Committed to innovation and growth - sustained leadership in oncology

Transcription

1 Committed to innovation and growth - sustained leadership in oncology UBS European Conference 2012 November 13, 2012 Dr. K. Mahler, Head of Investor Relations Dr. Stefan Frings, Global Head Medical Affairs Oncology

2 This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as believes, expects, anticipates, projects, intends, should, seeks, estimates, future or similar expressions or by discussion of, among other things, strategy, goals, plans or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1 pricing and product initiatives of competitors; 2 legislative and regulatory developments and economic conditions; 3 delay or inability in obtaining regulatory approvals or bringing products to market; 4 fluctuations in currency exchange rates and general financial market conditions; 5 uncertainties in the discovery, development or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products; 6 increased government pricing pressures; 7 interruptions in production; 8 loss of or inability to obtain adequate protection for intellectual property rights; 9 litigation; 10 loss of key executives or other employees; and 11 adverse publicity and news coverage. Any statements regarding earnings per share growth is not a profit forecast and should not be interpreted to mean that Roche s earnings or earnings per share for this year or any subsequent period will necessarily match or exceed the historical published earnings or earnings per share of Roche. For marketed products discussed in this presentation, please see full prescribing information on our website All mentioned trademarks are legally protected. 2

3 Performance update and strategy Update on oncology portfolio Summary and short term news flow 3

4 An increasingly challenging environment Where do we go from here? Regulators Medical benefit-risk ratio Efficacy (clinical endpoints) Safety ( zero tolerance) Payers Economic benefit-cost ratio Constrained funding capacity Demanding real outcome evidence Investors Economic risk-return ratio Declining Returns Declining Growth 4

5 Roche strategy: Focused on medically differentiated therapies Premium for innovation Generics OTC Pharma Dia MedTech Focus Regulators: Optimised benefit / risk ratio Payors: Optimised benefit / cost ratio Differentiation 5

6 Roche strategy: Leveraging Pharma & Diagnostics Through-out discovery to market Pharmaceuticals Research Development Commercialisation Unrestricted know-how and IP exchange More efficient development Faster adoption of PHC solutions (medicine and test) Research assay Diagnostics Technically validated IVD assay Clinically validated IVD assay 6

7 Roche: R&D well balanced from a risk & disease point of view 2012 Roche budget Oncology Metabolism Inflammation CNS Virology 0% 5% 10% 15% 20% 25% 30% Industry average probability of success Phase 0 to Registration Source: Bernstein Equity Research, Tufts University and Roche analysis 7

8 R&D productivity differs substantially among players Average annual NME peak sales ( ) 1 US$ bn $ 710 m Peak Sales (per $1 bn R&D) 4 x Roche $ 165 m Peak Sales (per $1 bn R&D) Average annual R&D investment ( ) 1 US$ bn 1 Peak sales and R&D calculated pro forma to account for major M&A Source: EvaluatePharma; BCG analysis; Roche analysis 8

9 Best-in-class pipeline 71 NMEs supporting long-term growth Phase I (36 NMEs) MDM2 ant solid & hem tumors Bcl-2 inh CLL and NHL HER3 MAb solid tumors ChK1 inh solid tum & lymphoma CSF-1R MAb solid tumors PI3K inh solid tumors CIF/MEK inh solid tumors ADC metastatic melanoma Tweak MAb oncology PI3k inh glioblastoma 2L Raf & MEK dual inh solid tumors ChK1 inh(2) solid tumors CD44 MAb solid tumors ALK inhibitor NSCLC MEK inh solid tumors PI3K inh solid tumors MEK inh solid tumors WT-1 peptide cancer vaccine MDM2 ant solid & hem tumors IL-17 MAb autoimmune diseases AKT inhibitor solid tumors IL-6 MAb RA PD-L1 MAb solid tumors CIM331RA atopic dermatitis Steap 1ADC prostate ca. TLR7 agonist HBV ADC ovarian ca. - infectious diseases ADC heme tumors GIP/GLP-1 dual ago type 2 diabetes ADC multiple myeloma GABRA5 NAM cogn. disorders ADC oncology V1 receptor antag autism BACE inh Alzheimer s ACE910 hemophilia A Phase II (24 NMEs) EGFR MAb solid tumors PI3K inh solid tumors PI3K/mTOR inh solid & hem tumors EGFL7 MAb solid tumors CD22 ADC heme tumors CD79b ADC heme tumors HER3/EGFR m. epithelial tumors glypican-3 MAb liver cancer etrolizumab ulcerative colitis rontalizumab SLE pateclizumab (LT alpha Mab) RA quilizumab (M1 prime Mab) asthma mericitabine HCV danoprevir HCV setrobuvir HCV inclaumab (P selectin Mab) ACS/CVD oxldl MAb sec prev CV events PCSK9 MAb metabolic diseases gantenerumab Alzheimer s MAO-B inh Alzheimer s mglur2 antag depression mglur5 antag TRD crenezumab Alzheimer s anti-factor D Fab geograph. atrophy Phase III (8 NMEs) onartuzumab (MetMAb) solid tumors obinutuzumab (GA101) hem. tumors lebrikizumab severe asthma aleglitazar CV risk reduction in T2D tofogliflozin (SGLT2) type 2 diabetes ocrelizumab MS bitopertin schizophrenia arbaclofen fragile X syndrome (FXS) Registration (3 NMEs) Perjeta (pertuzumab)* HER2+ mbc 1L Erivedge* advanced BCC T-DM1 HER2+ mbc As of September ; * Approved in US, filed in EU Oncology Immunology Virology CardioMetabolism Neuroscience Ophthalmology Others 9

10 Performance update and strategy Update on oncology portfolio Summary and short term news flow 10

11 Oncology: Roche s largest therapeutic area Roche 2011 sales Major Oncology products Other Pharma 32% Diagnostics 23% Oncology 45% CHF m 2011 Sales Avastin Herceptin MabThera/Rituxan Xeloda Tarceva Other oncology Sales in Oncology only; total MabThera/Rituxan sales CHF m 11

12 Evolution of cancer therapy Towards a highly targeted approach * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * * Chemotherapy e.g. Paclitaxel Targeted therapy + chemotherapy e.g. Herceptin, Perjeta, Zelboraf Highly targeted Antibody-Drug Conjugates e.g. T-DM1 12

13 HER2 franchise Building on the strength of Herceptin Pertuzumab Disrupts HER2:HER3 receptor dimers and downstream signaling In combination with Herceptin: potential to create new standard of care for women with HER2-positive metastatic BC T-DM1 Retains Herceptin s biologic activity Targeted intracellular delivery of a potent cell-killing agent, DM1 No need for conventional chemotherapy 13

14 Securing growth for HER2 franchise Pertuzumab and T-DM1 advancing the standard of care 2nd line mbc Xeloda + lapatinib T-DM1 (EMILIA) 1st line mbc Herceptin + chemo Herceptin & Perjeta + chemo (CLEOPATRA) T-DM1 & Perjeta (MARIANNE) Adjuvant BC Herceptin + chemo Herceptin subcutaneous + chemo (HannaH) Herceptin & Perjeta + chemo (APHINITY) T-DM1 & Perjeta + chemo Filing timelines Established standard of care Potential new standard of care Potential future standard of care 14

15 HER2 franchise Clinical updates reflect significant medical benefit Significant OS benefit (EMILIA) 25.1 months (Cap+Lap) to 30.9 months (T-DM1) Filed in US and EU Significant OS benefit (CLEOPATRA) To be presented at SABCS Approved in US, CH; filed in EU 1 Year treatment duration confirmed as the standard of care in early breast cancer 15

16 EMILIA Study T-DM1 in metastatic breast cancer Overall survival: confirmatory analysis HER2+ (central) LABC or MBC (N=980) Prior taxane and trastuzumab Progression on metastatic tx or within 6 months of adjuvant tx 1:1 T-DM1 3.6 mg/kg q3w IV Capecitabine 1000 mg/m 2 orally bid, days 1 14, q3w + Lapatinib 1250 mg/day orally qd Quality of life: Patient reported outcomes Time to symptom progression PD PD Proportion surviving No. at risk: Cap + Lap T-DM1 78.4% 85.2% 51.8% 64.7% Time (months) Median (mos) N Cap + Lap T-DM HR=0.80 (95% CI, 0.67, 0.95) P= In collaboration with Immunogen Median (mos) No. events Cap + Lap T-DM Stratified HR=0.682 (95% CI, 0.55, 0.85) P= Efficacy stopping boundary P= or HR=

17 Perjeta in HER2-positive 1 st line mbc CLEOPATRA study Progression-free survival (%) Perjeta+Herceptin+D: median 18.5 months Herceptin+D: median 12.4 months Time (months) HR = % CI p< Overall survival data to be presented at SABCS (Dec 2012) Δ = 6.1 months D=docetaxel 17

18 Herceptin & Perjeta in adjuvant setting Potentially increasing the cure rate: APHINITY study HER2-positive early breast cancer N=~4000 Herceptin + chemotherapy Herceptin & Perjeta + chemotherapy Primary end-point: 3 year Disease Free Survival FPI: H Follow-up: 3 years (median) Expect data 2016 Chemotherapy: FEC x 3 TH x 3 or AC x 4 TH x 4 or TCH x 6; Total duration of Herceptin treatment=1 year FEC = 5-fluorouracil, Epirubicin, Cyclophosphamide; TH=Taxotere, Herceptin; AC=cyclophosphamide, doxorubicin; TCH=Taxotere, Carboplatin, Herceptin 18

19 T-DM1 in early breast cancer A three-pronged approach Targeting indication with high unmet medical need Non-pCR adjuvant study T-DM1 single agent in patients with residual disease Setting high bar for clinically meaningful benefit Adjuvant study T-DM1 & pertuzumab vs. Herceptin & pertuzumab in adjuvant setting Utilizing pcr as surrogate end-point Neoadjuvant study T-DM1-based chemotherapy in neoadjuvant setting 19

20 Redefining HER2 blockade Increasing the efficacy and tolerability Tolerability Herceptin + chemotherapy T-DM1 T-DM1 & pertuzumab Herceptin & pertuzumab + chemotherapy Efficacy 20

21 Improve the standard of care Multiple shots on goal in hematological cancers 1L Indolent NHL MabThera MabThera Subcutaneous GA101 Aggressive NHL MabThera MabThera Subcutaneous GA101 Refractory indolent NHL MabThera MabThera Subcutaneous GA101 CLL MabThera GA Filing timelines Additional products in development: anti-cd22 and Bcl-2 Established standard of care Potential new standard of care Potential future standard of care MabThera IV/SC and GA101 (per their respective current/planned product profiles) are mostly used in combination with chemotherapy and, in some indications, as maintenance therapy following combined R-Chemo/GA101-Chemo induction 21

22 MabThera subcutaneous versus infusion MabThera IV administration can take all day Waiting room Pharmacy preparation IV line Rituximab IV administration + observation period MabThera SC injection takes 5 7 minutes Waiting room Prep Time saving SC vs IV administration MabThera SC administration No pharmacy dose preparation, no IV line, no mandatory observation period Ph III SABRINA presented at ASH

23 Bcl-2 selective inhibitor Bcl-2, an important target in hematological cancers GDC-0199 clinical activity in Phase 1 CLL trial RG 7601 (GDC-0199) is a Bcl-2 selective, small molecule BH3 mimetic currently in phase I Small molecule BH3 mimetics neutralize pro-survival proteins and promote apoptosis Cohort 1 Week 6 Week 12 Week 24 Pro-survival proteins, particularly Bcl-2, Bcl-x L, and Mcl-1 are overexpressed in hematopoietic and solid tumors and facilitate chemotherapeutic resistance Cohort 2 Week 6 Week 12 Week 24 Cohort 3 Week 6 Week 12 Week 24 Cohort 4 In collaboration with Abbott Week 6 Week 12 Week 24 23

24 Anti-CD22 Antibody Drug Conjugate in hematology Currently in phase II testing Early evidence of anti-tumor activity observed Screening After 4 cycles Right Inguinal lymph node 2.4 x 3.1 cm Previous treatments: two Rituxan +chemo regimens(r-chop and R-ICE) In collaboration with Seattle Genetics Right Inguinal lymph node < 1 cm x 1 cm No evidence of disease after 4 cycles Example: 79 year old patient with diffuse large B cell lymphoma 24

25 Antibody Drug Conjugates (ADCs) Extensive pipeline of ADCs for oncology indications Early Stage Research Late Stage Research Early Development Phase I/II Phase III Key Breast ESR ESR ESR ESR ESR ESR LSR LSR LSR Early Dev Anti-CD22 Anti-CD79b Anti-STEAP1 T-DM1 AML Melanoma Colon ESR ESR ESR RG7458 RG7598 RG7599 Lung Multiple Myeloma Ovarian ESR RG7600 Prostate ESR RG7636 Pancreatic ESR NHL Diagnostics As of July 25th,

26 Onartuzumab (MetMAb) A new compound that inhibits HGF-mediated activation HGF α HGF MetMAb α Cancers where Met may play a role Initiated/planned trials Non-small cell lung carcinoma (NSCLC) Triple negative metastatic breast cancer Potential additional indications Renal cell carcinoma (RCC) Hepatocellular carcinoma (HCC) Gastric cancer Prostate cancer Met Met Colorectal cancer (CRC) Ovarian cancer Glioblastoma multiforme (brain cancer) Head and neck squamous cell cancer Cell growth, migration, survival No Activity Monovalent format designed to prevent HGFmediated stimulation of pathway Preclinical activity across multiple tumor models Rationale for targeting Met Amplified, mutated, overexpressed or uniquely activated in various cancers Overexpression associated with worse prognosis HGF=Hepatocyte Growth Factor 26

27 Onartuzumab+Tarceva in Met+ lung cancer New example of Personalised Healthcare approach Progression Free Survival Overall Survival Probability of progression free Placebo + erlotinib MetMAb + erlotinib Median (mo) HR (95% CI) 0.53 ( ) Log-rank p-value No. of events Probability of survival Placebo + erlotinib MetMAb + erlotinib Median (mo) HR (95% CI) 0.37 ( ) Log-rank p-value No. of events Time to progression (months) PFS: HR=0.53 Overall survival (months) OS: HR=0.37 Spigel et al. ASCO % patients enrolled were Met-positive 27

28 Increasing evidence for the role of Met across multiple solid tumours Hazard Ratio HR=1 ITT population p-value Δ OS vs. control (mo) Met Met na na -4.0 onartuzumab+ Tarceva rilotumumab+ chemo tivantinib Source: ASCO 2011, ASCO 2012, Abstracts 4005,

29 Onartuzumab clinical development In multiple cancer types in parallel Non Small Cell Lung Metastatic Gastric 2nd/3rd line, Phase II 2 nd /3 rd line, Phase III 1 st line sq. Phase II 1 st line non-sq., Phase II 1 st line HER2-, Phase III (Met+) 1 st line HER2-, Phase II (all comers) Triple Negative Breast 1 st and 2 nd line, Phase II Metastatic Colorectal 1 st line, Phase II Glioblastoma 2 nd line, Phase II Indicates pivotal trial 29

30 Performance update and strategy Update on oncology portfolio Summary and short term news flow 30

31 Data to be presented in Q ASN (Oct 30-Nov 4) aleglitazar AleNEPHRO phii safety study ACR (Nov 9-14) rontalizumab ROSE study in lupus, phii data Actemra SC SUMMACTA/BREVACTA, ph III SABCS (Dec 4-8) Perjeta CLEOPATRA, 1 st line mbc, OS data ASH (Dec 8-11) MabThera/Rituxan SC SABRINA, front line fol. NHL, phiii Bcl-2 inh CLL and NHL, Ph I Anti-CD22 ADC Anti-CD79b ADC MDM2 Hem. malignancies, Ph I Cardiometabolism Immunology Oncology 31

32 Data availability / readouts A rich pipeline with major decision points up-coming Phase II mglur2 antagonist treatment resistant depression mglur5 antagonist treatment resistant depression crenezumab Alzheimer's (ABBY) Oncology Neuroscience Metabolism Virology Ph III Herceptin ebc HERA 2 years vs. 1 year gantenerumab 1 Alzheimer's Anti factor D geographic atrophy Immunology Ophthalmology bitopertin acute exacerbation of symptoms anti-pcsk9 metabolic diseases Ph II etrolizumab ulcerative collitis rontalizumab lupus 2 onartuzumab (MetMab) triple negative breast cancer Anti-EGFL7 solid tumours Phase III bitopertin schizophrenia negative symptoms aleglitazar renal function study (ALENEPHRO) EGFR ADCC Mab (RG7160, GA 201) solid tumours bitopertin schizophrenia sub-optimally controlled anti-pcsk9 metabolic diseases PI3 kinase (RG 7321) Solid tumours Tarceva EGFR+, adj NSCLC Ph I Bcl-2 (RG7601, GDC 0199) CLL and NHL dual PI3 kinase/mtor (RG7422 /GDC 0980) solid tumours Avastin high risk carcinoid MEKi (RG 7421)+Zelboraf met. melanoma danoprevir+setrobuvir+mericitabine hepatitis C (ANNAPURNA) obinutuzumab (GA 101) CLL Potential interim analysis 2 Presentation at ACR in November

33 We Innovate Healthcare 33