Join our LinkedIn Group
and stay connected!

Corporate Sponsors

Sponsoring Organization

Lead Sponsoring Publications

Additional Media Partners

Day 1  |  Day 2 |  Download Brochure 

TUESDAY, JUNE, 15

7:15 am Registration and Morning Coffee

Translating Pre-Clinical Predictions To Clinical Safety

8:15 Chairperson's Opening Remarks

Gary Gintant, Ph.D., Senior Group Leader, Department of Integrative Pharmacology, Global Pharmaceutical Research & Development, Abbott Laboratories

8:25 Preclinical Cardiac Safety: Moving Ahead of hERG

Gary Gintant, Ph.D., Senior Group Leader, Department of Integrative Pharmacology, Global Pharmaceutical Research & Development, Abbott Laboratories

This presentation will discuss newer data related to the utility of various assays in the pre-clinical assessment of cardiac safety. Specific topics will include a) novel and evolving preclinical models, and b) how to link contingency tables, likelihood ratios and PK/PD modeling with the ICH S7B integrated risk assessment to guide the efficient design of early clinical studies.

8:55 Cardiovascular Safety in Drug Development

Albert M. Kim, M.D., Ph.D., Senior Translational Medicine Expert, Cardiac Electrophysiology/Cardiovascular Discovery, Novartis Institutes for BioMedical Research, Inc.

There have been major advances in the evaluation of cardiac safety during drug development and the understanding of ionic mechanisms that stabilize and destabilize ventricular repolarization. This presentation will cover the major aspects of CV arrhythmia evaluation during drug development and the fundamentals of the integrated safety assessment. The relevance and limitations of pre-clinical data for translation into human clinical trials will be discussed. A case presentation will illustrate the application of these concepts and explore their strengths and weaknesses.

9:25 In vitro- In vivo Correlation of Cardiotoxicity for a Small Molecule cMET Inhibitor

Amy Kim, Ph.D., Senior Scientist, Genentech Inc.

9:55 Networking Coffee Break

Novel in vitro Approaches For Assessing Cardiac Liabilities

10:25 Enriched Human Cardiomyocytes from Embryonic Stem Cells for Drug Discovery and Safety Pharmacology

William Sun, Ph.D., Group Leader, Stem Cell Technology, Experimental Therapeutics Centre, A*STAR

Using a trangenic approach, we can generate a pure population of cardiomyocytes from human embryonic stem cells. The enriched cardiomyocytes contract spontaneously in culture and express markers of primary cardiomyocytes. Extracellular recordings from these cells using microelectrode array enable evaluation of compounds for drug-induced QT prolongation. Functional human cardiomyocytes from stem cells are thus useful for drug discovery and predictive toxicology.

10:55 High Content Cardiotoxicity Profiling with Engineered Heart Tissues: Mitochondrial Toxicity and Genomic Influences

Tetsuro Wakatsuki, Ph.D., Assistant Professor, Physiology, Biotechnology and Bioengineering Center, Medical College of Wisconsin

Our objective is to recapitulate genome-based cardiotoxicity in engineered heart tissues (EHTs) fabricated from various inbred rat strains that show different susceptibilities to cardiovascular diseases. The cell-matrix solution contracted around the scaffold to form a miniaturized sheet (4X4mm) of EHT and their contractility, mitochondrial membrane potential, respiration, ATP synthesis, and reactive oxygen spices (ROS) production are monitored in high-throughput to assess the physiological states of myocytes in EHTs. Effects of genomic influence that alter cardiotoxicity of small molecules will be discussed.

11:25 Evolution of in vitro Strategies for Cardiotoxicity Assessment

Adam W. Hendricson, Ph.D., Research Investigator, Lead Evaluation and Ion Channels, Bristol-Myers Squibb Co.

Early and accurate assessment of cardiovascular ion channel toxicity is fundamental to preclinical research. For maximum impact, an in vitro assay triage must provide meaningful throughput and clear connectivity with in vivo measurements. Evolving technologies and perspectives are changing the landscape of in vitro CV safety. The current presentation will detail advances in functional in vitro assay approaches to CV safety, including automated electrophysiology.

Sponsored by
11:55 Luncheon Presentation

12:25 pm Luncheon Presentations (Sponsorship Opportunities Available) or Lunch on Your Own

Drug-Class Associated Cardiotoxicity

1:25 Chairperson's Remarks

Thomas Force, M.D., Professor, Medicine; Clinical Director, Center for Translational Medicine, Thomas Jefferson University

1:35 Understanding Cardiotoxicity of Tyrosine Kinase Inhibitors: From Clinical Outcomes to Mechanisms of Cardiotoxicity

Thomas Force, M.D., Professor, Medicine; Clinical Director, Center for Translational Medicine, Thomas Jefferson University

2:05 Biologicals and Cardiac Toxicity Risk: Relating Toxicity to Mechanism of Action 

Noël Dybdal, Ph.D., D.V.M., Associate Director, Principal Scientist, Safety Assessment, Genentech, Inc.

Biological therapeutics in general and monoclonal antibodies specifically are highly targeted in their activity, risk of off-target toxicity is low. Adverse cardiovascular effects associated with these drugs to date result from on-target pharmacology and relate to their mechanism of action. Species specificity of biologics presents challenges that limit the extent to which cardiotoxicity risk can be assessed preclinically. The process and results of ongoing investigations into the mechanism of trastuzumab-associated cardiotoxicity will be presented and discussed as a case study.

2:35 PANEL DISCUSSION: How Well Can We Correlate In Vitro and In Vivo Models to Predict Cardiotoxicity?

Moderator: Thomas Force, M.D., Professor of Medicine and Clinical Director of the Center for Translational Medicine, Thomas Jefferson University

3:05 Sponsored Presentations (Opportunities Available)

3:35 Grand Opening Refreshment Break in the Exhibit Hall

5:45 Happy Hour in the Exhibit Hall

6:45 End of Day

Day 1  |  Day 2  |  Download Brochure