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

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Dr. Fermin Ruiz de Erenchun (Head Biologic Strategy Team) Dr. Bruno Eschli (IR Officer) 8th Annual Biosimilar Conference / Bernstein; December 2015

Recent developments and global trends in the

biosimilar market: What would oncology look like?

2

Biosimilar: Ten years on the making

Roche’s Strategy: Innovate, Protect, Expand

Portfolio outlook

HER2 franchise

CD20 franchise

Avastin franchise

Biosimilars: Ten years in the making

3

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015

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

US published final biosimilars guideline

– FDA pathway operating, 7 applications pending, one approval

Biosimilar entry timelines delayed (incl. Herceptin & MabThera)

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

*For definition and industry position on NCBs please refer to IFPMA Policy Statement:

http://www.ifpma.org/uploads/media/Non-comparable_Biotherapeutic_Products__English__01.pdfr

0.6 6.3

57.0

80 95

119

219

267

317

254

315

377

0

50

100

150

200

250

300

350

400

MAT Jun 2013 MAT Jun 2014 MAT Jun 2015

Sa

les in

CH

Fm

Infliximab

Somatropin

Filgrastim

Epo

Current biosimilar trends

So far, sales have not achieved initial expectations

4

MAT 870 CHFm (June 2015) (CAGR 25.5%)

*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

Generics versus biosimilars

Clear divide in uptake; complex market drivers

0%

20%

40%

60%

80%

100%

Year 0 Year 1 Year 2 Year 3 Year 4 Year 5 Year 6

5

Market share

Zyprexa (Eli Lilly)

Diovan (Novartis)

Filgrastim

EPO

Somatropin

Small molecule

Virtually disappear

Payer driven: 7 biosimilars

Efficacy visible immediately

High turnover of patients

Driven by price and patient offering

9 innovators, one biosimilar

Efficacy visible only longer term

No switching

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

1

1

2

3

3

Payer environment is one of multiple drivers for

Biosimilar uptake

6

Anti-TNF antibody market is not a good

analogue for oncology

7

Anti TNF

Other

biologics

IV Anti-TNF

SC

Anti-TNF

Biological

products used

to treat RA, IDB

& Psoriasis

Infliximab biosimilar could expand beyond it’s accessible market and obtain market

share from Enbrel® and Humira®

Remicade®

Biosimilar accessible market

Consolidation of biosimilar companies and shift to ‘Big Pharma’

8

• 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

Emerging trends

9

Biosimilar: Ten years on the making

Roche’s Strategy: Innovate, Protect, Expand

Portfolio outlook

HER2 franchise

CD20 franchise

Avastin franchise

Roche strategy is aligned with our business model

10

Protect high standards

Enforce efficacy and safety standards, defend intellectual property

Act to expand patient access in emerging markets

Change from global pricing to tiered pricing, including 2nd brand

Protect

Re-define the standard of care

Mode of administration, combination therapies and new drugs Innovate

Expand

Herceptin

More than 27,000 women in Western Europe did not develop metastatic disease

11 Weisgerber-Kriegl, U. et al. Estimation of the epidemiological effect of trastuzumab over 10 years in 5 European Countries. J. Clin. Onco., 2008.

ASCO Annual Meeting Proceedings: 26:15S

Incidence of HER2-positive MBC without Herceptin Number of women prevented from developing metastases

Num

ber

of

patients

27,737

20,000 Herceptin introduced

in adjuvant setting

Year

18,000

16,000

14,000

12,000

10,000

8000

6000

4000

2000

0

2000 2005 2010 2015

Innovate

Biosimilar pathways

in place

Biosimilar pathways

under development

2010 2015

Establishment of biosimilar guidelines has

increased driven by WHO efforts

12

Protect

Requirements and study designs are different

for the biosimilar versus innovator

13 * In some cases SoC may not exist; PD=pharmaco dynamics; OS=overall survival; PFS=progression free survival

Aspects of development Biosimilar Innovator

Patient population Sensitive and homogeneous

(patients are models)

Any

Clinical design Comparative versus innovator,

normally equivalence

Superiority vs standard of care

(SoC*)

Study endpoints Sensitive, clinically validated PD

markers

Clinical outcomes data or

accepted/established

surrogates (e.g. OS and PFS)

Safety Similar safety profile to

innovator; no new findings

Acceptable benefit/risk profile

versus SoC*

Immunogenicity Similar immunogenicity profile to

innovator

Acceptable risk/benefit profile

versus SoC*

Extrapolation Possible if justified Not allowed

Protect

How should extrapolation risk be managed?

The regulator’s perspective

Analytical

Non-clinical

Clinical

14

Protect

How should extrapolation risk be managed?

The physician’s perspective

Analytical

Non-clinical

Clinical

Analytical

Clinical

Non-clinical

I would like to

see a phase III

trial for each

indication

15

Protect

Phase III clinical trials will be required for

biosimilar antibodies

16 PD=pharmaco dynamics; Source: CHMP Assessment report for Zarzio, page 20; EMA/CHMP/651339/2008

PD markers only suitable for some products

Protect

What is the right patient population to establish

clinical similarity to Herceptin?

17

Topic mBC

Advanced metastatic population

eBC

Neoadjuvant/adjuvant population

PK Affected by patients status & tumor

burden

Homogeneous population can be

selected

PD Clinically validated PD marker not available

Clinical

efficacy/safety • 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.

Populations less likely to be confounded by

baseline characteristics and external

factors

Immunogenicity Immune system affected by performance

status and concomitant chemotherapies

received

Immune system impaired during

chemotherapy cycles, but likely to

recover to normal status thereafter

Protect

mBC=metastatic breast cancer; eBC=early breast cancer; PK=pharmaco kinetics; PD=pharmaco dynamics

mBC Phase III Start

Regulatory

Filing eBC

Phase III Start

Celltrion Q2 2010 Q1 2014

Mylan Q4 2012

Pfizer Q4 2013 Q2 2014

Samsung Q2 2014

Amgen Q4 2013

The regulatory thinking is evolving

The Herceptin case

Pfizer

Samsung

2011 2012 2013 2014 2010

mBC

eBC

Initiation of

clinical trial

Celltrion Mylan Pfizer

Celltrion

Amgen

Protect

mBC=metastatic breast cancer; eBC=early breast cancer

Innovative approaches to improve market access

19

Established markets

Environment increasingly complex

Payers more active/influential

Emerging markets

Build-up of healthcare systems,

but applying stricter cost regulations already

Expand

20

Biosimilar: Ten years on the making

Roche’s Strategy: Innovate, Protect, Expand

Portfolio outlook

HER2 franchise

CD20 franchise

Avastin franchise

Positive outlook provided at Investor Day 2015

Strong pipeline mitigates biosimilar impact

2014 2015E 2016E 2017E 2018E 2019E 2020E 2021E 2022E 2023E

Marketed

products

Sales

Pipeline

Biosimilars

MabThera, Herceptin, Avastin

NME launches

Venetoclax, Alectinib, Cotellic, Ocrelizumab, Atezolizumab,

Lebrikizumab, ACE910, Lampalizumab

21 NME=new molecular entities

Multiple major pivotal trials reading out near term

Significant filing and launch activities ahead

22

Year Molecule Indication Market

opportunity

Incremental

infrastructure

2015

Alectinib ALK+ NSCLC Low to medium

Cotellic/Zelboraf Melanoma Low

Venetoclax Hematology (CLL 17p del) Low

2016

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

2017

ACE 910 Hemophilia A Low to medium

Lampalizumab Geographic atrophy Low to medium

GALLIUM NHL (indolent) Low

Atezolizumab+chemo NSCLC (1L) Low

Post

2017

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

Multiple major pivotal trials reading out near term

Several read-outs to protect established franchises

23

Year Molecule Indication Market

opportunity

Incremental

infrastructure

2015

Alectinib ALK+ NSCLC Low to medium

Cotellic/Zelboraf Melanoma Low

Venetoclax Hematology (CLL 17p del) Low

2016

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

2017

ACE 910 Hemophilia A Low to medium

Lampalizumab Geographic atrophy Low to medium

GALLIUM NHL (indolent) Low

Atezolizumab+chemo NSCLC (1L) Low

Post

2017

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

Franchise strategies for long term growth

New indications, longer duration and SC conversion

24

Growth

opportunity Indication

Global peak

sales potential

HER2 franchise

Perjeta adjuvant (APHINITY)

Herceptin SC*

CD20 franchise

Gazyva aNHL (GOYA)

Gazyva iNHL (GALLIUM)

Venetoclax

MabThera SC*

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

25

Biosimilar: Ten years on the making

Roche’s Strategy: Innovate, Protect, Expand

Portfolio outlook

HER2 franchise

CD20 franchise

Avastin franchise

HER2 franchise

Strengthening standard of care

26

Established SoC Potentially new SoC New trials

Adjuvant BC Herceptin +

chemo

Herceptin SC+ chemo

(HannaH)

Herceptin & Perjeta + chemo (APHINITY)

1st line mBC Herceptin

+ chemo Herceptin & Perjeta + chemo (CLEOPATRA)

2nd line mBC Xeloda + lapatinib Kadcyla (EMILIA)

2017 2016 2012 2013 2014 2015 2011 2019 2018

Est. Biosimilars

launch (EU)

Neoadjuvant BC Herceptin + chemo

(NOAH)1 Herceptin & Perjeta + chemo

(Neosphere, Tryphaena)2

Kadcyla & Perjeta + chemo (KRISTINE)

atezolizumab + Herceptin + Perjeta

atezolizumab + Kadcyla

Ma

rke

t

(Pro

duct

launches)

P

ipe

lin

e

(Tri

al st

art

s)

eBC/mBC

eBC/mBC

atezolizumab (aPD-L1 MAb); mBC=metastatic breast cancer; eBC=early breast cancer; SC=subcutaneous; SoC=standard of care

HR=0.76 (95% CI: 0.67-0.86)

% E

ve

nt

-Fre

e

60

40

20

0

0 2 4 6 8 10

P<0.0001

0 1 2 3 4 5

P=0.016

100

80

28.8% 41.9%

% E

ve

nt

-Fre

e

60

40

20

0

100

80

HR=0.64 (95% CI: 0.44-0.93)

Without Herceptin With Herceptin

Years from Randomization1

HER2 positive eBC: Still high medical need

despite major advances

27

Years from Randomization2

Neoadjuvant - NOAH trial Adjuvant - HERA trial

Disease-Free Survival Event-Free Survival

1 Roche data on file; 2 L. Gianni et al, ASCO Annual Meeting 2013

eBC=early breast cancer

HER2 franchise: Significant growth opportunities

in approved indications remain

• Increased patient share

• Longer treatment duration

• Emerging markets

28

96%

84%

63% 58%

93%

<5%

51%

58%

25%

<5%. <5% <5% 0%

100%

Herceptin Perjeta 1L Perjeta 2L Kadcyla

mBC

Pa

tie

nt

sh

are

s

Sources: Market research tracking studies - Latest quarter Q315 in EU5 and US; mBC=metastatic breast cancer

US

EU5

EM

Neoadjuvant Adjuvant

Herceptin SC

Conversion rate exceeds 35% after two years

29

SC share of Herceptin sales in

launched countries

0%

5%

10%

15%

20%

25%

30%

35%

40%

Q2

13

Q3

13

Q4

13

Q1

14

Q2

14

Q3

14

Q4

14

Q1

15

Q2

15

Q3

15

Sa

les m

ark

et

sh

are

(%

)

Number of countries where

Herceptin SC has been launched

0

10

20

30

40

50

Q2

13

Q3

13

Q4

13

Q1

14

Q2

14

Q3

14

Q4

14

Q1

15

Q2

15

Q3

15

To

tal

nu

mb

er

of

co

un

trie

s

SC=subcutaneous

30

Biosimilar: Ten years on the making

Roche’s Strategy: Innovate, Protect, Expand

Portfolio outlook

HER2 franchise

CD20 franchise

Avastin franchise

CD20 franchise

Strategy for long term growth

31

MabThera

MabThera

SC

Gazyva

Gazyva Protect

Replace

Protect.. Replace.. Extend..

MabThera

Venetoclax

Polatuzumab

Atezolizumab aCD20/CD3 TCB

Gazyva

Me

dic

al

va

lue

MabThera

SC

• Await GOYA and GALLIUM

• Extend Gazyva with GREEN

• Rapidly and sustainably

convert the market to SC

• Increase medical benefit with Venetoclax in

NHL, CLL and expand into new diseases e.g.

Multiple Myeloma

• Additional NMEs in the clinic

SC=subcutaneous; CLL=chronic lymphocytic leukemia; NHL=non-hodgkin’s lymphoma; TCB=T cell bispecific;

NMEs=new molecular entities; Venetoclax in collaboration with AbbVie

Multiple approaches to protect MabThera sales

1L CLL Typical

5%

1L CLL Fit

6%

CLL 17p-del

1%

R/R CLL

5%

1L aNHL

27%

R/R aNHL

6%

iNHL

49%

GAZYVA (GOYA) in aNHL

(improve > SoC)

Gazyva (GALLIUM)

(improve > SoC)

Gazyva (GREEN)- Extend

chemo backbone

Venetoclax –

Extend efficacy

Rapidly and sustainably

convert market to SC

Broad development program for venetoclax as add on and in new tumour types

32

Rapidly and sustainably

convert market to SC

SoC=standard of care; SC=subcutaneous; CLL=chronic lymphocytic leukemia; iNHL=indolent non-hodgkin’s lymphoma; aNHL=aggressive NHL; R/R=relapsed/refractory

MabThera SC

NHL launch ongoing, strong uptake in most markets

33

• 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

34

Development plan hematology franchise I

8 NMEs in the clinic Compound Combination Study name Indication P 1 P 2 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

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

Ph1 Ph2 Ph3

NHL

AML

MM

CLL

CLL

NHL

= filed

35

Development plan hematology franchise II

8 NMEs in the clinic

Compound Combination Study name Indication P 1 P 2 P 3

polatuzumab* +Rituxan/Gazyva ROMULUS R/R FL and aNHL

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

Ph1 Ph2 Ph3

AML

NHL

MM

NHL

MDS

NHL

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

= additional trials starting in Q4 15 and Q1 16

Gazyva and venetoclax read-outs in CLL

36

Venetoclax1 R-

Venetoclax8

Gazyva-

bendamustine7

Gazyva-

chlorambucil2 R-chlorambucil2 R-FC3 Ibrutinib4 Idelalisib5 R-Benda-

Ibrutinib6

Line R/R R/R 1L 1L 1L 1L 1L R/R R/R R/R

N 78 49 158 238 233 408 31 61 54 30

ORR 77% 86% 78.5% 75.5% 65.9% 90% 71% 67% 56% 90%

CR/CRi 23% CR/CRi 41% CR/CRi 32.3% 22.2%

CR/CRi

8.3%

CR/CRi 44% 10 % 3% 4% 10%

MRD-

negative

BM: 55%

(6/11)*

BM: 75%

(15/20)

53% (ITT)

PB: 58.9%

BM: 27.8%

(ITT)

PB: 31% (41/132)

BM: 17% (15/88)

PB: 2% (3/150)

BM: 3% (2/72)

PB: 63%

(90/143) Not reported

Not

reported

Not

reported

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

References:

1. John Seymour, EHA 2014

2. Goede et al. J Clin Oncol 2013; 31:suppl; abstr 7004 (presentation update)

3. Böttcher et al. J Clin Oncol 2012 ;30:980-988

4. Byrd et al. Blood (ASH Annual Meeting Abstracts) 2012 120: Abstract 189

5. Flinn et al. Hematol Oncol 2013; 31 (Suppl. 1): Abstract 297

6. Brown et al. Haematologica 2012; 97(s1) : Abstract 0543

7. Stilgenbauer et al., ASH 2015 (GREEN subgroup analysis)

8. Ma Shuo et al., ASH 2015 (abstract 80273)

37

Biosimilar: Ten years on the making

Roche’s Strategy: Innovate, Protect, Expand

Portfolio outlook

HER2 franchise

CD20 franchise

Avastin franchise

Cancer immunotherapy (CIT): 8 NMEs in the clinic

38

T cell infiltration

T cell Trafficking

Cancer T cell recognition

anti-CEA/CD3 TCB

anti-CD20/CD3 TCB

anti-HER2/CD3 TCB

ImmTAC* (Immunocore)

anti-VEGF (Avastin)

Clinical development CIT Preclinical development CIT

* Partnered projects (external)

Established therapies outside CIT

Chen and Mellman. Immunity 2013

T cell killing

anti-PDL1 (atezolizumab)

anti-CSF-1R

IDOi (NewLink)

IDOi* (Incyte)

CPI-444* (Corvus)

anti-TIGIT

IDOi/TDOi* (Curadev)

EGFRi (Tarceva)

ALKi (Alectinib)

BRAFi (Zelboraf)

MEKi (Cotellic)

anti-CD20 (Gazyva)

anti-HER2 (Herceptin; Kadcyla; Perjeta)

various chemotherapies

lenalidomide

rociletinib* (Clovis)

Antigen presentation

anti-CD40

CMB305 vaccine* (Immune Design)

T-Vec oncolytic viruses* (Amgen)

Priming & activation

anti-CEA-IL2v FP

anti-OX40

anti-CD27* (Celldex)

entinostat* (Syndax)

anti-FAP-IL2v FP

Antigen release

• anti-Ang2/VEGF biMAb

(vanucizumab) has entered

phase II testing in mCRC

39

Setting new standards, developing combinations

venetoclax

alectinib Cotellic

aCSF-1R

aCEA-IL2v FP

aOX40

aCD40

IDO

aCEA/CD3 TCB

Launched portfolio

Immunotherapy portfolio

chemo

Targeted combinations approved

Chemotherapy combinations approved

CIT combinations in trials

CIT Chemotherapy combinations in trials

NMEs filed/recently approved

aCD20/CD3 TCB atezolizumab

40

Setting new standards, developing combinations

Building on established backbones

venetoclax

alectinib Cotellic

aCSF-1R

aCEA-IL2v FP

aOX40

aCD40

IDO

aCEA/CD3 TCB

chemo

Targeted combinations approved

Chemotherapy combinations approved

Roche combinations in trials

Chemotherapy combinations in trials

NMEs filed/recently approved

aCD20/CD3 TCB atezolizumab

CD20 franchise

HER2 franchise

Avastin franchise

Avastin+atezolizumab combos entered Ph3

41

Phase III Phase I 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

Adjuvant MIBC (Dx+)

atezo

Adjuvant NSCLC (Dx+)

atezo+Avastin

1L RCC

Status as of Nov 5, 2015

atezo

NSCLC (Dx+)

atezo

2/3L NSCLC

atezo+Avastin

1L Renal

atezo

1/2L Bladder

Phase II

IDO

Solid tumors

atezo+ipilimumab

Solid tumors

atezo+aCD40

Solid tumors

atezo+IFN-alfa

Solid tumors

atezo+aCSF-1R

Solid tumors

atezo+aCEA-IL2v FP

Solid tumors

atezo+aOX40

Solid tumors

atezo+IDO

Solid tumors

atezo+Zelboraf

Melanoma

atezo+Tarceva

NSCLC

atezo+Avastin+chemo

Solid tumors

atezo+Gazyva

R/R FL / aNHL

aCD20/CD3 TCB

heme tumors

atezo+Avastin

Solid tumors

atezo+Cotellic

Solid tumors

atezo+Zelboraf+Cotellic

Melanoma

atezo+lenalidomide

MM

atezo+chemo

Solid tumors

atezo

Solid tumors

aCSF-1R

Solid tumors

aOX40

Solid tumors

aCEA/CD3 TCB

Solid tumors

aCEA-IL2v FP

Solid tumors

atezo+alectinib

ALK+ NSCLC

atezo+/-azacitidine

MDS

atezo+Gazyva+chemo

R/R FL/aNHL

atezo+Kadcyla

HER2+ eBC/mBC

atezo+Herceptin+Perjeta

HER2+ eBC/mBC

atezo+Gazyva+lenalidomide

R/R FL/aNHL

atezolizumab trials

NME monotherapy

Immune doublets

Combinations with

Avastin, Herceptin,

Kadcyla, Gazyva

Combination pricing in oncology

(+)

– 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

“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

Future – price varies by single or combination use based on benefit

Single use or combination List price product A

(invoice price)

Price X

Price Y Product B

Product A + B

Product A

Product A + B Price Z

List price product B

(invoice price)

Price X+Y

42

Doing now what patients need next