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.

ProgRET will create a multidisciplinary and intersectoral European training network focusing on the mechanisms, diagnosis and therapy of dominantly inherited retinal diseases (IRD). IRD represent a major cause of blindness, affecting 350,000 people in Europe. IRD have long been considered incurable, however major advances have led to groundbreaking new treatments. Today, the most important challenges in the IRD field relate to an unsolved genetic diagnosis, unknown disease mechanisms and gene therapy development for autosomal dominant IRD (adIRD), representing 25–40% of all IRD cases. We have demonstrated an emerging role for splicing factors, structural variants and non-coding defects in patients with adIRD, and developed novel disease models and gene therapies for adIRD. ProgRET aims to dissect adIRD mechanisms using retinal stem cell and aquatic animal models, to advance adIRD diagnostics using a single-molecule multi-omics framework, and to develop innovative treatments based on RNA therapy and CRISPR-genome editing. These challenges will be tackled by integrating unique expertise and cutting-edge technology within ProgRET, including (multi-)omics, bioinformatics, functional genomics, RNA biology, gene regulation, stem cell technology, retinal organoids, animal models, genome editing and gene therapy. ProgRET will give Doctoral Candidates (DCs) unparalleled training opportunities in outstanding academic and industrial settings through training-by-research via individual research projects, secondments, and network-wide training sessions. All individual training and research activities will provide each DC with the necessary skills in academic and industrial research. ProgRET will make a career in both sectors attractive and improve their career prospects. Finally, our multidisciplinary network offers a unique opportunity to accelerate the understanding, diagnostics and therapeutics for adIRD in Europe, and to translate research findings to healthcare and society.

The loss of antibiotic effectiveness due to increasing antimicrobial resistance (AMR) is a serious threat to global public health. The IMI2 AMR Accelerator will develop new agents to treat and prevent infections caused by MDR and XDR bacteria, including Mycobacterium tuberculosis and non-tuberculous mycobacteria. The COMBINE proposal addresses Pillar A, the Capability Building Network (CBN) of the AMR Accelerator programme. The COMBINE consortium will form a Coordination and Support Office (CSO) that will support the delivery of projects across the AMR Accelerator, as well as with efficient communication among projects of the Accelerator and within the AMR community. In addition, we will establish an IT infrastructure that will allow for the FAIRification, collection, aggregation, storage, sharing, and analysis of vaccine and antibacterial preclinical and clinical data sets. When setting up the CSO, we will build on learnings from the two IMI ND4BB projects: ENABLE (an antibacterial discovery and development engine) and TRANSLOCATION (which has built an information centre for data sharing). COMBINE partners will work to accelerate scientific discoveries in the AMR field by optimisation and standardisation of animal infection models, and development of improved models for translation of preclinical animal efficacy data and statistical analysis of clinical data. This will set new standards for the translational and predictive relevance of preclinical data and facilitate optimized design for new clinical trials. Results will feed into study and trial design throughout the AMR Accelerator to achieve more stringent and reliable development programmes.

AntiMicrobial Resistance (AMR) is a global and serious threat to human health. Gram-negative bacteria are widely regarded as the culprit representing one of the gravest dangers. Indeed, there is a dearth of new agents able to address AMR in Gram-negative bacteria, especially compounds with novel modes of action. Finding and developing such compounds represents a huge scientific challenge, one that requires the collaboration of stakeholders bringing many different kinds of expertise. The world is coming together to tackle this issue and public-private partnerships represent an attractive way to hasten the pace and increase the probability of successfully identifying and developing novel antibiotics. Under the global umbrella of the AMR Accelerator, the Gram-Negative Antibacterials-NOW (GNA NOW) consortium pledges to a 6-years commitment to bring together key European academic and private experts in antibiotic discovery and development in order to support and manage a portfolio of novel mode of action drugs against Gram-negative bacteria. Starting with three initial compounds/series, dedicated project teams will work together to define and execute the most efficient project plans. The consortium will put in place robust governance and management structures to ensure that the most promising compounds are pursued diligently. Ultimately, the goal of GNA NOW is to progress one compound through completion of phase I studies plus one compound reaching Investigational New Drug (IND) stage and/or up to two compounds reaching clinical development candidate stage.