PSTC Japan Safety Biomarker Conference Session 1. Introduction

John Michael Sauer, PhDExecutive Director, Predictive Safety Testing Consortium

Takayoshi Nishiya, PhDSenior Director, Daiichi Sankyo

Thank you Planning Committee

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Chugai Nozomi Fujisawa

Naoto Toyota

C-Path Nicholas King

John-Michael Sauer

Daiichi Sankyo Ito Kazumi

Takayoshi Nishiya

Mitsubishi Takuya Fujita

Manami Miyake

Toshinobu Shimuzi

NIHS Yoshiro Saito

Novartis Yumiko Tsujimura

Otsuka Yuichi Shimomura

Pfizer Masanori Hizue

Chieko Muto

PMDA Akihiro Ishiguro

Yasuto Otsubo

Taiki Sato

RIKEN Piero Carninci

Masaaki Furuno

Linda Kostrencic

Todd Taylor

Takeda Jiri Aubrecht

Naomi Kamiguchi

Shingo Okubo

Yusuke Sudo

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Thank You to Our Host

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Thank You to Our Co-Sponsors

PSTC Japan Safety Biomarker Conference

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Why are we here today?

The objectives of the conference:

• Bring together biomarker stakeholders in order to share

scientific discoveries and approaches around safety biomarkers

• Identify collaborative opportunities across stakeholder groups

• To teach and to learn

PSTC Japan Safety Biomarker Conference

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Why are we here today?

The objectives of the conference:• International alignment around the implementation of safety

biomarkers in drug development

• Alignment on the regulatory qualification of biomarkers in general across the three major government agencies – FDA, EMA, and PMDA

Agenda – Day 1

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Time Session Proposed Session Description / Theme Session Chairs

10:30 – 11:00 1 Introduction John Michael-Sauer (C-Path)Takayoshi Nishiya (Daiichi Sankyo)

11:00 – 13:00 Lunch (poster session)

13:00 – 15:00 2 Beyond protein biomarkers: small circulating RNA• miRNA safety biomarkers – Jiri Aubrecht (Takeda)• miRNA – Tsuyoshi Yokoi (Nagoya Univ.)• small circulating RNA – Takahiro Ochiya (Tokyo Medical Univ.)

Takayoshi Nishiya (Daiichi Sankyo)Nicholas King (C-Path)

15:00 – 15:15 Break

15:00 – 17:30 3 Cluster/network analysis of genomics for disease grouping• New diagnostic examination (biomarkers) and treatment for mental disorders by

using of genomics, epigenetics and metabolomics technologies – Atsushi Takata(Yokohama City Univ.)

• Modeling of the transcriptional response to multidrug treatment for prediction of positive and negative effects of combinatorial drug therapy – Erik Arner(RIKEN)

• Building the Human Cell Atlas towards Medical Innovations – Jay Shin (RIKEN)• TGx-DDI – Qualification of a Preclinical Biomarker – Roland Frötschl (BfArM)

Piero Carninci (Riken) Jiri Aubrecht (Takeda)

18:00 Banquet

Agenda – Day 2

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Time Session Proposed Session Description / Theme Session Chairs

09:00 – 10:30 4 Safety testing and disease diagnosis• GLDH clinical qualification – Jiri Aubrecht (Takeda) • Validation of drug-induced liver injury biomarkers in Japan – Noriaki Arakawa (NIHS)

Yoshiro Saito (NIHS)Tanja Zabka (Genentech)

10:30 – 10:45 Break

10:45 – 12:00 4 Safety testing and disease diagnosis• Qualification of Clinical Skeletal Muscle Injury Biomarkers: An Innovative Approach –

Tanja Zabka (Genentech)• Diagnostic test/tool standardization – Masato Maekawa (Hamamatsu Medical Univ.)

Yoshiro Saito (NIHS)Tanja Zabka (Genentech)

12:00 – 13:00 Lunch

13:00 – 15:30 5 Biomarker qualification evidentiary considerations • Current evidentiary considerations progress across PMDA, FDA, and EMA – Nicholas King

(C-Path)• Case study: clinical and analytical validation of safety biomarkers – John-Michael Sauer

(C-Path)• Survey results and perspectives on analytical validation in Japan – Yoshiro Saito (NIHS)• Qualification at PMDA – Mineo Matsumoto (PMDA)

Yasuto Otsubo (PMDA)Masanori Hizue (Pfizer Japan)

15:30-15:45 Break

15:45 – 16:30 6 Closing • Conclusions and next steps• Include all session chairs for panel discussion to summarize the conference

Akihiro Ishiguro (PMDA)John Michael Sauer (C-Path)

PSTC Japan Safety Biomarker Conference

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Since the 2017 Safety Biomarker Conference…

• PSTC has initiated formal interactions with PMDA to qualify the kidney safety biomarkers for clinical use in Japan

• FDA qualified the kidney safety biomarker for clinical use as a composite measure

• PSTC has advance the qualification of GLDH with FDA and EMA

• PSTC has initiated the qualification of clinical skeletal muscle safety biomarkers with the FDA

Translational Safety Biomarkers

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Fluid-Based Safety Biomarkers: Can be used to accurately predict drug-induced tissue injury, similar to a routine clinical pathology measure.

Monitorability of Drug-Induced Tissue Injury

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Gaps:The Need for Better Safety Biomarkers

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Current biomarker standards do not exist or they have significant limitations

PSTC Members and Partners

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Partners

Consortium Members

www.c-path.org

Thank you