Current anti-tuberculosis (TB) drug regimens face serious limitations at times of increasing antimicrobial drugresistance. Fortunately, for the first time for centuries, several novel anti-TB compounds are available for clinicalevaluation. As the traditional approach to testing these in multiple combination regimens is too slow and inefficientnew approaches of clinical phase 2 study designs are required if we are to meet the targets of the WHO EndTBstrategy to save the lives of millions into the near future. Our consortium brings together a unique group of Europeanand international leaders in TB research and leading industry partners. Together we will provide the necessarycomprehensive range of expertise to meet the demands of the UNITE4TB scientific research agenda. Specifically, wewill develop a new global standard for phase 2 TB clinical trial designs, utilising simulation tools to identify optimaldoses in phase 2A trials and apply a multi-arm multi-stage adaptive randomised controlled 2B/C trial design capableof rapid and simultaneous evaluation of the best candidate regimens. Our innovative phase 2 trials will be performedto the highest regulatory standards, incorporating state-of-the-art microbiology, biomarker investigation and clinicalpharmacology. We will take advantage of existing global TB clinical trial networks with the capacity to enrol patientsat an unprecedented pace and number across four continents. Artificial intelligence/machine learning technologieswill be applied to validate state-of-the art molecular and imaging tools as treatment decision biomarkers with the aimof establishing new, real-time outcome measures. Our consortium will evaluate 3-5 new chemical entities (NCEs) atphase 2A and up to 17 novel combination regimens in phase 2B/C. Our objective is to identify those that have thegreatest chance of success in subsequent definitive phase 3 clinical trials and of becoming the global gold-standard TBregimens of the future.Page 3 of 114Associated with document Ref. Ares(2021)4227207 - 29/06/2021