Although biologics have demonstrated utility for treatment of rheumatoid arthritis, a significant proportion of patients fail to respond or develop dose-limiting side effects. This, together with the cost and inconvenient parenteral mode of administration, has prompted renewed efforts to develop a broader armamentarium to include safe, efficacious and
orally available small-molecule drugs. Inflammationassociated protein kinases fulfill these requirements and remain an attractive target for therapeutic development. However, despite promising performance in the discovery phase, several compounds have failed to deliver on efficacy and/or safety criteria in the clinical setting.
BioSeek has pioneered the development of an in vitro human cell-based technology to integrate human biology into drug discovery. BioMAP® Systems model the complex signals and phenotypic biology of specific therapeutic areas including inflammation/autoimmunity. BioMAP profiling generates a unique signature of human biological responses for every active compound. We have profiled a number of pathways associated kinase inhibitors, JAK, p38 MAPK or PI3K family members. BioMAP profiling reveals both common and unique anti-inflammatory/mechanism of action effects (efficacy), secondary and off-target activities (safety), and clinical insights (therapeutic guidance) for each of these target classes. Comparison of the resulting profiles using proprietary algorithms to BioSeek’s database containing profiles of thousands of experimental compounds and approved therapeutics provides an enhanced understanding of the mechanism of action of these target classes. Such actionable data can guide lead selection, lead optimization (SAR), mechanistic understanding of compound action. BioMAP profiling yields critical human cell-based information to guide nomination of candidates for preclinical development in the areas of inflammatory and autoimmune disease and enable develop safe and effective therapies.