|The intensive use and misuse of antibiotics has resulted in some level of antibiotic resistance in essentially all human bacterial pathogens. There is a growing concern that the loss of therapeutic options will present us with a post-antibiotic era where present and future medical advances are negated. Resistant bacteria dramatically reduce the possibilities of treating infections effectively, and drastically increase the risk of complications with a fatal outcome. Antimicrobial resistance, however, is an unavoidable consequence of antibiotic use and therefore new, effective antibacterials will always be needed and once developed should be used carefully, avoiding the overuse which can drive resistance. Despite the recognized need for new antimicrobials for clinical use, the reality is that only two new classes of antibiotics have been brought to market in the last 30 years and many drug developers have left the field. This urgency is especially true when considering resistant Gram-negative infections where carbapenem-resistance is rising and use of drugs of last resort, such as colistin, is increasing. The New Drugs 4 Bad Bugs (ND4BB) initiative is a series of programmes designed to directly address some of the scientific challenges associated with antibacterial drug discovery and development. The ND4BB ENABLE consortium will meet the challenges ahead by creating and optimising a portfolio of new antibiotics ranging from Hits through Phase 1 clinical studies.The overarching goals of the ENABLE consortium are to: 1) create a drug discovery platform with the expertise and resource base to prosecute multiple antibacterial programmes in parallel; and 2) increase the overall pipeline in the antibacterial area by applying this platform to optimise a variety of antibacterial programmes. More specifically the key objectives of the consortium are designed to increase the overall pipeline of high quality, novel mode of action medicines to treat serious systemic Gram-negative infections by identifying three antibacterial Leads, two antibacterial Candidates and progressing at least one compound into preclinical and Phase 1 clinical studies.The platform group is made up of academics and SMEs from across Europe with the diverse expertise including from clinical microbiology, in vivo pharmacology, computational and medicinal chemistry, ADME profiling, PKPD modelling, pharmaceutics, assay development and screening all needed to undertake this programme. This group, coupled with additional expertise and advice from within the EFPIA partners, will bring an unrivalled focus and breadth of judgment to this important area of research. The programmes are coming from institutions across Europe, initially with seven efforts from public partners, and arising from a novel discovery stage alliance between GSK and Sanofi. These initial programmes to be considered for ENABLE cover a diverse landscape of targets and approaches including natural products, PNA-peptides, synthetic small molecules, and follow ups / improvements to medicines already available. In addition, soon after initiation, ENABLE will launch an open call for additional efforts to create a sustainable portfolio of antibacterial discovery programmes moving forward. The ENABLE consortium will provide a unique opportunity for a productive collaboration between leading European academic researchers, SMEs and the pharmaceutical industry. We believe these interactions will be synergistic for everyone concerned. Bringing together different disciplines for the common goals outlined in this proposal will make Europe the world-leader in antimicrobial drug discovery. The creation of a cooperative environment in the lifetime of this project and beyond will fulfill the needs of European society in the battle against antibiotic resistance and make a sustainable impact on the future of antibacterial drug discovery.