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.

TRANSVAC2 is the follow-up project to its successful predecessor project TRANSVAC, the European Network of Vaccine Research and Development funded under FP7. The TRANSVAC2 consortium comprises a comprehensive collection of leading European institutions that propose to further advance with the previous initiative towards the establishment of a fully operational and sustainable European vaccine R&D infrastructure. TRANSVAC2 will support innovation for both prophylactic and therapeutic vaccine development based on a disease-overarching and one-health approach, thereby optimising the knowledge and expertise gained during the development of both human and animal vaccines. This will be achieved by bridging the translational gap in biomedical research, and by supporting cooperation between public vaccine R&D institutions of excellence, related initiatives and networks in Europe, and industrial partners. TRANSVAC2 will complement and integrate with existing European research infrastructures in both the public and private sectors. TRANSVAC2 will function as leverage and innovation catalyst between all stakeholders involved in vaccine R&D in Europe and -by providing integrated and overarching vaccine R&D services- will contribute to the development of effective products to address European and global health challenges, to controlling the burden and spread of infectious diseases, and reinforce the economic assets represented by vaccine developers in Europe. The impact of TRANSVAC2 will be maximised by two external advisory bodies. An independent Scientific & Ethics Advisory Committee will provide recommendations surrounding scientific-technical and ethical issues, whereas the coordination of TRANSVAC2 with other related initiatives and the further promotion of the long-term stability of a European vaccine R&D infrastructure will be supported by a Board of Stakeholders comprising representatives of policy and decision makers, industry associations and European infrastructures.

We propose a new phase of the successful Mathematics for Real-World Systems (MathSys) Centre for Doctoral Training that will address the call priority area "Mathematical and Computational Modelling". Advanced quantitative skills and applied mathematical modelling are critical to address the contemporary challenges arising from biomedicine and health sectors, modern industry and the digital economy. The UK Commission for Employment and Skills as well as Tech City UK have identified that a skills shortage in this domain is one of the key challenges facing the UK technology sector: there is a severe lack of trained researchers with the technical skills and, importantly, the ability to translate these skills into effective solutions in collaboration with end-users. Our proposal addresses this need with a cross-disciplinary, cohort-based training programme that will equip the next generation of researchers with cutting-edge methodological toolkits and the experience of external end-user engagement to address a broad variety of real-world problems in fields ranging from mathematical biology to the high-tech sector. Our MSc training (and continued PhD development) will deliver a core of mathematical techniques relevant to all applied modelling, but will also focus on two cross-cutting methodological themes which we consider key to complex multi-scale systems prediction: modelling across spatial and temporal scales; and hybrid modelling integrating complex data and mechanistic models. These themes pervade many areas of active research and will shape mathematical and computational modelling for the coming decades. A core element of the CDT will be productive and impactful engagement with end-users throughout the teaching and research phases. This has been a distinguishing feature of the MathSys CDT and is further expanded in our new proposal. MSc Research Study Groups provide an ideal opportunity for MSc students to experience working in a collaborative environment and for our end-users to become actively involved. All PhD projects are expected to be co-supervised by an external partner, bringing knowledge, data and experience to the modelling of real-world problems; students will normally be expected to spend 2-4 weeks (or longer) with these end-users to better understand the case-specific challenges and motivate their research. The potential renewal of the MathSys CDT has provided us with the opportunity to expand our portfolio of external partners focusing on research challenges in four application areas: Quantitative biomedical research, (A2) Mathematical epidemiology, (A3) Socio-technical systems and (A4) Advanced modelling and optimization of industrial processes. We will retain the one-year MSc followed by three-year PhD format that has been successfully refined through staff experience and student feedback over more than a decade of previous Warwick doctoral training centres. However, both the training and research components of the programme will be thoroughly updated to reflect the evolving technical landscape of applied research and the changing priorities of end-users. At the same time, we have retained the flexibility that allows co-creation of activities with our end-users and allows us to respond to changes in the national and international research environments on an ongoing yearly basis. Students will share a dedicated space, with a lecture theatre and common area based in one of the UK's leading mathematical departments. The space is physically connected to the new Mathematical Sciences building, at the interface of Mathematics, Statistics and Computer Science, and provides a unique location for our interdisciplinary activities.