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The Use of Cardiomyocytes for the Assessment of Proarrhythmic Risk

October 25–26, 2016
Arlington, Virginia

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Vision and Background

Human stem cell-derived cardiomyocytes (hiPSC-CMs) are increasingly used in drug discovery, toxicity assessment, and cell-based disease treatment. In vitro screening assays are also used to make decisions about which drug candidates to progress into development. From the public health perspective, assessing the cardiovascular toxicity potential of any new drug product or environmental toxicant is important. Comprehensive in vitro proarrhythmia (CiPA) assay is a new risk assessment paradigm proposed to replace the current thorough QT study which is currently needed for each new drug application. One of the proposals included in CiPA is to use hiPSC-CM to test drug-induced effects on the myocardial action potential to confirm the outcome of in silico modeling of drug-induced effects. The in silico modeling is based on the blocking activity of a given drug on the most important human myocardial ion channels involved in myocardial depolarization and repolarization. It is therefore important to understand the functional, morphological, and biochemical hallmarks of hiPSC-CMs and how this may relate to factors including the maturity of the hiPSC-CMs used and the specific conditions used to culture the cells. We need to understand how these cells behave in comparison to adult human ventricular or atrial CMs. Only when this is understood can we determine if they will provide a useful model for predicting in vivo activity. In addition, the acceptable translation of effects in stem cell-derived CM tested with environmental chemicals to human environmental exposure levels requires a thorough understanding of these same parameters. 

In light of the potential utility of this emergent technology, this workshop will engage experts in presenting and discussing various aspects of the phenotype of these cells (functional, proteins, biochemical) and comparing them to adult ventricular CMs, as a basis for assessing their potential uses in drug and chemical safety testing. Topics covered include description of cell phenotypes from different sources, in vitro culture conditions and quality assessment, assay methods and validation, in vitro/in vivo correlation, current experience and challenges, and outlining and prioritizing the further work needed. This workshop will include domestic and international scientists from government agencies, pharmaceutical industry, and academia to discuss the current state of the art and the path forward.

The specific objectives of the workshop include:

  1. Sharing of experiences using stem cell-derived cardiomyocytes (SC-CMs) including hiPSC-CMs and embryonic stem cells-derived cardiomyocytes (hESC-CMs) for the testing of electrophysiological effects and the assessment of resultant proarrhythmic risk or other drug-induced safety risks (e.g., contractility or calcium homeostasis).
  2. Define the cell characteristics needed for use in a given assay system.
  3. Discuss in vitro assay methods and markers needed to standardize the defined phenotype of hiPSC-CM and ensure quality.
  4. Discuss the role of electrophysiological studies of cardiac myocytes to predict the proarrhythmic potential of drugs.
  5. Identify advanced uses of hiPSC-CM that can be used to identify potential cardiovascular risk.
Conference Location

The CCT: The Use of Cardiomyocytes for the Assessment of Proarrhythmic Risk will be held on October 25–26, 2016, at the Hilton Hotel Crystal City at Washington Reagan National Airport, Arlington, Virginia, in close proximity to Washington, DC.

The Hilton Crystal City at Washington Reagan National Airport Hotel will be the headquarters hotel and conference facility. The Hilton Crystal City at Washington Reagan National Airport is the perfect base to see the sights of the USA’s capital city. The national monuments, government agencies, and museums are accessible via the Metro located within walking distance from this Arlington, Virginia hotel. Ride the complimentary shuttle bus daily between the hotel and Reagan National Airport (DCA), the Crystal City Metro station, and nearby shops, restaurants, and businesses.

Hilton Crystal City at Washington Reagan National Airport
2399 Jefferson Davis Highway
Arlington, VA, 22202
Tel:703.418.6800
Fax:703.418.3763

Housing

Discounted reservation rates for attendees have been arranged at the Hilton Crystal City at Washington Reagan National Airport in Arlington, VA:

  • 2 Queen Beds or 1 King Bed Guest Room for 189.00 USD per night

Attendees must book their rooms by September 22 in order to take advantage of the discounted room rates.

Book Online Now

Attendees may also call 1-800-HILTONS (445-8667) and request a reservation under the SOT Ocular Conference room block.

Discounted Parking Rates: Conference attendees will receive a discounted parking fee of $15.00 (with in and out privileges). For day guests, please stop by the Front Desk to pre-pay and mention you are with the SOT hi-PC CCT Conference Meeting to receive the discounted rate.

Organizing Committee
  • Douglas Keller, Chair, Sanofi, Bridgewater, NJ, USA
  • Jane Bai, Chair, US FDA, Silver Spring, MD, USA
  • Yvonne Will, Chair, Pfizer, Groton, CT, USA
  • Gary Gintant, Abbvie, North Chicago, IL, USA
  • Brian Guth, Boehringer-Ingelheim, Biberach, Germany
  • Jennifer B. Pierson, ILSI Health and Environmental Science Institute, Washington DC, USA
  • Ajay Pillai, NIH, Bethesda, MD, USA
  • Ruth Roberts, Council Contact, Apconix, Cheshire, United Kingdom
  • Norman Stockbridge, US FDA, Silver Spring, MD, USA
  • York Tomita, US FDA, Silver Spring, MD, USA
Abstract and Poster Information

The online system for abstract submissions is now open and will close at 11:59 pm ET on Friday, September 30, 2016.

We welcome both junior and senior scientists to present and share their research. Please contact SOT Headquarters if you have any questions regarding the meeting abstracts.

Program: Tuesday, October 25, 2016
7:00 AM–8:00 AM Registration and Breakfast Networking
8:00 AM–8:15 AM Greeting and Meeting Objectives

Janet Woodcock, MD, Center for Drug Evaluation and Research, US FDA
Norman Stockbridge, MD, PhD, US FDA

8:15 AM–9:45 AM Session 1—Essential Qualities of hiPSC-CM for Use in Assessing Human Arrhythmia Potential

The goal of this session is to assess the current state of our understanding of human stem cell-derived CMs and whether these cells are appropriate for use in high-throughput screening and regulatory assays. Issues to be discussed are:

  1. The current state of the art in assessing the stem cell-derived cardiomyocytes (SC-CMs) including hiPSC-CMs. The electrophysioloigcal characterization needed to qualify the fit-for-purpose utility of hiPSC-CMs.  
  2. In vitro assay methods to standardize the qualification of hiPSC-CM.
  3. The minimum set of markers needed for a qualification of hiPSC-CMs.

The meeting participants should finish the session with a clear idea of what the state-of-the-art is for iPSC-CM characterization and what needs to be done in the future to improve the quality of the cells and potential for use in regulatory assays.

Moderators: Jennifer B. Pierson, MPH, HESI; and Ajay Pillai, PhD, NIH

8:15 AM–8:40 AM
Screening Proarrythmia Potential Using SC-Derived Cardiomyocytes
Gary Gintant, MD
AbbVie, North Chicago, Illinois, USA
8:40 AM–9:05 AM Assessment of Concentration-Dependent Drug-Induced Repolarization Delay and Arrhythmias in an iPS Cell-Derived Cardiomyocytes Model
Yuko Sekino, PhD
NIHS, Tokyo, Japan
9:05 AM–9:30 AM Cellular Markers for Assessing Maturation of Human iPSC-Derived Ventricular Cardiac Myocytes for Proarrhythmia Assessment
Todd Herron, PhD
University of Michigan, Ann Arbor, Michigan, USA
9:30 AM–9:45 AM Break
9:45 AM–12:00 Noon Session 1 continued

Moderators: York Tomita, PhD, US FDA; and Yvonne Will, PhD, Pfizer

9:45 AM–10:10 AM Cardiotoxicity Caused by Protein Kinase Inhibitors: Gene Expression Signatures in iPSC-Derived Myocytes
Eric Sobie, PhD
Mount Sinai School of Medicine, New York, New York, USA
10:10 AM–10:35 AM Rate Correction of Field Potential Duration in hiPSC-Derived Cardiomyocytes: Sense and Nonsense
Georg Rast, PhD
Boehringer-Ingelheim, Biberach, Germany
10:35 AM–11:00 AM Regulatory Applications of Cardiomyocytes As a Tool to Assess Arrhythmic Risk
David Strauss, MD, PhD
US FDA, Silver Spring, Maryland, USA
11:00 AM–12:00 Noon   Session 1 Panel Discussion

Moderators: Todd Herron, PhD, University of Michigan; and Yuko Sekino, Japan

12:00 Noon–1:00 PM Lunch
1:00 PM–2:40 PM Session 2—Best Practices in Use of hiPSC-CM for Proarrhythmia Assessment

This session will build on Session 1 by relating the experience of stem cell-derived CM users in drug discovery and development projects, as well as applications in environmental science. Practical use of these CM will be discussed, bringing out the positive aspects as well as the areas where improvement is needed to replicate human in vivo effects.  Meeting participants will leave this session with an understanding of the current applications of these CM, and where improvements need to be made in order to better predict human arrhythmia potential.

Moderators: Ksenia Blinova, PhD, US FDA; and Li Pang, PhD, US FDA

1:00 PM–1:25 PM Subtype-Specific Promoter-Driven Optical Action Potential Recordings for Precise Disease Modeling and Drug Testing in iPSC-Derived Cardiomyocytes
Daniel Sinnecker, MD
Technical University of Munich, Germany
1:25 PM–1:50 PM The Role of iPS Cardiomyocytes in Cardiac Safety Assessment of Drugs: A Novartis Perspective
Peter Hoffmann, MD, PhD
Novartis, East Hanover, New Jersey, USA
1:50 PM–2:15 PM Evaluating Cellular Impedance as an Integrated Assay for Drug Effects on Human Stem Cell Derived Cardiomyocyte Beating
Matt Peters, PhD
Astra Zeneca, Waltham, Massachusetts, USA
2:15 PM–2:40 PM Predictivity of a hiPSC-CM Model for Preclinical Cardiac Electrophysiological Safety Screening: A GSK Experience
Kate Harris, PhD
GSK, Ware, United Kingdom
2:40 PM–2:55 PM Break
2:55 PM–4:45 PM Session 2 continued

Moderators: Frank Weichold, PhD, US FDA; and Douglas Keller, PhD, Sanofi

2:55 PM–3:20 PM Are hPSC-Cardiomyocytes Functionally Relevant if IKs is Absent but Beta-Adrenoceptor Signalling is Present?
Chris Denning, PhD
University of Nottingham, University Park, United Kingdom
3:20 PM–3:45 PM Human Stem Cell-Derived Cardiomyocytes: An Alternative Model to Evaluate Environmental Chemical Cardiac Toxicity and Development of Predictive Adverse Outcome Pathways
Kevin Dreher, PhD
US EPA, Research Triangle Park, North Carolina, USA
3:45 PM–4:45 PM Session 2 Panel Discussion

Moderators: Peter Hoffmann, MD, PhD, Novartis; and Lucie Low, MSc, PhD, NIH

4:45 PM–6:45 PM Poster Session
Program: Wednesday, October 26, 2016
7:00 AM–8:00 AM Breakfast and Networking
8:00 AM–9:30 AM Session 3—Advanced Uses of Stem Cell-Derived Cardiomyocytes

This session will highlight new models being developed for more integrative assessment of arrhythmic potential for in vitro-in vivo correlations. 2D and 3D constructs from stem cells as well as dosimetry will be covered. Future developments and applications of these models will be discussed by leaders in this field.

Moderators: Todd Herron, PhD, University of Michigan; and Dr. Peter Clements, BVM&S PhD, GSK

8:00 AM–8:30 AM Organs on Chips: New Tools for Tox
Francesco S. Pasqualini, PhD
University of Zurich, Zurich, Switzerland
8:30 AM–9:00 AM Human Cardiac Biowires As a New Platform for Cell Maturation, Drug Discovery, and Safety Testing
Milica Radisic, PhD
University of Toronto, Toronto, Ontario, Canada  
9:00 AM–9:30 AM Microphysiological Systems for High-Content Drug Screening
Kevin E Healy, PhD
University of California, Berkeley, Berkeley, California, USA
9:30 AM–9:50 AM Break
9:50 AM–10:20 AM Engineered Heart Tissues As a Drug Screening Platform
Arne Hansen, MD
University Medical Center Hamburg-Eppendorf, Hamburg, Germany
10:20 AM–10:50 AM PSCs for Accelerating Drug Discovery
Joseph Wu, MD, PhD
Stanford University, Palo Alto, California, USA
10:50 AM–11:50 AM Session 3 Panel Discussion
                                                 
Moderators: Brian Guth, PhD, Boehringer-Ingelheim; and Francesco S. Pasqualini, PhD, University of Zurich
11:50 AM–12:20 PM Panel Discussion—Select Speakers and Moderators to Review Key Messages from the Meeting

Moderators: Gary Gintant, AbbVie; and Jane Bai, PhD, US FDA
12:20PM–12:30 PM Concluding Remarks
Joseph Wu, MD, PhD
Stanford University, Palo Alto, California, USA
12:30 PM Meeting Adjourns
1:00 PM–3:00 PM Post-Meeting Action Discussion (Invitation Only)
Registration Information
Registration Type Early On-site
SOT Member $375 $425
Government Employees $375 $425
Scientific Liaison Coalition (SLC) Member $375 $425
Nonmember $475 $525
Student/Postdoc Member $200 $250
Student/Postdoc Nonmember $250 $300

Fees include all general sessions, program materials, and refreshments throughout the course of the meeting.

Registration fees may be paid by check (please list all registrants on the check stub), money order, credit card (Visa, MasterCard, Diner’s Club, or American Express), or by a US Government Purchase Order (check must be drawn from the US Department of the Treasury). Please use the registration form. All wire transfers should include an additional $40 processing fee.

Note: For individuals who are not members of SOT, participation in SOT’s hiPC CCT is available only to bona fide individuals who are engaged in or promote the field of toxicology or biotechnology research and support the growth and development of the toxicology field. For organizations, participation in the SOT’s hiPC CCT is available only to bona fide organizations with public policy positions and business practices that are generally consistent with SOT’s mission, goals, reputation, and its policies and principles as determined by SOT. SOT reserves the right to review applications for participation at SOT’s hiPC CCT to confirm that the applicant meets these criteria and may, at the SOT’s sole discretion, reject a registration by an individual or business or withdraw registration privileges at any time if any individual or organization is found to be inconsistent with SOT’s principles and interests.

Online Registration

Mail In Registration

  1. Mail/USPS Express packages:
    hiPC CCT, Society of Toxicology
    1821 Michael Faraday Drive, Suite 300
    Reston, VA 20190
  2. Fax: 703.438.3113

NOTE: To prevent double-billing, if you are registering by fax, DO NOT mail your original registration form. SOT needs only one copy for processing.

Registration Cancellation Refund Policy: All requests for cancellations and/or refunds must be received in writing to SOT Headquarters by September 25, 2016. These refunds will be processed, less a $30 fee, following the Meeting.

Disabled Attendees: If you need special assistance for this meeting, please contact SOT Headquarters at 703.438.3115.

Supporters

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