Recent developments and global trends in the biosimilar market: What would oncology look like?

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1 Recent developments and global trends in the biosimilar market: What would oncology look like? Dr. Fermin Ruiz de Erenchun (Head Biologic Strategy Team) Dr. Bruno Eschli (IR Officer) 8 th Annual Biosimilar Conference / Bernstein; December 2015

2 Biosimilar: Ten years on the making Roche s Strategy: Innovate, Protect, Expand Portfolio outlook HER2 franchise CD20 franchise Avastin franchise 2

3 Biosimilars: Ten years in the making EU pioneered the biosimilar concept Six products approved, including the first mab biosimilar (infliximab) Uptake did not achieve saving expectations WHO leading global efforts; many emerging countries implemented WHO biosimilar guidelines as a reference Differential adoption of WHO biosimilar guidelines led to registration of Non-Comparable Biotherapeutic products (NCBs)*, driven by: Capacity issues at National Regulatory Agencies Local economic development policies US published final biosimilars guideline FDA pathway operating, 7 applications pending, one approval Biosimilar entry timelines delayed (incl. Herceptin & MabThera) *For definition and industry position on NCBs please refer to IFPMA Policy Statement: English 01.pdfr 3

4 Sales in CHFm Current biosimilar trends So far, sales have not achieved initial expectations MAT 870 CHFm (June 2015) (CAGR 25.5%) MAT Jun 2013 MAT Jun 2014 MAT Jun Infliximab Somatropin Filgrastim Epo *Excludes US as no biosimilars have been approved in the US so far (Omnitrope was approved under the 505(b) pathway) IMS Health; MAT=moving annual total 4

5 Generics versus biosimilars Clear divide in uptake; complex market drivers Market share 100% 80% 60% Somatropin EPO 2 1 Driven by price and patient offering 9 innovators, one biosimilar Efficacy visible only longer term No switching 40% 20% Filgrastim 1 Payer driven: 7 biosimilars Efficacy visible immediately High turnover of patients Diovan (Novartis) Zyprexa (Eli Lilly) 0% Year 0 Year 1 Year 2 Year 3 Year 4 Year 5 Year Small molecule Virtually disappear Sources: IMS Biosimilar Dashboard, IMS & Roche analysis 1 Volume market share based on EU5 average; 2 Volume market share based on average of France & Germany EPO; 3 Data based on % remaining sales in EU 5

6 Payer environment is one of multiple drivers for Biosimilar uptake 6

7 Anti-TNF antibody market is not a good analogue for oncology Infliximab biosimilar could expand beyond it s accessible market and obtain market share from Enbrel and Humira Remicade Biosimilar accessible market SC Anti-TNF Biological products used to treat RA, IDB & Psoriasis Other biologics Anti TNF IV Anti-TNF 7

8 Emerging trends Consolidation of biosimilar companies and shift to Big Pharma New players are Big Pharma companies with fully developed vertical capabilities Brand sales model as the most likely go-to-market scenario Integration (Pfizer & Hospira) or partnerships with generic companies or CMOs provide portfolio synergies and comprehensive commercial capabilities 8

9 Biosimilar: Ten years on the making Roche s Strategy: Innovate, Protect, Expand Portfolio outlook HER2 franchise CD20 franchise Avastin franchise 9

10 Roche strategy is aligned with our business model Innovate Re-define the standard of care Mode of administration, combination therapies and new drugs Protect Protect high standards Enforce efficacy and safety standards, defend intellectual property Expand Act to expand patient access in emerging markets Change from global pricing to tiered pricing, including 2nd brand 10

11 Number of patients Innovate Herceptin More than 27,000 women in Western Europe did not develop metastatic disease 20,000 Herceptin introduced in adjuvant setting 18,000 16,000 14,000 12,000 10, Year Number of women prevented from developing metastases Incidence of HER2-positive MBC without Herceptin 27, Weisgerber-Kriegl, U. et al. Estimation of the epidemiological effect of trastuzumab over 10 years in 5 European Countries. J. Clin. Onco., ASCO Annual Meeting Proceedings: 26:15S 11

12 Protect Establishment of biosimilar guidelines has increased driven by WHO efforts Biosimilar pathways in place Biosimilar pathways under development 12

13 Protect Requirements and study designs are different for the biosimilar versus innovator Aspects of development Biosimilar Innovator Patient population Clinical design Sensitive and homogeneous (patients are models) Comparative versus innovator, normally equivalence Any Superiority vs standard of care (SoC*) Study endpoints Safety Immunogenicity Sensitive, clinically validated PD markers Similar safety profile to innovator; no new findings Similar immunogenicity profile to innovator Clinical outcomes data or accepted/established surrogates (e.g. OS and PFS) Acceptable benefit/risk profile versus SoC* Acceptable risk/benefit profile versus SoC* Extrapolation Possible if justified Not allowed * In some cases SoC may not exist; PD=pharmaco dynamics; OS=overall survival; PFS=progression free survival 13

14 Protect How should extrapolation risk be managed? The regulator s perspective Clinical Non-clinical Analytical 14

15 Protect How should extrapolation risk be managed? The physician s perspective Clinical Clinical I would like to see a phase III trial for each indication Non-clinical Analytical 15

16 Protect Phase III clinical trials will be required for biosimilar antibodies PD markers only suitable for some products PD=pharmaco dynamics; Source: CHMP Assessment report for Zarzio, page 20; EMA/CHMP/651339/

17 Protect What is the right patient population to establish clinical similarity to Herceptin? Topic PK PD Clinical efficacy/safety Immunogenicity mbc Advanced metastatic population Affected by patients status & tumor burden Difficult to select homogeneous group. Need to control and stratify for multiple factors (e.g. prior use of chemotherapy, performance status ). Population with heterogeneous characteristics affecting final clinical outcome. Immune system affected by performance status and concomitant chemotherapies received ebc Neoadjuvant/adjuvant population Homogeneous population can be selected Clinically validated PD marker not available Populations less likely to be confounded by baseline characteristics and external factors Immune system impaired during chemotherapy cycles, but likely to recover to normal status thereafter mbc=metastatic breast cancer; ebc=early breast cancer; PK=pharmaco kinetics; PD=pharmaco dynamics 17

Protect The regulatory thinking is evolving The Herceptin case Initiation of clinical trial 2010 2011 2012 2013 2014 mbc Celltrion Mylan Pfizer Samsung ebc Amgen Celltrion Pfizer mbc Phase

18 Protect The regulatory thinking is evolving The Herceptin case Initiation of clinical trial mbc Celltrion Mylan Pfizer Samsung ebc Amgen Celltrion Pfizer mbc Phase III Start Regulatory Filing ebc Phase III Start Celltrion Q Q Mylan Q Pfizer Q Q Samsung Q Amgen Q mbc=metastatic breast cancer; ebc=early breast cancer

19 Expand Innovative approaches to improve market access Established markets Environment increasingly complex Payers more active/influential Emerging markets Build-up of healthcare systems, but applying stricter cost regulations already 19

20 Biosimilar: Ten years on the making Roche s Strategy: Innovate, Protect, Expand Portfolio outlook HER2 franchise CD20 franchise Avastin franchise 20

21 Positive outlook provided at Investor Day 2015 Strong pipeline mitigates biosimilar impact Sales NME launches Venetoclax, Alectinib, Cotellic, Ocrelizumab, Atezolizumab, Lebrikizumab, ACE910, Lampalizumab Pipeline Biosimilars MabThera, Herceptin, Avastin Marketed products E 2016E 2017E 2018E 2019E 2020E 2021E 2022E 2023E NME=new molecular entities 21

22 Multiple major pivotal trials reading out near term Significant filing and launch activities ahead Year Molecule Indication Post 2017 Market opportunity Incremental infrastructure Alectinib ALK+ NSCLC Low to medium Cotellic/Zelboraf Melanoma Low Venetoclax Hematology (CLL 17p del) Low Ocrelizumab Multiple Scelerosis Medium Atezolizumab NSCLC, bladder (2/3L) Medium Lebrikizumab Asthma, AD, IPF, COPD Large APHINITY Adj HER2+ breast cancer Low GOYA NHL (aggressive) Low ACE 910 Hemophilia A Low to medium Lampalizumab Geographic atrophy Low to medium GALLIUM NHL (indolent) Low Atezolizumab+chemo NSCLC (1L) Low Taselisib (PI3Ki) HER2-/HR+ breast cancer Low to medium Idasanutlin (MDM2) Acute myeloid leukemia Low to medium Oncology Neuroscience Ophthalmology Immunology Small: up to CHF 0.5 bn medium= CHF 0.5 to CHF 1bn large > CHF1bn NSCLC=non-small cell lung cancer; CLL=chronic lymphocytic leukemia; AD=atopic dermatitis; IPF=idiopathic pulmonary fibrosis; COPD=chronic obstructive pulmonary disease; NHL=non-Hodgkin s lymphoma; Venetoclax in collaboration with AbbVie 22

23 Multiple major pivotal trials reading out near term Several read-outs to protect established franchises Year Molecule Indication Post 2017 Market opportunity Incremental infrastructure Alectinib ALK+ NSCLC Low to medium Cotellic/Zelboraf Melanoma Low Venetoclax Hematology (CLL 17p del) Low Ocrelizumab Multiple Scelerosis Medium Atezolizumab NSCLC, bladder (2/3L) Medium Lebrikizumab Asthma, AD, IPF, COPD Large APHINITY Adj HER2+ breast cancer Low GOYA NHL (aggressive) Low ACE 910 Hemophilia A Low to medium Lampalizumab Geographic atrophy Low to medium GALLIUM NHL (indolent) Low Atezolizumab+chemo NSCLC (1L) Low Taselisib (PI3Ki) HER2-/HR+ breast cancer Low to medium Idasanutlin (MDM2) Acute myeloid leukemia Low to medium Oncology Neuroscience Ophthalmology Immunology Small: up to CHF 0.5 bn medium= CHF 0.5 to CHF 1bn large > CHF1bn NSCLC=non-small cell lung cancer; CLL=chronic lymphocytic leukemia; AD=atopic dermatitis; IPF=idiopathic pulmonary fibrosis; COPD=chronic obstructive pulmonary disease; NHL=non-Hodgkin s lymphoma; Venetoclax in collaboration with AbbVie 23

24 Franchise strategies for long term growth New indications, longer duration and SC conversion Growth opportunity HER2 franchise CD20 franchise Indication Perjeta adjuvant (APHINITY) Herceptin SC* Gazyva anhl (GOYA) Gazyva inhl (GALLIUM) Venetoclax MabThera SC* Global peak sales potential Small: up to CHF 0.5 bn medium= CHF 0.5 to CHF 1bn large > CHF1bn *Sales replacing current intravenous products; SC=subcutaneous; inhl=indolent non-hodgkin s lymphoma; anhl=aggressive NHL 24

25 Biosimilar: Ten years on the making Roche s Strategy: Innovate, Protect, Expand Portfolio outlook HER2 franchise CD20 franchise Avastin franchise 25

26 Pipeline (Trial starts) Market (Product launches) HER2 franchise Strengthening standard of care Est. Biosimilars launch (EU) 2nd line mbc Xeloda + lapatinib Kadcyla (EMILIA) 1st line mbc Herceptin + chemo Herceptin & Perjeta + chemo (CLEOPATRA) Adjuvant BC Herceptin + chemo Herceptin SC+ chemo (HannaH) Herceptin & Perjeta + chemo (APHINITY) Neoadjuvant BC Herceptin + chemo (NOAH) 1 Herceptin & Perjeta + chemo (Neosphere, Tryphaena) 2 Kadcyla & Perjeta + chemo (KRISTINE) ebc/mbc atezolizumab + Herceptin + Perjeta ebc/mbc atezolizumab + Kadcyla Established SoC Potentially new SoC New trials atezolizumab (apd-l1 MAb); mbc=metastatic breast cancer; ebc=early breast cancer; SC=subcutaneous; SoC=standard of care 26

% Event -Free % Event -Free HER2 positive ebc: Still high medical need despite major advances Adjuvant - HERA trial Neoadjuvant - NOAH trial 100 100 80 28.8% 80 41.

27 % Event -Free % Event -Free HER2 positive ebc: Still high medical need despite major advances Adjuvant - HERA trial Neoadjuvant - NOAH trial % % Disease-Free Survival 40 Event-Free Survival 20 HR=0.76 (95% CI: ) 20 HR=0.64 (95% CI: ) 0 P< P= Years from Randomization 1 Years from Randomization 2 Without Herceptin With Herceptin 1 Roche data on file; 2 L. Gianni et al, ASCO Annual Meeting 2013 ebc=early breast cancer 27

28 Patient shares HER2 franchise: Significant growth opportunities in approved indications remain 100% 96% 93% US EU5 84% EM 63% 51% 58% 58% Increased patient share Longer treatment duration Emerging markets 25% 0% <5% <5%. <5% <5% Herceptin Perjeta 1L Perjeta 2L Kadcyla Adjuvant Neoadjuvant mbc Sources: Market research tracking studies - Latest quarter Q315 in EU5 and US; mbc=metastatic breast cancer 28

29 Total number of countries Sales market share (%) Herceptin SC Conversion rate exceeds 35% after two years Number of countries where Herceptin SC has been launched SC share of Herceptin sales in launched countries 50 40% 40 35% 30% 30 25% 20 20% 15% 10 0 Q2 13 Q3 13 Q4 13 Q1 14 Q2 14 Q3 14 Q4 14 Q1 15 Q2 15 Q % 5% 0% Q2 13 Q3 13 Q4 13 Q1 14 Q2 14 Q3 14 Q4 14 Q1 15 Q2 15 Q3 15 SC=subcutaneous 29

30 Biosimilar: Ten years on the making Roche s Strategy: Innovate, Protect, Expand Portfolio outlook HER2 franchise CD20 franchise Avastin franchise 30

31 Medical value CD20 franchise Strategy for long term growth Protect.. Replace.. Extend.. Replace Venetoclax Polatuzumab Atezolizumab acd20/cd3 TCB Protect Gazyva Gazyva Gazyva MabThera MabThera MabThera MabThera SC SC Rapidly and sustainably convert the market to SC Await GOYA and GALLIUM Extend Gazyva with GREEN SC=subcutaneous; CLL=chronic lymphocytic leukemia; NHL=non-hodgkin s lymphoma; TCB=T cell bispecific; NMEs=new molecular entities; Venetoclax in collaboration with AbbVie Increase medical benefit with Venetoclax in NHL, CLL and expand into new diseases e.g. Multiple Myeloma Additional NMEs in the clinic 31

32 Multiple approaches to protect MabThera sales 1L CLL Typical 5% 1L CLL Fit 6% CLL 17p-del 1% Gazyva (GREEN)- Extend chemo backbone Venetoclax Extend efficacy Rapidly and sustainably convert market to SC Gazyva (GALLIUM) (improve > SoC) inhl 49% 1L anhl 27% R/R CLL 5% Rapidly and sustainably convert market to SC R/R anhl 6% GAZYVA (GOYA) in anhl (improve > SoC) Broad development program for venetoclax as add on and in new tumour types SoC=standard of care; SC=subcutaneous; CLL=chronic lymphocytic leukemia; inhl=indolent non-hodgkin s lymphoma; anhl=aggressive NHL; R/R=relapsed/refractory 32

MabThera SC NHL launch ongoing, strong uptake in most markets First EU launches in 2014, ongoing or imminent in further countries Encouraging initial uptake in majority of

33 MabThera SC NHL launch ongoing, strong uptake in most markets First EU launches in 2014, ongoing or imminent in further countries Encouraging initial uptake in majority of markets, comparable to Herceptin SC Slower conversion in countries with strong incentives to use IV (Germany) or limited reimbursement (UK) SC=subcutaneous; IV=intravenous 33

34 Development plan hematology franchise I 8 NMEs in the clinic NHL CLL NHL CLL MM AML Compound Combination Study name Indication P Ph1 1 Ph2 P 2 Ph3 P 3 Gazyva +bendamustine GADOLIN inhl (Rituxan refractory) Gazyva +CHOP GOYA anhl Gazyva +chemo GALLIUM 1L inhl Gazyva +FC/bendamustin/Clb GREEN CLL and R/R CLL venetoclax* +Rituxan/+Rituxan+bendamustine CONTRALTO R/R FL (inhl) venetoclax +Rituxan+CHOP/Gazyva+CHOP CAVALLI 1L anhl venetoclax +Rituxan+bendamustine R/R NHL venetoclax R/R CLL and R/R NHL venetoclax +Rituxan R/R CLL and SLL venetoclax +Gazyva CLL14 CLL venetoclax +Rituxan MURANO R/R CLL venetoclax R/R CLL 17p venetoclax R/R CLL after ibru/idel venetoclax +Rituxan+bendamustine R/R CLL and CLL venetoclax +Gazyva R/R CLL and CLL venetoclax R/R MM venetoclax +bortezomib+dexamethasone R/R MM venetoclax AML venetoclax +decitabine/+azacitidine/+ldarac AML = filed venetoclax (Bcl2 inhibitor); NME=new molecular entity; inhl=indolent non-hodgkin`s lymphoma; anhl=agressive NHL; CLL=chronic lymphoid leukemia; R/R CLL=relapsed/refractory CLL; MM=multiple myeloma; AML=acute myeloid leukemia; CHOP=cyclophosphamide, doxorubicin, vincristine and prednisone; FC=fludarabine, cyclophosphamide; LdAraC=low dose cytarabine; * venetoclax in collaboration with AbbVie 34

35 Development plan hematology franchise II 8 NMEs in the clinic Compound Combination Study name Indication P Ph1 1 Ph2 P 2 Ph3 P 3 polatuzumab* +Rituxan/Gazyva ROMULUS R/R FL and anhl NHL NHL NHL MM MDS AML polatuzumab +Gazyva+benda/Rituxan+benda R/R FL (inhl) and anhl polatuzumab +Gazyva+CHP/Rituxan+CHP 1L anhl polatuzumab +Gazyva+lenalidomide R/R FL and anhl Q4 polatuzumab +Gazyva+venetoclax R/R FL and anhl Q4 undisclosed ADC R/R NHL atezolizumab +Gazyva R/R FL (inhl) and anhl atezolizumab +Gazyva+lenalidomide R/R FL and anhl Q4 atezolizumab +CHOP anhl Q4 atozolizumab +bendamustine R/R FL and anhl Q4 atezolizumab +Gazyva+polatuzumab R/R FL and anhl Q1 atezolizumab +lenalidomide MM atezoliozumab +azacitidine MDS acd20/cd3 TCB Heme tumors LSD1 inhibitor** AML idasanutlin Heme tumors = additional trials starting in Q4 15 and Q1 16 polatuzumab vedotin (acd79b ADC); atezolizumab (apd-l1 MAb); acd20/cd3 TCB (RG7828); LSD1 inhibitor (RG6016); idasanutlin (MDM2 antagonist); inhl=indolent non-hodgkin`s lymphoma; R/R FL=relapsed/refractory follicular lymphoma; anhl=agressive NHL (DLBCL); MM=multiple myeloma; MDS=myelodysplastic syndrom; AML=acute myeloid leukemia; *in collaboration with Seattle Genetics; ** in collaboration with Oryzon Genomics 35

Gazyva and venetoclax read-outs in CLL Venetoclax 1 R- Venetoclax 8 Gazyvabendamustine 7 Gazyvachlorambucil 2 R-chlorambucil 2 R-FC 3 Ibrutinib 4 Idelalisib 5 Line R/R R/R 1L 1L 1L 1L 1L R/R R/R R/R

36 Gazyva and venetoclax read-outs in CLL Venetoclax 1 R- Venetoclax 8 Gazyvabendamustine 7 Gazyvachlorambucil 2 R-chlorambucil 2 R-FC 3 Ibrutinib 4 Idelalisib 5 Line R/R R/R 1L 1L 1L 1L 1L R/R R/R R/R N ORR 77% 86% 78.5% 75.5% 65.9% 90% 71% 67% 56% 90% CR/CRi 23% CR/CRi 41% CR/CRi 32.3% MRDnegative BM: 75% BM: 55% (15/20) (6/11)* 53% (ITT) PB: 58.9% BM: 27.8% (ITT) 22.2% CR/CRi PB: 31% (41/132) BM: 17% (15/88) 8.3% CR/CRi PB: 2% (3/150) BM: 3% (2/72) R-Benda- Ibrutinib 6 44% 10 % 3% 4% 10% PB: 63% (90/143) Not reported Not reported Not reported References: 1. John Seymour, EHA Goede et al. J Clin Oncol 2013; 31:suppl; abstr 7004 (presentation update) 3. Böttcher et al. J Clin Oncol 2012 ;30: Byrd et al. Blood (ASH Annual Meeting Abstracts) : Abstract Flinn et al. Hematol Oncol 2013; 31 (Suppl. 1): Abstract Brown et al. Haematologica 2012; 97(s1) : Abstract Stilgenbauer et al., ASH 2015 (GREEN subgroup analysis) 8. Ma Shuo et al., ASH 2015 (abstract 80273) CLL=chronic lymphoid leukemia; R=Rituxan; FC=fludarabine; R/R=relapsed/refractory; 1L=first-line; ORR=overall response rate; CR=complete response; CRi=complete response with incomplete bone marrow recovery; MRD=minimal residual disease; BM=bone marrow; PB=peripheral blood * MRD tests performed in local unvalidated laboratories in a small number of patients; in patients with a CR who have been tested 36

37 Biosimilar: Ten years on the making Roche s Strategy: Innovate, Protect, Expand Portfolio outlook HER2 franchise CD20 franchise Avastin franchise 37

Cancer immunotherapy (CIT): 8 NMEs in the clinic T cell Trafficking Priming & activation anti-cea-il2v FP anti-ox40 anti-cd27* (Celldex) entinostat* (Syndax) anti-fap-il2v FP T cell infiltration

38 Cancer immunotherapy (CIT): 8 NMEs in the clinic T cell Trafficking Priming & activation anti-cea-il2v FP anti-ox40 anti-cd27* (Celldex) entinostat* (Syndax) anti-fap-il2v FP T cell infiltration anti-vegf (Avastin) anti-ang2/vegf bimab (vanucizumab) has entered phase II testing in mcrc Antigen presentation anti-cd40 CMB305 vaccine* (Immune Design) T-Vec oncolytic viruses* (Amgen) Clinical development CIT Preclinical development CIT Established therapies outside CIT * Partnered projects (external) Chen and Mellman. Immunity 2013 Antigen release EGFRi (Tarceva) ALKi (Alectinib) BRAFi (Zelboraf) MEKi (Cotellic) anti-cd20 (Gazyva) anti-her2 (Herceptin; Kadcyla; Perjeta) various chemotherapies lenalidomide rociletinib* (Clovis) T cell killing anti-pdl1 (atezolizumab) anti-csf-1r IDOi (NewLink) IDOi* (Incyte) CPI-444* (Corvus) anti-tigit IDOi/TDOi* (Curadev) Cancer T cell recognition anti-cea/cd3 TCB anti-cd20/cd3 TCB anti-her2/cd3 TCB ImmTAC* (Immunocore) 38

39 Setting new standards, developing combinations Launched portfolio chemo acsf-1r acea-il2v FP aox40 atezolizumab acea/cd3 TCB Immunotherapy portfolio acd20/cd3 TCB IDO acd40 alectinib Cotellic venetoclax Targeted combinations approved Chemotherapy combinations approved CIT combinations in trials CIT Chemotherapy combinations in trials NMEs filed/recently approved 39

40 Setting new standards, developing combinations Building on established backbones acea-il2v FP chemo acsf-1r aox40 acea/cd3 TCB HER2 franchise atezolizumab acd20/cd3 TCB IDO acd40 Avastin franchise CD20 franchise alectinib Cotellic venetoclax Targeted combinations approved Chemotherapy combinations approved Roche combinations in trials Chemotherapy combinations in trials NMEs filed/recently approved 40

41 Avastin+atezolizumab combos entered Ph3 atezo Solid tumors atezo+chemo Solid tumors atezo+tarceva NSCLC atezo+zelboraf Melanoma atezo+cotellic Solid tumors atezo+avastin Solid tumors atezo+gazyva R/R FL / anhl atezo+avastin+chemo Solid tumors atezo+lenalidomide MM atezo+zelboraf+cotellic Melanoma atezo+alectinib ALK+ NSCLC atezo+/-azacitidine MDS atezo+gazyva+chemo R/R FL/aNHL atezo+gazyva+lenalidomide R/R FL/aNHL atezo+herceptin+perjeta HER2+ ebc/mbc Status as of Nov 5, 2015 Phase I atezo+kadcyla HER2+ ebc/mbc acea-il2v FP Solid tumors aox40 Solid tumors acea/cd3 TCB Solid tumors IDO Solid tumors acsf-1r Solid tumors acd20/cd3 TCB heme tumors atezo+ipilimumab Solid tumors atezo+ifn-alfa Solid tumors atezo+acd40 Solid tumors atezo+aox40 Solid tumors atezo+acsf-1r Solid tumors atezo+acea-il2v FP Solid tumors atezo+ido Solid tumors Phase II atezo NSCLC (Dx+) atezo 2/3L NSCLC atezo+avastin 1L Renal atezo 1/2L Bladder Phase III atezo 2/3L NSCLC atezo 2/3L Bladder atezo+avastin+chemo 1L non sq NSCLC atezo+chemo 1L non sq NSCLC atezo+chemo 1L sq NSCLC atezo 1L non sq NSCLC (Dx+) atezo 1L sq NSCLC (Dx+) atezo+chemo 1L TNBC atezo+avastin 1L RCC atezo Adjuvant MIBC (Dx+) atezo Adjuvant NSCLC (Dx+) atezolizumab trials NME monotherapy Immune doublets Combinations with Avastin, Herceptin, Kadcyla, Gazyva 41

42 Combination pricing in oncology Ensures benefits of combination therapies are reflected while considering the limits of healthcare budgets Now unit of drug has same price, whether used as single agent or in combination Single use or combination Future price varies by single or combination use based on benefit Product A Product B Product A + B Product A + B List price product A (invoice price) List price product B (invoice price) Price X Price Y Price Z Price X+Y (+) Addresses the reality of combination treatments, particularly oncology Takes healthcare budget into consideration (-) Not all drug combos are from the same company High complexity with many possible combinations 42

43 Doing now what patients need next

Improving the standard of care

Improving the standard of care Alan Hippe CFO Roche London, November 2015 This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such