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.

Opportunistic infections are defined as infections caused by pathogens primarily affecting immunocompromised subjects. Due to the immunodeficiency, they are difficult to treat and together the top 2 killer worldwide. Opportunistic pathogens comprise bacteria, viruses, fungi and parasites. Complement as a chief conductor of innate immunity plays a crucial role in immune defence against opportunistic pathogens. Research in this field is exploding, but also suffers from poorly coordinated intersectoral training of early stage researchers (ESRs). CORVOS, for COmplement Regulation and Variation in Opportunistic infectionS will train 15 widely recruited and highly motivated ESRs. They will fill the current scientific gap in the understanding of the role of complement in opportunistic infections, and translate this knowledge into clinical practice. ESRs will become creative alumni, all with a jointly awarded Double PhD of two European universities and equipped with entrepreneurial and clinical skills, making them attractive human resources to academia and industry alike. CORVOS is an ambitious pan-European initiative of 10 European universities, 3 biomedical companies, 2 research institutes and 3 hospitals that comprises an interdisciplinary doctoral programme including cross-sectoral secondments and training in transferrable skills. CORVOS includes 12 internationally renowned multidisciplinary scientists, 8 of them members of the European Complement Network. This established organization will ensure that the high quality and efficient implementation of the CORVOS training programme will sustain after its funding and will be embedded into existing doctoral and research training programmes across Europe. Ultimately, CORVOS doctoral and research training programme enables intersectoral research together with the transfer and exploitation of knowledge required to develop diagnostic and treatment options to save millions of lives currently lost to opportunistic infections.