Chugai Pharmaceutical Co., Ltd. · TSE:4519
Chugai Pharmaceutical — Technical Presentation (October 2011)
54 slides from Chugai Pharmaceutical's technical presentation, Oct 28, 2011
Slide 1: Personalized Healthcare (PHC) Approach in Chugai
Personalized Healthcare (PHC) Approach in Chugai CHUGAI PHARMACEUTICAL CO., LTD. Senior Vice President Head of Lifecycle Management & Marketing Unit Yutaka Tanaka October 28, 2011
Slide 2: Forward-Looking Statements
Forward-Looking g Statements This presentation may include forward-looking statements pertaining to the business and prospects of Chugai Pharmaceutical Co., Ltd. (the “Company”). These statements reflect the Company’s current analysis of existing information and trends. Actual results may differ fro
Slide 3: Concept of Personalized Healthcare: PHC
Concept p of Personalized Healthcare: PHC Stratified to A heterogeneous group homogeneous groups Method for stratification to specific properties Biomarkers Efficacy (+) Risk of AR (+) Efficacy (-) Efficacy (-) Ri k off AR (+) Risk Ri k off AR ((-)) Risk One therapy (medicine) for all Efficacy (+) R
Slide 4: Transition in Pharmaceutical Development
Transition in Pharmaceutical Development p Biologics g First Generation Interferon Erythropoietin G Growthth Factor F t G CSF G-CSF Second Generation Humanized Monoclonal Antibody Third Generation PHC Progress of Molecular Next Target Biological Pathology Molecular Targeted g Agent g 4
Slide 5: Economical Effect of PHC Approach in Pharmaceutical Companies
Economical Effect of PHC Approach in Pharmaceutical Companies p PHC approach benefits pharmaceutical Companies Improvement p of compliance Economical Effect Increase Fewer patients of who are eligible market share for treatment Acceleration of market penetration Price for speed value Minimization of
Slide 6: PHC Benefits
PHC Benefits PHC offers benefits to all stakeholders of Chugai, such as patients and physicians p y Patients Physicians & Access A tto best b t Healthcare Providers treatment Maximum available benefit Minimum toxicity Burden of national PHC Regulators & healthcare cost Policy Makers Efficien
Slide 7: PHC Approach in Chugai
PHC Approach pp in Chugai g By leading PHC, ◇ Chugai Ch gai will ill accelerate paradigm shift in healthcare healthcare, and will offer benefits to all stakeholders of Chugai, including patients and physicians physicians. ◇ Chugai will be the leading company to accelerate innovation of new drugs dru
Slide 8: Scheme for PHC Approach in Chugai
Scheme for PHC Approach pp in Chugai g Build collaboration scheme with Roche Diagnostics to conduct research and development p of biomarkers from earlyy stage g Development of pharmaceuticals Development of diagnostics - Biomarker selection Modification and Chugai to - Optimization search biomarkers
Slide 9: Maximization of Product Value and Enlargement of Opportunity to Create New Drugs
Maximization of Product Value and Enlargement g of Opportunity pp y to Create New Drugs g PHC helps faster market penetration and leads to innovation of new drugs g Herceptin for HER2 metastatic breast cancer Creation of new innovative drug Expanding indication Adjuvant/neo-adjuvant** Pertuzumab* in
Slide 10: ToGA Study (Trastuzumab for GAstric Cancer)
ToGA Study (Trastuzumab for GAstric Cancer) Phase III, randomised, open-label, international, multicenter study 5 FU or Capecitabine 5-FU + Cisplatin on ( 290) (n=290) HER2-positive omizatio advanced GC 5 FU or Capecitabine 5-FU Rando (n=584) + Cisplatin + Trastuzumab (n=294) Bang YJ et al.： Lancet
Slide 11: Development Compounds Targeting HER2
Development p Compounds p Targeting g g HER2 1. Pertuzumab An anti anti-HER2 HER2 monoclonal antibody which inhibits HER2 HER2-HER HER family dimerization In development as first line treatment in HER2-positive metastatic breast cancer in combination with Trastuzumab plus Docetaxel (CLEOPATRA, p
Slide 12: R&D Portfolio based on PHC Strategy
R&D Portfolio based on PHC Strategy gy Phase I Phase II Phase III Filed AF802 MRA/Actemra RG435/Avastin * EPOCH/Epogin - NSCLC (PI/II) - PC (PI/II) - GC - CIA CIF/RG7167 RG435/Avastin * - aBC - Solid tumors - Glioblastoma (relapsed) - Glioblastoma CKI27/RG7304 RG1415/Tarceva RG1273/Pertuzumab - Soli
Slide 13: Role of Clinical Diagnostics for The Personalized Healthcare (PHC)
Role R l off Clinical Cli i l Diagnostics Di ti for The Personalized Healthcare (PHC) ( ) Yoshiaki Tazawa Roche Diagnostics KK Lifecycle Management of Molecular Diagnostics October 28, 2011 13
Slide 14: Various Roles of Diagnostic Tests throughout the Medical Scenes
Various Roles of Diagnostic Tests throughout the Medical Scenes Diagnostics test has been getting more important for improving quality of advanced therapy Predicting P di ti efficacy ffi and/or for PHC adverse reaction Monitoring Screening Prevention high risk program Diagnosis Therapy Monitoring di
Slide 15: Ideal concept of Personalized Healthcare: PHC
Ideal concept of Personalized Healthcare: PHC Illnesses are not always y homozygous Efficacy: low Risk of AR: high Pharmaco- genomics(PGx) Efficacy: low Risk of AR: low Companion Diagnostics Efficacy: hi Effi high h (CoDx) Risk of AR: high One therapy for all Efficacy: high Efficacy: low Risk of AR:
Slide 16: More therapies and designated Companion Dxs now available in the medical practice
More therapies and designated Companion Dxs now available in the medical practice p Disease Pharmaceuticals CoDxs Breast cancer Herceptin (Trastuzumab) Expression of HER-2/neu protein or Stomach cancer gene NSCLC Iressa (Gefitinib) Mutation of EGFR gene Colorectal cancer Erbitux (Cetuximab) Mutation
Slide 17: Herceptin Therapy and HER2 Test (Breast Cancer)
Herceptin p Therapy py and HER2 Test (Breast ( Cancer)) HER2 test to identify HER2 amplification level to stratify patients for treatment with Herceptin or Tykerb HER-2 test Herceptin e cept + cchemotherapy e ot e apy P b bilit Probability (FISH: gene amplification) extended survival in patients wit
Slide 18: Efficacy of Gefitinib and EGFR mutation in NSCLC (IPASS trial)
Efficacy of Gefitinib and EGFR mutation in NSCLC (IPASS trial) i l) Gefitinib EGFR M+ (n=132) Probability 1.0 Gefitinib EGFR M－(n=91) of PFS CP EGFR M＋ (n=129) CP EGFR M－ M (n=85) ( 85) 0.8 Gefitinib HR=0.19, 95% CI 0.13, 0.26, p<0.0001 06 0.6 CP, HR=0.78, 95% CI 0.57, 1.06, p=0.1103 0.4 0.2 0.0 0 4
Slide 19: The Current Progress of PHC Approach
The Current Progress g of PHC Approach pp New drugs with CoDx currently approved by FDA Aug 17: vemurafenib and BRAF V600E Mutation assay Aug A 26: 26 crizotinib i ti ib and d ALK in-situ i it hybridization h b idi ti R&D collaboration currently stimulated Kyowa Hakko Kirin and Kyowa Medex
Slide 20: Draft Guidance: In Vitro Companion Diagnostic Devices
Draft Guidance for Industry and Food and Drug Administration Staff In Vitro Companion Diagnostic Devices DRAFT GUIDANCE This guidance document is being distributed for comment purposes only. Document issued on: July 14, 2011 You should submit comments and suggestions regarding this draft document wi
Slide 21: PHC: Leveraging Pharma & Diagnostics Collaborating throughout discovery to market
PHC: Leveraging Pharma & Diagnostics Collaborating throughout discovery to market Pharmaceuticals Research Development Commercialisation Unrestricted know-how More efficient Faster adoption of PHC solutions g and IP exchange p development ((medicine and test)) Technically validated Clinically valida
Slide 22: Core Dx technologies and Platforms to enhance CoDx development
Core Dx technologies g and Platforms to enhance CoDx development Life Sciences In Vitro Diagnostics Molecular Tissue Applied Science Professional Diagnostics Diabetes Care* Diagnostics Diagnostics Academia/Pharma Molecular Lab Central Lab Doc. Office, Wards Pathology Lab Patient Biochemicals/IB Bloo
Slide 23: Assay Procedure of cobas BRAF V600E kit
Assay Procedure of cobas BRAF V600E kit 23
Slide 24: PHC: Roche internal collaborations
PHC: Roche internal collaborations Significant increase due to focused PHC strategy 169 = Companion Dx Projects Genentech = R&D Collaborations Privatisation Ventana A Acquisition i iti 10 2005 2006 2007 2008 2009 2010 24
Slide 25: Roche Pharma: a leading pipeline
Roche Pharma: a leading pipeline 12 NMEs in late-stage development New molecular PHC approach entities (NMEs) 12 HCV p pol inh1 √ Virology 10 ocrelizumab MS Glycine Glycine CNS reuptake inh reuptake inh aleglitazar aleglitazar M t b li Metabolic taspoglutide dalcetrapib Inflammation √ dalcetrapib le
Slide 26: Personalised Healthcare becoming a reality
Personalised Healthcare becoming a reality Six late-stage compounds require a companion diagnostics g test T-DM1 MetMAb1 Metastatic breast cancer Non-small cell lung cancer (HER-2 expression level) (MET status) Pertuzumab Lebrikizumab1 Metastatic breast cancer Asthma (HER-2 expression level) (perios
Slide 27: We Innovate Healthcare
We Innovate Healthcare 27
Slide 28: R&D Portfolio Based on PHC Approach in Chugai
R&D & Portfolio o t o o Based ased o on PHC C Approach in Chugai CHUGAI PHARMACEUTICAL CO., LTD. Portfolio Management Unit Department Manager of R&D Portfolio Management Dept. Hisanori Takanashi October 28, 2011
Slide 29: R&D Portfolio Based on PHC Approach
R&D Portfolio Based on PHC Approach pp Phase I Phase II Phase III Filed AF802 MRA/Actemra RG435/Avastin * EPOCH/Epogin - NSCLC (PI/II) - PC (PI/II) - GC - CIA CIF/RG7167 RG435/Avastin * - aBC - Solid tumors - Glioblastoma (relapsed) - Glioblastoma CKI27/RG7304 RG1415/Tarceva RG1273/Pertuzumab - Soli
Slide 30: GC33: Antibody against glypican-3 positive hepatocellular carcinoma
GC33 A recombinant humanized antibody against glypican glypican-3 3 positive hepatocellular carcinoma 30
Slide 31: Glypican-3 and GC33
Glypican-3 yp and GC33 Glypican-3 (GPC3) Glypican-3 Glypican 3 GPI-anchored GPI h d heparan h sulfate lf t proteoglycan NH2 It is highly expressed in the majority (70–100%) of hepatocellular carcinoma (HCC) One of onco-fetal antigen S Said to play a role in tumor growth 60kDa S Heparan H GC3
Slide 32: GPC3 mRNA Expression Profile
GPC3 mRNA Expression Profile Clinical Tissue Samples 4500 4000 on level 3500 3000 2500 expressio 2000 1500 1000 mRNA e 500 phagus phagus a. Site ncreas Bile Ducts Pancreas Ducts Stomach mach ostate ostate Kidney Brreast Ovary dney Brreast Colon Liver Colon Lung Lung Liver Stom Bile D Kid Meta L Esop
Slide 33: Anti-tumor Efficacy Correlation to GPC3 Levels
Anti-tumor Efficacy Correlation to GPC3 Levels In GC33, antigen level dependent antitumor activities observed Negative Low Moderate High ensity IHC Inte GPC3 expression Low Moderate High AACR 2010: # 2426 33
Slide 34: Treatment Duration and GPC3 Expression Analysis of Phase I Study
Treatment Duration and GPC3 Expression Analysis of Phase I Study GPC3-IHC High GPC3-IHC high (n=9) 2202 2405 1406 4101 2101 2202 3102 1406 2101 Cohort 1 Cohort 2 1403 3102 3304 3405 2405 Cohort 3 1403 Cohort 4 3304 Subjects who could 3405 not complete the primary phase 4101 0 50 100 150 200 250 300
Slide 35: GPC3 IHC Development Plan
GPC3 IHC Development p Plan NDA Approval GC33 P1 P2 P3 GPC3 IHC GPC3-IHC Home-brew assay GPC3 assessment using P1 specimens (manual) Analytical Clinical Clinical Utility for Validation Validation stratification marker Filing Approval IVD Perform IHC Diag clinical IVD development analysis of P2 assay
Slide 36: AF802: High Sensitivity to ALK
AF802: High g Sensitivity y to ALK A new selective treatment against ALK mutation positive non-small cell lung cancer 36
Slide 37: EML4-ALK Fusion Gene
EML4-ALK Fusion Gene A New Target for Non-small Non small Cell Lung Cancer Identification of the transforming Development of lung adenocarcinoma EML4 ALK fusion gene in non EML4-ALK non-small small in EML4 EML4-ALK ALK transgenic mice cell lung cancer Nature, 2007: 448, 561-6 PNAS 2008: 105, PNAS, 1
Slide 38: AF802: High Sensitivity to ALK
AF802: High g Sensitivity y to ALK AF802 402 ki kinases IC50（µM） (including the mutated kinases) 100 10 1 0.1 0.01 0.001 TREEspot Flt3 ALK AXL FAK ALK LYN LTK YES InsR IGF1R lck KDR Fyn BRK EGFR Src GAK Kitt Abl MEK1 FGFR2 cdk1 DDR1 EphA2 PDGFR MET PKA RON cdk2 HER2 Raf1 >50% inhibition at 10 nM AF8
Slide 39: Efficacy of AF802
Efficacy of AF802 Xenograft Model NCI-H2228: EML4-ALK Xenograft Tumors CH5424802 600 po, qdx11 Control p-ALK (IHC) Apoptosis Cleaved PARP olume (mm3) Control 400 Control CH 2 mg/kg Tumor vo 200 PARP Cleaved AF802 6 mg/kg PARP 0 20 mg/kg β-Actin 18 20 22 24 26 28 Vehicle or 20 mg/kg AF802, 110 4 h af
Slide 40: Crizotinib-resistant Mutations
Crizotinib-resistant Mutations Cell-free kinase inhibition C i ti ib Crizotinib Kinase inhibition (%) 120 100 C1156Y 80 60 Native L1196M 40 Choi, et al., N. Eng. J. Med. 363, 1734-1739 (2010) 20 0 Secondary mutations within EML4-ALK K 20 0.1 -20 01 1 10 100 1000 Crizotinib (nM) AF802 e inhibition (%
Slide 41: ALK Diagnosis: as a Prerequisite for the Treatment
ALK Diagnosis: as a Prerequisite for the Treatment • In situ hybridization – Fluorescence in situ hybridization (FISH) – Chromogenic Ch i in i situ it hybridization h b idi ti (CISH) • Immunohistochemistry (IHC) • Real-time Real time polymerase chain reaction (RT (RT-PCR) PCR) FISH (1) CISH (2) IHC
Slide 42: Phase I/II study of AF802 in Japan
Phase I/II study y of AF802 in Japan p Target g Non-small cell lung cancer with ALK fusion gene Objectives PI part: dose finding (initial dose: 40 mg/day) • To investigate the safety, tolerability, and PK parameters of CH5424802 • To determine the recommended dose of CH5424802 in PII part PII
Slide 43: MetMAb: Antibody against cMet positive NSCLC
MetMAb A recombinant humanized antibody against cMet positive non-small cell lung cancer 43
Slide 44: Unique Features of MetMAb
Unique q Features of MetMAb MetMAb Typical Ab - Monovalent: Does not dimerize Met - Bivalent: Potential for Met dimerization - Produced in E.coli - Produced in CHO - Non-glycosylated N l l t d (No (N ADCC) - Glycosylated G antibody (ADCC) ( CC) 44
Slide 45: NSCLC: cMet Oncogene is a Therapeutic Target in Non-small Cell Lung Cancer
NSCLC: cMet Oncogene is a Therapeutic Target g in Non-small Cell Lung g Cancer Met is amplified, mutated, Cancer Signaling Cancer Signaling overexpressed in many tumours, No MetMAb + MetMAb including g NSCLC. Associated with a worse prognosis in NSCLC HGF HGF Met activation is implicated in resi
Slide 46: A Phase II Study Testing Tarceva ± MetMAb in Second-/third-line NSCLC
A Phase II Study Testing Tarceva ± MetMAb in Second-/third-line NSCLC Design A randomized, phase II, multicenter, double-blind, placebo-controlled study evaluating the safety and activity of MetMAb, in combination with Tarceva (Erlotinib) Population Adult patients (> 18 yrs) who have inoperable loca
Slide 47: NSCLC: Significant Survival Benefit in Dx+ 2/3 line NSCLC Treated with MetMAb + Tarceva
NSCLC: Significant Survival Benefit in Dx+ 2/3 line NSCLC Treated with MetMAb + Tarceva M t Dx+ Met D + OS HR= 0.37 St Strong ITT OS HR=0.8 Moderate Overall survival (months) Met Dx- OS HR= 1.78 Weak Negative 47
Slide 48: Lebrikizumab: Anti-IL-13 antibody against periostin high asthma
Lebrikizumab A recombinant humanized anti-IL-13 antibody against periostin high asthma 48
Slide 49: Lebrikizumab: Science Rationale of IL-13 for Asthma
Lebrikizumab : Science Rationale of IL-13 for Asthma Pathophysiology p y gy of IL-13 in Asthma B cell Lung IL13 IgE IL4 Mast cell e.g., TSLP IL5 Cytokines IL9 IL13 Inflammation Chemokines Eosinophils, T cells, OX40L IL4 Basophils, etc IL13 T cell TGF Fibrosis DC Fibroblast,, Macrophage IL13 IL9 Air
Slide 50: Mode of Action: Blocks IL-13 Binding to IL-4R
Mode of Action：Blocks IL-13 Binding to IL-4R and Inhibits IL-13 Signaling g g through g IL-4/IL-13R1 Lebrikizumab IInhibits hibit recruiting iti IL-4Ra IL 4R tto IL IL-4Ra/IL-13Ra1 4R /IL 13R 1 complex l after ft bi binding di lebrikizumab/IL-13 complex to IL-13 Is expected to have effect on
Slide 51: Periostin Gene is Highly Expressed in Bronchial Epithelial Cells in Half of Asthmatics
Periostin Gene is Highly Expressed in Bronchial Epitherial p Cells in Half of Asthmatics IL-13 responsive gene signature in bronchial epithelium Th2 cytokine expression asthmatics th ti asthmatics th ti & controls t l i b in bronchial hi l bi biopsies i Level of periostin induced by IL-13 is project
Slide 52: Study Overview of P2 (MILLY)
Study y Overview of P2 ((MILLY)) 1:1 randomized, double-blind, placebo-controlled study to evaluate efficacy Design and safety of lebrikizumab vs placebo 18-65 year old patients with asthma who are inadequately controlled on Population inhaled corticosteroids (ICS) Sample Size 218 [ 200 originally p
Slide 53: Asthma: Relative Change in FEV1 from Baseline with Lebrikizumab
Asthma: Relative Change in FEV1* from Baseline in Asthma Patients Treated with Lebrikizumab ALL EFFICACY EVALUABLE SUBJECTS Relative Mean FEV1 change at week 12 % Total ITT Periostin Periostin Change population High Low FEV 1 Pl Placebo b 4 3% 4.3% 5 8% 5.8% 3 5% 3.5% Time (Weeks) Lebrikizumab 9.8%
Slide 54: Contacts
Contacts: Chugai: Corporate Communications Dept. Corporate Communications Group Tel: +81 (0)3-3273-0881 Fax: +81 (0)3-3281-6607 e-mail: [email protected] p@ g p jp Hitoshi Aikawa, Koichi Kawahara, Kae Miyata, Hiroshi Araki Investor Relations Group p Tel: +81 (0)3-3273-0554 Fax: +81 (0)3-3281-660
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