Derisking Drug Discovery
We view disease modeling as a competitive game changer in future drug development. iPSCs combined with the latest gene editing technologies can build highly relevant disease models that directly reflect human disease at a patient-specific level. The use of such models is likely to positively impact attrition during Phase II efficacy studies. Our strategy for competitiveness, therefore, expands well beyond libraries and Medchem. Combined with our high-end target free discovery platform and medicinal chemistry capacities, our approach is worldwide unique.
Patient-derived material lies at the foundation of a new era of disease models with exceptional functional significance. Patient blood or skin samples can be used to generate induced pluripotent stem cells (iPSCs), that can, through a series of tightly controlled steps, be differentiated to produce relevant cell types. Numerous high profile studies have shown these cells can reproduce authentic cellular ‘patho-morphometries’ ex vivo, and thus are ideal for drug discovery. Such patient derived, differentiated material can be produced under industrial-scaled, standardized conditions, in a fully automated fashion.
further increase the relevance of the disease model. iPSCs-derived cell systems can be differentiated to replicate the complex 3D organization of adult tissues. This more closely reflects the environment in which the target cells exist in the patient. Ksilink operates a dedicated, micropillar screening system that can be used to screen 384-well organoid cultures, thereby enabling fast high-content screening procedures. Together with academic experts in organoid reconstruction, Ksilink is pushing the limits of disease modeling.
we identify chemical compounds capable of rescuing diseased cells and re-establishing a healthy phenotype. Such target-free screens allow Ksilink to observe how compounds work in living, patient-derived cells. Using accurate, multi-parametric imaging algorithms developed in-house, thousands of compounds can be rapidly queried for their ability to partially or fully re-establish a ‘healthy’ phenotypic profile. Compounds capable of thus ‘curing’ the patient-derived diseased cells are potentially of high functional value.
the compound itself identifies the most effective target. Once an effective compound is identified, a number of combinatorial approaches can then be used to identify cellular targets of the compounds. For instance, a differential transcriptome analysis in combination with genetic sensitizer screens can effectively zoom in on critical pathways affected by the compounds of interest.
Ksilink can leverage an established strength — its world-leading expertise in hit to lead and lead to candidate optimization. We work with proven experts who in the last 5 years alone have brought 7 new molecular entities (NMEs) to the market. This expertise is paired with a large, proprietary compound library of 200,000 compounds, which is highly divers and fully annotated. Using this outstanding drug development capacity we subject hits that mediate a pharmacological rescue of diseased profiles to target-free optimization. In parallel, a combination of target identification technologies is being used to deconvolve targets and mechanisms of action underlying efficacious compounds.