58 th ASH Annual Meeting, San Diego. Roche Analyst Event. Monday, 5 December 2016

Transcription

1 58 th ASH Annual Meeting, San Diego Roche Analyst Event Monday, 5 December 2016

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. 3

3 Introduction Karl Mahler Head Investor Relations

4 Agenda Welcome Karl Mahler, Head of Investor Relations New paths in hematology Nancy Valente, M.D., Vice President, Product Development Hematology/Oncology Gazyva - New standard of care in FL (inhl) David Traub, M.D., Lifecycle Leader anti-cd20 Franchise Venclexta New data in CLL, NHL, AML and MM Reema Mewar, Ph.D., Lifecycle Leader Venclexta/Venclyxto Polatuzumab vedotin A potent ADC in NHL Michael Wenger, M.D., Senior Group Medical Director Q&A 5

5 line extensions NMEs 2016 onwards: Significant launch activities Venclexta R/R CLL with 17p del Cotellic + Zelboraf BRAFmut melanoma Alecensa 2L ALK+ NSCLC Tecentriq 2L+ bladder cancer Tecentriq 2L+ all-comers NSCLC OCREVUS RMS/ PPMS Emicizumab (ACE910) Hemophilia A Lampalizumab Geographic atrophy Gazyva Refractory inhl (GADOLIN) Perjeta + Herceptin ebc HER2+ (APHINITY) Tecentriq+Avastin+chemo 1L NSCLC Gazyva 1L inhl (GALLIUM) Tecentriq + Avastin 1L RCC Actemra Giant cell arteritis (GiACTA) Alecensa 1L ALK+ NSCLC Oncology/ hematology Neuroscience Ophthalmology Immunology Outcome studies are event-driven: timelines may change. Standard approval timelines of 1 year assumed. FDA Breakthrough Therapy Designation 6

6 Roche significantly advancing patient care Five BTD designations in hematology 14 Breakthrough Therapy Designations Rank Company # 1 Roche 14 2 Novartis 11 3 BMS 10 4 Merck 9 5 AbbVie 7 6 Pfizer 7 Year Molecule Actemra (Giant cell arteritis) Alecensa (1L ALK+ NSCLC) Ocrevus (PPMS) Venclexta (AML) Venclexta + Rituxan (R/R CLL) Actemra (Systemic sclerosis) Tecentriq (NSCLC) Venclexta (R/R CLL 17p del) Emicizumab/ACE 910 (Hemophilia A) Esbriet (IPF) Lucentis (Diabetic retinopathy) Tecentriq (Bladder) Alecensa (2L ALK+ NSCLC) Gazyva (1L CLL) Source: as at Oct 2016; PPMS=Primary Progressive Multiple Sclerosis; CLL=Chronic Lymphocytic Leukemia; AML=acute myeloid leukemia; NSCLC=Non-Small Cell Lung Cancer; IPF=Idiopathic Pulmonary Fibrosis 7

7 ASH 2016: Improving upon on standard of care Key presentations DLBCL Polatuzumab shows promise DLBCL (Ph2 ROMULUS in R/R and Ph1/2 in 1L) Rituxan-CHOP remains standard of care FL Establishing Gazyva as SOC (Ph3 GALLIUM FL in 1L and Ph3 GADOLIN in Rituxan- ref FL) MabThera SC comparable to IV (Ph3 SABRINA) CLL Venclexta unfolding (run-in data for Ph3 CLL14) CLL AML AML/MDS Venclexta + LDAC with strong efficacy in 1L unfit AML (Ph2) MM MM Strong efficacy of Venclexta in R/R MM (Ph1 monotherapy and combination data) Hemophilia Hemophilia Real world data of patients with hemophilia A to support further development of emicizumab 8

8 New paths in hematology Nancy Valente, M.D. Vice President, Product Development Hematology/Oncology

9 Unmet need in hematology Hematology portfolio & strategy Cancer immunotherapy Emicizumab update 10

10 Today: Hematology indications still represent large unmet need DLBCL DLBCL 40% of DLBCL patients relapse and succumb to their disease FL FL Still no cure, many patients experience multiple relapses before succumbing to their disease CLL CLL Still no cure, many patients achieve incomplete responses and require chronic treatment AML/MDS AML/MDS SOC in AML has made little progress in decades, combinations will significantly improve outcomes for patients MM MM Foundation of therapy based on two drug classes associated with significant side effects; targeted therapy combinations to advance SOC Hemophilia Hemophilia High unmet need for patients with inhibitors to Factor VIII; Existing therapies are hampered by burden on therapy and compliance

11 Blood cancer: Still high unmet medical need Incidence cases reach 330,000 pts 1 acd20/cd3 TCB 1 acd20/cd3 TCB 2 polatuzumab vedotin idasanutlin LSD1 inhibitor BET inhibitor ChK1 inhibitor = Roche marketed = Roche in development undisclosed ADC ¹ Datamonitor; incidence rates includes the 7 major markets (US, Japan, France, Germany, Italy, Spain, UK); NHL=non-hodgkin`s lymphoma; DLBCL (anhl)=diffuse large B-cell lymphoma; FL (inhl)=follicular lymphoma; ALL=acute lymphoblastic leukemia; AML=acute myeloid leukemia; CLL=chronic lymphoid leukemia; MM= multiple myeloma; MDS=myelodysplastic syndrome; Venclexta in collaboration with AbbVie; Cotellic in collaboration with Exelixis; Gazyva in collaboration with Biogen; polatuzumab vedotin in collaboration with Seattle Genetics; LSD1inhibitor in collaboration with Oryzon Genomics; ChK1i in collaboration with Array BioPharma 12

12 Unmet need in hematology Hematology portfolio & strategy Cancer immunotherapy Emicizumab update 13

13 Gazyva initial trial program completed New standard of care in inhl and CLL CLL11: Ph III 1L Chronic Lymphocytic Leukemia (CLL) 1L CLL n=781 Gazyva + chlorambucil Rituxan + chlorambucil chlorambucil GADOLIN: Ph III Rituxan-refractory Follicular Lymphoma (FL) Primary end-point: PFS Approved in Q Rituxan-refractory FL (indolent NHL) n=411 Induction Maintenance PFS CR, PR, Gazyva + bendamustine Gazyva SD q2mo x 2 years bendamustine Approved in Q GALLIUM: Ph III 1L Follicular Lymphoma (FL) Induction 1L FL (indolent NHL) n=1401 Gazyva + CHOP or Gazyva + CVP or Gazyva + bendamustine Rituxan + CHOP or Rituxan + CVP or Rituxan + bendamustine CR, PR Maintenance Gazyva q2mo x 2 years Rituxan q2mo x 2 years PFS Stopped at interim analysis GOYA: Ph III 1L Diffuse Large B-cell Lymphoma (DLBCL) Front-line DLBCL (aggressive NHL) n=1418 Gazyva + CHOP Rituxan + CHOP PFS Endpoint not met Gazyva in collaboration with Biogen; CHOP=Cyclophosphamide, Doxorubicin, Vincristine and Prednisone; CVP=Cyclophosphamide, Vincristine and Prednisolone 14

14 Establishing Gazyva as new CD20 backbone Improving the standard of care in inhl and CLL Rituxan sales split by indication 1L CLL 5% 1L CLL Fit 6% Gazyva in 1L CLL (CLL 11) Gazyva in 1L FL (inhl) (GALLIUM) Gazyva in Rituxan-refractory FL (inhl) (GADOLIN) inhl 49% 1L anhl 27% R/R CLL 6% R/R anhl 6% CLL=chronic lymphocytic leukemia; inhl=indolent non-hodgkin s lymphoma; FL=follicular lymphoma; anhl=aggressive NHL; DLBCL=diffuse large B cell lymphoma; Gazyva in collaboration with Biogen 15

15 Evolving landscape in NHL Increasing segmentation and new surrogate endpoints Present Future Competition No competition for 17 years Increased competition 2024 Segmentation All comers studies Combination therapies for diagnostic subsegments ABC Unclassified GCB DLBCL (anhl) New Endpoints Traditional Endpoints PFS OS 5 yrs 7 yrs Potential Surrogate MRD CLL 15mo CR30 NHL 30mo Traditional Endpoints PFS OS 5 yrs 7 yrs Induction Induction Early Filing ABC=activated B-cell, GCB=germinal center B-cell 16

16 Increasing segmentation in 1L DLBCL (anhl) New combinations based on Rituxan backbone Elevated BCL-2 ~50% Double Positive BCL-2 and myc* Double Hit BCL-2 and myc ~50% ABC Unclassified GCB ~30% ~15% ~55% Rituxan backbone Lenalidomide (ROBUST) Ibrutinib (PHOENIX) *46% of ABC patients are double positive (Hu S et l. Blood, 2013); Source: Roche internal data presented during REFORCE F2F Feb- 2015; Johnson N et al, JCO 2012; Hu S et al, Blood 2013; Iqbal J et al. Clin Can Res 2011; Iqbal J et al. JCO, 2006; Davis et al. Nature 2010; Haberman T et al, JCO 2006; Thieblemont C et al. JCO 2011 ABC=activated B-cell, GCB=germinal center B-cell 17

17 Surrogate endpoints to accelerate development Predict long-term outcome early on Novel endpoints: MRD in CLL CR30 months in FL PET-CT negative CR in DLBCL MRD=minimal residual disease; PET-CT=positron emission tomography-computed tomography 18

18 Developing new combinations in NHL Building on the CD20 backbone and new agents Rituxan + Chemo Eliminate or replace Rituxan or Gazyva + with Polatuzumab + targeted agent Venclexta Anti CD20/CD3 Polatuzumab TCB + NME ADC + Venclexta Tecentriq TCB=T cell bispecific; NME=new molecular entity; ADC=antibody drug conjugate 19

19 Innovative trial designs in NHL needed Prioritization and early decision making important Backbone Approved Combination Studies Venclexta Polatuzumab R/G + Chemo Tecentriq Lenalidomide Ibrutinib G + Pola Venclexta Tecentriq Lenalidomide Polatuzumab Tecentriq R/G Idasanutlin Tecentriq + Lenalidomide Ibrutinib Venclexta Lenalidomide Venclexta in collaboration with AbbVie; Polatuzumab vedotin in collaboration with Seattle Genetics 20

20 Overview hematology pipeline 14 molecules in the clinic including 9 NMEs * Venclexta in collaboration with AbbVie; Polatuzumab vedotin in collaboration with Seattle Genetics; LSD1i in collaboration with Oryzon Genomics; 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 21

21 Unmet need in hematology Hematology portfolio & strategy Cancer immunotherapy Emicizumab update 22

22 Why is immunotherapy important in hematology? History in hematology Broad portfolio & strong scientific rationale Rituxan was technically the first cancer immunotherapy Gazyva was the first glyoengineered antibody to enhance ADCC and ADCP Tecentriq showed tumor shrinkage in Phase I hematologic malignancies Checkpoint inhibitors have shown promising efficacy in Hodgkin s disease, NHL and MM ADCC=antibody-dependent cellular cytotoxicity; ADCP=antibody-dependent cellular phagocytosis; NHL=non-hodgkin`s lymphoma; MM=multiple myeloma; AML=acute myeloid leukemia; MDS=myelodysplastic syndrom; FL=follicular lymphoma; DLBCL=diffuse large B cell lymphoma; TCB=T cell bispecific 23

23 CIT development program by tumor type = approved; *External collaborations; Other CIT NMEs besides Tecentriq As of Nov 5 th 24

24 acd20/cd3 TCBs as new backbone in NHL Two shots on goal acd20/cd3 TCB binds to tumor cells via CD20 and to T cells via CD3, thereby enabling T cell mediated killing TCB=T cell bispecific; T cell=cytotoxic T lymphocyte (CTL) 25

25 E C 5 0 (n M ) % tu m o r c e ll ly s is Preclinical data for acd20/cd3 TCBs presented PD-L1 combinations active acd20/cd3 TCB 1 (gred) acd20/cd3 TCB 2 (pred) acd20/cd3 TCB 1 + apd-l1 acd20/cd3 TCB 2 with increased T cell activity in vitro CD20 TCB (2:1) Other CD20- targeted TCBs (1:1) T C B c o n c e n tr a tio n [p M ] acd20/cd3 TCB 2 with increased T cell activity ex vivo CD20 TCB (2:1) Other CD20- targeted TCB (1:1) 2 0 Peiyin W et al., ASH 2016 Bacac M et al., ASH 2016 TCB=T cell bispecific 26

26 Unmet need in hematology Hematology portfolio & strategy Cancer immunotherapy Emicizumab update 27

27 Emicizumab (ACE910) in hemophilia A Phase III inhibitor data expected in 2016 * ** Development program on track Two year follow-on data presented at WFH confirm efficacy and safety profile Additional Phase III studies in non-inhibitors and paediatrics have started Nogami K. et al, presented at WFH 2016 ; ABR=annual bleeding rate; OLE=open label extension; *1 patient discontinued administration due to mild injection site erythema; **1 patient did not participate in the extension study since prior treatment was sufficiently efficacious 28

28 Gazyva - New standard of care in FL (inhl) David Traub, M.D. Lifecycle Leader anti-cd20 Franchise

29 Introduction: Gazyva Gazyva in NHL Gazyva development program MabThera/Rituxan SC 30

30 MoA: Gazyva (glycoengineered anti-cd20 MAb) Optimized for enhanced ADCC and ADCP Product profile Gazyva is a type II anti-cd20 antibody with a glycoengineered Fc portion to enhance binding to the FcγRIII receptor on immune cells and a variable region that binds CD20 in a distinct orientation Compared to Rituxan, Gazyva enhances: 1. Direct cell death 2. Antibody-dependent cellmediated cytotoxicity (ADCC) 3. Antibody-dependent cellular phagocytosis (ADCP) MOA=mechanism of action; ADCC=antibody-dependent cellular cytotoxicity; ADCP=antibody-dependent cellular phagocytosis; Gazyva (obinutuzumab); Rituxan (rituximab); 1. Mössner E. et al., Blood 2010; 2. Ferrara C. et al., Biotechnol Bioeng 2006; 3. Dalle S. et al., Mol Cancer Ther

31 Gazyva initial trial program completed New standard of care in inhl and CLL CLL11: Ph III 1L Chronic Lymphocytic Leukemia (CLL) 1L CLL n=781 Gazyva + chlorambucil Rituxan + chlorambucil chlorambucil GADOLIN: Ph III Rituxan-refractory Follicular Lymphoma (FL) Primary end-point: PFS Approved in Q Rituxan-refractory FL (indolent NHL) n=411 Induction Maintenance PFS CR, PR, Gazyva + bendamustine Gazyva SD q2mo x 2 years bendamustine Approved in Q GALLIUM: Ph III 1L Follicular Lymphoma (FL) Induction 1L FL (indolent NHL) n=1401 Gazyva + CHOP or Gazyva + CVP or Gazyva + bendamustine Rituxan + CHOP or Rituxan + CVP or Rituxan + bendamustine CR, PR Maintenance Gazyva q2mo x 2 years Rituxan q2mo x 2 years PFS Stopped at interim analysis GOYA: Ph III 1L Diffuse Large B-cell Lymphoma (DLBCL) Front-line DLBCL (aggressive NHL) n=1418 Gazyva + CHOP Rituxan + CHOP PFS Endpoint not met Gazyva in collaboration with Biogen; CHOP=Cyclophosphamide, Doxorubicin, Vincristine and Prednisone; CVP=Cyclophosphamide, Vincristine and Prednisolone 32

32 Introduction: Gazyva Gazyva in NHL (GALLIUM; GADOLIN; GOYA) Gazyva development program MabThera/Rituxan SC 33

33 Gazyva in 1L FL (inhl) 34% risk reduction of disease progression PFS by INV GALLIUM phase III results: Primary endpoint met at interim analysis (median observation time of 35 months) Investigator assessed PFS HR expected to translates to a 1.5x longer mpfs (9 years instead of 6 years) Gazyva based immunochemotherapy and maintenance new standard of care in 1L FL Marcus R. et al., ASH 2016; FL=follicular lymphoma; R=Rituxan; G=Gazyva; PFS=progression free survival; INV=investigator; IRC=independent review committee; HR=hazard ratio; OS=overall survival; Data cut-off: January 31,

34 Gazyva in Rituxan-relapsed FL (inhl) 42% risk reduction of death in FL patients OS (FL patients) GADOLIN phase III update: OS benefit in FL patients and all inhl patients PFS benefit confirmed by nearly two years of additional follow-up Results establish Gazyva + bendamustine induction followed by Gazyva maintenance as standard of care for Rituxan-relapsed FL patients Cheson B. et al., ASH 2016; FL=follicular lymphoma; inhl=indolent non-hodgkin`s lymphoma; B=bendamustine; PFS=progression free survival; OS=overall survival; HR=hazard ratio; Data cut-off: April 1,

35 Gazyva in 1L DLBCL (anhl) Outcome informs future research activities PFS by INV GOYA Phase III results: G-CHOP did not improve INV-assessed PFS compared with R-CHOP Outcomes for secondary time-to-event endpoints were consistent with that for the primary endpoint R-CHOP remains standard of care in this setting Vitolo U. et al., ASH 2016; DLBCL=diffuse large B cell lymphoma; anhl=agressive non-hodgkin`s lymphoma; G=Gazyva; R=Rituxan; CHOP=Cyclophosphamide, Doxorubicin, Vincristine and Prednisone; PFS=progression free survival; INV=investigator; HR=hazard ratio; OS=overall survival; Data cut-off: April 30,

36 Introduction: Gazyva Gazyva in NHL Gazyva development program MabThera/Rituxan SC 37

37 Development program in NHL Gazyva trials in DLBCL NHL Compound Combination Study name Indication P Ph1 1 P Ph2 2 P Ph3 3 Gazyva +bendamustine GADOLIN FL (inhl) (Rituxan refractory) Gazyva +CHOP GOYA 1L DLBCL (anhl) Gazyva +chemo GALLIUM 1L FL ( inhl) Venclexta* +Rituxan/+Rituxan+bendamustine CONTRALTO R/R FL (inhl) Venclexta +Rituxan+CHOP CAVALLI 1L DLBCL (anhl) Venclexta +Rituxan+bendamustine R/R NHL Venclexta R/R CLL and R/R NHL Venclexta +Gazyva/Rituxan+polatuzumab R/R DLBCL (anhl) and R/R FL (inhl) polatuzumab +Rituxan/Gazyva ROMULUS R/R DLBCL (anhl) and R/R FL (inhl) polatuzumab +Gazyva/Rituxan+bendamustin R/R DLBCL (anhl) and R/R FL (inhl) polatuzumab +Gazyva+CHP/Rituxan+CHP 1L DLBCL (anhl) polatuzumab +Gazyva/Rituxan+lenalidomide R/R DLBCL (anhl) and R/R FL (inhl) Tecentriq +Gazyva or +tazemetostat1** Tecentriq +Gazyva+lenalidomide R/R FL (inhl) R/R DLBCL (anhl) and R/R FL (inhl) Tecentriq +Gazyva/Rituxan+benda or CHOP 1L FL (inhl) and 1L DLBCL (anhl) Tecentriq +Gazyva/Rituxan+polatuzumab R/R DLBCL (anhl) and R/R FL (inhl) idasanutlin +Gazyva/Rituxan R/R DLBCL (anhl) and R/R FL (inhl) undisclosed ADC R/R NHL ASH ASH ASH ASH ASH inhl=indolent non-hodgkin`s lymphoma; anhl=agressive NHL; DLBCL=diffuse large B cell lymphoma; FL=follicular lymphoma; CHOP=cyclophosphamide, doxorubicin, vincristine and prednisone; * Venclexta in collaboration with AbbVie; Gazyva in collaboration with Biogen; polatuzumab vedotin in collaboration with Seattle Genetics; **External collaboration; ADC=antibody drug conjugate 38

38 Development program in CLL, MM, AML, MDS and CLL CLL MM AML MDS Compound Combination Study name Indication Ph1 P 1 Ph2 P 2 Ph3 P 3 Gazyva +chemo CLL11 CLL Gazyva +FC/bendamustin/Clb GREEN CLL and R/R CLL Venclexta +Rituxan R/R CLL and SLL Venclexta +Gazyva CLL14 CLL Venclexta +Rituxan MURANO R/R CLL Venclexta Venclexta R/R CLL 17p R/R CLL after ibru/idel Venclexta +Rituxan+bendamustine R/R CLL and untreated CLL Venclexta +Gazyva R/R CLL and untreated CLL Venclexta R/R MM Venclexta +bortezomib+dexamethasone R/R MM Tecentriq Venclexta monotherapy or +daratumumab** or +lenalidomide or +lenalidomide+daratumumab R/R MM AML Venclexta +decitabine/+azacitidine AML Venclexta +low dose cytarabine (LDAC) 1L AML Venclexta LSD1 inhibitor +Cotellic +idasanutlin R/R AML unfit for chemo AML idasanutlin +cytarabine R/R AML Tecentriq +azacitidine MDS acd20/cd3 TCB1 Hematologic tumors ASH CLL=chronic lymphoid leukemia; R/R CLL=relapsed/refractory CLL; MM=multiple myeloma; AML=acute myeloid leukemia; MDS=myelodysplastic syndrome; FC=fludarabine, cyclophosphamide; *Venclexta in collaboration with AbbVie; Gazyva in collaboration with Biogen; Cotellic in collaboration with Exelixis; **External collaboration 39

39 Introduction: Gazyva Gazyva in NHL Gazyva development program MabThera/Rituxan SC 40

40 MabThera/Rituxan SC Launches ongoing, strong uptake in most markets Approved in the EU in NHL and CLL Encouraging initial uptake in the EU markets, comparable to Herceptin SC Rituxan SC filed in the US SC=subcutaneous; MabThera/Rituxan SC partnered with Halozyme 41

41 Rituxan SC in 1L FL (inhl) Reducing healthcare burden without compromising on safety and efficacy Progression free survival SABRINA Phase III update: Comparable response rates and time-to-event data for SC versus IV administration No new clinically relevant safety signals were identified SC administration has positive implications for patients and healthcare professionals Davies A.. et al., ASH 2016; FL=follicular lymphoma; SC=subcutaneous; IV=intravenous; R=Rituxan; CHOP=cyclophosphamide, doxorubicin, vincristine and prednisone; CVP=Cyclophosphamide, Vincristine and Prednisolone; PFS=progression free survival; OS=overall survival; ORR=overall response rate; CR=complete responses; CRu=complete response unconfirmed; EOI, end-ofinduction; OS, overall survival; HR=hazard ratio 42

42 Venclexta New data in CLL, NHL, AML, MM Reema Mewar, Ph.D. Lifecycle Leader Venclexta/Venclyxto

43 Introduction: Venclexta Venclexta in CLL Venclexta in AML Venclexta in NHL Venclexta in MM Venclexta development program 44

44 MoA: Venetoclax* (BCL-2 inhibitor) Restoration of apoptosis through BCL-2 inhibition BCL-2 overexpression allows cancer cells to evade apoptosis by sequestering pro-apoptotic proteins. Venetoclax binds selectively to BCL-2, freeing pro-apoptotic proteins that initiate programmed cell death (apoptosis). MOA=mechanism of action; * venetoclax in collaboration with AbbVie 45

45 Introduction: Venclexta Venclexta in CLL (CLL14) Venclexta in AML Venclexta in NHL Venclexta in MM Venclexta development program 46

46 Venclexta* + Gazyva in 1L unfit CLL First efficacy data from Ph3 run-in CLL14 study design Run-in of phase III (CLL14): Gazyva + Venclexta tolerable in elderly patients with CLL and clinically meaningful comorbidities The treatment induced substantial responses with a high number of minimal residual disease (MRD) negative responses 3 months after end of therapy (at month 15) Ph3 was fully recruited as of August 2016 Fischer K. et al., ASH 2016; *Venclexta (venetoclax) in collaboration with AbbVie; CLL=chronic lymphoid leukemia; MRD=minimal residual disease 47

47 Introduction: Venclexta Venclexta in CLL Venclexta in AML Venclexta in NHL Venclexta in MM Venclexta development program 48

48 P ro b a b ilit y P ro b a b ilit y B e s t p e r c e n t c h a n g e fro m b a s e lin e Venclexta* + LDAC in 1L unfit AML 61% ORR achieved Bone marrow blast count Phase 1 (600 mg), n=7 Phase 2 (600 mg), n= P a t ie n t s (n = 5 8 ) Phase II results: ORR of 61% in all patients 71% of patients achieved a 50% decrease in BM and peripheral blast counts Combination demonstrates significant and durable activity in patients aged 65y with treatment-naïve AML ineligible to receive intensive chemotherapy 0.3 R e s p o n d e r s (C R + C R i+ P R ), n = N o n -r e s p o n d e r s, n = I= c e n s o r e d e v e n t M o n th s s in c e in it ia tio n o f t re a tm e n t Wei AH. et al., ASH 2016; *Venclexta in collaboration with AbbVie; AML=acute myeloid leukemia; LDAC=low dose cytarabine; 0.4 ORR=overall response rate; CR=complete response; CRi=complete remission with incomplete marrow recovery; PR=partial response; 0.3 PD=progressive disease; BM=bone marrow R e s p o n d e r s (C R + C R i+ P R ), n = 3 7 Overall survival N o n -r e s p o n d e r s, n =

49 Introduction: Venclexta Venclexta in CLL Venclexta in AML Venclexta in NHL (CAVALLI, CONTRALTO) Venclexta in MM Venclexta development program 50

50 Venclexta* in NHL Early CD20+chemo combination data Zelenetz AD. et al., ASH 2016 Zinzani PL. et al., ASH 2016 Phase I/II interim results (CAVALLI): ORR is promising in NHL population High CR rate (7/8; 87.5%) observed in the DLBCL population with co-expression of BCL-2 and Myc, who have a poor prognosis. Ph2 completed enrollment of 210 patients Phase II interim results (CONTRALTO): Longer follow-up is required to establish the role of Ven + BR in R/R FL Higher BCL-2 expression may be associated with higher CR rates with Ven + BR *Venclexta in collaboration with AbbVie; NHL=non-hodgkin`s lymphoma; R/R FL=relapsed/refractory follicular lymphoma; ; R=Rituxan; B=bendamustine; ORR=overall response rate; PET-CT=positron emission tomography-computed tomography; CHOP=cyclophosphamide, doxorubicin, vincristine and prednisone; PFS=progression free survival 51

51 Introduction: Venclexta Venclexta in CLL Venclexta in AML Venclexta in NHL Venclexta in MM Venclexta development program 52

52 Venclexta* in R/R MM Combination efficacy data Moreau P. et al., ASH 2016 Phase I combination results: Combination was well tolerated Patients non-refractory to bortezomib had an ORR of 90% and reponses were more durable (median TTP, 11.3 vs 1.8 months) Results support on-going Ph3 trial in R/R MM *Venclexta in collaboration with AbbVie; R/R MM=relapsed/refractory multiple myeloma; ORR=objective response rate; scr=surgical complete response; CR=complete response; VGPR=very good partial response; PR=partial response; TTP=time to progression 53

53 Introduction: Venclexta Venclexta in CLL Venclexta in AML Venclexta in NHL Venclexta in MM Venclexta development program 54

54 Development program in NHL Venclexta trials in NHL NHL Compound Combination Study name Indication P Ph1 1 P Ph2 2 P Ph3 3 Gazyva +bendamustine GADOLIN FL (inhl) (Rituxan refractory) Gazyva +CHOP GOYA 1L DLBCL (anhl) Gazyva +chemo GALLIUM 1L FL ( inhl) Venclexta* +Rituxan/+Rituxan+bendamustine CONTRALTO R/R FL (inhl) Venclexta +Rituxan+CHOP CAVALLI 1L DLBCL (anhl) Venclexta +Rituxan+bendamustine R/R NHL Venclexta R/R CLL and R/R NHL Venclexta +Gazyva/Rituxan+polatuzumab R/R DLBCL (anhl) and R/R FL (inhl) polatuzumab +Rituxan/Gazyva ROMULUS R/R DLBCL (anhl) and R/R FL (inhl) polatuzumab +Gazyva/Rituxan+bendamustin R/R DLBCL (anhl) and R/R FL (inhl) polatuzumab +Gazyva+CHP/Rituxan+CHP 1L DLBCL (anhl) polatuzumab +Gazyva/Rituxan+lenalidomide R/R DLBCL (anhl) and R/R FL (inhl) Tecentriq +Gazyva or +tazemetostat1** Tecentriq +Gazyva+lenalidomide R/R FL (inhl) R/R DLBCL (anhl) and R/R FL (inhl) Tecentriq +Gazyva/Rituxan+benda or CHOP 1L FL (inhl) and 1L DLBCL (anhl) Tecentriq +Gazyva/Rituxan+polatuzumab R/R DLBCL (anhl) and R/R FL (inhl) idasanutlin +Gazyva/Rituxan R/R DLBCL (anhl) and R/R FL (inhl) undisclosed ADC R/R NHL ASH ASH inhl=indolent non-hodgkin`s lymphoma; anhl=agressive NHL; DLBCL=diffuse large B cell lymphoma; FL=follicular lymphoma; CHOP=cyclophosphamide, doxorubicin, vincristine and prednisone; * Venclexta in collaboration with AbbVie; Gazyva in collaboration with Biogen; polatuzumab vedotin in collaboration with Seattle Genetics; **External collaboration; ADC=antibody drug conjugate 55

55 Development program in CLL, MM, AML, MDS CLL, MM and AML CLL MM AML MDS Compound Combination Study name Indication Ph1 P 1 Ph2 P 2 Ph3 P 3 Gazyva +chemo CLL11 CLL Gazyva +FC/bendamustin/Clb GREEN CLL and R/R CLL Venclexta +Rituxan R/R CLL and SLL Venclexta +Gazyva CLL14 CLL Venclexta +Rituxan MURANO R/R CLL Venclexta Venclexta R/R CLL 17p R/R CLL after ibru/idel Venclexta +Rituxan+bendamustine R/R CLL and untreated CLL Venclexta +Gazyva R/R CLL and untreated CLL Venclexta R/R MM Venclexta +bortezomib+dexamethasone R/R MM Tecentriq Venclexta monotherapy or +daratumumab** or +lenalidomide or +lenalidomide+daratumumab R/R MM AML Venclexta +decitabine/+azacitidine AML Venclexta +low dose cytarabine (LDAC) 1L AML Venclexta LSD1 inhibitor +Cotellic +idasanutlin R/R AML unfit for chemo AML idasanutlin +cytarabine R/R AML Tecentriq +azacitidine MDS acd20/cd3 TCB1 Hematologic tumors ASH ASH ASH ASH ASH ASH CLL=chronic lymphoid leukemia; R/R CLL=relapsed/refractory CLL; MM=multiple myeloma; AML=acute myeloid leukemia; MDS=myelodysplastic syndrome; FC=fludarabine, cyclophosphamide; *Venclexta in collaboration with AbbVie; Gazyva in collaboration with Biogen; Cotellic in collaboration with Exelixis; **External collaboration 56

56 Polatuzumab vedotin A potent ADC in NHL Michael Wenger, M.D. Senior Group Medical Director

57 Introduction: Polatuzumab vedotin Polatuzumab vedotin in 1L DLBCL Polatuzumab vedotin in R/R FL/DLBCL Polatuzumab vedotin development program 58

58 MoA: Polatuzumab vedotin (anti-cd79b ADC) Potential to become part of a future backbone Anti-CD79b targets to B-cell malignancies MMAE Microtubule disrupter Variable chain linker cleavable by lysosomal proteases Product profile ADC designed for targeting microtubule inhibitor MMAE to cells expressing CD79b Linker is stable in the bloodstream but releases the drug payload inside the target cell MOA=mechanism of action; ADC=antibody drug conjugate; MMAE=monomethyl auristatin E 59

59 Introduction: Polatuzumab vedotin Polatuzumab vedotin in 1L DLBCL Polatuzumab vedotin in R/R FL/DLBCL Polatuzumab vedotin development program 60

60 Polatuzumab + Rituxan-CHP in 1L DLBCL Early efficacy and safety data Study design End of treatment responses by PET-CT Duration of response Phase Ib/II results Phase 2 dose of 1.8 mg/kg established Safety profile is inline with R-CHOP CR of 70% and PR of 15% achieved Efficacy promising as patients treated in the dose-expansion were strongly weighted in the high-risk category by the IPI Tilly H. et al., ASH 2016; DLBCL=diffuse large B cell lymphoma; CHP=cyclophosphamide, doxorubicin and prednisone; CR=complete responses; PR=partial responses; PD=progressive disease; IPI=International Prognostic Index 61

61 Introduction: Polatuzumab vedotin Polatuzumab vedotin in 1L DLBCL Polatuzumab vedotin in R/R FL/DLBCL Polatuzumab vedotin development program 62

62 Polatuzumab + Gazyva in R/R FL/DLBCL Promising early efficacy FL: Overall response by PET-CT ROMULUS phase II results: Acceptable safety profile Promising clinical activity in heavily pretreated R/R FL or DLBCL patients ORR observed in 69% of FL and 40% of DLBCL patients DLBCL: Overall response by PET-CT Phillips T. et al., ASH 2016; R/R=relapsed/refractory; FL=follicular lymphoma; DLBCL=diffuse large B cell lymphoma; ORR=objective response rate; CR=complete responses; PR=partial responses; SD=stable disease; PD=progressive disease; PFS=progression free survival; PET-CT=positron emission tomography computed tomography; Data cut-off: July 26,

63 Polatuzumab + BR/BG in R/R FL/DLBCL Promising efficacy with bendamustine R/R FL: Overall response by PET-CT Phase Ib/II results: R/R DLBCL: Overall response by PET-CT Acceptable safety profile Clinical activity in heavily pretreated R/R FL or DLBCL patients Enrollment for Ph2 expansion and randomization part (overall 200 patients) has been completed Herrera A. et al., ASH 2016; R/R=relapsed/refractory; FL=follicular lymphoma; DLBCL=diffuse large B cell lymphoma; BR=bendamustine+Rituxan; BG=bendamustine+Gazyva; ORR=objective response rate; CR=complete responses; PR=partial responses; SD=stable disease; PD=progressive disease; PET-CT=positron emission tomography computed tomography; Data cut-off: July 26,

64 Introduction: Polatuzumab vedotin Polatuzumab vedotin in 1L DLBCL Polatuzumab vedotin in R/R FL/DLBCL Polatuzumab vedotin development program 65

65 Development program in NHL Polatuzumab vedotin trials in FL and DLBCL NHL Compound Combination Study name Indication P Ph1 1 P Ph2 2 P Ph3 3 Gazyva +bendamustine GADOLIN FL (inhl) (Rituxan refractory) Gazyva +CHOP GOYA 1L DLBCL (anhl) Gazyva +chemo GALLIUM 1L FL ( inhl) Venclexta* +Rituxan/+Rituxan+bendamustine CONTRALTO R/R FL (inhl) Venclexta +Rituxan+CHOP CAVALLI 1L DLBCL (anhl) Venclexta +Rituxan+bendamustine R/R NHL Venclexta R/R CLL and R/R NHL Venclexta +Gazyva/Rituxan+polatuzumab R/R DLBCL (anhl) and R/R FL (inhl) polatuzumab +Rituxan/Gazyva ROMULUS R/R DLBCL (anhl) and R/R FL (inhl) polatuzumab +Gazyva/Rituxan+bendamustin R/R DLBCL (anhl) and R/R FL (inhl) polatuzumab +Gazyva+CHP/Rituxan+CHP 1L DLBCL (anhl) polatuzumab +Gazyva/Rituxan+lenalidomide R/R DLBCL (anhl) and R/R FL (inhl) Tecentriq +Gazyva or +tazemetostat1** Tecentriq +Gazyva+lenalidomide R/R FL (inhl) R/R DLBCL (anhl) and R/R FL (inhl) Tecentriq +Gazyva/Rituxan+benda or CHOP 1L FL (inhl) and 1L DLBCL (anhl) Tecentriq +Gazyva/Rituxan+polatuzumab R/R DLBCL (anhl) and R/R FL (inhl) idasanutlin +Gazyva/Rituxan R/R DLBCL (anhl) and R/R FL (inhl) undisclosed ADC R/R NHL ASH ASH ASH inhl=indolent non-hodgkin`s lymphoma; anhl=agressive NHL; DLBCL=diffuse large B cell lymphoma; FL=follicular lymphoma; CHOP=cyclophosphamide, doxorubicin, vincristine and prednisone; * Venclexta in collaboration with AbbVie; Gazyva in collaboration with Biogen; polatuzumab vedotin in collaboration with Seattle Genetics; **External collaboration; ADC=antibody drug conjugate 66

66 Doing now what patients need next 67