Rethinking Translational Predictivity using HiPSC-Derived Models: A Retrospective Analysis for Cardiac Liabilities

Date: Thursday, June 28, 2018

About:

Human induced pluripotent stem cell (hiPSC) derived models are heavily explored as alternatives for animal models used in preclinical discovery and safety assessment. Here, Jean-Pierre Valentin from UCB Biopharma will provide a retrospective review on three compounds which showed preclinical and clinical cardiac liabilities. To understand to what extend hiPSC-derived cardiomyocytes could have predicted their side effects, the three compounds were tested using Ncardia’s human iPSC-derived cardiomyocytes in combination with ACEA’s xCELLigence Cardio ECR system. The hiPSC-derived models demonstrated value in refining the integrated cardiac safety assessment.

Using real-time kinetic analysis, this physiologically-relevant human cardiac model allows for the detection of both acute as well as chronic drug-induced toxicities. In the last few years, this predictive validity of hiPSC-derived cardiomyocytes has also been substantiated by various case studies and publications. As a result, pharma are slowly integrating these assays into their early safety assessment to detect potential safety hazards and improve compound selection prior to entering the costly and time-consuming animal studies.

Learning Objectives

  • Uses of iPSC-derived cell types in cardiac screening/safety applications
  • Humanizing drug discovery/development, “mimic the clinic”
  • ‘Real-world’ examples / case studies

Speakers:
Jean-Pierre Valentin, PhD, HDR, ERT, FSBiol, FRCPath, DSP
Senior Director, Head of Investigative Toxicology
UCB Biopharma SPRL

Jean-Pierre holds a Ph.D. in Physiology & Pharmacology 1990, from the University of Montpellier, France. Following a post-doc at UCSF, Jean-Pierre joined the Pierre Fabre Research Centre (1992-98) where he contributed to the discovery and progression into development of 3 candidate drugs. He joined AstraZeneca to build from inception, develop and lead the Department of Safety Pharmacology where he contributed to the safety evaluation of ~200 candidate drugs across a wide range of therapy areas, leading to the development and successful registration of several marketed products. In February 2014, he joined UCB-Biopharma as Senior Director Head of Investigative Toxicology, based in Belgium. He is a member of several scientific societies; Past President of the Safety Pharmacology Society; co-chair of the HESI subcommittee on QT/Arrhythmia, and the ABPI-NC3Rs-Animal Model Framework. He is involved in training and education programs and is author/co-author of several patents and >180 peer review publications and book chapters.

Xiaoyu Zhang, PhD
Senior Scientist, R & D/Applications
ACEA Biosciences Inc.

Xiaoyu Zhang received her Ph.D. in Cell Molecular and Development Biology from the University of California, Riverside, conducted postdoctoral training and research at Burnham Institute for Medical Research. Dr. Zhang joined ACEA Biosciences in 2011. She has been leading the FDA CiPA studies, cardiac safety screening program and RTCA Cardio/CardioECR applications development.

Greg Luerman, PhD
Technical Director, North America
Ncardia

Dr. Greg Luerman is Technical Director at Ncardia. Following his graduate studies at the University of Louisville School of Medicine, Dr. Luerman earned a Michael J Fox Foundation postdoctoral fellowship within the Pfizer Neuroscience Research Unit where he lead bioassay development on a Parkinson’s disease therapeutic team. He moved on to establish a preclinical cardiac safety/tox and drug discovery assays at ChanTest (now Charles River). Now at Ncardia, Dr. Luerman oversees North American scientific operations.

Dr. Matthew Nystoriak 
Assistant Professor of Medicine, Division of Cardiovascular Medicine
University of Louisville

Dr. Matthew Nystoriak is an Assistant Professor of Medicine, Division of Cardiovascular Medicine, and member of the Diabetes and Obesity Center at the University of Louisville. He graduated (PhD) from the Department of Pharmacology at the University of Vermont, College of Medicine, and completed his postdoctoral training in Physiology and Biophysics at the University of Washington in Seattle, and Pharmacology at the University of California, Davis. His current work aims to develop a better understanding of the cross-talk between myocardial energetic demand and coronary microvascular function by elucidating cellular mechanisms coupling intermediary metabolism with vascular ion channel function. In addition, his laboratory is testing how electrical signaling in the cardiovascular system is affected by exposure to chemical constituents of electronic cigarettes.

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