Roche Virtual Late Stage Pipeline Event Basel, 13 September 2018, 14:00-16:00 CEST

Transcription

1 Roche Virtual Late Stage Pipeline Event 2018 Basel, 13 September 2018, 14:00-16:00 CEST

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 Roche Virtual Late Stage Pipeline Event 2018 Welcome Karl Mahler Head of Investor Relations

4 Updated IR homepage went online Interactive Finance information tool with extended functionality New Finance information tool Sales of our top 25 products (instead top 20 products) Information 5 years back (CER and reported growth rates) Growth of the recently launched products Visualisation of operating costs as % of sales Visualization of Core reconciliation Easily export as PDF, Excel or PP Pipeline Link to Roche R&D (pred) Link to Biooncology (gred) Diagnostics Link to Diagnostic news flow Sustainability Sustainability download center: Search our position papers Link to sustainability homepage 4

5 Positive outlook provided at the Roche Pharma Day 2015 Where do we stand right now? Graph published at the Roche Pharma Day 2015 on Nov 5 th, 2015 Sales NME launches venetoclax, alectinib, Cotellic, ocrelizumab, atezolizumab, lebrikizumab, ACE910, lampalizumab Pipeline Today we will provide an up-date on: Priorities for the next years to come Biosimilars MabThera, Herceptin, Avastin Growth outlook for newly launched drugs Development status for late stage pipeline assets Marketed products Deep dive into Neuroscience E 2016E 2017E 2018E 2019E 2020E 2021E 2022E 2023E 5

6 Agenda Welcome Karl Mahler, Head of Investor Relations Pharma strategy Daniel O Day, CEO Roche Pharmaceuticals Late stage NMEs in oncology, ophthalmology and infectious diseases Sandra Horning, M.D., Chief Medical Officer and Head Global Product Development Late stage NMEs in neuroscience Paulo Fontoura, M.D. Ph.D., Head of Neuroscience Clinical Development Commercial opportunities Alexander Hardy, Head of Global Product Strategy Q&A Appendix: Target population data 6

7 Roche Virtual Late Stage Pipeline Event 2018 Pharma Strategy Daniel O Day CEO Roche Pharmaceuticals 7

8 Replace and extend the business Through continuously improving standard of care Replace existing businesses Entering new franchises Why did we get more optimistic over the past years? MabThera/Rituxan Herceptin Avastin Lucentis Tamiflu Gazyva, Venclexta, polatuzumab vedotin, mosunetuzumab (acd20/cd3 TCB1) Perjeta, Kadcyla, H+P SC Tecentriq, entrectinib, ipatasertib faricimab (VA2) Port Delivery System baloxavir marboxil Multiple Sclerosis: Ocrevus Hemophilia A: Hemlibra Neuroscience: SMA, Autism, Huntington s, Alzheimer s, NMO (+) New molecular entities (NME) fast approval and up-take for Ocrevus, Alecensa, Perjeta, Venclexta, Hemlibra (+) Pipeline development with highest number of NMEs in late stage, in particular in Neuroscience, Ophthalmology, Infectious Diseases SMA=spinal muscular atrophy; NMO=Neuromyelitis Optica; SC=subcutaneous; H+P=Herceptin+Perjeta 8

9 CHF New product growth expected to show strong momentum Considerable optionality Sensitivity analysis: Assuming conservative planning assumptions of 60-70% erosion from biosimilars consensus sales growth* (CHF) Avastin 6.7 bn Mabthera 7.4 bn to fill: ~10 bn 1 4 bn Ocrevus Tecentriq Hemlibra Gazyva Alecensa In-market & mature 2 Pipeline value bn 2.3 bn 2.1 bn 1.0 bn 1.1 bn (0.6 bn) 0.4 bn Herceptin 7.0 bn 2017 Sales Perjeta Kadcyla Herceptin H+P SC 2022 Sales Total ~11 bn Up-side potential to consensus above are: Venclexta, SMA (risdiplam), Huntington (HTT- ASO), Autism (balovaptan), Alzheimer (gantenerumab & crenezumab), Ophthalmology (Port Delivery System), Infectious disease (baloxavir marboxil), Oncology (idasanutlin, ipatasertib, mosunetuzumab) * Source: Roche post-hy2018 consensus; 1 Gap value including the total HER2 franchise change from 2017 to 2022, assuming Lucentis will be replaced by faricimab; 2 Esbriet, Tarceva, Xolair, Pulmozyme, Rocephin, CellCept, Mircera, NeoRecormon/Epogin, Activase/TNKase, Xeloda, Valcyte/Cymevene, Actemra, Tamiflu, Madopar, Pegasys; 3 etrolizumab 9

10 Successfully managing the transition New products contribution* MabThera/Avastin contribution Core operating profit Pharma % of Pharma sales 10.1% 13.6% 19.7% 36.6% 35.3% 31.5% 46.2% 45.1% 47.2% CHFbn HY 2016 HY 2017 HY 2018 HY 2016 HY 2017 HY 2018 HY 2016 HY 2017 HY 2018 * Venclexta sales are booked by partner AbbVie 10

11 Roche pharma innovation strategy Transforming healthcare and our company in period of portfolio transition Pipeline & commercial delivery World-leading data & advanced analytics Organisational transformation Diverse, multidisciplinary talent base to drive innovation & execution 11

12 Pipeline & Commercial Delivery Portfolio evolution in industry context Roche has strong development presence across large therapeutic areas CAGR Other Onc Lung Breast Hem Deep-dive 2017 prescription drug sales by therapeutic area (USDbn) 11% 6% 4% 2% 4% 4% 4% 10% 0% 9% 104 Oncology 83 Immunology Other Neuro MS Neuroscience Infectious disease CV Metabolic disease Respiratory Hem RD Rare disease & Hemophilia 17 Ophthalmology 10 Dermatology Roche focus Source: EvaluatePharma; MS=Multiple Sclerosis; CV=Cardiovascular; RD=Rare Diseases 12

13 Pipeline & Commercial Delivery Transforming standard of care in oncology Hematology (33 USDbn) Breast (14 USDbn) Lung (12 USDbn) ALL ipatasertib idasanutlin Incidence rates (330,000 pts) 1 polatuzumab vedotin mosunetuzumab Incidence rates (490,000 pts) 1 ipatasertib Incidence rates (560,000 pts) 1 entrectinib Extending market leadership Entering new markets Play a key role in defined cancers n New market opportunities 1. Datamonitor: incidence rates includes the 7 major markets (US, Japan, France, Germany, Italy, Spain, UK); CLL=Chronic lymphoid leukemia; DLBCL=Diffuse large B-cell lymphoma; inhl=indolent Non-Hodgkin's lymphoma; AML=Acute myeloid 13 leukemia; MM=Multiple myeloma; MDS=Myelodysplastic syndrome; ALL=Acute lymphoblastic leukemia; TNBC=Triple Negative Breast Cancer; SCLC=Small Cell Lung Cancer; NSCLC=Non-Small Cell Lung Cancer

14 Pipeline & Commercial Delivery Pushing towards new frontiers Creating new opportunities across therapeutic areas and modalities Oncology Neuroscience & rare diseases Ophthalmology, infectious disease T-cell bispecific Platform Leading portfolio of T-cell engagers across hematology and solid tumors risdiplam First oral therapy for spinal muscular atrophy Port Delivery System First long-acting delivery in namd Personalized Cancer Vaccine Leading patient specific RNA vaccine for cancer HTT-ASO First disease-modifying therapy for Huntington s disease baloxavir marboxil First single dose treatment for influenza 14

15 CHFm CHFm CHFm Pipeline & Commercial Delivery Accelerate success of recent launches Successful launches across multiple disease areas Key line extensions Blockbuster in just 10 months 10% total market share (US) ~32% share of new/switch patients Q2 17 Q3 17 Q4 17 Q1 18 Q2 18 Inhibitor launch started in Q Successful launch; >20% US market share Non-inhibitor launch expected in Q BTD granted, convenient 4 weekly schedule Positive Ph III results US market leadership in 1L ALK+ NSCLC achieved within 8 months of launch China National Drug Administration granted rapid approval Q2 15 Q2 16 Q2 17 Q2 18 Lung cancer 1L NSCLC: IMpower150, 130, 132 1L ES-SCLC: IMpower133 1L sq NSCLC: IMpower131 Renal cancer: 1L mrcc: IMmotion151 Breast cancer: 1L TNBC: IMpassion130 Accelerated growth by adjuvant launch Listed on NCCN, St. Gallen Q2 15 Q2 16 Q2 17 Q2 18 Transforming SoC in CLL/AML/MM FDA approval in R/R CLL (MURANO) Ph III data in 1L CLL expected in H2 18 (CLL14) and in R/R MM in H1 19 (BELLINI) Early filing in in 1L AML NCCN=National Comprehensive Cancer Network; NSCLC=Non Small Cell Lung Cancer; ES SCLC=Extensive Stage Small Cell Lung Cancer; TNBC=Triple Negative Breast Cancer; RCC=Renal Cell Carcinoma; SoC=Standard of Care; R/R CLL=Relapsed Refractory Chronic Lymphocytic Leukemia; AML=Acute Myeloid Leukemia; MM=Multiple Myeloma; Venclexta in collaboration with AbbVie 15

16 Organisational Transformation Transforming our operating model Building an effective organization for the future R&D Manufacturing Commercial HY 2018 vs. HY 2017 US +11% Europe US Example: Filing of IMpassion130 in 12 weeks (down from 26w) Volume +3% Core COGS and Period Costs LATAM APAC EEMEA International Fit-for-purpose teams enabling fast, but rigorous decision making Faster filing initiatives (e.g. regulatory acceleration, dossier optimizing) PHC and data strategy driving insights and R&D efficiencies Lean management production program Favorable product mix Management of inventory Simplified structures, processes & culture to drive effectiveness Productivity initiatives Resource shift to support key launches EM=Emerging Market; PHC=Personalized Healthcare; COGS=cost of goods sold 16

17 Data & Advanced Analytics Driving our vision of personalized healthcare (PHC) Transforming R&D and patient care Access meaningful data at scale Create insights through advanced analytics Realize value from insights Clinical trial data Smarter, more efficient R&D Real world data Improved access & personalized care 17

18 INVESTMENT RETURN Data & Advanced Analytics PHC can lift full Pharma value chain Improving our return on investment Additional value PHC CURVE CURRENT CURVE Development Commercial TIME (YEARS) Lower costs Faster speed to market Higher return PHC=Personalized Healthcare 18

19 Data & Advanced Analytics Efforts already creating tangible business value Example: New biologic insights and pan-tumor strategies Retrospectively identified PIK3CA/AKT1/PTEN-altered sub-population with increased benefit Utilizing FMI database to expand ipatasertib clinical trial program across different tumors Unstratified HR: 0.44 (95% CI ) TNBC HER2-/HR+ FMI key in identifying relevant patient sub-populations FMI=Foundation Medicine 19

20 Data & Advanced Analytics Efforts already creating tangible business value Example: Tecentriq control arm and reimbursement Retrospectively replicating docetaxel control arm in Tecentriq OAK trial Revised NICE decision: Extrapolation of data for reimbursement decision Leveraging Flatiron data for more effective clinical development & reimbursement decisions NICE=National Institute for Health and Care Excellence; ERG=Evidence Review Group 20

21 2018 update: Positive outlook confirmed NMEs launched Perjeta, Kadcyla, Gazyva, Esbriet, Cotellic, Alecensa, Venclexta, Tecentriq, Ocrevus, Hemlibra Upcoming NME launches baloxavir marboxil, polatuzumab vedotin, entrectinib, idasanutlin, satralizumab, ipatasertib, H+P SC, mosunetuzumab, HTT-ASO, risdiplam, balovaptan, crenezumab, gantenerumab, faricimab, PDS, etrolizumab Sales Recently launched / pipeline Marketed products E 2019E 2020E 2021E 2022E 21

22 Roche Virtual Late Stage Pipeline Event 2018 Late stage NMEs in oncology, ophthalmology and infectious diseases Sandra Horning, M.D. Chief Medical Officer and Head Global Product Development

23 Late stage pipeline at record high * 14 NMEs with near-term news flow Hematology CLL:, Venclexta Gazyva DLBCL: polatuzumab vedotin, Venclexta NHL, DLBCL: mosunetuzumab AML: Venclexta, idasanutlin MM: Venclexta 2. Breast Cancer HER2+ BC: Perjeta, Kadcyla, Herceptin, Tecentriq TNBC: Tecentriq, ipatasertib HR+ BC: ipatasertib 5 5. Other oncology RCC: Tecentriq, Avastin 1L melanoma: Tecentriq, Cotellic, Zelboraf SCCHN: Tecentriq UBC: Tecentriq 1L OC: Avastin CRPC: Tecentriq, ipatasertib 1L HCC: Tecentriq, Avastin 6. Hemophilia A Hemlibra Neuroscience SMA: risdiplam DMD: a-myostatin adnectin fusion protein Huntington s: HTT-ASO (RG6042) Autism: balovaptan Alzheimers`s: crenezumab, gantenerumab Neuromyelitis Optica: satralizumab 9. Immunology Ulcerative colitis: etrolizumab Crohn`s disease: etrolizumab 3. Lung Cancer Nasal polyps: Xolair 1L NSCLC: Tecentriq, Avastin 1L SCLC: Tecentriq 7 6. Ophthalmology DME, namd: faricimab Systemic sclerosis: Actemra 6 1/2L ALK+ NSCLC: Alecensa ROS1+ NSCLC: entrectinib 8 AMD: Port Delivery System 6 4. Pan tumor NTRK+ tumors: entrectinib 9 8. Infectious diseases Influenza A/B: baloxavir marboxil * For further information on target patient populations please consult the appendix; For further details on the late stage pipeline please consult the HY 18 results presentation appendix or visit the IR homepage 23

24 BTD s and priority reviews reflecting the quality of our research 24

25 Late stage pipeline at record high * Hematology CLL:, Venclexta Gazyva DLBCL: polatuzumab vedotin, Venclexta NHL, DLBCL: mosunetuzumab AML: Venclexta, idasanutlin MM: Venclexta 2. Breast Cancer HER2+ BC: Perjeta, Kadcyla, Herceptin, Tecentriq TNBC: Tecentriq, ipatasertib HR+ BC: ipatasertib 5 5. Other oncology RCC: Tecentriq, Avastin 1L melanoma: Tecentriq, Cotellic, Zelboraf SCCHN: Tecentriq UBC: Tecentriq 1L OC: Avastin CRPC: Tecentriq, ipatasertib 1L HCC: Tecentriq, Avastin 6. Hemophilia A Hemlibra Neuroscience SMA: risdiplam DMD: a-myostatin adnectin fusion protein Huntington s: HTT-ASO (RG6042) Autism: balovaptan Alzheimers`s: crenezumab, gantenerumab Neuromyelitis Optica: satralizumab 9. Immunology Ulcerative colitis: etrolizumab Crohn`s disease: etrolizumab 3. Lung Cancer Nasal polyps: Xolair 1L NSCLC: Tecentriq, Avastin 1L SCLC: Tecentriq 7 6. Ophthalmology DME, namd: faricimab Systemic sclerosis: Actemra 6 1/2L ALK+ NSCLC: Alecensa ROS1+ NSCLC: entrectinib 8 AMD: Port Delivery System 6 4. Pan tumor NTRK+ tumors: entrectinib 9 8. Infectious diseases Influenza A/B: baloxavir marboxil * For further information on target patient populations please consult the appendix; For further details on the late stage pipeline please consult the HY 18 results presentation appendix or visit the IR homepage 25

26 Hematology portfolio rejuvenation progresses on early filings 9 NMEs in combination testing = early filings in 2018 *Venclexta in collaboration with AbbVie; Polatuzumab vedotin in collaboration with Seattle Genetics; Cotellic in collaboration with Exelixis; ChK1i in collaboration with Array BioPharma; NHL=non-hodgkin`s lymphoma; CLL=chronic lymphoid leukemia; MM=multiple myeloma; MDS=myelodysplastic syndrom; AML=acute myeloid leukemia; MCL=mantle cell lymphoma 26

27 Venclexta in CLL, AML and MM MRD negativity included in the label for R/R CLL Bcl-2 inhibitor Phase III (MURANO): PB MRD negativity maintained over time 1 Bendamustine + Rituxan Venclexta + Rituxan Venetoclax designed to selectively bind and inhibit Bcl-2 Inhibiting Bcl-2 releases pro-apoptotic proteins, which trigger apoptosis through the apoptosome Label update for Venclexta+Rituxan in R/R CLL (MURANO) to include MRD negativity results Ph III (CLL14) Venclexta+Gazyva in 1L unfit CLL interim analysis expected in Q Ph III (BELLINI) Venclexta+bor/dex in R/R MM final analysis expected in H Priority review granted for Venclexta+HMA/LDAC in 1L AML ineligible for intense chemotherapy (PDUFA date Dec 25) Hillmen P. et al., ASCO 2018; PB MRD=peripheral blood minimal residual disease; HMA=hypomethylating agent; LDAC=low dose aracytarabine; bor=bortezomib; dex=dexamethasone; Venclexta in collaboration with AbbVie 27

28 Polatuzumab vedotin in DLBCL PFS/OS benefit regardless of prior treatment and disease status Anti-CD79b mab drug conjugate Phase II update (GO29365): Phase III (POLARIX): 2 anti-cd79b PFS R/R DLBCL OS Overall Survival 1L DLBCL MMAE= monomethyl auristatin E ADC designed for targeting toxic payload to cells expressing CD79b Linker stable in the bloodstream, releases the drug payload inside the target cell CR, PFS, OS were positive with PFS HR of 0.31 (p<0.0001) and OS HR of 0.35 (p=0.0008) Polatuzumab vedotin can be safely administered in combination with BR Accelerated filing of Ph II data in H Ph III (POLARIX) in 1L DLBCL on-going Sehn L. H. et al., ASCO 2018; ADC=antibody drug conjugate; MMAE=monomethyl auristatin E; PFS=progression free survival; OS=overall survival; HR=hazard ratio; CR=complete response; BR=bendamustine+Rituxan; Polatuzumab vedotin in collaboration with Seattle Genetics 28

29 Mosunetuzumab in hematology (FL, DLBCL, MCL) First clinical data to be presented at ASH Anti-CD20/CD3 T cell bispecific 3 anti-cd20 anti-cd3 Anti-CD20/CD3 bispecific antibody simultaneously binds T cells and B cells T cell receptor cross-linking activates the bound T cell and B cell killing is initiated Fast and economic off-the-shelf solution compared to CAR T cells Complete response in R/R DLBCL patient relapsed on CAR T therapy PET scan 30 year old female with R/R DLBCL Prior treatment included R-CHOP, and R-ICE followed by autologous HSCT Relapsed 6 months after receiving CD19-directed CAR T cell therapy and subsequently enrolled on mosunetuzumab Ph I trial Complete response observed after 3 cycles of mosunetuzumab Patient proceeded to allogeneic transplant after achieving a complete response on mosunetuzumab therapy Clinical activity observed across multiple histologies including: R/R FL, R/R DLBCL, R/R mantle cell lymphoma (MCL), transformed FL and Richter transformed CLL Durable complete responses observed in patients refractory to anti-cd20 antibodies and to chemotherapy Mosunetuzumab: Ph I monotherapy data in NHL to be presented at ASH 2018 CAR T cells=chimeric antigen receptor; R-CHOP=Rituxan, cyclophosphamide, doxorubicin, vincristine, prednisolone; R-ICE=Rituxan, ifosfamide, carboplatin, etoposide; HSCT=Hematopoietic stem cell transplantation 29

30 Idasanutlin in AML Promising activity as monotherapy and in combination MDM2 antagonist Ph III (MIRROS) trial design 4 Responding patients may receive optional consolidation with up to 2 additional cycles First-in-class, oral, selective, MDM2 antagonist activates p53-mediated apoptosis and inhibits tumor growth Among first small molecules to disrupt non-enzyme protein/protein interaction (Vassilev et al., Science 2004) Ph I (NCT ) in heavily pretreated AML patients: idasanutlin+cytarabine showed 29% ccr rate (all patients) and 42% ccr rate in patients dosed with Ph III dose with a mdor >8m Ph III (MIRROS): idasanutlin+cytarabine in R/R AML one of the largest R/R AML studies Ph Ib/II combination (NCT ): Venclexta+idasanutlin showed clinical activity (38% ccr with 600mg Venclexta and 200mg idasanutlin) in heavily pre-treated elderly unfit R/R AML Possible NME filing based on MIRROS in 2020 Martinelli G, et al., EHA 2016; Daver N. et al., ASH 2017; idmc=independent data monitoring committee; OS=overall survival; ccr, composite response rate (CR+CRp+CRi); CR=complete remission rate; CRp=complete remission with incomplete platelet recovery; CRi=complete remission with incomplete count recovery, DoR, duration of response 30

31 Late stage pipeline at record high * Hematology CLL:, Venclexta Gazyva DLBCL: polatuzumab vedotin, Venclexta NHL, DLBCL: mosunetuzumab AML: Venclexta, idasanutlin MM: Venclexta 2. Breast Cancer HER2+ BC: Perjeta, Kadcyla, Herceptin, Tecentriq TNBC: Tecentriq, ipatasertib HR+ BC: ipatasertib 5 5. Other oncology RCC: Tecentriq, Avastin 1L melanoma: Tecentriq, Cotellic, Zelboraf SCCHN: Tecentriq UBC: Tecentriq 1L OC: Avastin CRPC: Tecentriq, ipatasertib 1L HCC: Tecentriq, Avastin 6. Hemophilia A Hemlibra Neuroscience SMA: risdiplam DMD: a-myostatin adnectin fusion protein Huntington s: HTT-ASO (RG6042) Autism: balovaptan Alzheimers`s: crenezumab, gantenerumab Neuromyelitis Optica: satralizumab 9. Immunology Ulcerative colitis: etrolizumab Crohn`s disease: etrolizumab 3. Lung Cancer Nasal polyps: Xolair 1L NSCLC: Tecentriq, Avastin 1L SCLC: Tecentriq 7 6. Ophthalmology DME, namd: faricimab Systemic sclerosis: Actemra 6 1/2L ALK+ NSCLC: Alecensa ROS1+ NSCLC: entrectinib 8 AMD: Port Delivery System 6 4. Pan tumor NTRK+ tumors: entrectinib 9 8. Infectious diseases Influenza A/B: baloxavir marboxil * For further information on target patient populations please consult the appendix; For further details on the late stage pipeline please consult the HY 18 results presentation appendix or visit the IR homepage 31

32 Ipatasertib in TNBC and HR+ BC Strong PFS and OS benefit in TNBC Highly selective AKT inhibitor 5 Phase II (LOTUS) update: PFS (PIK3CA/AKT1/PTEN-altered tumor) FMI NGS assay: Oral, highly specific inhibitor of all three activated isoforms of AKT, blocking the PI3K/AKT signaling pathway and potentially preventing cancer cell growth and survival Clinical development in tumors with high frequency of PI3K/AKT pathway activation (TNBC, HR+ mbc, CRPC) detects all classes of genetic alterations in 324 oncogenes 17 therapies currently approved for inclusion in the report PFS HR was 0.44 for patients with PIK3CA/AKT1/PTEN-altered tumors vs 0.6 for all-comers OS trend with stratified HR in all-comers of 0.62; Final Ph II OS results expected in 2019 Ph III (IPATunity130) in 1L PIK3CA/AKT1/PTEN-altered advanced TNBC (cohort 1) and in HR+/HER2- mbc (cohort 2) on-going Ph III (IPATential150) in 1L castration-resistant prostate cancer (CRPC) on-going Dent R. et al., ASCO 2018; TNBC=triple negative breast cancer; HR=hormone receptor; BC=breast cancer; PFS=progression free survival; OS=overall survival; ITT=intent to treat; HR=hazard ratio; Ipatasertib in collaboration with Array BioPharma. 32

33 Late stage pipeline at record high * Hematology CLL:, Venclexta Gazyva DLBCL: polatuzumab vedotin, Venclexta NHL, DLBCL: mosunetuzumab AML: Venclexta, idasanutlin MM: Venclexta 2. Breast Cancer HER2+ BC: Perjeta, Kadcyla, Herceptin, Tecentriq TNBC: Tecentriq, ipatasertib HR+ BC: ipatasertib 5 5. Other oncology RCC: Tecentriq, Avastin 1L melanoma: Tecentriq, Cotellic, Zelboraf SCCHN: Tecentriq UBC: Tecentriq 1L OC: Avastin CRPC: Tecentriq, ipatasertib 1L HCC: Tecentriq, Avastin 6. Hemophilia A Hemlibra Neuroscience SMA: risdiplam DMD: a-myostatin adnectin fusion protein Huntington s: HTT-ASO (RG6042) Autism: balovaptan Alzheimers`s: crenezumab, gantenerumab Neuromyelitis Optica: satralizumab 9. Immunology Ulcerative colitis: etrolizumab Crohn`s disease: etrolizumab 3. Lung Cancer Nasal polyps: Xolair 1L NSCLC: Tecentriq, Avastin 1L SCLC: Tecentriq 7 6. Ophthalmology DME, namd: faricimab Systemic sclerosis: Actemra 6 1/2L ALK+ NSCLC: Alecensa ROS1+ NSCLC: entrectinib 8 AMD: Port Delivery System 6 4. Pan tumor NTRK+ tumors: entrectinib 9 8. Infectious diseases Influenza A/B: baloxavir marboxil * For further information on target patient populations please consult the appendix; For further details on the late stage pipeline please consult the HY 18 results presentation appendix or visit the IR homepage 33

34 Entrectinib in NTRK+ and ROS1+ tumors Pivotal data to be presented at WCLC and ESMO Selective NTRK/ROS1 inhbitor 6 Ph II (STARTRK2) trial design: Pivotal, open-label, multicenter, global, basket study FMI NGS assay: Selective, CNS-active inhibitor of ROS1/NTRK/ALK tyrosine kinases Activating ROS1 rearrangements occur in 1-2% of NSCLC Activating rearrangements in TRK have been identified >17 different solid tumors, including head and neck, thyroid, sarcoma and brain detects all classes of genetic alterations in 324 oncogenes 17 therapies currently approved for inclusion in the report PhI/II results in ROS1+ mnsclc: 69% ORR*, 83% intracranial ORR* in patients with brain metastases, mdor of 28.6m, mpfs of 29.6m Ph II (STARTRK2) data in ROS1+ NSCLC at WCLC and for NTRK+ tumors at ESMO Filing expected in early 2019 Myung-Ju A. et al., WCLC 2017; FMI=Foundation medicine; NGS=next generation sequencing; ORR=overall response rate; *=by blinded independent central review; mdor=median duration of response; mpfs=median progression free survival 34

35 Late stage pipeline at record high * Hematology CLL:, Venclexta Gazyva DLBCL: polatuzumab vedotin, Venclexta NHL, DLBCL: mosunetuzumab AML: Venclexta, idasanutlin MM: Venclexta 2. Breast Cancer HER2+ BC: Perjeta, Kadcyla, Herceptin, Tecentriq TNBC: Tecentriq, ipatasertib HR+ BC: ipatasertib 5 5. Other oncology RCC: Tecentriq, Avastin 1L melanoma: Tecentriq, Cotellic, Zelboraf SCCHN: Tecentriq UBC: Tecentriq 1L OC: Avastin CRPC: Tecentriq, ipatasertib 1L HCC: Tecentriq, Avastin 6. Hemophilia A Hemlibra Neuroscience SMA: risdiplam DMD: a-myostatin adnectin fusion protein Huntington s: HTT-ASO (RG6042) Autism: balovaptan Alzheimers`s: crenezumab, gantenerumab Neuromyelitis Optica: satralizumab 9. Immunology Ulcerative colitis: etrolizumab Crohn`s disease: etrolizumab 3. Lung Cancer Nasal polyps: Xolair 1L NSCLC: Tecentriq, Avastin 1L SCLC: Tecentriq 7 6. Ophthalmology DME, namd: faricimab Systemic sclerosis: Actemra 6 1/2L ALK+ NSCLC: Alecensa ROS1+ NSCLC: entrectinib 8 AMD: Port Delivery System 6 4. Pan tumor NTRK+ tumors: entrectinib 9 8. Infectious diseases Influenza A/B: baloxavir marboxil * For further information on target patient populations please consult the appendix; For further details on the late stage pipeline please consult the HY 18 results presentation appendix or visit the IR homepage 35

36 Faricimab in DME and namd Ph III studies in DME initiated Anti-VEGF/Ang2 bimab Phase II (BOULEVARD) results in DME: 7 Adjusted mean BCVA gains from baseline * anti-ang2 anti-vegf optimized Fc First bispecific antibody (bimab) in ophthalmology binding simultaneously to VEGF and Angiopoetin2 (Ang2) Ang2 inhibition could improve bloodretinal barrier stability and reduce retinal vascular inflammation Dugel P. et al. Angiogenesis 2018 Robust BCVA gains at 6m with a mean of letters gained from baseline and a statistically significant gain of +3.6 letters over Lucentis Secondary endpoints, e.g DRSS, CST reduction support superior efficacy Ph II (AVENUE, 24wks STAIRWAY) results in namd to be presented at Retina Society meeting Ph III (YOSEMITE, RHINE) in DME vs Eylea achieved first-patient-in Dungel P. et al., Angiogenesis 2018; DME=diabetic macular edema; namd=neovascular age-related macular degeneration; BCVA= best-corrected visual acuity; *Linear model adjusted for baseline BCVA, previous macular laser treatment status, BCVA category ( 64 letters vs 63 letters); ETDR= Early Treatment Diabetic Retinopathy Study; DRSS=Diabetic Retinopathy Severity Score; CST=central subfield thickness 36

37 Port Delivery System with ranibizumab Reduces treatment burden, addresses key unmet need in wamd Port Delivery System (PDS) 8 Phase II (LADDER) results: Time to first refill Refillable intraocular implant using proprietary needle assembly In-office refills Customized formulation of ranibizumab Around 80% patients 6m time to first refill Visual and anatomic outcomes for PDS 100mg/mL comparable to monthly intravitreal (IVT) Lucentis PDS insertion/refill procedures well tolerated, systemic safety profile comparable to IVT Lucentis Ph III (ARCHWAY) using 6m fixed dosing interval has been initiated Awh C. et al., ASRS 2018; wamd=wet age-related macular degeneration; Lucentis (ranibizumab) 37

38 Late stage pipeline at record high * Hematology CLL:, Venclexta Gazyva DLBCL: polatuzumab vedotin, Venclexta NHL, DLBCL: mosunetuzumab AML: Venclexta, idasanutlin MM: Venclexta 2. Breast Cancer HER2+ BC: Perjeta, Kadcyla, Herceptin, Tecentriq TNBC: Tecentriq, ipatasertib HR+ BC: ipatasertib 5 5. Other oncology RCC: Tecentriq, Avastin 1L melanoma: Tecentriq, Cotellic, Zelboraf SCCHN: Tecentriq UBC: Tecentriq 1L OC: Avastin CRPC: Tecentriq, ipatasertib 1L HCC: Tecentriq, Avastin 6. Hemophilia A Hemlibra Neuroscience SMA: risdiplam DMD: a-myostatin adnectin fusion protein Huntington s: HTT-ASO (RG6042) Autism: balovaptan Alzheimers`s: crenezumab, gantenerumab Neuromyelitis Optica: satralizumab 9. Immunology Ulcerative colitis: etrolizumab Crohn`s disease: etrolizumab 3. Lung Cancer Nasal polyps: Xolair 1L NSCLC: Tecentriq, Avastin 1L SCLC: Tecentriq 7 6. Ophthalmology DME, namd: faricimab Systemic sclerosis: Actemra 6 1/2L ALK+ NSCLC: Alecensa ROS1+ NSCLC: entrectinib 8 AMD: Port Delivery System 6 4. Pan tumor NTRK+ tumors: entrectinib 9 8. Infectious diseases Influenza A/B: baloxavir marboxil * For further information on target patient populations please consult the appendix; For further details on the late stage pipeline please consult the HY 18 results presentation appendix or visit the IR homepage 38

39 Baloxavir marboxil in Influenza A & B Priority review granted by the FDA CAP-dependent endonuclease inhibitor Phase III (CAPSTONE-1) results for acute uncomplicated influenza 9 First-in-class small molecule inhibiting viral RNA replication via a novel and highly selective mode of action Oral single-dosing due to long half-life + well tolerated Significant reduction in time to alleviation of symptoms by >24 hrs vs placebo (p<0.0001) Time to cessation of viral shedding reduced by 48 hrs vs Tamiflu (p<0.0001) potentially leading to reduced transmission rates Positive Ph III (CAPSTONE-2, high risk) results to be presented at upcoming conference Priority review for acute, uncomplicated influenza in >12yrs old patients (PDUFA date Dec 24) Ph III trials for hospitalized patients and pediatrics initiated Kawaguchi, et al. ESWI 2017; Portsmouth, et al. IDWeek 2017; a 95% CI of median time could not be obtained by Brookmeyer and Crowley method (1982); b Not determined; Baloxavir marboxil co-developed with Shionogi with Roche holding worldwide license excluding Japan and Taiwan 39

40 Roche Virtual Late Stage Pipeline Event 2018 Late stage NMEs in neuroscience Paulo Fontoura M.D. Ph.D. Head of Neuroscience Clinical Development

41 Late stage pipeline at record high * Hematology CLL:, Venclexta Gazyva DLBCL: polatuzumab vedotin, Venclexta NHL, DLBCL: mosunetuzumab AML: Venclexta, idasanutlin MM: Venclexta 2. Breast Cancer HER2+ BC: Perjeta, Kadcyla, Herceptin, Tecentriq TNBC: Tecentriq, ipatasertib HR+ BC: ipatasertib 5 5. Other oncology RCC: Tecentriq, Avastin 1L melanoma: Tecentriq, Cotellic, Zelboraf SCCHN: Tecentriq UBC: Tecentriq 1L OC: Avastin CRPC: Tecentriq, ipatasertib 1L HCC: Tecentriq, Avastin 6. Hemophilia A Hemlibra Neuroscience SMA: risdiplam DMD: a-myostatin adnectin fusion protein Huntington s: HTT-ASO (RG6042) Autism: balovaptan Alzheimers`s: crenezumab, gantenerumab Neuromyelitis Optica: satralizumab 9. Immunology Ulcerative colitis: etrolizumab Crohn`s disease: etrolizumab 3. Lung Cancer Nasal polyps: Xolair 1L NSCLC: Tecentriq, Avastin 1L SCLC: Tecentriq 7 6. Ophthalmology DME, namd: faricimab Systemic sclerosis: Actemra 6 1/2L ALK+ NSCLC: Alecensa ROS1+ NSCLC: entrectinib 8 AMD: Port Delivery System 6 4. Pan tumor NTRK+ tumors: entrectinib 9 8. Infectious diseases Influenza A/B: baloxavir marboxil * For further information on target patient populations please consult the appendix; For further details on the late stage pipeline please consult the HY 18 results presentation appendix or visit the IR homepage 41

42 Risdiplam in spinal muscular atrophy (SMA) Early positive efficacy data from Ph II/III study in babies SMN2 splicing modifier Phase II/III (FIREFISH) interim Part 1 data in Type 1 SMA: 10 CHOP-INTEND Score: Individual Patient Plots Median change from baseline in CHOP-INTEND Score Oral and systemically available SMN2 splicing modifier Durably increases SMN protein both in the CNS and in the periphery Potentially best in class efficacy profile To date well tolerated at all doses assessed 94% of patients treated for a minimum of 4 months had at least a 4-point improvement No patients have lost the ability to swallow or reached permanent ventilation Broadest clinical program including Type 1 to 3; Presymptomatic study starting in 2018 Potential NME filing in 2019 Risdiplam in collaboration with PTC Therapeutics and the SMA Foundation; Khwaja O. et al., CureSMA 2018; SMA=spinal muscular atrophy; CHOP-INTEND=Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (16-item 64-point motor assessment designed specifically to evaluate the motor skills of infants with SMA); * Patients started on low starting dose 42

43 HTT-ASO (RG6042) in Huntington`s disease (HD) First drug to reduce toxic mhtt Antisense RNA targeting total HTT Phase I/II (NCT ) results: 11 Significant dose dependent reduction in mhtt in the CSF mhtt levels still declining 3m after treatment start wthtt allele Antisense drug (RG6042) mhtt allele Antisense drug binds to wthtt and mhtt sequence leading to RNase H1 mediated degradation of wild-type and mutant HTT mrna Addresses all patients Highest doses achieved mean reductions of the mhtt protein of approximately 40% with maximum reductions greater than 60%; Levels were still declining in the majority of patients Safe and well tolerated over 4 monthly doses with no dose-limiting toxicities identified and no patients discontinuing Exploratory post-hoc analysis showed correlation of mhtt reduction and improved scores in HD tests Ph III study expected to start in 2018 Tabrizi S. et al., AAN 2018; mhtt=mutant huntingtin; wthtt=wild-type huntingtin; CSF=cerebrospinal fluid; HTT-ASO licensed from IONIS Pharmaceuticals 43

44 Balovaptan in autism spectrum disorder (ASD) Early positive data from first Ph II study in adults V1a receptor antagonist Phase II (VANILLA) results: 12 Oral, selective V1a receptor antagonist Vasopressin V1a receptor modulates social behavior and is implicated in ASD Good pharmacokinetic profile and well tolerated in Ph I and II studies Primary efficacy endpoint (SRS-2) not met; however dose dependent treatment effect on the Vineland TM -II composite score shows significant improvement in socialization and communication Ph II study (av1ation) in children and adolescents with ASD ongoing, with Vineland TM -II being the primary endpoint, as agreed with health authorities Ph III trial (V1aduct) in adults with ASD started enrolling in August 2018 Bolognani F. et al., IMFAR 2017 (submitted for publication); ASD=autism spectrum disorder; SRS-2=social responsiveness scale-2; Vineland TM -II=Vineland Adaptive Behavior Scale 2nd Edition 44

45 Anti-amyloid-β mabs in Alzheimer`s disease (AD) Target engagement data presented Anti-amyloid-β mabs Crenezumab (ABBY/BLAZE) Aβ oligomer levels Gantenerumab (OLE SR/MR) Brain Aβ reduction over time Aβ monomers Aβ oligomers & fibrils Amyloid plaque 43% crenezumab gantenerumab Crenezumab Designed to neutralize neuro-toxic Aβ oligomers 3 Ph III fully recruited (CREAD program) 4,5,6 Final data (CREAD1/2) expected in 2020 Gantenerumab Targets aggregated Aβ forms; binds oligomers and plaques 7,8 Ph III started (GRADUATE program) 9,10 Yang T. et al., AAIC 2018 Significantly reduces Aβ oligomer levels in CSF 43%, supplementing previous Ph II efficacy signals in mild AD sub-groups First DMT to demonstrate inhibition of Aβ oligomers in patients Klein G. et al., AAIC 2018 Nearly half of patients below threshold of Aβ positivity at 2yrs - many patients approaching Aβ floor level Crenezumab in collaboration with AC Immune; Gantenerumab in collaboration with MorphoSys; 3. Adolfsson O, et al. J Neurosci 2012; 32: ; 4. NCT ; 5. NCT ; 6. Blaettler T, et al. AAIC 2016; 7. Bohrmann B, et al. J Alzheimer s Dis 2012; 8. Ostrowitzki S, et al. Arch Neurol 2012; 9. NCT ; 10. NCT ; Aβ=amyloid-β; mab=monoclonal antibody; CSF=cerebrospinal fluid; AD=Alzheimer`s disease; DMT=disease modifying treatment; SR=Scarlet Road; MP-NP=Marguerite Road non-pretreated; MR-P=Marguerite Road pretreated; PET=Positron Emission Tomography; OLE=open label extension 45

46 Digital tools revolutionizing understanding of disease progression in the multiple sclerosis spectrum FLOODLIGHT: Digital tools enabling earlier and augmented detection of progression FLOODLIGHT OPEN: Large (N=~10.000) non-interventional global study detecting and measuring progression initiated in Q Building on a wealth of data generated in on-going clinical programs with Ocrevus > people with MS treated globally within 14 months after first launch Superior efficacy in long term data consistent with primary outcomes in both, progressive and relapsing MS Expanding populations and clinical measures of progressive disease Ph IIIb (ORATORIO-HAND) placebo-controlled study with Ocrevus in PPMS including patients in wheelchairs and using upper limb function as 1EP Ph IIIb (CONSONANCE and ENSEMBLE) study with Ocrevus across progressive MS spectrum ORATORIO-HAND and CONSONANCE: Validating digital outcomes with traditional clinical endpoints for measuring progression MS=multiple sclerosis; PPMS=primary progressive MS; 1EP=primary end point 46

47 Roche Virtual Late Stage Pipeline Event 2018 Commercial Opportunities Alexander Hardy Head of Global Product Strategy

48 Differentiation and market opportunities Oncology Hematology/Hemophilia A Ophthalmology & infectious diseases Multiple sclerosis Access and pricing 48

49 Breakthrough innovation remains key for pharma Roche: Highest number of BTDs in the industry reflecting the quality of our research 1 Selected oncology products launched over ; 2 Market shares represent sales of target product relative to sales competing products in similar indications; BTD=Breakthrough Therapy Designation; Data source: Evaluate Pharma, Decision Resources, Prismaccess 49

50 Near term pipeline carries significant revenue potential Submission Molecule Indication Hemlibra Hemophilia A, non-inhibitors polatuzumab vedotin R/R DLBCL Venclexta 1L AML 2018 Tecentriq 1L NSq NSCLC Tecentriq 1L ES SCLC Tecentriq 1L TNBC Tecentriq + Avastin 1L RCC entrectinib ROS1+, NTRK+ NSCLC idasanutlin AML Tecentriq+Cotellic+/-Zelboraf BRAFm Mel, BRAFwt Mel 2019 Tecentriq neoadj TNBC Venclexta + Gazyva 1L CLL Venclexta R/R MM Tecentriq + Avastin 1L HCC ipatasertib Tecentriq 2020 Tecentriq Tecentriq + Avastin 1L CRPC, 1L TNBC, HER2-/HR+ BC 1L muc CRPC 1L OC 2021 polatuzumab vedotin 1L DLBCL Market opportunity Submission Molecule Indication 2018 baloxavir marboxil Influenza A & B 2019 satralizumab Neuromyelitis optica risdiplam anti-myostatin crenezumab HTT-ASO balovaptan PDS faricimab etrolizumab Oncology / Hematology Ophthalmology Neuroscience Immunology Infectious disease SMA DMD Alzheimer s disease Huntington s disease Autism wamd DME UC/CD Small: up to CHF 0.5 bn Market opportunity medium= CHF 0.5 to CHF 1bn large > CHF1bn 50

51 Differentiation and market opportunities Oncology Hematology/Hemophilia A Ophthalmology & infectious diseases Multiple sclerosis Access and pricing 51

52 Sales USDbn Oncology market driven by continued innovation Targeted therapies and CIT class keep growing Oncology market 1 : 11% CAGR Sales split (USDbn) by indication polatuzumab vedotin 72 idasanutlin mosunetuzumab ipatasertib entrectinib entrectinib ipatasertib hematology breast lung other targeted therapies CIT chemo / other CIT=Cancer Immunotherapy; 1 Source: EvaluatePharma 52

53 HER2+ breast cancer HER2 franchise projected to continue growth Perjeta in ebc: Raising the cure rate of HER2+ BC HER2 franchise growth driven by adjuvant Perjeta 75% of Herceptin sales in ebc (neoadjuvant + adjuvant) Perjeta adjuvant approved in US, EU, and 18 other countries Indicated for higher risk patients (70-75% of ebc population) Label specifies full 18 cycles of treatment Neoadj Adjuvant 1L mbc 2L mbc New Patient Share (US) 1 ~ 90% ~ 35% ~70% ~60% Value proposition: Subcutaneous formulation (SC) Reduced treatment burden 5 min administration time At home administration potential Capacity/Resources Infusion chair capacity constrained Hospital staff resources constrained Herceptin + Perjeta Fixed Dose SC in Ph III trial CHFm 3'000 2'500 2'000 1'500 1' HER2 franchise sales +11% +7% +19% +8% YoY CER growth Kadcyla Perjeta Herceptin Q2 15 Q2 16 Q2 17 Q2 18 ebc=early breast cancer; mbc=metastatic breast cancer; 1. New patient share data as of June

54 TNBC and HR+/HER2- breast cancer Expanding into areas with high unmet need Breast cancer market Incidence rates 1 HER2+ ~20% TNBC ~15% HR+/HER2- ~65% TNBC Tecentriq: First-in-class positive Ph III (IMpassion130): PFS endpoint met (ITT), positive OS trend in PD-L1+ TNBC (40% of pts) Further ebc opportunity: 4 Tecentriq Ph III trials in neoadjuvant/adjuvant Ipatasertib: Positive Ph II results (LOTUS): PFS endpoint met, OS trend Ph III for iptasertib initiated (IPATunity130) in Dx+ advanced TNBC (Pi3K pathway activated in 30% of pts) Combination potential for Tecentriq + ipatasertib HR+/ HER2- mbc Ipatasertib: Ph III initiated (IPATunity130) in Dx+ advanced HR+/HER2- mbc (Pi3K pathway activated in 40% of HR+/HER2- patients) Combination potential for Tecentriq + ipatasertib Breast cancer market growing from USD ~17bn in 2017 to ~33bn in TNBC=Triple Negative Breast Cancer, HR+=hormone receptor positive; Source: 1 Datamonitor: incidence rates includes the 7 major markets (US, Japan, France, Germany, Italy, Spain, UK); 2 Evaluate Pharma 54

55 Lung cancer Broad coverage with differentiated growth opportunities Lung cancer market Incidence rates 1 Driver mutations NSCLC EGFR, ALK, ROS1/NTRK Alecensa rapidly established as market leader in 1L ALK+ Entrectinib setting a new SOC in ROS1+/NTRK+ Tecentriq: Only CIT agent with positive data in 2L EGFR+/ALK+ SCLC Tecentriq to be first CIT in combination with chemo in 1L SCLC 1L NSq NSCLC Early NSCLC Novel combinations, biomarkers Tecentriq: 3 positive Ph III trials, including multiple chemos Uniquely differentiated with abraxane and Avastin combinations Strong efficacy in patients with liver metastases (~20% pts) Pivotal studies in neoadjuvant and adjuvant started 40% of NSCLC patients don t respond to 1L CIT + chemo and no SOC established for CIT experienced patients Total lung cancer market growing from USD ~14bn in 2017 to ~33bn in CIT=Cancer Immunotherapy; SCLC=small cell lung cancer; NSCLC=non-small cell lung cancer, Sq=squamous, NSq=non-squamous, SOC=standard of care; 1 Datamonitor: incidence rates includes the 7 major markets (US, Japan, France, Germany, Italy, Spain, UK); 2 Evaluate Pharma 55

56 Gastrointestinal (GI) and Genitourinary (GU) cancers Tecentriq + Avastin well positioned in various indications Renal Hepatocellular Other GI / GU Historical SOC Future SOC sunitinib Tecentriq +Avastin PFS HR: 0.74 (PD-L1+) sunitinib Tecentriq +Avastin ORR: 2% ORR: 61% Benefit across all risk types: Tecentriq (IMmotion151) first-in-class with benefit in favorable risk patients (~30% of patients), Filing in 2018 (PD-L1+), OS data expected 2019 (ITT) Differentiated safety: Tecentriq + Avastin demonstrated good safety profile; Potential to become backbone for future CIT combinations Adjuvant opportunity: Ph III trial in adjuvant RCC initiated First in class: First CIT to show benefit in HCC FDA BTD: Plan to expand Ph Ib trials and submit to health authorities, with confirmatory Ph III trial (IMbrave150) initiated Ongoing trials: Colorectal cancer: acea/cd3 TCB in 3L+ CRC Prostate cancer: ipatasertib in 1L and Tecentriq in 2/3L CRPC Bladder cancer: Tecentriq in 1L muc and advujant PDL1+ high risk MIBC Total RCC market USD ~5.5 bn by Total HCC market USD ~3.9 bn by RCC=renal cell carcinoma; HCC=hepatocellular carcinoma, CIT=cancer immunotherapy, BTD=breakthrough therapy designation, CRC=colorectal cancer; CRPC=castration resistant prostate cancer, mubc=metastatic urothelial carcinoma; MIBC=muscle invasive bladder cancer; 1 Evaluate Pharma 56

57 Differentiation and market opportunities Oncology Hematology/Hemophilia A Ophthalmology & infectious diseases Multiple sclerosis Access and pricing 57

58 Hematology (CLL, DLBCL, inhl) Redefining the standard of care Hematology Market CLL DLBCL inhl Incidence rates 1 Venclexta combinations induce deep responses, and long treatment-free remissions Polatuzumab driving high CR rates with durable responses Gazyva established as SOC in 1L inhl with estimated 3 yrs longer mpfs than Rituxan SOC chemo R/R benda 1L clb R/R benda 1L CHOP R/R benda 1L chemo R+chemo R+benda R+clb R+benda R-CHOP R+benda R+chemo G+ chemo G+clb G+benda G+chemo Future SOC R+Venclexta G+Venclexta Pola+BR / mosunetuzumab Pola+R-CHOP mosunetuzumab FDA approved June 18, NCCN cat 1 listing CLL14 data exp. Q4 18 Plan to file pola in 2018, BTD, PRIME Ph III trial initiated (POLARIX) mosunetuzumab data in NHL at ASH 2018 Gazyva listed on NCCN guidelines Total CLL, NHL (DLBCL/iNHL) market growing to 9bn & 15bn, respectively by CLL=chronic lymphocytic leukemia; anhl=agressive non-hodgkin s lymphoma; inhl=indolent non-hodgkin s lymphoma; R/R=relapsed refractory; DLBCL=diffuse large B-cell lymphoma; R=Rituxan; G=Gazyva; clb=chlorambucil; benda=bendamustine; 1 Datamonitor: incidence rates includes the 7 major markets (US, Japan, France, Germany, Italy, Spain, UK); 2 Evaluate Pharma; Venclexta in collaboration with AbbVie 58

59 Hematology (MM, AML) Expanding with transformative therapies Hematology Market AML MM Incidence rates 1 Advancing the SOC in a market which has been historically difficult to treat Multiple combinations in development to address 2-3L market R/R 1L ineligible for intense chemo R/R Historical SOC LDAC low dose cytarabine LDAC low dose cytarabine HMA azacitadine/decitabine bortezomib + dexamethasone Future SOC idasanutlin + LDAC Venclexta + LDAC Venclexta + HMA Venclexta + btz + dex Status Ph III (MIRROS) trial on-going NDA submitted for Venclexta+HMA; Pivotal Ph III (Viale-A and Viale-C) on-going; 50% of 1L AML patients are ineligible for intense chemo Ph III (BELLINI) trial read-out in H1 19 Several combos in early stage pipeline including Venclexta, Tecentriq, and undisclosed CD3-bispecific targeting MM Total MM & AML market growing to USD 25bn & 7bn, respectively by AML=Acute Myeloid Leukemia; MM=Multiple Myeloma; R/R=relapsed refractory; DLBCL=diffuse large B-cell lymphoma; R=Rituxan; G=Gazyva; clb=chlorambucil; benda=bendamustine; HMA=hypomethylating agent; LDAC=low dose aracytarabine; 1 Datamonitor: incidence rates includes the 7 major markets (US, Japan, France, Germany, Italy, Spain, UK); 2 Evaluate Pharma; Venclexta in collaboration with AbbVie 59

60 Hemophilia A Hemlibra provides transformational advance for hemophilia market Severity & treatment-based segmentation Needs-based segmentation Ondemand 50% 20% 5% 75-80% Prophylaxis 50% 10% 15% 45% Mild: ~25% Moderate: ~20% Severe: ~50% Inhibitor: ~5% PWHA moderate/severe Inhibitors Non-inhibitors with bleeds Pediatric Non-inhibitors without bleeds Mild Hemlibra target population Total hemophila A market growing to USD 13bn by PWHA=People with Hemophilia A; Source: Treated patients MORSE 2017 (prevalence), UKHCDO Annual Report 2016 and internal assumptions (treatment rate); 1 Source: Evaluate Pharma 60

61 Differentiation and market opportunities Oncology Hematology/Hemophilia A Ophthalmology & infectious diseases Multiple sclerosis Access and pricing 61

62 Mean VA difference Ophthalmology Innovating beyond Lucentis with novel MOAs and long acting delivery High unmet medical need Roche has the broadest Ph III pipeline in retina from baseline by country (LOCF) a Days UK NED Total FR GER IT More injections Fewer injections New MOAs needed to improve both efficacy and durability High treatment burden of anti-vegf therapies in real world associated with suboptimal visual outcomes 1 Growing market driven by aging population and incidence of diabetes Faricimab: First bi-specific antibody in ophthalmology PDS with ranibizumab: Breakthrough LAD platform significantly reduces the treatment burden, potentially improving real world treatment outcomes Significant future development efforts: Novel MOAs, new LAD platforms, and personalized healthcare/digital approaches Total retina medical market USD ~10bn in LAD=long-acting delivery; MOA=mode of action; 1 F.G. Holz et al., Br J Ophthalmol 2015; 2 Evaluate Pharma 62

63 Influenza A & B Baloxavir marboxil* with first new MOA in 20 years Potential to be first in disease in High Risk and Hospitalized Influenza Patients Note: Revenue potential is illustrative and not to scale. Peak revenue opportunity > CHF 1bn * Baloxavir marboxil was discovered by Shionogi & Co., Ltd. and is being developed globally by the Roche Group (which includes Genentech in the U.S.) and Shionogi & Co., Ltd. Under the terms of this agreement, Roche holds worldwide rights to baloxavir marboxil excluding Japan and Taiwan, which will be retained exclusively by Shionogi & Co., Ltd. 63

64 Differentiation and market opportunities Oncology Hematology/Hemophilia A Ophthalmology & infectious diseases Multiple sclerosis Access and pricing 64

65 Multiple sclerosis Goal to be market leader in MS Ocrevus uniquely differentiated in RMS & PPMS Strong launch indicators and growth potential Efficacy RMS Superior to SOC DMT PPMS First therapy to show efficacy in setting MS projected revenue uptake curves 1 Ocrevus US new/switch patient share 2 32% Ocrevus Safety Convenience 50,000+ patients; 4-year safety data presented; no PML cases related to drug IV twice yearly Tecfidera Gilenya Aubagio Tysabri Copaxone (incl. generic) ABREPS Tysabri Tecfidera Access Priced below or similar to high efficacy therapies, broad payer coverage in US, reimbursement ongoing in EU Y1 Y2 Y3 Y4 Y5 Y6 Y7 Y8 Y9 Y10 Aubagio Gilenya Other US: Total Patient 10% Market Share March 2018 #1 New MS prescription in US As of March Sales split: RMS/PPMS HY 2018 Total MS market USD ~23bn in SOC=Standard of Care; RMS=Relapsing Multiple Sclerosis; PPMS=Primary Progressive Multiple Sclerosis; DMT=disease modifying therapy; 1 Source: Evaluate Pharma 2. US IMS and Symphony claims data Q

66 Differentiation and market opportunities Oncology Hematology/Hemophilia A Ophthalmology & infectious diseases Multiple sclerosis Access and pricing 66

67 We consider a number of factors when we price a medicine Value Patient benefit Health system impact Societal impact Science Unmet medical need Innovation Clinical evidence Market Price of analogues Budget impact Cost effectiveness General Economy (GDP) 67

68 Price Index Our principles for pricing and access Reflecting the benefit medicines bring to patients Personalized reimbursement models (PRM) wherever possible Pricing reflects GDP per capita (economic strength of countries) Two recent examples of responsible pricing PRM fully implemented PRM in use, optimisation underway PRM implementation underway Standard Price = Global Price (anchor point) 25% discount to Rebif list price in the US Floor Net Price for Tier Cost of therapies in MS increased 400% since Last drug to launch in MS: 9% premium to average price 1 Developing Low Income Markets e.g. India, Vietnam, Kenya, Bolivia M&D COGS Developing Middle Income Markets e.g. Russia, China, Brazil Established High Income Markets E.g. All Europe, Japan, US, and other lead markets 50% discount to BPA prophylaxis in the US ICER review: USD 71m in lifetime savings for Hemlibra prophylaxis vs. BPA prophylaxis BPA=Bypassing agent; 1. Source National MS Society 68