ULTRA-DD (Unrestricted Leveraging of Targets for Research Advancement and Drug Discovery) will be an European-wide, highly collaborative and inclusive consortium, to validate new targets for drug discovery by (1) generating high quality research tools, with an emphasis on chemical probes; (2) generating the chemical probes in the most cost-effective manner, using structure-guided methods and harnessing the chemical libraries and medicinal chemistry skills of the EFPIA participants; (3) testing the chemical probes in models of human disease based on continuous access to cells from patients with selected inflammatory diseases; and (4) making all reagents and knowledge available to the research community without restriction on use, to expand the impact well beyond the ULTRA-DD partners. In addition to our focus on chemical probes, we will also generate a defined set of antibodies targeting extracellular and membrane bound proteins of relevance to disease. To accomplish the above, ULTRA-DD will create two scientific Cores and formalize a collaborative network of SMEs, academic scientists and clinicians. The Protein Characterization and Tool-Generation Core will comprise four integrated laboratories: University of Oxford’s Structural Genomics Consortium laboratory, led by Chas Bountra (OXF-SGC), ETH in Zurich (ETHZ), led by Ruedi Aebersold, Karolinska Institutet (KI-MBB), led by Susanne Gräslund, and the University of Toronto’s SGC laboratory (UTOR-SGC, will not receive IMI funds), led by Cheryl Arrowsmith, and chemical biology teams in Bayer (Bayer), Janssen (JPNV), Novartis (NOV) and Pfizer (Pfizer). The Clinical Immunology Core will generate high quality assays from patient-derived cells and tissues in selected inflammatory diseases, and test effects of the chemical and antibody probes. This Core comprises the Kennedy Institute (UOXF-KENN) in the Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences at the University of Oxford (UOXF-NDORMS), led by Marc Feldmann, the Centre for Molecular Medicine (KI-CMM) at Karolinska Institutet, led by Lars Klareskog and Per-Johan Jakobsson, and DiscoveRx (DRX, Sanj Kumar), an SME based in Birmingham, UK (will not receive IMI funds). The activities within the Cores will be enhanced significantly and the impact of the output expanded dramatically through the involvement of a Collaborative Network of SMEs, IMI projects, academic scientists and Disease Foundations (Appendices 1-3; none of these networks will receive IMI funds). The network will include a Target Prioritization Network (TPN) of top genomicists and clinicians; a Science and Technology Network (STN) that contributes expertise across the ULTRA-DD “gene to chemical probe” pipeline; and an Inflammatory Disease Network (IDN) of clinicians and translational scientists that provides enhanced access to disease-relevant expertise and patient tissue, as well as an expanded array of innovative assays. Each member of the ULTRA-DD network will commit to the open access policy. ULTRA-DD will be managed by the SGC (London, UK), which is a charitable company that has an enviable track record in managing the scientific, legal and financial aspects of open access public-private partnerships. The vision of ULTRA-DD is to create an open access consortium that provides industry with a stream of high quality target-disease associations and tools to study them. Our aspiration is to provide the evidence that convinces industry to launch >10 novel proprietary drug discovery programs based on ULTRA-DD open access output during the course of the project and in the nearest years following completion (2020).ULTRA-DD will meet the deliverables by integrating teams of tool-generating scientists with expert clinicians with access to patient tissue, under an open access, milestone-driven framework, and will expand its output through organized collaborations with innovative European scientists, leading non-European scientists