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R1439(Aleglitazar) Investor science conference call from ADA 2009 New Orleans, 8 June 2009 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 www.roche.com for full information on Roche products mentioned. 2 Introduction Dr. Karl Mahler, Head of Investor Relations Agenda Diabetes management & cardiovascular risk reduction • Metabolism/Diabetes in Roche Pharma – Luke Miels, Head of Strategic Marketing for Metabolic Diseases • R1439(aleglitazar) PPAR αγ co-agonist phase IIb SYNCHRONY data – Michael Lincoff, MD, Professor of Medicine, Department of Cardiovascular Medicine, Cleveland Clinic, Ohio, USA • R1439(aleglitazar) PPAR αγ co-agonist phase III and future plans – Dr. Klaus Hinterding, Aleglitazar Lifecycle Leader • R1583(taspoglutide) GLP-1 phase III update – Dr. Rajiv Patni, Taspoglutide Lifecycle Leader • Metabolism/Diabetes franchise update – Luke Miels, Head of Strategic Marketing for Metabolic Diseases • Questions & Answers (45 minutes) Total duration: Up to 1½ hour 4 CNS Roche pharma pipeline overview R1594(ocrelizumab) R1678(schizophrenia) Five Disease Biology Areas R3487(Alzheimer’s) Virology 4 ph. I compounds Pegasys To Tamiflu da R3484(HPV16) y’s foc R7128(HCV pol. inh.) us Metabolism R7227(HCV pro. inh.) R1439(aleglitazar) R1583(taspoglutide) R1658(dalcetrapib) Inflammation R7201(SGLT-2 inh) 6 ph. I compounds MabThera/Rituxan Actemra R1594(ocrelizumab) Oncology Anti-IL 13 9 ph. I compounds Avastin MabThera/Rituxan Herceptin Xeloda Tarceva R1273(pertuzumab) R1507(IGF-1R mAb) R3502(trastuzumab-DM1) R3616(hedgehog inh.) R7159(3rd gen anti-CD20) Apomab Dacetuzumab Dulanermin 15 ph. I compounds Promising Emerging Early 5 On hand late stage mid-term stage Roche in metabolic diseases Growing need for innovative products Diabetes: The epidemic continues; Dyslipidemia: Silent danger on the often accompanied by high blood rise; causes clogged arteries, heart pressure and obesity disease and stroke over time US, top-5 EU type 2 diabetes US, EU dyslipidemia 40 200 prevalence and forecast prevalence and forecast 35 160 30 25 120 20 15 80 10 40 Million prevalence Million Million prevalence Million 5 0 0 US Top-5 EU US EU 2007 2011 2017 2007 2010 2017 Source: Type 2 Diabetes: Global Epidemiology, Strategyst Consulting, 2004 Sources: Wood MacKenzie, IMS therapy forecaster, Roche assumptions, Decision Resources, Cardium Study#4, 2007; 6 Datamonitor Pipeline, Insight dyslipidemia 2007 Metabolism/Diabetes in Roche Pharma Luke Miels, Head of Strategic Marketing for Metabolic Diseases Metabolism R&D strategy is focusing on targets with the potential to lower cardiovascular risk Assumptions • Type 2 diabetes is also a cardiovascular disease • Glucose reduction alone is not sufficient Target priorities • Effects beyond pure glucose/HbA1c reduction • Innovation that the market will reward • Focused development plans including “Personalised Health Care” (PHC) approach • First- and/or best-in-class potential 8 Roche: Promising outlook in Metabolism Leading compounds with differentiated profiles… R1439(aleglitazar) PPAR αγ co-agonist • Phase II data very encouraging • Phase III transition and outline of the development strategy R1658(dalcetrapib) CETP inhibitor • First-in-class, high unmet medical need • Phase III progressing in line with expectations • Scientific publications to differentiate its unique structure 9 Roche: Promising outlook in Metabolism and potential to be best-in-class … R1583(taspoglutide) GLP-1 analogue • Phase III status and plans to address updated FDA guidelines • Roche perspective on GLP-1s and C-cell thyroid tumors R7201 SGLT-2 inhibitor • Goal to be best-in-class • Phase II initiated • Phase III decision by 1H 2010 10 R1439(aleglitazar) PPAR αγ co-agonist phase IIb SYNCHRONY data Michael Lincoff, MD, Professor of Medicine, Department of Cardiovascular Medicine, Cleveland Clinic, Ohio, USA High unmet need despite best standard of care 60-90% of CV events not prevented despite wide use of statins Major clinical trials aiming at cardiovascular risk reduction 100% 4S, The Lancet, 1994 80% Lipid, NEJM, 1998 Care, NEJM, 1996 60% HPS, The Lancet, 2002 40% WOSCOP, NEJM, 1999 20% AFCAPS/TexCAPS, JAMA, 1998 0% TNT, NEJM, 2005 4S Lipid Care HPS WOSCOP AFCAPS/ TNT TexCAPS % event not prevented % event prevented Despite statin treatment a residual risk of >65% remains for major cardiovascular events 12 Sources: Am. J of Medicine (2005) 118, 1067-1077; J Am. Coll of Card (2005) 46(7) 1225-1228 Aleglitazar: Proof of concept Pioglitazone has shown benefit on CV morbidity & mortality • PROACTIVE outcomes trial: Significant 16% relative-risk reduction on main secondary endpoint of death, myocardial infarction or stroke • Beneficial and significant effects on CV outcomes confirmed by meta-analysis of randomized trials • Beneficial and significant effects on atherosclerosis demonstrated in two imaging studies – PERISCOPE (IVUS1) in patients with type 2 diabetes and coronary artery disease – CHICAGO (CIMT2) in patients with type 2 diabetes • Pioglitazone is not labeled for reduction of CV morbidity and mortality 13 1IVUS: Intravascular ultrasound 2CIMT: Carotid Intima-Media Thickness Aleglitazar: A balanced and rationally-designed dual PPAR α/γ co-agonist • Potential for dual PPAR agonists to reduce the cardiovascular risk in type 2 diabetes patients post acute coronary syndrome by improving – Lipid profile and – Glycemic control • Other dual PPAR agonists have had a variety of safety concerns, likely due to an imbalance of effect on the α and γ receptors • Aleglitazar is rationally designed to have balanced activity on both the α and γ receptors to optimize lipid and glucose levels and minimize adverse effects • Favorable effects on dyslipidemia and glycemic control in pre-clinical, phase I & II studies, with a favorable toxicity profile Aleglitazar: Potential to reduce cardiovascular risk in type 2 diabetes patients who had acute coronary syndrome 14 SYNCHRONY phase II study: Determine the optimal dose balancing efficacy, safety, and tolerability 44 weeks,weeks, single-blind,single-blind, placeboplacebo run-inrun-in Randomization:Randomization: ~55~55 patientspatients perper treatmenttreatment groupgroup (n=332)(n=332) 1616 weeksweeks 1616 weeksweeks double-blinddouble-blind openopen labellabel AleglitazarAleglitazar AleglitazarAleglitazar AleglitazarAleglitazar AleglitazarAleglitazar PioglitazonePioglitazone PlaceboPlacebo 5050 μμgg QDQD 150150 μμgg QDQD 300300 μμgg QDQD 600600 μμgg QDQD 4545 mgmg QDQD 44 weeksweeks follow-upfollow-up 15 Aleglitazar: Statistically significant dose-dependent reductions in HbA1c Placebo Aleglitazar Pioglitazone 50 μg 150 μg 300 μg 600 μg 45 mg 0.6 0.4 0.2 0 p=0.048 -0.2 -0.4 -0.6 p<0.0001 p<0.0001 from baseline HbA1c (%) -0.8 p<0.0001 LS mean (SE) absolute change -1 -1.2 p<0.0001 P values vs. placebo. 16 Source: Lincoff AM, Henry R, et al. Poster presented at ACC 2009 Aleglitazar: Statistically significant reductions in fasting plasma glucose Placebo Aleglitazar Pioglitazone 50 μg 150 μg 300 μg 600 μg 45 mg 10 0 -10 -20 p=0.013 -30 -40 p<0.0001 p<0.0001 p<0.0001 fasting plasma glucose (mg/dl) -50 -60 LS mean (SE) absolute change from baseline p<0.0001 P values vs. placebo. 17 Source: Lincoff AM, Henry R, et al. Poster presented at ACC 2009 Aleglitazar: Statistically significant reductions in triglycerides Placebo Aleglitazar Pioglitazone 20 50 μg 150 μg 300 μg 600 μg 45 mg 10 0 -10 p=0.006 -20 p=0.0007 -30 from baseline triglycerides LS mean (SE) percent change -40 P<0.0001 P<0.0001 -50 P<0.0001 P values vs. placebo. 18 Source: Lincoff AM, Henry R, et al. Poster presented at ACC 2009 Aleglitazar: Statistically significant reductions in atherogenic LDL cholesterol Placebo Aleglitazar Pioglitazone 10 50 μg 150 μg 300 μg 600 μg 45 mg 5 0 p=0.96 -5 -10 p=0.08 p=0.012 -15 from baseline LDL-C p=0.003 LS mean (SE) percent change -20 -25 p<0.0001 P values vs. placebo. 19 Source: Lincoff AM, Henry R, et al. Poster presented at ACC 2009 Aleglitazar: Statistically
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