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.

Rare Eye Diseases (REDs) are a major cause of visual impairment and blindness in Europe, affecting patients of all ages. The RESTORE VISION Consortium identified a group of 7 REDs all affecting the cornea and ocular surface that cause severe vision impairment and blindness and have inadequate treatment options today. Onset and progression is characterised by overlapping common pathophysiologic mechanisms: defective corneal wound healing, nerve degeneration, stem-cell dysfunction and aberrant vessel ingrowth. The 7 REDs targeted are Aniridia-Associated Keratopathy, Neurotrophic Keratopathy, Limbal Stem Cell Deficiency, Ocular Cicatricial Pemphigoid, EEC Syndrome, Ocular Graft versus Host Disease and Corneal Neovascularisation, affecting over 500k patients in Europe. Current management is often prohibitively expensive, has low efficacy and leads to debilitating side effects, pointing to a critical medical problem and area of unmet medical need. RESTORE VISION brings together actors from across the full value chain: 6 leading research institutions, 3 SMEs and a European patient organisation. We take a ground-breaking approach to improve eye health by verifying disease pathomechanisms, using cutting-edge models for each rare disease to test novel and repurposed compounds and determine drug mechanisms of action, formulating compounds as safe eye drop suspensions or subconjunctival drugs, and performing several first-in-human trials of novel therapies. New therapeutics with game-changing potential will be evaluated for the first time. Our pioneering ‘streams’ approach is based on the repurposing of 6 existing drugs and the development of 3 new compounds, all with solid preliminary data showing remarkable effects in restoring the cell physiology, immune, avascular, neural and signalling environment in the cornea. This innovative approach shortcircuits lengthy and complex regulatory and drug development processes, ensuring rapid translation into the clinic.