynamic management system to execute the profiling and portfolio strategy, aided by clearly defined go/no-go decision points. The expected outcome of ERA4TB is a series of highly active, bactericidal, orally available drugs to constitute two or more new combination regimens with treatment-shortening potential ready for Phase II clinical evaluation. These regimens will be compatible with drugs used to treat common comorbidities, such as HIV-AIDS and diabetes, and should impact UN Sustainable Development Goal 3, namely, ending TB by 2030.

Common mechanisms and pathways in Stroke and Alzheimer's disease. It has long been recognized that stroke and (Alzheimer’s Disease) AD often co-occur and have an overlapping pathogenesis. As such, these two diseases are not considered fellow travelers, but rather partners in crime. This multidisciplinary consortium includes epidemiologists, geneticists, radiologists, neurologists with a longstanding track-record on the etiology of stroke and AD. This project aims to improve our understanding of the co-occurrence of stroke and AD. An essential concept of our proposal is that stroke and AD are sequential diseases that have overlapping pathyphysiological mechanisms in addition to shared risk factors. We will particularly focus on these common mechanisms and disentangle when and how these mechanisms diverge into causing either stroke, or AD, or both. Another important concept is that mechanisms under study will not only include the known pathways of ischemic vasculopathy and CAA, but we will explore and unravel novel mechanisms linking stroke and AD. We will do so by exploiting our vast international network in order to link various big datasets and by incorporating novel analytical strategies with emerging technologies in the field of genomics, metabolomics, and brain MR-imaging.

Tuberculosis (TB) remains one of the most devastating infectious diseases worldwide, killing over 4,000 people every day. Prevention of tuberculosis infection by novel vaccines would provide the most cost-effective approach to achieve the goals of the WHO End TB strategy and the Sustainable Development Goals of the United Nations. While there are few promising TB vaccine candidates available, innovation by new platforms and strategies is needed to ensure that the most effective and affordable vaccines are developed. TBVACHORIZON will innovate and diversify the global TB vaccine pipeline by pursuing four objectives: 1. Define the composition, spatial organisation and functioning of protective immune responses in the Mycobacterium tuberculosis-infected lung. 2. Evaluate whether mucosal re-vaccination with BCG and other live attenuated vaccines improves protective efficacy against tuberculosis infection in mice, non-human primates and humans. 3. Identify host immune response profiles and biomarkers of natural and vaccine-induced immune protection in the lung. 4. Support next generation TB vaccine development by standardised head-to-head testing of selected vaccine candidates in animals and the establishment of novel delivery systems, adjuvant formulations and GMP platforms for live attenuated vaccines. TBVACHORIZON will increase our understanding and develop tools pertaining to immune protection in the lung, the major site of tuberculosis infection. This knowledge will be exploited to develop mucosal strategies for translating towards clinical evaluation and possible implementation. The interwoven activities will consolidate Europe’s leading role in TB vaccine research and innovation, with the ultimate goal of accelerated availability of affordable, accessible and more effective TB vaccines.