Clinical Development at Roche: Driving the paradigm shift

Transcription

1 Clinical Development at Roche: Driving the paradigm shift Jean-Jacques Garaud, MD Global Head Pharma Development, Chief Medical Officer Roche UBS Global Life Science Conference, New York, September 22, 2008

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 Our new R&D model: Paradigm changes Genentech offer Development perspective Franchises and assets Summary 3

4 New R&D model Innovation truly at its core Translational Medicine Customized /original design System Biology Understanding complexity Innovation Modeling and Simulation Driving decision-making process Biomarkers Relevant tools 4

5 Biomarkers A central element throughout the life cycle of a medicine Biomarkers are critical for translational medicine, exploratory and confirmatory development strategies - Improved decision making in R&D (e.g. tools for profiling targets, compounds, PD Markers) - Understanding pathways and mechanisms (e.g. pt. subpopulations, optimized patient stratification) - Drivers for pharmacodiagnostic development e.g. increased benefit/risk ratio, companion diagnostics) Biomarkers are a central element throughout the lifecycle of a medicine from target ID to market 5

6 Development does never stop Continuous with integration of biomarkers across development More Internal Innovation Research Development Marketing Discovery Phase Exploratory Phase Biomarker Development Learning (reducing uncertainty) Clinical Research & Exploratory Development PoC Modeling & Simulation Confirmatory Phase Confirming Clinical Development Biostatistics Co-Develop with Diagnostics Biomathematics 6

7 Our new R&D model: Paradigm changes Genentech offer Development perspective Franchises and assets Summary 7

8 Key objectives of combining Genentech and Roche building a leading organization Research and Early Development Late Development Manufacturing Commercial Admin & other Enhance innovation Allow diversity of approaches in research Encourage sharing of IP, technologies, networks etc. Post 2015 partnership Improve operational efficiency Reduce complexity Eliminate duplications Leverage combined scale in the US and globally 8

9 Enhance innovation by maintaining diversity of approaches Genentech: Keep Founders Research Center independent Oncology Inflammation Inflammation CNS + Oncology Inflammation Inflammation CNS Virology* Metabolism Roche: Keep existing Disease Biology Area (DBA) model Transfer Palo Alto activities: Virology DBA to South San Francisco Inflammation DBA to Nutley No changes outside the US * Located on Genentech site in South San Francisco 9

10 Our new R&D model: Paradigm changes Genentech offer Development perspective Franchises and assets Summary 10

11 Roche Pharma pipeline overview Focused on five Disease Biology Areas Oncology Xeloda MabThera Herceptin Avastin Tarceva Pertuzumab T-DM1 R1507 (IGF-1R mab) Apomab Apo2L/TRAIL Anti-CD40 mab Hedgehog antagonist 18 phase I compounds On Hand RA/Inflammation MabThera Actemra R1594 ocrelizumab R667 RARg 9 phase I compounds Metabolic R1658 CETP Inh. R1583 GLP-1 R1439 dual PPAR 9 phase I compounds Promising Late Stage Virology Pegasys Tamiflu R3484 HPV16 R1626 HCV pol. Inh. R7128 HCV pol. Inh. R7227 HCV prot. inh. Emerging Mid-Term CNS ocrelizumab RRMS R1678 Schizophrenia R3487 Alzheimer s 3 phase I compounds Early Stage 11

12 Key drivers for long term development in place Develop the short term drivers while not leaving the others Inherent development risk Low High ILLUSTRATIVE Oncology Inflammation existing Earlier Phases Maturity of portfolio Virology CNS Metabolic 12

13 Major Roche-managed oncology submissions Industry-leading oncology pipeline Avastin mbc + standard chem (EU) Herceptin gastric Ca (EU) Phase 3 Avastin mbc + docetaxel (EU) Avastin glioblastoma 2nd line (EU) MabThera CLL (EU) Tarceva NSCLC 1 st line maint (EU) Tarceva + Avastin NSCLC 1 st line maint (EU) Xeloda adj BC Avastin adj CC (EU) Avastin gastric Ca metastatic (EU) Avastin ovarian Ca (EU) Avastin prostate Ca (EU) Avastin+Herceptin mbc 1st line (EU) MabThera inhl maint 1 st line (EU) Avastin HER2- adj BC (EU) Avastin adj mbc Her 2+(EU) Avastin adj NSCLC (EU) Tarceva+Avastin NSCLC 2nd line (EU) Xeloda adj CC combo oxaliplatin Xeloda+Avastin adj CC (EU) pertuzumab (R1273) HER 2+ mbc (EU) MabThera+Avastin aggressive NHL (EU) Tarceva adj NSCLC (EU) post 2011 Phase 2 Avastin glioblastoma 1st line (EU) Avastin NSCLC squamous (EU) IGF-1R inh humab(r1507) Ewing s sarcoma pertuzumab (R1273) early BC (EU) Tarceva+Avastin NSCLC 1 st line (EU) TDM1 (R3502) mbc (EU) Status as of June 30, 2008 Unless stated otherwise, submissions will occur in US and EU 13

14 Avastin still early in its journey Realising full potential across tumour types Tumour Early/adjuvant (Potential for cure) Advanced/metastatic (Extending life) 1 st -line of treatment 2 nd -line of treatment Colon, colorectal Phase III (AVANT, NSABP C-08) Launched [EU, US, JP; broad label in 1st and subsequent lines] Lung (NSCLC) Phase III (E1505) Launched [EU majority of chemos, US carboplatin/paclitaxel] Phase III (BETA Lung w/tarceva) Breast (HER2-) Phase III (BEATRICE, E5103) Launched [EU, US w/paclitaxel] Phase III (RIBBON-1) Phase III (RIBBON-2, incl. w/xeloda) Breast (HER2+) Phase III (BETH w/herceptin) Phase III (AVEREL w/herceptin) Kidney (RCC) Launched [EU; with interferon] Avastin also tested in gastric, ovarian and prostate cancer, anhl, and brain (GBM) 14 (Trial names) [Approval status]. More trials are ongoing than listed above.

15 Avastin and cetuximab in combination with irinotecan-based regimen Study Regimen PFS Study arm Crystal Folfiri +/- Cetuximab PFS control Benefit (detriment) ITT K-Ras WT K-Ras mut AVF 2107 IFL +/- Avastin ITT K-Ras WT K-Ras mut HR p 15

16 Avastin in 1st line mcrc: the only biologic with significant survival benefit Study Regimen OS Study arm Crystal Folfiri +/- Cetuximab OS control Benefit (detriment) ITT K-Ras WT AVF 2107 IFL+/-Avastin ITT <0.001 K-Ras WT HR p 16

17 Avastin and cetuximab in combination with oxaliplatin-based regimen Study Regimen PFS Study arm Opus Folfox +/- Cetuximab PFS control Benefit (detriment) ITT K-RAS WT K-Ras mut Cairo 2 Xelox-Avastin +/- Cetuximab ITT K-Ras WT na 0.1 K-Ras mut na HR p 17

18 Avastin in Refractory Glioblastoma Multiforme (GBM) High unmet medical need Lesion Screening Week 12 Week 24 Incident Primary Brain Tumors population in line with mrcc 20,000 incident patients in top 5 EU countries (mrcc: 17,000) Phase II data demonstrated encouraging six-month PFS and ORR in patients with relapsed GBM, exceeding historical estimates of 15% Avastin in relapsed GBM ph. II data on track to be filed by end 2008 Phase III in first-line Glioblastoma in preparation T. F. Cloughesy et al., ASCO 2008, abstract 2010b (Monday) 18

19 Attacking the HER2 pathway from multiple angles Pertuzumab and Trastuzumab-DM1 moving forward Herceptin Pertuzumab Trastuzumab-DM1 Mechanism Specifically targeting HER2 Inhibits HER2-mediated signalling First in class HER dimerization inhibitor Inhibits multiple HERmediated pathways Binds to HER2 and delivers intracellularly a potent cytotoxic agent in a targeted manner Phase of development Approved for adjuvant and mbc (HER2+) Phase III in 1st line mbc (CLEOPATRA) FPI Q Phase II FPI Q Efficacy data Survival benefit In adjuvant and metastatic HER2+ BC Ph. II data at ASCO 08 ORR: 24% Clinical benefit rate: 50% Promising phase I data at ASCO 2008 Clinical benefit rate: 53% Newsflow Unprecedented benefit standard of care Phase III in 1st line mbc ongoing First ph.ii data at ASCO BC

20 Exciting mid- and early-stage opportunities in oncology IGF1-R Inhibitor Impressive early results Potential broad use in cancer therapy 3rd generation anti-cd20 Potential for improvement over MabThera Increased direct cell death Increased ADCC Lower CDC Restaging Week 6 Unique Features: Selective to IGF pathway which is a key factor in tumor growth Drivers of Value: IGF pathway linked to many tumor types Phase I in NHL Unique Features: fully humanized MAb recognizing type II CD 20 epitope Drivers of Value: superior to rituximab in vitro and in pre-clinical models Phase II ongoing Phase I data at ASH ADCC= (antibody dependent cell-mediated cytotoxicity); CDC= (complement dependent cytotoxicity) 20

21 Implementing biomarker strategy for all pipeline drugs Oncology leads the way Ph I / II Ph III / Market IGF-1R mab (R1507) Range of candidate markers Herceptin HER2 expression HER2 gene amplification MDM2 antag (R7112) P53 wild-type Avastin Range of candidate markers for investigation PLX4032 (R7204) T-DM1 (R3502) BRAF V600E gene mutation HER2 expression HER2gene amplification Pertuzumab Tarceva Range of candidate markers for investigation EGFR expression (IHC) EGFR gene copy # (FISH) EGFRmutations KRAS mutations Prospectively assessing opportunities for patient selection Identifying patients who have an improved clinical benefit to launched drugs 21

22 Oncology: Major newsflow expected in H MabThera in relapsed CLL: REACH Randomized ph. III, 552 patients Fludarabine+cyclophosphamide +/-MabThera Avastin in 1st line mbc: RIBBON-1 Phase III study, 1200 patients, 2 analyses: Anthracycline-/taxane-based +/- Avastin, and Xeloda +/- Avastin Expect data H2 08 Expect topline data H2 08 Tarceva+Avastin in 2nd line NSCLC: BETA lung Tarceva+/-Avastin Enrollment completed Q2 08 Potentially label-enabling for Avastin Expect topline data H2 08 Tarceva 1st line maintenance NSCLC: SATURN 4 chemo cycles followed by T vs. placebo Enrollment completed Q2 08 Potentially label-enabling for Tarceva Expect topline data H

23 Key drivers for long term development in place Develop the short term drivers while not leaving the others Inherent development risk Low High ILLUSTRATIVE Oncology Inflammation existing Earlier Phases Maturity of portfolio Virology CNS Metabolic 23

24 Rheumatoid Arthritis: Not all patients respond to current therapy Gold standard therapy anti-tnf + MTX % ACR70 Responders Unmet Medical Need Only 1 of 3 patients receives significant benefit anti-tnf + MTX anti-tnf alone ACR 70=70% Improvement in: MTX alone Disease activity patient Disease activity physician Patient assessment of Pain Physical disability Acute phase reactants CRP,ESR 24

25 Actemra: The first IL-6 receptor inhibitor Unprecedented level of remission in moderate to severe patients with RA mil-6r Tocilizumab gp130 mil-6r Largest clinical programme of any biologic for RA Consistently high & durable remission rates - across different disease stages Rapid treatment response - as early as 2 weeks New data presented at EULAR 2008: RADIATE: Rapid and significant improvements in patients who have failed up to 3 anti-tnf inhibitors 1 AMBITION: Only biologic to have demonstrated superiority vs. methotrexate as monotherapy 2 Filed in US & EU Nov 07 (RA) Approved in Japan Apr 08 (RA, sjia, pjia) 1 Emery et al., EULAR 2008, Abstract OP Jones et al., EULAR 2008, Abstract OP

26 Key drivers for long term development in place Develop the short term drivers while not leaving the others Inherent development risk Low High ILLUSTRATIVE Oncology Inflammation existing Earlier Phases Maturity of portfolio Virology CNS Metabolic 26

27 CETP Inhibitor R1658 is a unique CETPi In contrast to the majority of other CETPi, R1658 has a different chemical backbone to Torcetrapib In patients treated with R1658, HDL is of normal composition In pre-clinical models and in clinical trials up to phase II, data showed that R1658 at therapeutic doses had a similar safety profile to placebo, including effects on blood pressure and RAAS activation R1658 (Dalcetrapib) Torcetrapib F F F F H N S O F F F O O N F O F N O O 27

28 Relationship Between Changes in LDL-C and HDL-C Levels and CHD Risk 1% decrease in LDL-C reduces CHD risk by 1% 1% increase in HDL-C reduces CHD risk by 1% Third Report of the NCEP Expert Panel. NIH Publication No Large mortality and morbidity study running Only true evaluation of the CV benefits of raising HDL-C by CETPi R1658 is being investigated to reduce CV risk on top of current recommended standard of care for CV risk factors Currently the only route to approval of CETPi 28

29 Taspoglutide: investigational once-weekly GLP-1 analogue for the treatment of type-ii diabetes Significantly reduces blood glucose over only eight weeks Provides substantial weight loss in a dose-response fashion Additional titration study confirmed the safety and tolerability of taspoglutide Efficacy, safety and tolerability profile encouraging Phase III recruitment started in Q Taspoglutide (R1583) has the potential to be the first once weekly, long-acting human GLP-1 analogue 29

30 Key drivers for long term development in place Develop the short term drivers while not leaving the others Inherent development risk Low High ILLUSTRATIVE Oncology Inflammation existing Earlier Phases Maturity of portfolio Virology CNS Metabolic 30

31 CD20 targeting: new treatment strategy for MS Very promising signals from Phase II with rituximab Total cumulative mean number of gadolinium lesions was reduced by 91 %, p<0.0001) Patients with relapses over 24 weeks in the treated arm was 14.5 % compared to 34.3 % in the placebo (58 percent relative reduction, p = ) Ocrelizumab: Phase II placebocontrolled program in RRMS 31

32 Our new R&D model: Paradigm changes Genentech offer Development perspective Franchises and assets Summary 32

33 Roche R&D opportunities in summary Innovation-driven business focused on differentiated products that add medical value Network approach to foster innovation and build on our core business Leverage combination of Pharmaceuticals and Diagnostics in-house to develop more targeted treatment options (personalised healthcare) Numerous short- and mid-term drivers of growth with low development risk Broad pipeline for long-term sustainable growth Our unique strategy provides Roche with a competitive edge for sustainable outperformance 33

34 We Innovate Healthcare 34

35 Avastin s position as standard of care in first-line mcrc and mnsclc remains unchallenged Avastin in 1st line and 2nd line mcrc: the only biologic with significant survival benefit Avastin: only biologic with a statistically significant overall survival (OS) benefit in 1st line and 2nd line mcrc Avastin: only biologic offering a progression-free survival (PFS) benefit regardless of mutations in K-Ras gene Avastin: only biologic with a statistically significant OS benefit in K-Ras wild-type patients Avastin remains the best option for the majority of patients with mnsclc E2100 and AVAIL: Robustness and consistency of data across endpoints in two phase III studies The longest median overall survival in first-line non-squamous mnsclc ARIES and SAiL data presented at ASCO 08 further establish safety / tolerability and broad applicability for non-squamous mnsclc 35

36 Avastin in 2nd line mcrc: the only biologic with significant survival benefit Study Regimen OS Study arm Epic Irinotecan +/- Cetuximab OS control Benefit (detriment) ITT K-Ras WT na E 3200 FOLFOX+/-Avastin ITT HR p 36