Organ-Chips Accurately Model and Predict Thrombotic Side Effect Caused by Anti-CD154 Monoclonal Antibody hu5c8; Emulate Publishes Results of Collaborative Research with Janssen
Emulate, Inc. announced today a published study that demonstrates that its Blood Vessel-Chip accurately modeled and predicted thrombosis, or clotting of blood, induced by certain monoclonal antibody drugs, specifically anti-CD154 monoclonal antibody (mAb) hu5c8. The Emulate study, published in Clinical Pharmacology and Therapeutics, is co-authored with scientists at Janssen Research & Development, LLC. The effort is part of a collaboration between Emulate and Janssen to better predict drug safety and human response in the drug development process. The study successfully accomplished the collaboration’s goal of initial validation of the Blood Vessel-Chip’s modeling of thrombosis for use in safety testing of drug compounds.
The researchers introduced an anti-CD154 therapeutic antibody (Hu5c8) into the Blood Vessel-Chip’s living microenvironment to observe the antibody’s biological activity. The Blood Vessel-Chip features a vascular channel lined with human cells that comprises the endothelium lining of blood vessels; this channel was perfused with human whole blood. The researchers tested the potential for the antibody to cause blood clots. In previous clinical trials during the period of 1999-2002, anti-CD154 antibodies were studied in patients with various autoimmune diseases,1 and their clinical development was terminated due to the unexpected serious side effect of thrombosis observed in patients in the studies. The safety issues observed in the clinic were not predicted by preclinical animal testing.
“These results are a prime example of how our Organs-on-Chips technology can identify safety and efficacy issues earlier and more reliably in the drug development process, enabling the design and selection of drug candidates that have a higher potential of success in human clinical trials,” said Geraldine A. Hamilton, President and Chief Scientific Officer of Emulate. “This significant accomplishment of recreating thrombosis in an Organ-Chip is a milestone that we achieved through our collaboration with Janssen and academic colleagues at the Wyss Institute at Harvard University and at the University of Twente.”