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Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

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Page 1: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung
Page 2: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

18th ECCO / 40th ESMO

Roche Analyst EventMonday, September 28, 2015

Page 3: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Agenda

Welcome and introductionKarl Mahler, Head of Investor Relations, Roche

The immunobiology of combinations and predictive biomarkersIra Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech

ECC 2015 Roche cancer immunotherapy highlights:- Atezolizumab phase II bladder and lung cancer dataDaniel S. Chen, M.D., Ph.D., Cancer Immunotherapy Franchise Head Product Development, Genentech/Roche- Atezolizumab regulatory update and further development programCathi Ahearn, Lifecycle Leader atezolizumab lung and GU Cancers, Genentech/Roche

Q&A

3

Page 4: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Strong newsflow yet to come in 2015

4

Vienna, 25 -29 Sep

• atezolizumab- NSCLC: POPLAR , BIRCH,

P1b chemo combo update- Bladder: P2 (2L cohort)

• alectinib- NSCLC: P2 update

• CEA IL2v, IDO inh.: P1 update solid tumors

San Antonio, 8-12 Dec

• atezolizumab- TNBC: P1b abraxane combo

San Antonio, 19-22 Nov

• atezolizumab- GBM: P1

Barcelona, 7-10 Oct

• ocrelizumab- RMS: P3 OPERA I/II - PPMS: P3 ORATORIO

Orlando, 5-8 Dec

• venetoclax- CLL: P2 R/R p17del

• Gazyva- NHL: P3 GADOLIN update- CLL: P3 GREEN update

• atezolizumab + Gazyva- r/r NHL

San Francisco, 18-21 Nov

• atezolizumab- mM: P1 vemurafenib combo

• cobimetinib + ZelborafBRAF+mM: coBRIM OS data

Presentations planned

Page 5: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

The immunobiology of combinations and predictive biomarkers

Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech

Page 6: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Blocking PD-1/PD-L1 pathway

6

• PD-1/PD-L1 interaction inhibits T cell activation, attenuates effector function, maintains immune homeostasis

• Many tumors up-regulate PD-L1 and evade T cell killing

• Baseline expression of PD-L1 in tumors can be a readout of T cell activity

IFNg-mediatedup-regulation

of tumor PD-L1Shp-2

Stat

“Adaptive expression” of PD-L1

MAPKPI3K

pathways

or tumor-infiltrating immune cells

IFNγ-mediatedup-regulation of

tumor PD-L1

IFNγR

T cell receptor

MHC I

PD-1

PD-L1

IFNγ

Page 7: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

PD-L1 IHC: staining for TCs and ICsAssay sensitivity critical in detecting both cell types

7

Tumor cells (TCs)

Immune cells (ICs)

Tumor and immune cells (TCs and ICs)

WCLC 20151IMvigor 210 ECC 2015, 2POPLAR ECC 2015

Predictive of benefit in lung cancer (ORR/PFS/OS)2

Predictive of benefit in bladder cancer (ORR/OS)1

Page 8: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

PD-L1 expression patterns with SP142 are largely consistent in time and space

8

Archival tissue vs. fresh biopsy

PD-L1 cut-off Number of paired metachronous biopsies with the same PD-L1 score, n/N(%)

TC3 or IC3 9/11 (82%)

TC2/3 or IC2/3 11/11 (100%)

TC1/2/3 or IC1/2/3 9/11 (82%)

Primary tumor vs. metastasis

PD-L1 cut-off Number of paired synchronous biopsies with the same PD-L1 score, n/N(%)

TC3 or IC3 13/14 (93%)

TC2/3 or IC2/3 14/14 (100%)

TC1/2/3 or IC1/2/3 11/14 (79%)

Sample origin does not contribute to variability of SP142 assay

CRI EATI CIMT AACR 2015

Page 9: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Immune cell staining is more prevalent across indications

9

RCC UBC NSCLC TNBC

Study (N) WO29074 (253)Phase II

GO 29023 (592)Phase II

POPLAR (287)Phase II

PCD4989g (413)Phase I

IC>=1% 59% 68% 57% 58%

IC>=5% 21% 33% 19% 22%

IC>=10% 8% 6% 6% 8%

TC>=1% 15% 22% 38% 14%

TC>=5% 6% 15% 25% 4%

TC>=50% <1% 4% 11% 1%

IC>1%TC>1%

22%

57%

38% 14%

2% 1% 11% 3.5%

58%68%59%

15%

CRI, 2015

Page 10: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Adaptive expression of PD-L1 by tumor cells is inconsistent with PD-L1+ IC’s being predictors of response

10

Tumor

IFNγ+ T cell effectors

* Taube et al (2012) Science Transl. Med.

T effector cells home to tumor bed

T effector cellsFibroblastTumor cellMyeloid/dendritic cell

Page 11: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Adaptive expression of PD-L1 by tumor cells is inconsistent with PD-L1+ IC’s being predictors of response

11

Tumor

* Taube et al (2012) Science Transl. Med.

T effector cells enter the tumor parenchyma

T effector cellsFibroblastTumor cellMyeloid/dendritic cell

Page 12: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Tumor

* Taube et al (2012) Science Transl. Med.

Release of INFγ induces PD-L1 expression by surrounding tumor and immune cells

T effector cellsFibroblastTumor cellMyeloid/dendritic cellPD-L1-positive cell

Adaptive expression of PD-L1 by tumor cells is inconsistent with PD-L1+ IC’s being predictors of response

12

Page 13: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Tumor

* Taube et al (2012) Science Transl. Med.

But in the majority of tumors, PD-L1 is only expressed by

infiltrating immune cells

T effector cellsFibroblastTumor cellMyeloid/dendritic cellPD-L1-positive cell

Adaptive expression of PD-L1 by tumor cells is inconsistent with PD-L1+ IC’s being predictors of response

13

Page 14: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Adaptive expression of PD-L1 by tumor cells is inconsistent with PD-L1+ IC’s being predictors of response

14

Tumor

* Taube et al (2012) Science Transl. Med.

• Why can PD-L1 expression by immune infiltrating cells more predictive than PD-L1+ tumor cells?

• Do PD-L1+ myeloid cells, not tumor cells, regulate T cell function at baseline?

• What is the actual mechanism of PD-1-mediated suppression?

Page 15: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

P

P

P

P

P

P

P

P

? ?

ZAP70

PI3K

Shp2

Dendritic cell/macrophage

T cell

TCR

MHCp

CD28

B7.1/B7.2

PD-1

PD-L1

AACR 2015, manuscript in preparation

PD-L1/PD-1 interaction may negatively regulate signaling by T cell receptors or co-stimulatory molecules (e.g. CD28)

15

Page 16: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

New in-house data: PD-L1/PD-1 interaction regulates co-stimulatory molecule (CD28) signaling preferentially

16

P

P

P

P

P

P

P

P

ZAP70

PI3K

Shp2

Dendritic cell/macrophage

T cell

TCR

MHCp

CD28

B7.1/B7.2

PD-1

PD-L1

AACR 2015, manuscript in preparation

Page 17: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

B7.1

CD28

PD-L

1 PD

-1

TCR

pMH

C

PD-L

1 B7

.1

T cell

Myeloid cell

Significance of IC staining: Infiltrating cells positively and negatively regulate T cell function

Tumor

17

Page 18: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

ScleroticDesmoplasticRegulated by methylationIntrinsic PD-L1 regulation

PD-L1 TC3 tumors exhibit a desmoplastic and sclerotic TME with low intra-epithelial and stromal IC

Adaptive PD-L1 regulationIntra-epithelial/stromal IC

Presence of Teff cellsCD8 IHC

PD-L1 IC3 tumors represent immune-rich/CD8 high tumors

PD-L1 TC3 vs IC3 NSCLC tumors have distinct

tumor TME

TC3 IC3

ASCO 2015

PD-L1 expression by TCs in NSCLC is controlled by epigenetic regulation, and may not reflect immune regulation

18

Page 19: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

1

2

3

4

5

6

7

Priming & activationanti-CEA-IL2vanti-FAP-IL2vanti-OX40anti-CTLA4anti-CD27anti-41BBanti-cytokine

Antigen presentationanti-CD40INFαoncolytic virusesneo-epitope vaccines

Antigen releasePro-inflammatory

EGFRiALKiBRAFiMEKiChemoBTKiHDAC

T cell infiltrationanti-VEGFanti-Ang2/VEGF

Cancer cell killinganti-PDL1anti-PD-1 anti-CSF-1RIDOi anti-TIGITanti-TIManti-LAG3A2AiIDO/TDOiTDO

T cell trafficking

Immuno-suppression

Cancer cell recognition

TCBcImmTACsCARTBiTes

• Immunotherapeutics

• Targeted therapies

• SoC chemotherapies

Cancer Immunotherapy targets and combinations may include the following:

Strategic vision: Lead by developing best-in-class combination therapies

19

Page 20: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Several chemotherapeutics combine well with atezo pre-clinically

20

Platinum doublet 1 Platinum doublet 2

aPD-L1

combo

Chemo

10 16 29 36

500

1000

1500

2000

2500

Tum

orvo

lum

e, m

m3

Day

00 10 16 30 40 50

500

1000

1500

2000

2500

3000Tu

mor

volu

me,

mm

3

Day

00

aPD-L1

combo

Chemo

aPD-L1

combo

Platinum chemo 1

Chemo

0

500

1000

1500

2000

2500

3000

0 6 12 16 22 29 36

Tum

or V

olum

e, m

m3

Day

6 12 16 22 29 36

500

1000

1500

2000

2500

3000

Tum

orvo

lum

e, m

m3

Day

00

aPD-L1

Platinum chemo 2

Chemo

0

500

1000

1500

2000

2500

3000

0 6 12 16 22 29 36

Tum

or V

olum

e, m

m3

Day

6 12 16 22 29 36

500

1000

1500

2000

2500

3000

Tum

orvo

lum

e, m

m3

Day

00

combo

aPD-L1

Platinum chemo 3

Chemo

0

500

1000

1500

2000

2500

3000

0 6 12 16 22 29 36

Tum

or V

olum

e, m

m3

Day

6 12 16 22 29 36

500

1000

1500

2000

2500

3000

Tum

orvo

lum

e, m

m3

Day

00

combo

Unpublished data

Page 21: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

80

40

20

0

60

Tumor CD4+FoxP3+ (T regulatory cells)

40

20

0

60

80Tumor CD11b+Ly6C+ (MDSCs)

Ctrl

Pla

t 1

Pla

t2

Pla

t 3

Taxa

ne1

Taxa

ne2

Ctrl

Pla

t 1

Pla

t2

Pla

t 3

Taxa

ne1

Taxa

ne2

60

40

20

0

Tumor CD8+ (T cells)

% C

D45

+ c

ells

%Fo

xP3+

of C

D4+

cells

%Ly

s6c+

of C

D11

b+ c

ells

Unpublished dataMDSC=myeloid derived suppressor cells

Ctrl

Pla

t 1

Pla

t2

Pla

t 3

Taxa

ne1

Taxa

ne2

Chemotherapy as immunotherapyCreation of favorable immune profiles – mouse data

21

Page 22: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Chemotherapy as immunotherapyCreation of favorable immune profiles – patient data

22

Pre-treatment Post FOLFOX

CD8 CD8

Pre-treatment Post FOLFOX+bev+Atezo

CD8 CD8

PD-L1 PD-L1

IC0 IC2

CRI EATI CIMT AACR 2015

Page 23: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Treatment (e.g. chemotherapy)

Response Progression

infla

mm

atio

n

Optimal window for initiating immunotherapy combination

Diagnosis

Return to the “equilibrium” inflammatory state

Hypothetical curve

CD8 CD8 CD8

CD8 staining images are illustrative

Modulation of tumor immune status by chemotherapy may be transient

23

Page 24: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Treatment (e.g. chemotherapy)

Response

infla

mm

atio

n

Optimal window for initiating immunotherapy combination

Diagnosis

Hypothetical curve

CD8 CD8

Immunotherapy

CD8

Maintenance of inflamed state

CD8 staining images are illustrative

Combinations may help in maintaining tumor inflamed state

24

Page 25: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

• PD-L1 expression in tumor microenvironment supresses anti-cancer T cell responses

• Pre-clinical data points to an important role of ICs in regulating T cell function

• PD-L1 expression patterns reflect the biology of individual tumor types

• PD-L1 phenotypes appear remarkably stable in throughout lines of therapy and in primaries vs. mets: but assays must be optimized

• Pre-clinical data suggests chemotherapy alters tumor immune status to transiently increase inflammation

• Combinations of chemotherapy and atezolizumab may extend the inflammatory state for durable responses

25

Summary

Page 26: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

ECC 2015 Roche cancer immunotherapy highlights:Atezolizumab phase II bladder and lung cancer data

Daniel S. Chen, M.D., Ph.D., Cancer Immunotherapy Franchise Head Product Development, Genentech/Roche

Page 27: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

27

High unmet need in urothelial bladder cancerNo new therapy with survival benefit in 30 years

Advanced UC:– Median survival is short– Durable responses not routinely observed– High grade 3-4 toxicities with chemotherapy

Vinflunine1: Only approved agent (EU) in 2L– No survival benefit vs BSC in ITT– ORR of 8.6% (vs 0% for BSC)1, median DoR: 7.4 mo– Vinflunine was tested in a “pure” 2L population

BSC, best supportive care; HR, hazard ratio.References: 1Bellmunt et al. J Clin Oncol. 2009; ©2009 by American Society of Clinical Oncology .

Vinflunine OS (ITT Population)1

Time (months)

Ove

rall

Surv

ival

(pro

babi

lity)

mOSVinflunine + BSC: 6.9 mo

BSC: 4.6 mo

Current therapy: Only few patients treated due to high toxicity and multiple comorbidities

Page 28: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

IMvigor 210: 2L bladder phase II study (cohort 2)

28

• PD-L1 expression and prevalence on immune cells

IC1n = 108

35%

IC0n = 103

33%

IC2/3n = 100

32%

• Imvigor 201 enrolled an all-comer population

• Ventana SP142 assay prospectively measured tumor-infiltrating immune cell (IC) PD-L1 expression

• Tumor cell (TC) scoring conducted as an exploratory endpoint

• Study design

Locally advanced or metastatic UBCTransitional cell histologyProgression during/following Pt-chemoECOG PS 0-1Tumor tissue evaluable for PD-L1 testinga

No autoimmune disease or corticosteroid use

Atezolizumab1200 mg IV q3w until loss of clinical benefit

Response assessment q9 weeks

(q12 weeks after 54 weeks)

• Co-primary Endpoints: ORR per RECIST v.1.1 (centralindependent review); investigator-assessed ORRper modified RECIST

• Key Secondary Endpoints: PFS, DOR, OS, Safety

IHC status of treated patients in IMvigor 210 Study (n = 311)

Page 29: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

29

IMvigor 210 efficacy: Objective response rate

• IMvigor 210 met its co-primary endpoints in all subgroups tested

• ORR by independent review assessed (RECIST v1.1) and investigator (mRECIST) were concordant

RECIST v1.1 Criteria by Independent Reviewa

PD-L1 subgroup n CR (%) ORR (%) 95% CI P valueb

IC2/3 100 8% 27% 19, 37 < .0001

IC1/2/3 208 5% 18% 13, 24 .0004

All 311 4% 15% 11, 20 .0058

IC1 108 3% 10% 5, 18 N/Ac

IC0 103 1% 9% 4, 16 N/Ac

aObjective response evaluable population: all treated patients had measurable disease at baseline per Inv-RECIST v1.1.bP-value for Ho: ORR = 10% versus Ha: ORR ≠ 10%, where 10% ORR is historical control, α = 0.05. cNo formal hypothesis testing conducted.Data cutoff May 5, 2015. Follow up ≥ 24 weeks.

Additional unconfirmed responses - likely to mature in subsequent analyses

Page 30: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

IMvigor 210: Changes in target lesionsConsistent with phase I data

30

100

0

-100

*

51/85 (60%) target lesion shrinkage

Mea

n SL

D R

educ

tion

from

Bas

elin

e, %

-100

-80

-60

-40

-20

0

20

40

60

80

100 a

* *

Phase II IMvigor 210 PD-L1 IC2/3

Phase I (PCD) UBC cohort PD-L1 IC2/3*

*Redrawn from Petrylak et al., ASCO 2015

29/42 (69%) target lesion shrinkage

Initial response profile of IMvigor comparable with Phase I data in PDL1-high subgroup

– PD – SD – PR – CR – Unknown

Page 31: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Atezolizumab in bladder cancer: Durable response

100

0

-100

Cha

nge

in S

LD fr

om B

asel

ine,

%

0 9 18 27 36 45

Time on Study (weeks)

100

0

-100

New Lesion

IC0

PD-L1 status

IC2/3

IC1

100

0

-100

Phase 2 IMvigor 210 cohort 2

• Responses were durable with median DOR not reached in any subgroup

• Median follow-up time: 7 mo (range, 0-11 mo)

• Responses ongoing in 43/47 patients (92%)

31

Page 32: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

IMvigor 210 efficacy: PFS and OSMedian OS not reached for PD-L1 IC2/3 subgroup

32NR, not reached; NE, not estimable. Data cutoff May 5, 2015. Follow up ≥ 24 weeks.

– IC2/3– IC0/1+ Censored

100

80

60

40

20

0

5 6 7 8 9 10 111 2 3 4

Prog

ress

ion-

Free

Sur

viva

l

0Time, months

Survival IC2/3, n = 100 IC0/1, n = 211 All, n = 311

6 mo-OS, % (95% CI) 70% (60, 79) 56% (49, 63) 60% (55, 66)

Median OS, mo (95% CI) NR (7.6, NE) 6.7 (5.7, 8.0) 7.9 (6.7, NE)

Median PFS,a mo (95% CI) 2.1 (2.1, 4.1) 2.1 (2.0, 2.1) 2.1 (2.1, 2.1)

Time, months

Median follow up: 7 mo(range, 0-11 mo), 142 events

12

– IC2/3– IC0/1+ Censored

100

80

60

40

20

0

5 6 7 8 9 10 111 2 3 4

Ove

rall

Surv

ival

0 12

Page 33: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

IMvigor 210 efficacy by prior chemotherapySubgroup analyses

33

• Median DOR was not yet reached in any of the subgroup populations

ORR, % (95% CI)a

Subgroup IC2/3 AllPrior systemic regimens, metastatic settingb

1 26% (12, 43) 12% (7, 19)

2 39% (17, 64) 18% (9, 30)

≥ 3 20% (6, 44) 13% (6, 24)

Metastatic sites at baseline

Lymph node only 38% (19, 59) 33% (20, 49)

Visceral 17% (9, 28) 10% (6, 14)

Liver 15% (4, 34) 6% (2, 13)

ECOG PS 1 19% (10, 31) 10% (6, 15)

Hemoglobin < 10 g/dL 21% (7, 42) 9% (3,18)

aPer RECIST v1.1 (independent review). bIn patients with 0 prior regimens, ORR was 26% (11, 46) in IC2/3 patients (n = 27) and 20% (11, 31) in all-comer patients (n = 70). Data cutoff May 5, 2015. Follow up ≥ 24 weeks.

Page 34: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

IMvigor 210: 2L bladder phase II study (cohort 2)Atezolizumab - potential to change the SOC

34

• Atezolizumab efficacy– Co-primary endpoints of ORR in all subgroups met– Significant improvement over a historical 10% ORR (vinflunine 8.6% ORR, median DoR: 7.4 mo1)– Durable responses in heavily pretreated population; consistent with data from Phase I– Median duration of response not reached; consistent with Phase I data– Overall survival immature

• Atezolizumab safety– Atezolizumab well tolerated with low discontinuation rates– Superior safety over chemotherapy– No treatment related renal toxicity or treatment related deaths

1Bellmunt et al. J Clin Oncol. 2009

Page 35: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Atezolizumab in advanced or metastatic NSCLC

35

Prevalence of screened patients with TC2/3and/or IC2/3 tumors was 34%.

• Primary endpoint:ORR (IRF-assessed by RECIST v1.1)

• Secondary endpoints:PFS, DoR, ORR (investigator-assessed by RECIST v1.1 and modified RECIST), OS, safety

• Primary endpoint:OS in ITT and PD-L1 expression subgroups

• Secondary endpoints:PFS, ORR and DOR in ITT and PD-L1 expression, safety

Disease progression on a prior platinum therapy

N = 287

Stratification Factors:PD-L1 IC expression(0 vs 1 vs 2 vs 3)a , squamous vs non-squamous, prior chemo regimens: 1 vs 2

Docetaxeluntil disease progression

Atezolizumabuntil loss of

clinical benefitR

1:1

BIRCH: Phase II PD-L1 selected*

POPLAR: randomized phase II in all-comer population

*Tumor PD-L1 expression by IHC (TC2/3 and/or IC2/3); aarchival or fresh tissue required for pre-dose testing

Atezolizumab dosed at 1200 mg IV q3w in all cohorts.

Atezolizumab dosed at 1200 mg IV q3w in all cohorts, docetaxel at 75 mg/m2 IV q3w .

Primary analysis conducted with 173 events,minimum follow-up 13 months

Cohort 1; n = 142No prior chemo

Cohort 2; n= 2712L; 1 prior

platinum chemoCohort 3; n=254

3L+; >1 prior platinum chemo

PD

Until loss of clinical benefit

Phase II atezolizumab in PDL1- selected*a

adv. NSCLCECOG PS 0 or 1N = 667

Page 36: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

BIRCH: Objective response rate to atezolizumabPrimary endpoint met in all predefined subgroups

36

BIRCH:

• ORR data compared to historic controls for primary efficacyanalyses (per data in 2013) using a hierarchical procedure

Study POPLAR

2/3L

TC3 orIC3

TC2/3 or IC2/3 ITT

n 47 105 287

ORRa,b 38% 22% 15%

Study BIRCH

1LCohort 1

2LCohort 2

3L+Cohort 3

TC3 or IC3

TC2/3 or IC2/3

TC3 or IC3

TC2/3 or IC2/3

TC3 or IC3

TC2/3 or IC2/3

n 65 139 122 267 115 253

ORRa,b 26% 19% 24% 17% 27% 17%

POPLAR:

• ORR data similar to BIRCH

Highest ORR in TC3 or IC3 patients

Page 37: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

BIRCH efficacy by overall survival6 month landmark data comparable to POPLAR

37aIRF Data cut-off May 28, 2015.

Overall survival TC2/3 or IC2/3 Overall survival TC3 or IC3

Subgroup 6-mo OS

Cohort 1 (1L) 79%

Cohort 2 (2L) 80%

Cohort 3 (3L+) 75%

Median NE(10.6, NE)

Median NE(10.4, NE)

Median NE(NE, NE)

Minimum follow up = 6 mo

Median NE(11.2, NE)

Median 14.0 mo(14.0, NE)

Median NE(8.4, NE)

Subgroup 6-mo OS

Cohort 1 (1L) 82%

Cohort 2 (2L) 76%

Cohort 3 (3L+) 71%

Median follow up: 8.8 mo (1L), 7.9 mo (2L) and 8.6 mo (3L+) Median follow up: 8.8 mo (1L), 7.9 mo (2L) and 8.6 mo (3L+)

Page 38: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

POPLAR efficacy: OS in ITT population (n=287)Statistical significance reached vs docetaxel

38aStratified HR.Data cut-off May 8, 2015.

Median 12.6 mo(9.7, 16.4)

Median 9.7 mo(8.6, 12.0)

Minimum follow up = 13 months HRa = 0.73 (0.53, 0.99)

P value = 0.040

AtezolizumabDocetaxelCensored+

Event/patient ratio: 60% (54% for atezolizumab, 66% for docetaxel)

Page 39: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

POPLAR: Overall survival by PD-L1 subgroupsEfficacy increasing with higher PD-L1 expression

39

0.1 1

In favor of docetaxel

0.73

0.59

0.54

0.49

Hazard Ratioa

In favor of atezolizumab

TC3 or IC3 (16%)

TC2/3 or IC2/3 (37%)

TC1/2/3 or IC1/2/3 (68%)

TC0 and IC0 (32%)

ITT (N = 287)

0.2 1 2

Subgroup (% of enrolled patients)

1.04

7.4 (6.0, 12.5)

9.7 (8.6, 12.0)

9.7 (8.6, 12.0)

9.2 (7.3, 12.8)

11.1 (6.7, 14.4)

15.1 (8.4, NE)

12.6 (9.7, 16.4)

9.7 (6.7, 12.0)

15.5 (11.0, NE)

15.5 (9.8, NE)

aUnstratified HR for subgroups and stratified HR for ITT; Data cut-off May 8, 2015.

Median OS (95% CI), mo

Docetaxeln = 143

Atezolizumabn = 144

Atezolizumab: Doubled likelihood of survival in PD-L1-high tumors (IC2/3 or TC2/3)

Page 40: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

POPLAR: OS by PD-L1 expression subgroupAtezolizumab increased OS by 7.7 mo in IC2/3 orTC2/3 subgroup

40aUnstratified HR.Data cut-off May 8, 2015.

TC3 or IC3 (n = 47) HRa = 0.49 (0.22, 1.07)

P value = 0.068

TC2/3 or IC2/3 (n = 105) HRa = 0.54 (0.33, 0.89)

P value = 0.014

TC1/2/3 or IC3 (n = 195) HRa = 0.59 (0.40, 0.85)

P value = 0.005HRa = 1.04 (0.62, 1.75)

P value = 0.871

TC0 and IC0 (n = 92)

Median 15.5 mo(9.8, NE)

Median 11.1 mo(6.7, 14.4)

Median 7.4 mo(6.0, 12.5)

Median 9.7 mo(6.7, 12.0)

Median 9.7 mo(8.6, 12.0)

Median 15.5 mo(11.0, NE)

Median 9.2 mo(7.3, 12.8)

Atezolizumab Docetaxel Censored+

Median 15.1 mo(8.4, NE)

Page 41: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

POPLAR: PD-L1/PD-1 ligand and receptorfamily members predict clinical benefit in NSCLC

41

Atezolizumab (PD-L1 high)

Atezolizumab (PD-L1 low)

Docetaxel (PD-L1 low)

Docetaxel (PD-L1 high)

OS HR: 0.46 (95%CI: 0.27 – 0.78)

Atezolizumab (PD-L2 high)

Atezolizumab (PD-L2 low)

Docetaxel (PD-L2 low)

Docetaxel (PD-L2 high)

OS HR: 0.39 (95%CI: 0.22 – 0.69)

Atezolizumab (B7.1 high)

Atezolizumab (B7.1 low)

Docetaxel (B7.1 low)

Docetaxel (B7.1 high)

OS HR: 0.44 (95%CI: 0.26 – 0.77)

Atezolizumab (PD-1 high)

Atezolizumab (PD-1 low)

Docetaxel (PD-1 low)

Docetaxel (PD-1 high)

OS HR: 0.43 (95%CI: 0.24 – 0.76)

Schmid et al., ECC 2015

Page 42: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

POPLAR and BIRCH safety summary

42

POPLAR BIRCH

Atezolizumabn = 142

Docetaxeln = 135

All patientsn = 659

Median treatment duration 3.7 mo 2.1 mo 4.2 mo

All Grade AEs, any cause 96% 96% 94%

Treatment-related AEs 67% 88% 64%

Grade 3-4 AEs, any cause 40% 53% 38%

Treatment-related Grade 3-4 AEs 11% 39% 11%

Treatment-related Grade 5 AEs 1%a 2% 0.2%d

Patients withdrawing from treatment due to AEs 8% 22% 5%c

POPLAR: Grade 5 event termsa

Atezolizumab (n = 6): Cardiac failure, pneumonia, ulcer hemorrhage, pneumothorax,pulmonary embolism, embolismDocetaxel (n = 5): Sepsis (n = 2), deathb (n = 2), acute respiratory distress syndromeSafety population includes patients who received any amount of either study treatment.aOne atezolizumab-related Grade 5 event (cardiac failure); three docetaxel-relatedGrade 5 events (one each of sepsis, death and acute respiratory distress syndrome)bCause unknown. Data cut-off May 8, 2015.

BIRCH: cCauses of atezolizumab withdrawal (all cohorts):pneumonitis (0.6%), pneumonia (0.5%), pneumonia aspiration (0.3%),septic shock (0.3%), cerebrovascular accident (0.3%),sudden death (0.3%), thrombocytopenia (0.3%).dOne Grade 5 treatment-related event (pneumonia).Data cut-off May 8, 2015.

Page 43: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

BIRCH and POPLAR summaryClinically meaningful efficacy in patients with advanced NSCLC

43

• BIRCH: Met pre-specified primary efficacy endpoint of ORR for all subgroups

• 6-month OS rate is consistent with POPLAR results; more mature OS data are awaited

• Median DOR was 7 mo in 3L+, not reached in 1L/2L in TC3 or IC3

• Majority of responses still ongoing: > 61% in TC3 or IC3

• POPLAR: Significant OS improvement in patients receiving atezo vs docetaxel in all-comers

• Improved OS correlated with increasing PD-L1 expression

• Trend toward survival improvement in squamous and non-squamous NSCLC

• Median DoR was 14.3 mo for atezolizumab

• Majority of responses still ongoing: 57%

Page 44: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Atezolizumab combo with Pt-based chemotherapyin 1L NSCLCPhase Ib study design

44

atezolizumab 15mg/kg IV q3w+ carboplatin q3w + nab-paclitaxel

q1w

atezolizumab 15mg/kg IV q3w+ carboplatin q3w + pemetrexed q3w

atezolizumab 15mg/kg IV q3w+ carboplatin q3w + paclitaxel q3w

1L NSCLC n=37

E

D

C

4-6 cycles

atezolizumab

atezolizumab +/-pemetrexed

maintenance

Treat to PD or

loss of clinical benefit

Treat to PDor

loss of clinicalbenefit

Treat to PDor

loss of clinical benefit

atezolizumab

Page 45: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Atezolizumab combo with Pt-based chemotherapyin NSCLC: phase Ib safety and efficacy update

45

259.8

50

76.5 31.3 53.7

505.9

2522

0102030405060708090

100

Patie

nts,

%

Complete response Partial response Stable disease

Data preliminary*: 25 patients per arm for final analysis

Arm Ccb/pac

n=8

Arm Dcb/pem

n=17

Arm Ecb/nabn=16

Alln=41

ORR, n %) 4 (50) 13 (76.5) 9 (56.3) 26 (63.4)

CR, n (%) 0 (0) 0 (0) 4 (25) 4 (9.8)

PR, n (%) 4 (50 13 (76.5) 5 (31.3) 22 (53.7)

SD, n (%) 4 (50) 1 (5.9) 4 (25) 9 (22.0)

PD, n (%) 0 (0) 2 (11.8) 2 (12.5) 4 (9.8)

Disease control rate by chemo combo Summary of responses by RECIST v1.1

cb/pacArm C

All NSCLCpatients

cb/pemArm D

cb/nabArm E

100% 82.4% 81.3% 85.5%

*Includes all patients dosed by 10 Nov 2014; data cut-off: 10 Feb 2015

High ORR and DCR: supporting potential synergy between atezolizumab and chemotherapy

Historic ORR for platinum-based chemo doublets: 20-30%

Page 46: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Atezolizumab PhIb chemo combination efficacyEncouraging depth and duration of response

46Includes all patients dosed by 10 Nov 2014; data cut-off: 10 Feb 2015; SLD, sum of longest diameters; *PD for reasons other than new lesions

Arm C (cb/pac) N=8 Arm D (cb/pem) N=17 Arm E (cb/nab) N=16

100

50

0

–50

–100

9 –7

Complete responsePartial responseProgressive diseaseStable disease

–12

–31–31–38–41–42–47–50–53–57–57–57–58–69

Max

imum

SLD

red

uctio

n fr

om b

asel

ine

(%)

–100

Cha

nge

in S

LD fr

om b

asel

ine

(%)

Time on study (days)0 42 84 126 168 210 252 294 336 378 420450

–100–80–60–40–20

020406080

100PR/CR(n=4)Stable disease (n=4)DiscontinuedNew lesion

ORR = 50.0% (4/8) ORR = 76.5% (13/17) ORR = 56.3% (9/16)

100

50

0

–50

–100

11 9–17

–21 –21 –22–43

–67–72 –72 –76–86 –87

–100 –100* *

Complete responsePartial responseProgressive diseaseStable disease

100

50

0

–50

–16–22 –23 –25

–43 –45

–64

–84

Complete responsePartial responseProgressive diseaseStable disease

0 42 84 126 168Time on study (days)

210 252 294 336 378 420450

–100–80–60–40–20

020406080

100 PD(n=2)PR/CR(n=13)Stable disease (n=1)DiscontinuedNew lesion

0 42 84 126 168Time on study (days)

210 252 294 336 378 420450

–100–80–60–40–20

020406080

100 PD(n=2)PR/CR(n=9)Stable disease (n=4)DiscontinuedNew lesion

Page 47: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

47

• High response rate (63% for the combined NSCLC cohort) supporting potential synergy betweenatezolizumab and chemotherapy

• Low rates of discontinuation, AEs were similar to chemotherapy

• No unexpected toxicities in combination with standard first-line chemotherapy, no pneumonitis or otherrespiratory AEs of concern

Conclusions from phase Ib atezolizumab chemo combinations

Several phase III studies in monotherapy and combinations in NSCLC are underway

Page 48: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

ECC 2015 Roche cancer immunotherapy highlights:Atezolizumab regulatory update and further development program

Cathi Ahearn, Lifecycle Leader Atezolizumab Genentech/Roche

Page 49: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Establishing atezolizumab represents theearly portion of Roche’s CIT strategy

49

2016 2017 2018 2025

Lead scientific understandingIdentify and target the biological mechanisms of CIT

responsiveness across tumor types

2L+ bladder2L+ NSCLC

Launch rapidlyLeverage Dx

Broaden across indicationsEarlier treatment settings, broader patient population

Differentiate through portfolioAtezo+NME-based combinations

CIT - cancer immunotherapy

Page 50: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Atezolizumab strategy in bladder cancerRapid launch in a setting of high unmet need

Fast-to-market strategy

Development program in bladder cancer

• 1° Endpoint: ORR• Cohort 2 data at ECC 2015• Cohort 1 data expected in 2016

2L+ Bladdern=767

atezolizumab

1200 mg IV Q3 weeks

Chemotherapy

Phase III IMvigor 211

Adjuvant Bladder (MIBC) Dx–sel

monotherapy, n=440

atezolizumab

1200 mg IV Q3 weeks

Observation

Phase II IMvigor 210

Phase III IMvigor 010

Metastatic BladderCohort 1 (n=100): Cis-IneligibleCohort 2 (n=311): Prior platinum

Atezolizumab 1200 mg IV Q3 weeks

• 1° Endpoint: OS• Data expected 2017

Confirmatory Phase 3

Improve long-term outcomes• 1° Endpoint: DFS• Data expected 2019

50

Filing: US Early 2016, EU 1H 2016

Page 51: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Fast-to-market strategy

Atezolizumab lung cancer strategyMarket entry in PD-L1-selected relapsed/refractory NSCLC

POPLAR

All comers2/3L mNSCLC n=287

atezolizumab1200 mg IV Q3 weeks

docetaxel 75 mg/m2 IV Q3 weeks

BIRCH

PD-L1-selectedmNSCLC n=667

atezolizumab1200 mg IV Q3 weeks

mNSCLC = metastatic Non Small-Cell Lung Cancer51

Development in 2L+ NSCLC

• 1° Endpoint: OS

• OS data: ECC 2015

• 1° Endpoint: ORR

• First presentation:

ECC 2015

OAK

All comers2/3L mNSCLC n=1225

Docetaxel 75 mg/m2 IV Q3 weeks

• 1° Endpoint: OS

• Data expected 2016

atezolizumab1200 mg IV Q3 weeks

Confirmatory Phase 3

Filing: US Early 2016, EU 1H 2016

Phase II

Phase II

Phase III

Page 52: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Broaden in lung cancer: Ongoing phase 3 programs

52

Study Indication Treatment arms Primary completion*

1L Combination studies – All comers (PD-L1 subgroup analysis)

IMpower150

n=1200Non-squamous

Atezo + Carbo + PacAtezo + Carbo + Pac + Avastin

Carbo + Pac + Avastin2017 (PFS)

IMpower130

n=550Non-squamous Atezo + Carbo + Nab-pac

Carbo + Nab-pac 2017 (PFS)

IMpower131

n=1200Squamous

Atezo + Carbo + PacAtezo + Carbo + Nab-pac

Carbo + Nab-pac2017 (PFS)

1L Monotherapy studies – PD-L1 Selected

IMpower110

n=400Non-squamous Atezo

Cis or Carbo + Pem 2017 (PFS)

IMpower111

n=400Squamous Atezo

Cis or Carbo + Gem 2017 (PFS)

Adjuvant Monotherapy study– PD-L1 Selected

IMpower010

n=845

Adj. NSCLC AtezoBest supportive care Post 2018 (DFS)

Atezo=atezolizumab; Carbo=Carboplatin; Pac=Paclitaxel; Nab-pac= Nab-paclitaxel; Cis=Cisplatin; Pem=Pemetrexed; Gem=Gemcitabine* Outcome studies are event driven, timelines may change, OS endpoint included for all studies

Page 53: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Roche atezolizumab lung cancer strategyComplete offering across all lines of treatment

1L Dx+ mono1L all-comers with chemo,chemo+Avastin

Leverage diagnosticsto rapidly launch

atezolizumab2L+ Dx+ mono

Combinations with targeted tx, immune tx

Personalize cancer immunotherapy

Broaden into 1L via first in class

combinations

chemo

Hypothetical timeline

Adjuvant mono

2015

2018+

2017

Pivotal data

53

Page 54: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Roche’s CIT strategy: Expanding the utility ofcancer immunotherapy

54

2016 2017 2018 2025

Lead scientific understandingIdentify and target the biological mechanisms of CIT

responsiveness across tumor types

2L+ bladder2L+ NSCLC

Launch rapidlyLeverage Dx

Broaden across indicationsEarlier treatment settings, broader patient population

Differentiate through portfolioAtezo+NME-based combinations

Page 55: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Roche cancer immunotherapy programIndustry-leading portfolio with 7 internal NMEs

55

Page 56: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

2014-2016: Launch atezolizumab rapidly in PDL1-selected patients

56

*Evaluate tumor:Is the tumor inflamed?

Atezo

InflamedY

Non-InflamedN

PDL1-selected

Page 57: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

2016-2018: Broaden indications and leapfrog competition into 1L All-comers

57

InflamedY

Non-InflamedN

*Evaluate tumor:Is the tumor inflamed?

PDL1+ PDL1-

+ Chemo / Atezo + Chemo / SOC

+ Chemo / Atezo + Chemo / SOC

+ Chemo / Atezo + Chemo / SOC

+ Chemo / Atezo + Chemo / SOC

T Cells at Periphery (Excluded Infiltrate)

No T Cells(Immunologic

Ignorance, Immune Desert)

HYPOTHETICAL

Page 58: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

2018-2020+: Aim for personalized cancer immunotherapy through combinations

58

InflamedY

Non-InflamedN

*Evaluate tumor:Is the tumor inflamed?

High PDL1 expression

No identified target

Low/No PDL1 expression

No Identified target

How do we boost T Cell function?

Improve understanding of immune biology

How do we (re)activate

T Cells?

How do we drive T Cell infiltration? (VEGF,

cytokines, collagen targets)

How do we deepen Atezo responses?

No Effectors

ACTIVATE / RECRUIT

INFILTRATE

Improve understanding of immune biology

O , C s)

Atezo± Other

CIT (aTIGIT, IDOi, TCBs)

Atezo + Chemo /SOC

Atezo+ TCBs

(or IFN)

Atezo+ aOX40(or aCD40, vaccine)

Atezo+ Other CIT (aCSF1R, TCBs,

IL2v)

Atezo+ Avastin

(or A2V)

Atezo+ Chemo /SOC

T Cells at Periphery

MHC Loss

BYPASS

KILL

How do we kill cancer cells that do not express MHC?

HYPOTHETICAL

Page 59: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

The wonderful world of combinations!Tidal wave of combination data coming

59

• Cancer Immunotherapy targets and combinations may include the following:

1

2

3

4

5

6

7

Priming & activationanti-CEA-IL2vanti-FAP-IL2vanti-OX40anti-CTLA4anti-CD27anti-41BBanti-cytokine

Antigen presentationanti-CD40INFαoncolytic virusesneo-epitope vaccines

Antigen releasePro-inflammatory

EGFRiALKiBRAFiMEKiChemoBTKiHDAC

T cell infiltrationanti-VEGFanti-Ang2/VEGF

Cancer cell killinganti-PDL1anti-PD-1 anti-CSF-1RIDOi anti-TIGITanti-TIManti-LAG3A2AiIDO/TDOiTDO

T cell trafficking

Immuno-suppression

Cancer cell recognition

TCBcImmTACsCARTBiTes

• Immunotherapeutics

• Targeted therapies

• SoC chemotherapies

Page 60: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Roche cancer immunotherapy at ECC 2015

60

aPDL1NSCLC (Dx+)

aPDL1 2/3L NSCLC

aPDL1+Avastin1L Renal aPDL1

1/2L Bladder

Phase II Phase IIIPhase IaPDL1

2/3L NSCLCaPDL1

2/3L BladderaPDL1+Avastin+chemo

1L non sq NSCLCaPDL1+chemo1L non sq NSCLCaPDL1+chemo

1L sq NSCLCaPDL1

1L non sq NSCLC (Dx+)aPDL1

1L sq NSCLC (Dx+)aPDL1+chemo

1L TNBC

aPDL1Adjuvant MIBC (Dx+)

aPDL1Adjuvant NSCLC (Dx+)

aPDL1+Avastin1L RCC

Status as of Sept 28, 2015

IDOSolid tumors

aPDL1+ipilimumabSolid tumors

aPDL1+aCD40Solid tumors

aPDL1+IFN-alfaSolid tumors

aPDL1+aCSF-1RSolid tumors

aPDL1+aCEA-IL2v FP Solid tumors

aPDL1+aOX40Solid tumors

aPDL1 + IDOSolid tumors

aOX40Solid tumors

aCEA/CD3 TCBSolid tumors

aPDL1+Zelboraf Melanoma

aPDL1+TarcevaNSCLC

aPDL1+Avastin+chemoSolid tumors

aPDL1 + GazyvaR/R FL / aNHL

aCD20/CD3 TCBSolid tumorsaCEA-IL2v FPSolid tumors

aPDL1+Avastin Solid tumors

aPDL1+cobimetinib Solid tumors

aPDL1+Zelboraf+cobiMelanoma

aPDL1+lenalidomideMM

aPDL1+chemoSolid tumors

aPDL1Solid tumors

aCSF-1RSolid tumors

aPDL1 trials

NME monotherapy

Immune doublets

Additions in 2015

Data at ECC 2015

Page 61: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Cancer immunotherapy newsflow in H2 2015

61

Vienna, 25 -29 Sep

• atezolizumab- NSCLC: POPLAR final, BIRCH, P1b chemo combo update;- Bladder: P2 (2L cohort)

• CEA IL2v, IDO inh.: P1 update solid tumors

• atezolizumab- TNBC: P1b abraxane combo

• atezolizumab- GBM: P1

• atezolizumab + Gazyva- r/r NHL

• atezolizumab- mM: P1 vemurafenib combo

San Francisco, 18-21 Nov

San Antonio, 19-22 Nov

Orlando, 5-8 Dec

San Antonio, 8-12 Dec

Planned presentations

Page 62: Roche Analyst Event · Ira Mellman, Ph.D., Vice President, Cancer Immunology, gRED Genentech ECC 2015 Roche cancer immunotherapy highlights: - Atezolizumab phase II bladder and lung

Doing now what patients need next