Human ips/es Cell Technology and Its Application to Toxicology Testing

Transcription

1 Human ips/es Cell Technology and Its Application to Toxicology Testing -Especially focusing on in vitro cardiac function toxicity- Atsushi Sanbuissho, PhD Daiichi Sankyo Co., Ltd. Kenji Yasuda, Prof Tokyo Medical Dental Univ. New Energy and Industrial Technology Development Organization (NEDO) JAPAN Independent Government Agency

2 Current Status in Pharmaceutical Industry Critical issue: High rate attrition of new drugs (8/9 clinical candidates fail during Ph I~III) Poor efficacy and safety concerns are major cause of attrition. To overcome the species difference is key to the solution. We need: New technologies to predict efficacy and toxicity in humans with improved reliability at an early pre-clinical stages via HTS screening To streamline validation of new technologies with collaboration among industry, government, and academia. 1

3 Human-iPS/ES Cell-Based Technology: Potential Platform of Drug Development to Overcome Species Difference Regenerative Medical Techniques Human-iPS/ES cells Target/Toxicity Screening (Disease-specific ips cell model) Expected to provide innovative tools for drug development via HTS screening. 2

4 Human Stem Cell Technology Utilization Project in Japan New Energy and Industrial Development Organization (NEDO) A public organization in Japan to promote research and development of industrial, energy and environmental technologies as well as application of the technologies developed Development of Drug Screening System with Application of ips Cells (2008 to 2013) Keio University Differentiation of ips cells into cardiomyocytes Tokyo Medical and Dental University On-chip single/multiple cell-based model and technology Users forum: Daiichi Sankyo, Takeda, Astellas, Eisai. 13 Japanese pharmaceuticals and 4 CROs Input form the expected users 3

5 Preliminary Work Plan Technology development Input from users NEDO project: Development of Drug Screening System with Application of ips Cells Tokyo Med. Dent. Univ. Keio Univ. Users forum ips/es cell based cardiac toxicity assay system 2013 Japan domestic project Basic system development Initial step: International workshop to review/discuss current issues of ips/es based toxicology testing Critical inputs for Evaluation, validation and standardization of toxicity assay Possibility for other application of ips/es technology Validation and standardization HESI Emerging Issue Global project Scientists from industry, academia and regulatory 4

6 Expected Outcome Industry: Applicability in drug screening Government: Regulatory perspective ips/es cell based cardiac toxicity assay system Academia: Scientific input Consensus on the protocol of standardization/validation for ips cell application in cardiac toxicity screening Basic understanding on applicability of ips cell in toxicity prediction shared globally among industry, academia and regulatory scientists Proposal for further researches on application of ips cells in other toxicity evaluations 5

7 Position of Our Proposed Project in the HESI Combined Challenges Map Relative impact Animal use and welfare Vaccine development, use and safety Genomics Human health: scientific evaluation of sensitive populations Sustainability Stem cell technology Food safety Communication and perception of risk versus benefit Improved risk assessment through biomonitoring and epidemiology Possible expansion of our project in the HESI combined challenge map Risk / benefit: regulation of chemicals in commerce Translational biomarkers Risk assessment of sensitive/ vulnerable populations Environmental quality Emerging contaminants Safety of genetically modified organisms and foods Regulatory framework for new methods Computational tools / toxicology Use of science in setting public policy Omics in risk assessment Risk assessment of co-exposures Nanomaterials/ nanotechnology Paradigm shifts in risk assessment / life cycle assessment Individual susceptibility Improved testing and assessment strategies Regulatory framework for carcinogenicity testing Alternatives to animal models Epigenetics in risk assessment Utilize the patient-specific ips Exposure-based risk assessment Cardiac toxicity assay system: one of the most advanced system using stem cell technology Improved biomonitoring through biomarkers Time: immediate (2010) to long-term (2020) 6

8 Summary New cardiac toxicity assay system with stem cell derived human cardiomyocyte based on the novel technology is now under development. This technology has the potential to improve the current risk assessment of the pro-arrhythmic potential in the drug development. For validation, standardization and practical application of this assay system, global input from expertise of multidiscipline are needed. HESI EI project can organize a global forum of tripartite scientists to provide the critical input for further development of this new assay system. This project is expected to be expanded to the full scope of ips cell technology such as application to other types of toxicities and/or chemicals, and is related to other topics in the HESI combined challenges map. 7

9 This project can be the first HESI Emerging Issue project of ips/es cell technology application. Through this project, a general framework for evaluation of future stem cell technology application will be provided. 8

10 Appendix 9

11 Expected Activities in the HESI Project Cross validation: Positive/ negative control data collection Comparison with current standard assays in the global industry-government-academia collaboration Further development: Improvement / refinement of the experimental devices and assay protocol through the cross validation Standardization: Determination of the specification of the total assay system Cells: Source of the human cardiomyocytes, Criteria to use in the assay Cell chip: Cells/ electrodes arrangement Field potential recording: Required specification of the recording device Data analysis: Automated analysis software Evaluation: Index of pro-arrhythmic potential 10

12 Framework of the HESI Project NEDO Yasuda-Lab, TMDU Daiichi Sankyo HESI Project Cardiactoxicity assay system with human stem cell derived cardiomyocytes Test compound Project member Data Idea Request Publication, Workshop Final goal: Establishment of the global standard proarrhythmic risk evaluation system for the all chemicals 11