Investor science event at ADA 2008 San Francisco, 9 June 2008

Transcription

1 Investor science event at ADA 2008 San Francisco, 9 June 2008 Forward-looking statements 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. Please see for full information on Roche products mentioned. 2

2 Introduction Dr. Karl Mahler, Head of Investor Relations Agenda Metabolism/Diabetes in Roche Pharma Luke Miels, Head of Strategic Marketing, Metabolism & Anemia, Roche Pharma Taspoglutide (R1583) phase II data at ADA 2008 Dr. Robert E. Ratner, Medstar Research Institute, Hyattsville, Maryland, USA Prof. Dr. med. Michael Nauck, Diabeteszentrum, Bad Lauterberg im Harz, Germany Questions & Answers with Dr. Robert E. Ratner (until 7:00 pm) Taspoglutide (R1583) phase III and future plans Rajiv Patni, Taspoglutide Lifecycle Leader, Strategic Marketing, Roche Pharma Innovation in diabetes self-management Matthias Axel Schweitzer, MD, MBA, Head of Medical Affairs, Diabetes Care, Roche Diagnostics Metabolism/Diabetes franchise update Luke Miels, Head of Strategic Marketing, Metabolism & Anemia, Roche Pharma Questions & Answers Total duration: 1½ hour 4

3 Roche Pharma s key therapeutic areas Current and future pillars of growth Oncology Xeloda MabThera Herceptin Avastin Tarceva Pertuzumab R1507 (IGF-1R mab) Apomab Apo2L/TRAIL 16 phase I compounds Today s focus On Hand RA/Autoimmune MabThera Actemra R1594 ocrelizumab PNP inhibitor 9 phase I compounds Metabolism R1658 CETP Inh. R1583 GLP-1 R1439 dual PPAR R1579 DPP-IV 7 phase I compounds Promising Late Stage Virology Tamiflu Pegasys R3484 HPV16 R1626 HCV pol. Inh. R7128 HCV pol. Inh. R7227 HCV prot. inh. Emerging Mid-Term CNS ocrelizumab RRMS R phase I compounds Early Stage 5 Roche in Metabolism Substantial potential for innovative products Diabetes: The epidemic continues; still large unmet need Dyslipidemia: HDL-raising therapy the next treatment frontier Million prevalence US, top-5 EU type 2 diabetes prevalence and forecast US Top-5 EU Million prevalence US, EU dyslipidemia prevalence and forecast US EU Source: Type 2 Diabetes: Global Epidemiology, Strategyst Consulting, 2004 Sources: Wood MacKenzie, IMS therapy forecaster, Roche assumptions, Decision Resources, Cardium Study#4, 2007; Datamonitor Pipeline Insight dyslipidemia

4 Metabolism/Diabetes in Roche Pharma Luke Miels, Head of Strategic Marketing, Metabolism & Anemia, Roche Pharma Roche: Driving improvements in diabetes Leverage of both divisions Roche Pharma Differentiated diabetes medicines with clear competitive advantages Roche Diagnostics Continuous improvement in diabetes care & management Taspoglutide (R1583) GLP-1 analogue (phase III) Carmegliptin (R1579) DPP-IV inhibitor (phase II) Aleglitazar (R1439) dual α-γ PPAR agonist (phase II) Additional 4 phase I compounds in diabetes bg meters, test strips and lancing devices Insulin delivery systems Disease management, information management solutions and decision support Combined: Driving significant improvements in diabetes care 8

5 Overview Discuss phase II data with the principal investigators Transition of taspoglutide (R1583) into phase III Phase III plan and high-level target product profile Update on Diabetes Care in Roche Diagnostics Overview of the late stage Metabolism portfolio in Roche Pharma 9 Taspoglutide (R1583) phase II data at ADA 2008 Dr. Robert E. Ratner, Medstar Research Institute, Hyattsville, Maryland, USA Prof. Dr. med. Michael Nauck, Diabeteszentrum, Bad Lauterberg im Harz, Germany

6 Converting native GLP-1 into taspoglutide Native GLP-1 Taspoglutide Serine protease cleavage site Aib 8 Aib 8,35 substitutions Aib 35 DPP-IV cleavage site The active form of GLP-1, GLP-1 (7-37) is rapidly degraded by DPP-IV through cleavage of 2 amino acids (His and Ala) to GLP-1 (9-37) Aminoisobutyric acid (Aib) 8,35 substitutions block N- and C-terminal enzymatic degradations Once-weekly dosing supported by zinc-based formulation, a simple and effective mechanism Taspoglutide is the first investigational onceweekly, long-acting human GLP-1 analogue 11 Taspoglutide provided significant reductions in A1c and FPG along with weight loss in diabetic patients Once-weekly 10 mg and 20 mg were most effective at achieving A1c targets, body weight, and FPG reductions Approx 80% of patients achieved ADA (7%) A1c target following 8 weeks of treatment Significant reductions in A1c and weight loss were achieved after only 8 weeks of treatment in patients inadequately controlled on metformin monotherapy Addition of taspoglutide resulted in no increased risk of hypoglycemia than metformin alone Fasting plasma glucose (FPG) reductions observed following the first injection Safety and tolerability profile supports entry into phase III Taspoglutide, the first investigational once-weekly, long-acting, human GLP-1 analogue, provided significant reductions in A1c and FPG as well as weight loss with an acceptable safety and tolerability profile for use in patients with type 2 diabetes 12

7 Main efficacy conclusion from the dose titration study (ADA presentation no. 10-OR) HbA1c Placebo 20/20 mg once weekly 20/30 mg once weekly 20/40 mg once weekly Weeks 13 Metformin combination study objectives were to characterize dose range, efficacy & safety of taspoglutide Screening (max 3 weeks) Randomization (baseline) Treatment (8 weeks) Follow-up (4 weeks) Metformin 1.5g/day Metformin 1.5g/day Metformin 1.5g/day Metformin 1.5g/day Metformin 1.5g/day Metformin 1.5g/day + Taspoglutide 5 mg once weekly Metformin + Taspoglutide 10 mg once weekly Metformin + Taspoglutide 20 mg once weekly Metformin + Taspoglutide 10 mg once every two weeks Metformin + Taspoglutide 20 mg once every two weeks Metformin + Placebo once weekly Metformin Day 1 (first injection) ~ 50 patients per treatment group 14

8 79 and 81% of patients treated with taspoglutide achieved ADA target A1c ( 7%) Patients (%) A1c 7% A1c 6.5% Placebo 5 mg once weekly 10 mg once weekly 20 mg once weekly 10 mg once every 2 weeks 20 mg once every 2 weeks 15 Taspoglutide provided significant A1c reductions over only eight weeks (from baseline) A1c (%) Placebo 5 mg once weekly 10 mg once weekly 20 mg once weekly 10 mg once every 2 weeks 20 mg once every 2 weeks 6.6 Baseline Week 2 Week 4 Week 6 Week 8 Taspoglutide safely reduced A1c below 7.0% with more than 1%-point reduction after only eight weeks * All taspoglutide doses were statistically significant (p<0.0001) 16

9 Taspoglutide provided significant dose-related weight loss in only eight weeks (from baseline) 0 Placebo Change from baseline (kg) mg once weekly 10 mg once weekly 20 mg once weekly 10 mg once every 2 weeks 20 mg once every 2 weeks Baseline Week 2 Week 4 Week 6 Week 8 17 Taspoglutide provided significant dose-related weight loss in only eight weeks (from placebo) 0 Δ change from placebo (kg) * + 5 mg once weekly 10 mg once weekly 20 mg once weekly 10 mg once every 2 weeks 20 mg once every 2 weeks Taspoglutide 20 mg once weekly provided a 2 kg weight loss in only eight weeks * p=0.0035, + p<0.0001, p=

10 Taspoglutide provided significant reductions in FPG in only eight weeks Appreciable reductions seen by weeks 1-2 FPG change from baseline (mg/dl) Δ change from placebo (mg/dl) * Baseline Week 2 Week 4 Week 6 Week 8 * p=0.0002, + p< Placebo 5 mg once weekly 10 mg once weekly 20 mg once weekly 10 mg once every 2 weeks 20 mg once every 2 weeks 19 Taspoglutide safety profile As expected, the most common adverse event was transient, dose-related, mildto-moderate nausea Episodes of nausea tended to occur during the first day after administration 18% placebo-adjusted incidence in 10 mg once-weekly group The frequency of vomiting in the groups that received taspoglutide once-weekly was similar to placebo In most patients, vomiting occurred only once and resolved within one day Most cases of nausea and vomiting resolved spontaneously while treatment continued Addition of taspoglutide resulted in no increased risk of hypoglycemia than metformin alone No acute pancreatitis was observed in the phase II program Safety and tolerability profile supports entry into phase III 20

11 Taspoglutide is an investigational once-weekly, longacting human GLP-1 analogue for the treatment of T2D Significantly improves both A1c and FPG over only eight weeks Provides substantial weight loss in a dose-response fashion Additional phase II titration study confirmed the safety and tolerability of taspoglutide Efficacy, safety and tolerability profile supports entry into phase III Data from this study shows that taspoglutide has the potential to be the first once weekly, long-acting human GLP-1 analogue 21 Questions & Answers, session 1 Moderator: Dr. Karl Mahler, Head of Investor Relations

12 Taspoglutide (R1583) phase III and future plans Rajiv Patni, Taspoglutide Lifecycle Leader, Strategic Marketing, Roche Pharma Taspoglutide phase III program Targeted and competitive Taspoglutide phase III program designed to confirm promising phase II data and generate competitive launch label Head-to-head comparisons: Sitagliptin, exenatide, insulin glargine Patient population: Treatment-naïve multiple OADs Add-on to metformin Based on phase II data, two taspoglutide doses will be tested in all phase III studies: 10 mg once weekly 10 mg once weekly for 1 month up-titrate to 20 mg once weekly First-patient-in expected 2H month treatment period with follow-up extension phases 24

13 Approximately 2,500 type 2 diabetic patients will be randomized into taspoglutide s phase III program Study Study Sample size Background OAD 1 Monotherapy vs. placebo 330 Treatment-naïve 2 Taspoglutide vs. sitagliptin vs. placebo 630 Metformin 3 Taspoglutide vs. insulin glargine 990 Metformin 4 Taspoglutide vs. exenatide 990 Metformin, TZDs, or metformin + TZDs 5 6 Add-on to sulfonylurea (± metformin) vs. placebo Add-on to pioglitazone + metformin vs. placebo Sulfonylurea (+/- metformin) Pioglitazone + metformin 25 Innovation in diabetes self-management Matthias Axel Schweitzer, MD, MBA, Head of Medical Affairs, Diabetes Care, Roche Diagnostics

14 Diabetes self-management requires an optimized and integrated approach combining different components Requirements for optimal diabetes self-management Education Lifestyle modification bg monitoring Treatment CV risk factor management Diabetes basics Insulin treatment Insulin pump treatment Weight normalization Dietary adoption Physical exercise Accuracy + preciseness Structured bg measurement Data visualization & analysis Treatment advice Aid in therapy decisions Treatment initiation Treatment adjustment (Insulin bolus recommendation) Treatment intensification Hypertension Obesity Dyslipidemia Smoking Information management systems 27 Roche s innovation response to people with diabetes offering products in 5 important areas to manage diabetes functional integration/connectivity of product solutions Connectivity solutions & Information management Blood glucose monitoring systems Single strip systems Integrated strip systems Insulin pump systems Advising systems mmol/l Time Continuous glucose monitoring systems* plus an attractive portfolio of diabetes medicines * In development 28

15 Roche s innovation response to people with diabetes turning information into appropriate treatment decisions along an entire value chain bg measurement Structured measurement data visualization & analysis Treatment support Treatment Accu-Chek meters -AC Aviva (single strip meter) - AC Compact Plus (integrated strip systems) Accu-Chek information management tools - AC 360 View tool - AC SMART Pix - AC 360 software Accu-Chek advising systems - AC Advisor - AC Pocket Compass 3.0 Accu-Chek insulin pump systems - AC Spirit Anti-diabetic medicines - GLP-1, DPP-IV, dual PPAR, GKA, etc. 29 Roche s innovation response to people with diabetes adding the glucose lowering potential of all single diabetes management components OAD GLP-1 Insulin SMBG Information management & advice SMBG + OAD/GLP-1 SMBG + insulin SMBG + insulin + inf. manag. & advice Potential to decrease HbA1c (average efficacy) -0.5 % -1.0 % -1.5 % -2.0 % -2.5 % -3.0 % -3.5 % * * * * ** *** Sources: * ESC Pocket Guidelines, Diabetes, Pre-Diabetes and Cardiovascular Disease, European Heart Journal (2007);28: ** Jansen JP; Current Medical Research And Opinions. 2006; 22: ** Sarol Jr. JN et al; Medical Research And Opinions. 2005; 21: *** Garg S. et al; ADA, EASD 2007 *** Boizel R, Benhamou PY, Renard E. Diabetes Metab 2007 Apr 30 30

16 Roche Diabetes Care clinical trials Have demonstrated positive impact of SMBG as part of an integrated diabetes selfmanagement approach on mortality and morbidity ROSSO-Study, Diabetologia, 2005 Have proven better outcome in insulin treated patients by adding information management and treatment advice tools to daily diabetes self-management Garg et al: Diab Technol & Therapeutics, 2008 Boizel et al_diabetes Metab, 2007 Aim to show that in type 2 diabetes (T2D), structured performance of SMBG including convenient data visualization and analysis ( episodic testing ), optimizes initiation of antidiabetic drug treatment and its therapy control and improves diabetes outcome Provides evidence for medical differentiation of Accu-Chek product solutions against stand-alone offerings of competitors SMBG = self monitoring blood glucose 31 Accu-Chek Advisor study Integrated diabetes self-management in T1D on multiple daily insulin injection (MDI) Significant reduction in HbA1c through information management and treatment advice (insulin bolus calculator) via a handheld medical device with Accu-Chek Advisor insulin guidance software (Barbara Davis Center, US, T1DM, MDI, N=121, 12 months) HbA1c = 0.4% HbA1c = 0.71 % T1D = type 1 diabetes Garg et al: Diab Technol & Ther: 10;

17 Accu-Chek 360 View tool for episodic testing Integrated diabetes self-management in T2D A paper based tool to measure, document and use information out of 7-point bg profiles, performed on 3 consecutive days and additional diabetes information It is designed for episodic testing enabling therapy initiation, monitoring and control according to international clinical guidelines Clinical studies are underway to show its medical value and improved diabetes outcome 4/4/07 4/5/07 4/6/07 7:10 9:20 12:00 2:10 6:45 8:35 11:00 7:00 9:15 12:30 2:20 7:15 9:20 11:41 6:45 9:00 12:00 2:10 7:30 9:4511: x x x x x x x x x xx x x x x x x x x xx 33 Accu-Chek portfolio enables episodic testing Integrated diabetes self-management in T2D bg algorithms Data visualization and analysis Treatment support Episode 04/07/2008 Algorithm for accurate, precise and structured bg measurements Data download, data visualization and analysis One page printouts or further data visualization and analysis via AC 360 software Informed therapy decision on drug initiation or adjustment 34

18 Roche s competitive edge in diabetes For Diabetes Care in Roche Diagnostics Full offering of Accu-Chek products SMBG, information management systems, insulin delivery - enabling integrated diabetes self-management Medical value of an integrated approach has been proven in clinical trials Optimized self-management approach may increase bg test frequency and differentiates Accu-Chek from competitors For the Roche Group Use Roche Diagnostic s strength to support Roche Pharma s development program Collaborating in recruitment and conduct of clinical trials Building on strong relationships with a scientific network of KOLs and longstanding customer relationships with endocrinologists, GPs, patient advocacy groups, etc. Exploiting strong Roche Accu-Chek brand recognition and value in the diabetes community With this and the development of anti-diabetic drugs, Roche sees a unique opportunity in providing integrated diabetes self-management 35 Metabolism/Diabetes franchise update Luke Miels, Head of Strategic Marketing, Metabolism & Anemia, Roche Pharma

19 Taspoglutide s target product profile Aiming for best-in-class Taspoglutide s competitive profile Competitor A (bid GLP-1) Competitor B (qd GLP-1) Competitor C (qw GLP-1) Taspoglutide s competitive advantage: Human GLP-1 analogue Once weekly dosing Over-all better efficacy and tolerability Taspoglutide s competitive advantage: Once weekly dosing Potential for better efficacy Effective starting dose Simple titration regimen Taspoglutide s competitive advantage: Human GLP-1 analogue Auto injector device Ease of injection (needle size, no reconstitution) Effective starting dose Simple titration regimen Taspoglutide: Aiming for best-in-class 37 Early-stage pipeline Several decision points ahead Carmegliptin (R1579) DPP-IV inhibitor Phase II Pre-clinical weight loss Aleglitazar (R1439) PPAR co-agonist Phase II 2 year carcinogenicity Phase I 7 projects Primary driver for full development: Clinically-meaningful differentiation 38

20 Dalcetrapib (R1658) CETP inhibitor A unique CETPi molecule In contrast to other CETP inhibitors, Dalcetrapib has a different chemical backbone to Torcetrapib In pre-clinical models and in clinical trials up to phase II, data showed that Dalcetrapib at therapeutic doses had a similar safety profile to placebo, including effects on blood pressure and Renin Angiotensin Aldosterone System (RAAS) activation Phase III is on track Publications of safety data up to 48 weeks treatment at upcoming scientific meetings Dalcetrapib Torcetrapib F F F F O F O F O H N S F F F O N N O O 39 Metabolism pipeline: Conclusion Roche Pharma is well-positioned Focus on differentiated molecules Taspoglutide represents a best-in-class opportunity and has the potential to compete vs oral anti-diabetic drugs Dalcetrapib CETP inhibitor phase III is on track and the molecule is structurally distinct vs Torcetrapib Further update expected at AHA Nov

21 Questions & Answers, session 2 Moderator: Dr. Karl Mahler, Head of Investor Relations We Innovate Healthcare 42

22 Appendix 43 Most common adverse events in the metformin combination study Placebo n=49 Once weekly 5 mg n=50 10 mg n=49 20 mg n=50 Once every 2 weeks 10 mg n=50 20 mg n=49 Nausea, n (%) 3 (6) 11 (22) 12 (24) 26 (52) 16 (32) 20 (10) Diarrhea, n (%) 4 (8) 4 (8) 5 (10) 5 (10) 8 (16) 9 (18) Vomiting, n (%) 2 (4) 2 (4) 2 (4) 11 (22) 6 (12) 12 (24) Headache, n (%) 3 (6) 1 (2) 3 (6) 6 (12) 7 (14) 6 (12) Decreased appetite, n (%) (10) 3 (6) 4 (8) 3 (6) Dyspepsia, n (%) (8) 6 (12) 3 (6) 2 (4) Abdominal distension, n (%) (4) 2 (4) 3 (6) 6 (12) Withdrawals for gastrointestinal AE, n (%) (4) 2 (4)