Category: Advances in Bioanalytics and Biomarkers
Confluence Discovery Technologies (CDT) is a full service CRO that specializes in supporting drug discovery and development projects from idea to IND. Fully equipped laboratories staffed with extensive drug discovery experience allow CDT to support entire programs (screening, computational and medicinal chemistry, biochemistry/mechanistic enzymology, cell biology, biomarker and in vivo pharmacology) or developing and executing on specific assays.
Target, mechanism, disease and safety biomarkers play a critical role in both preclinical and clinical safety and efficacy studies supporting drug discovery/translational research. Herein we describe a target biomarker study involving BVD-523 (ulixertinib), a first-in-class small molecule inhibitor targeting the downstream ERK kinases and currently under investigation in Phase 1 human clinical trials (NCT0178429) (NCT02296242) where it has shown encouraging early results. RSK is a direct substrate of ERK and a phospho-RSK (pRSK) biomarker assay was developed and used to quantify target modulation to support pharmacokinetic/pharmacodynamics relationships in both preclinical and clinical studies of BVD-523. Using this assay, a correlation was observed between BVD-523 drug levels and inhibition of ERK activity as measured by pRSK/RSK ratio in patient blood following oral dosing. These data supported an understanding of the relationship among drug levels, ERK inhibition and disease efficacy in cancer patients. This case study exemplifies a CDT approach to develop a translatable biomarker assay; this and other approaches will be presented.
For additional information on the assays presented here or on how CDT could help you with your biomarker needs, please visit CDT scientists at Booth # 953.
Heidi Hope– Associate Research Fellow/Group Leader - Screening and Signal Transduction, Confluence Discovery Technologies, Saint Louis, MO
Associate Research Fellow/Group Leader - Screening and Signal Transduction
Confluence Discovery Technologies
Saint Louis, MO
Heidi Hope PhD is an Associate Research Fellow and Group Leader of Screening and Signal Transduction at Confluence Discovery Technologies. She has 25 plus years of post-doctorate research experience in academic and industrial settings and served as a senior scientist and project lead at Pfizer. Her areas of expertise include biochemistry, cell biology and signal transduction focusing on the treatment of inflammatory diseases and cancer. Dr. Hope is also involved in science education efforts in the St Louis area and is a Fellow of the St. Louis Academy of Sciences. Dr. Hope received her BS with Honors from Stanford University and her PhD in Biochemistry from Washington University in St Louis.