Unrestricted Leveraging of Targets for Research Advancement and Drug Discovery

Although the number of annual drug approvals has recently been trending upward[1], the number of first in class therapies has remained relatively constant, often less than 10 per year. For such new medicines for pioneer targets, the level of attrition in Phase II proof-of-concept clinical studies remains the biggest hurdle[2], in large part because the target-disease associations derived from the currently dominant cell or animal pre-clinical models of disease most often do not translate into clinical efficacy.

Thus, it is increasingly appreciated that the use of disease models based on human samples will be critical both to increase our understanding of pathophysiology and to improve the productivity of the sector. However, securing regular access to well-annotated samples from patients is challenging to organize, raises ethical issues and requires new organizational models.

To address this challenge, we have established a partnership between; i) the clinical academic community which cares for the patients and provides deep disease expertise; ii) the academic research community that provides the molecular and technological insights necessary for mechanistic studies; iii) the industrial pharmaceutical sector with its strength in e.g. the development of high quality chemical and antibody modulators of protein function and iv) with the engagement from Disease Foundations[3].

Within ULTRA-DD and the SGC Open-Source Target Discovery Partnership; our aim is to identify and validate under-explored protein targets by profiling the highest quality target-directed chemical and antibody probes in the highest quality patient-cell derived assays, providing biomarker and phenotypic read-outs in a more disease relevant context.

ULTRA-DD is focused on defining and validating novel targets in auto-immune and inflammatory diseases by the use of patient-cell derived assays. This is made possible by our collaborating clinicians and hospitals in Oxford and Stockholm, allowing us excellent access to tissue and cells from e.g. lupus, myositis, ankylosing spondylitis and dupuytren’s disease patients. Common co-morbidities for these patients indicate that the disease mechanisms could also be important in other indications, including IBD and RA, which will be explored through collaboration.

Additional funding sources allows us to move forward with similar studies also in neuroscience and oncology, as part of the global SGC research efforts.

ULTRA-DD has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement n° 115766, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. 


[1] http://www.forbes.com/sites/bernardmunos/2015/01/02/the-fda-approvals-of-2014/
[2] Getting pharmaceutical R&D back on target. Bunnage ME, Nature Chemical Biology, 2011, 7, 335–339.
[3] Preclinical target validation using patient-derived cells. Edwards AM et al. Nat Rev Drug Discov. 2015 Mar;14(3):149-50