7th DIA Cardiac Safety Workshop in Japan - Leading into a New Era of Cardiovascular Safety Assessment

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OVERVIEW
There are ongoing discussions surrounding cardiovascular (CV) safety assessments of drugs in development. Although the implementation of the ICH E14/S7B guidelines is considered a success, proarrhythmia risk assessment continues to be one of the most important and challenging issues in drug development. The proarrhythmia risk assessment regulatory paradigm entered a new era in 2015 with the release of the ICH-E14 Q&A R3 document, which allows the use of Concentration Response Modeling of QTc data in lieu of the E14 ‘by-time point’ analysis as the primary basis for regulatory decisions. This revision effectively allows pharmaceutical sponsors to use routine early phase (SAD/MAD) studies, with intensive PK and QT data collection, to meet current regulatory requirements instead of the E14 mandated Thorough QT/QTc study.

Concomitantly, development of new non-clinical CV risk assessment strategies, such as the use of induced pluripotent stem cells (iPS) derived cardiomyocyte and in silico cardiac models have been making advances both in Japan and abroad.

In addition to the well documented proarrhythmia risk, other CV risks including those associated with drug-induced changes in blood pressure, cardiac function and cardiomyocyte (structure), have been recognized as important issues requiring attention and appropriate assessment during drug development.

Furthermore, the increasing importance of the emerging field of cardio-oncology, reflects the success of new cancer therapies in improving life expectancy of cancer patients on one hand, and the recognized CV risks of innovative anticancer drugs including molecular targeted therapies on the other hand. A wide range of cardiotoxicities associated with existing and new anticancer therapies were reported, including cardiomyocyte injury and heart failure, vascular injury and hypertension or thrombosis, accelerated coronary artery disease and proarrhythmia, amongst others.

In this workshop, we will invite clinical, industry and regulatory experts to discuss a range of hot topics, including: Non-clinical proarrhythmia risk assessment using iPS derived cardiomyocyte and in silico models such as CiPA, JiCSA and iSMART; Clinical proarrhythmia risk assessment models and the implementation of QTc Concentration Response Modeling in Japan and new ECG biomarkers; A research update and future directions for the assessment of cardiac contractile function; A cardio- oncology session including mechanism of drug-induced cardiotoxicity, and strategies for early detection and assessment of cardiotoxicity.

The 7th Cardiac Safety Workshop in Japan will provide a unique opportunity to learn of and discuss the current state and future directions of CV risk assessments and how to prepare for a new regulatory paradigm of cardiovascular safety assessments. We look forward to welcoming you to the workshop.

Date and Time:

October 25-26 (Thu-Fri),2018

Venue:

Nihonbashi Life Science Hub

REGISTRATION

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Program

DAY 1 | Thursday, October 25, 2018 | Proarrhythmia Risk Assessments

Time	Program Title
9:30-10:00	REGISTRATION
10:00-10:10	WELCOME AND OPENING REMARKS Akio Uemura, PhD - Senior Vice President & Managing Director, DIA Japan Kaori Shinagawa, MD, PhD - Senior Scientist for Clinical Medicine, Office of New Drug ll, Pharmaceuticals and Medical Devices Agency (PMDA)
10:10-12:10 SESSION1（PART1）	Clinical Proarrhythmic Risk Assessment SESSION CO-CHAIRS：　 Boaz Mendzelevski - Cardiac Safety Consultants Ltd. Kaori Shinagawa, MD, PhD - Senior Scientist for Clinical Medicine, Office of New Drug ll, Pharmaceuticals and Medical Devices Agency (PMDA) ・Regulatory Perspective for Clinical Proarrhythmic Risk Assessment Kaori Shinagawa, MD, PhD - Senior Scientist for Clinical Medicine, Office of New Drug ll, Pharmaceuticals and Medical Devices Agency (PMDA) ・Differentiating Drug-Induced ion Channel Effects on the ECG: Potential Role of the ECG under CiPA (Presentation via Internet) Jose Vicente, PhD - Staff Fellow, Division of Cardiovascular and Renal Products, Office of Drug Evaluation I, Office of New Drugs, Center for Drug Evaluation and Research, U.S. Food and Drug Administration (FDA) ・Regulatory Perspective for CR Modeling in Early Phase Studies and Other Biomarkers for Clinical Proarrhythmic Risk Assessment Krishna Prasad, DrMed, MD, MRCP, FRCP - Group Manager (CardioVasc, Oncology, and Antiinfective Product Teams), Medicines and Healthcare products Regulatory Agency (MHRA) *・Experience from QT Assessment Using Concentration-* QTc Modeling of Early Phase Studies Börje C. Darpö, MD, PhD - Chief Scientific Officer, Cardiac Safety, ERT ・Effects of Moxifloxacin on the Proarrhythmic Surrogate Markers in Healthy Subjects: Exposure-Response Modeling using ECG Data of Thorough QT/QTc Study Atsushi Sugiyama, MD, PhD - Professor and Chairman, Department of Pharmacology, School of Medicine, Toho University Faculty of Medicine ・Experience with CR Modelling across Different Types of Early Phase Clinical Trials** Jörg Täubel, MD, FFPM - Chief Executive Officer, Richmond Pharmacology Ltd.
12:10-13:30	LUNCH
13:30-14:00 SESSION 1 (PART 2)	Clinical Proarrhythmic Risk Assessment SESSION CO-CHAIRS： Boaz Mendzelevski, MD - Cardiac Safety Consultants Ltd. Kaori Shinagawa, MD, PhD - Senior Scientist for Clinical Medicine, Office of New Drug ll, Pharmaceuticals and Medical Devices Agency (PMDA)
14:00-16:00 SESSION 2	Non Clinical Proarrhythmic Risk Assessment SESSION CO-CHAIRS： Katsuyoshi Chiba, PhD - Senior Director and Head, Group III, Medicinal Safety Research Laboratories,Research Function, R&D Division, Daiichi Sankyo Co., Ltd. Yasunari Kanda, PhD - Head of Division of Pharmacology, National Institute of Health Sciences Keynote Lecture: ・Prediction and Quantification of Torsadogenic Potential Using Classical and New Assay Models Atsushi Sugiyama, MD, PhD - Professor and Chairman, Department of Pharmacology, School of Medicine, Toho University Faculty of Medicine ・CiPA: Validation Efforts and Update Gary Gintant, MA, PhD - Research Fellow, AbbVie Inc. ・JiCSA Update: Proarrhythmia Risk Assessment Using Human iPS Cell-derived Cardiomyocytes Yasunari Kanda, PhD - Head of Division of Pharmacology, National Institute of Health Sciences ・iSmart (investigation of in silico / in vitro model for Arrhythmogenic Risk Prediction) Update　 Keiichi Asakura, PhD - Senior Scientist, Pharmacokinetics and Safety Assessment Department, Nippon Shinyaku Co., Ltd. ・Panel Discussion PANELIST All speakers in Session 2
16:00-16:30	COFFEE BREAK
16:30-17:45 SESSION 3	Abstract Session 1 SESSION CO-CHAIRS： Naoki Furuyama, DVM, PhD - Takeda Pharmaceutical Company Limited Yuji Kumagai, MD, PhD - Director of Clinical Trial Center, Kitasato University Hospital ・Can We Rely on Automated ECG Machine Measurements for Clinical Trial Decisions? Robert Kleiman - Chief Medical Officer and Vice President, Global Cardiology, ERT ・Heart Rate Correction When the Drug Affects Heart Rate Georg Ferber - Statistical Consultant, Statistik Georg Ferber GmbH ・Intensive QT Investigation as Standard Practice in Early Clinical Programs in Lieu of Thorough QT Study Sanae Yasuda, PhD - Senior Director, Clinical Pharmacology, Medicine Development Center, Eisai Co., Ltd. ・Evaluation of a Proposed Novel Biomarker, the JTpeak Interval, for Evaluation of Proarrhythmic Liability Börje C. Darpö, MD, PhD - Chief Scientific Officer, Cardiac Safety, ERT ・Influence of Food on QT, J-Tpeak and Tpeak - Tend Intervals Jörg Täubel, MD, FFPM - Chief Executive Officer, Richmond Pharmacology Ltd.
17:45-19:30	NETWORKING RECEPTION

※Unless otherwise disclosed, DIA acknowledges that the statements made by speakers are their own opinion and not necessarily that of the organization they represent,or that the DIA. Speakers and agenda are subject to change without notice. Recording of any DIA tutorial/workshop/meeting information in any type of media,is prohibited without prior written consent from DIA.

DAY 2 | Friday, October 26, 2018 | Cardio-Oncology and Other Cardiac Safety Issues

Time	Program Title
9:00-9:30	REGISTRATION
9:30-10:30 SESSION 4	Cardiovascular Safety in Oncology Drug Development: Mechanisms of Cardiotoxicity SESSION CO-CHAIRS： Katsuyoshi Chiba, PhD - Senior Director and Head, Group III, Medicinal Safety Research Laboratories, Research Function, R&D Division, Daiichi Sankyo Co., Ltd. Atsushi Sugiyama, MD, PhD - Professor and Chairman, Department of Pharmacology, School of Medicine, Toho University Faculty of Medicine ・Drug-Induced Cardiac Toxicity: Translating Non-Clinical Observations into Early Clinical Investigation Atsuhiko T. Naito, MD, PhD - Associate Professor, School of Medicine, Toho University Faculty of Medicine ・Development and Standardization of in vitro Contractility Method Using Human iPS Cell-Derived Cardiomyocytes Yasunari Kanda, PhD - Head of Division of Pharmacology, National Institute of Health Sciences ・Molecular Pathways and Pathophysiology of TKI Induced Cardiotoxicity Junichi Ishida - The University of Tokyo Hospital
10:30-10:45	COFFEE BREAK
10:45-12:15 SESSION 5	Strategies for Early Detection of Cardiotoxicity SESSION CO-CHAIRS： Atsushi Sugiyama, MD, PhD - Professor and Chairman, Department of Pharmacology, School of Medicine, Toho University Faculty of Medicine Kyosuke Takeshita, MD, PhD, FAHA - Department of Clinical Laboratory Medicine, Saitama Medical Center, Saitama Medical University ・Integrated Approach to Early Detection of Drug-Induced Cardiotoxicity Hiroshi Akazawa, MD, PhD - Lecturer, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo ・Imaging Biomarkers for Early Detection of Drug-Induced Cardiotoxicity Kyosuke Takeshita, MD, PhD, FAHA - Department of Clinical Laboratory Medicine, Saitama Medical Center, Saitama Medical University ・Preclinical Human Contractility Safety Testing Najah Abi Gerges - Vice President, Research & Development, AnaBios Corporation ・Panel Discussion PANELIST - All speakers in Session 4 and 5
12:15-13:30	LUNCH
13:30-15:10 SESSION6（PART1）	Strategies to Assess, Prevent and Mitigate Oncology Drugs Cardiotoxicity SESSION CO-CHAIRS：Yuji Kumagai, MD, PhD - Director of Clinical Trial Center, Kitasato University Hospital ・Cardiovascular Safety Assessments of Oncology Drugs in Clinical Development Boaz Mendzelevski - Cardiac Safety Consultants Ltd.　・Important Adverse Effects of Molecular-Targeting Drugs in Aspects of Cardio-Oncology Manabu Minami, MD, PhD - Institute for Advancement of Clinical and Translational Science (iACT), Kyoto University Hospital ・TKI Induced Cardiotoxicity and Drug-Induced Thrombosis Wataru Shioyama, MD, PhD - Deputy Manager, Department of Cardiovascular Medicine, Onco- Cardiology Unit, Osaka International Cancer Institute ・Oncology Drug-Induced Cardiotoxicity: Strategies to Assess, Prevent and Mitigate Cardiotoxicity Pre- and Post-Approval Krishna Prasad, DrMed, MD, MRCP, FRCP - Group Manager (CardioVasc, Oncology, and Antiinfective Product Teams), Medicines and Healthcare products Regulatory Agency (MHRA) ・Cardio-Oncology from the Regulator's Perspective Hitoshi Kanno, MD, PhD - Reviewer, Office of New Drug V, Pharmaceuticals and Medical Devices Agency (PMDA)
15:10-15:40	COFFEE BREAK
15:40-16:10 SESSION6（PART2）	Strategies to Assess, Prevent and Mitigate Cardiotoxicity ・Panel Discussion PANELIST　All speakers in Session 6
16:10-16:40 SESSION7	Abstract Session 2 SESSION CO-CHAIRS： Yasunari Kanda, PhD - Head of Division of Pharmacology, National Institute of Health Sciences Kaori Shinagawa, MD, PhD - Senior Scientist for Clinical Medicine, Office of New Drug ll, Pharmaceuticals and Medical Devices Agency (PMDA) ・A Case of Spontaneous Smoking Echo in a Patient with Bladder and Pancreatic Cancer - Detection of Prothrombotic Status with Echocardiography Takako Morooka - Department of Medical Technique, Nagoya University Hospital ・Efficacy to Safety Endpoints - Design and Technology Considerations Jeff Heilbraun, MS - VP Strategic Development, Bioclinica
16:40-17:00	CLOSING REMARKS Katsuyoshi Chiba, PhD - Senior Director and Head, Group III, Medicinal Safety Research Laboratories,Research Function, R&D Division, Daiichi Sankyo Co., Ltd.

※Private Social Function Policy DIA does not allow hospitality functions to be held during any DIA meeting sessions, scheduled exhibit hours, or social events. Therefore,the hours noted below are the only hours that are acceptable for hospitality functions.
Wednesday, October 24 All times are acceptable
Thursday, October 25 Before 8:00 and after 21:00
Friday, October 26 Before 8:00 and after 19:00