pred (Roche Pharma Research & Early Development) gred (Genentech Research & Early Development)

Pipeline summary

Marketed products additional indications

Global Development late-stage trials

pRED (Roche Pharma Research & Early Development)

gRED (Genentech Research & Early Development)

Roche Group Q1 2015 results

Diagnostics

Foreign exchange rate information

Changes to the development pipeline

Q1 2015 update

2

New to Phase I

New to Phase II

New to Phase III

New to Registration

1AI

RG7813 CEA IL2v + PD-L1MAb - solid tumors

1 NME (Trophos acquisition)

RG6083 olesoxime - SMA

1 NME (shown to reflect upcoming submission)

RG7853 alectinib - ALK-mut. pos. NSCLC 2L

1 AI (previous P2 in solid tumors split out) RG7604 taselisib - NSCLC sq. 2L 1 NME RG7604 taselisib - ER+/HER2-neg mBC 7 AIs RG7413 etrolizumab - Crohn’s disease RG7446 PD-L1 MAb Dx-pos. patients - NSCLC sq. 1L RG7446 PD-L1 MAb Dx-pos. patients - NSCLC non-sq. 1L RG7446 PDL1 MAb + chemo -NSCLC sq. 1L RG7446 PDL1 MAb + chemo -NSCLC non sq. 1L RG7446 PD-L1 MAb + chemo +/- Avastin - NSCLC non sq. 1L RG7853 alectinib Alk-mut.pos. - NSCLC 1L

Removed from Phase I

Removed from Phase II

Removed from Phase III

Removed from

Registration

2 NMEs

RG7410 TAAR1 ago - schizophrenia

RG7342 mGlu5 PAM - schizophrenia

2 NMEs

RG7790 setrobuvir–HCV

RG7321 pictilisib – solid tumors

1 AI RG435 Avastin - NSCLC adj. 1 AI following US approval RG3645 Lucentis - diabetic retinopathy 1 AI following EU approval

RG435 Avastin – cervical cancer Status as of April 22, 2015

Roche Group development pipeline

3

Phase I

(31 NMEs + 12 AIs)

Raf & MEK dual inh solid tumors

ChK1 inh solid tum & lymphoma

Oncology

Other disease areas

Status as of April 22, 2015

lumretuzumab (HER3 MAb) solid tumors idasanutlin (MDM2 ant) s. & hem tumors

New Molecular Entity (NME) Additional Indication (AI)

Oncology Immunology Infectious Diseases CardioMetabolism Neuroscience Ophthalmology Other

RG-No Roche Genentech managed CHU Chugai managed

PD-L1+Zelboraf+/-cobimetinib melanoma

Steap 1 ADC prostate ca.

PD-L1+Avastin+chemo solid tumors

PD-L1 MAb+Tarceva NSCLC EGFR+ PD-L1 MAb+cobimetinib solid tumors

venetoclax+Gazyva CLL CLL PD-L1 MAb solid tumors

ERK inh solid tumors CEA IL2v solid tumors LSD1 inh AML

ADC solid tumors MDM2 (4) IV prodrug AML

ADC ovarian ca

PD-L1 MAb+ipi/IFN solid tumors

OX40 MAb solid tumors

Lucentis sust. deliv. AMD/RVO/DME

PDE10A inh schizophrenia Nav1.7 inh pain

VEGF-ANG2 MAb wAMD a-synuclein MAb Parkinson's Disease

SMN2 splicer spinal muscular atrophy TLR7 agonist HBV RG7795

RG3645 RG7203 RG7893

aldosterone synth inh met. diseases RG7641

RG7716 RG7935 RG7800 HIF1 alpha LNA solid tumors

RG7304 RG7741 RG7116 RG7388 RG7446 RG7450 RG7446 RG7446 RG7446 RG7601 RG7446 RG7842 RG7813 RG6016 RG7841 RG7775 RG7882 RG7446 RG7888 RG6061

CEA CD3 TCB solid tumors RG7802

CD40 iMAb+PD-L1 MAb solid tumors RG7876 MSLN PE cFP solid tumors RG7787

PD-L1 MAb+Gazyva lymphoma RG7446

- RG7880 inflammatory diseases - autoimmune diseases RG7625 - infectious diseases RG7689 DBO β-lactamase inh bact. infections RG6080

TAU MAb Alzheimer’s RG7345

emactuzumab RG7155 (CSF-1R) + PDL1 s.tumors

SERD (2) ER+(HER2-neg) mBC RG6047 IDO inh solid tumors RG6078

duligotuzumab (RG7597 HER3/EGFR)+ cobi s. tum.

CEA IL2v + PD-L1 MAb solid tumors RG7813 RG7601 venetoclax heme indications

New Molecular Entity (NME) Additional Indication (AI)

RG-No Roche Genentech managed CHU Chugai managed

RG105 MabThera is branded as Rituxan in US and Japan

RG1569 Actemra is branded as RoActemra in EU

RG7159 Gazyva is branded as Gazyvaro in EU Oncology Immunology Infectious Diseases CardioMetabolism Neuroscience Ophthalmology Other

Roche Group development pipeline

4

Phase II

(22 NMEs + 14 Als)

Phase III

(9 NMEs + 27 Als)

Registration

(1

NME + 2 Als)

1 US only : FDA submission decision pending 2 Approved in US, submitted in EU

* FPI imminent

crenezumab Alzheimer’s RG7412 lampalizumab geographic atrophy RG7417

Perjeta HER2+ BC neoadj

RG12732

cobimetinib + Zelboraf m. melanoma RG7421

MabThera SC RG105 CLL Avastin glioblastoma 1L RG435

RG3502 Kadcyla +/- Perjeta HER2+ mBC 1L

ocrelizumab RMS RG1594

Gazyva DLBCL1L RG7159

ocrelizumab PPMS RG1594

Actemra large-vessel vasculitisCHU lebrikizumab severe asthma RG3637

Zelboraf melanoma adj RG7204

RG1273 Perjeta+Herceptin HER2+gastric ca 1L

Actemra giant cell arteritis RG1569 etrolizumab ulcerative colitis RG7413

RG1273 Perjeta+Herceptin HER2+ mBC 2L

alectinib ALK+ NSCLC 1L RG7853

Gazyva iNHL rituximab-ref RG7159

Gazyva follicular lymphoma 1L RG7159

venetoclax+Rituxan CLL rel/ref RG7601

Kadcyla RG3502 HER2+ gastric cancer 2L

RG1450 gantenerumab Alzheimer’s PD-L1 MAb NSCLC 2L RG7446

Kadcyla + Perjeta HER2+ BC adj RG3502

Kadcyla + Perjeta HER2+ BC neoadj RG3502

IL-6R MAb neuromyelitis optica CHU

Perjeta+Herceptin RG1273 HER2+ BC adj

Kadcyla HER2+ BC adj RG3502

venetoclax+Gazyva CLL 1L RG7601

Avastin ovarian cancer 1L RG4351

RG4351 Avastin rel. ovarian ca. Pt-sensitive

PD-L1 MAb bladder cancer 2L RG7446

bitopertin obsessive compulsive dis. RG1678 danoprevir HCV RG7227

basimglurant TRD RG7090 sembragiline RG1577 (MAO-B inh) Alzheimer’s

Actemra systemic sclerosis RG1569 polatuzumab vedotin hem tumors RG7596

V1 receptor antag autism RG7314 ipatasertib RG7440 solid tumors

lebrikizumab RG3637 idiopathic pulmonary fibrosis

LptD antibiotic antibacterial

venetoclax 17p del CLL rel/ref RG7601

PD-L1 MAb +Avastin RCC RG7446

Flu A MAb influenza RG7745 IL-31R MAb atopic dermatitis CHU

RG6013 FIXa/FX bispecific MAb hemophilia A

PD-L1 MAb NSCLC 2/3L RG7446

RG1662 GABRA5 NAM Down Syndrome ADC lifastuzumab vedotin Pt-resist. OC RG7599

PD-L1 MAb bladder cancer 1/2L RCC RG7446 emactuzumab (RG7155 CSF-1R) PVNS/s. tumors

taselisib NSCLC sq 2L RG7604

venetoclax DLBCL RG7601 vanucizumab (RG7221 Ang2-VEGF MAb) mCRC

glypican-3 MAb liver cancer RG7686

GIP/GLP-1 dual ago type 2 diabetes RG7697

Esbriet SSc–interstitial lung disease RG6062

cobimetinib+paclitaxel TNBC RG7421

Avastin+Tarceva EGFR mut+ NSCLC RG435

venetoclax+Rituxan FL rel/ref RG7601 SERD ER+(HER2-neg) mBC RG6046

URAT 1 inh gout CHU RG7929

RG3502 Kadcyla HER2+ NSCLC

RG3637 lebrikizumab IPF

alectinib ALK+ NSCLC 2L RG7853

RG7929

olesoxime spinal muscular atrophy RG6083

PD-L1+chemo NSCLC non-sq 1L RG7446 NSC PD-L1 RG7446 +chemo+Avastin NSCLC non-sq 1L PD-L1+chemo NSCLC sq 1L RG7446* PD-L1 MAb Dx+ NSCLC sq 1L RG7446* PD-L1 MAb Dx+ NSCLC non-sq 1L RG7446* taselisib ER+(HER2-neg) mBC RG7604

etrolizumab Crohn’s disease RG7413

Status as of April 22, 2015

NME submissions and their additional indications

Projects currently in phase 2 and 3

5

* lead market China

Unless stated otherwise, submissions are planned to occur in US and EU lebrikizumab (RG3637) severe asthma PD-L1 MAb (RG7446) NSCLC 2/3L

2016

Pt resistant OC emactuzumab (RG7155)

PVNS and solid tumors vanucizumab (RG7221)

colorectal cancer FIXa/FX bispecific MAb (RG6013) hemophilia A SERD (RG6046) ER+(HER2-neg) mBC ocrelizumab (RG1594) RMS

2015

Alk+ NSCLC 2L alectinib (RG7853) Alk+ NSCLC 1L PDL-1 MAb (RG7446) combo Avastin RCC

2017

danoprevir* (RG7227) HCV basimglurant (RG7090) depression crenezumab (RG7412) Alzheimer‘s gantenerumab (RG1450) Alzheimer‘s V1 receptor antag (RG7314) autism etrolizumab (RG7413) ulcerative colitis sembragiline (RG1577) Alzheimer‘s LptD antibiotic (RG7929) antibacterial lebrikizumab (RG3637) idiopathic pulmonary fibrosis

Flu A MAb (RG7745) influenza GABRA5 NAM (RG1662) Down syndrome etrolizumab (RG7413) Crohn’s disease

2018 and beyond

New Molecular Entity Oncology Immunology Infectious Diseases CardioMetabolism Neuroscience Ophthalmology Other Status as of April 22, 2015

* approved in EU

Unless stated otherwise, submissions are planned to occur in US and EU

Submissions of additional indications for existing

products

Projects currently in phase 2 and 3

6

2015

Avastin (US) GBM Gazyva iNHL rituximab refractory

Avastin +Tarceva(EU) EGFR mut+ NSCLC

*Avastin (US) ovarian cancer 1st _L

*Avastin (US) rel. ovarian ca. Pt-sens

2018 and beyond

Gazyva follicular lymphoma 1L

2017

2016

Major granted and pending approvals 2015

7

EU

US

Approved

Pending approvals

Avastin cervical cancer April 2015 Perjeta HER2+ BC neoadj Filed September 2014 cobimetinib + Zelboraf m. melanoma Filed September 2014 MabThera SC CLL Filed November 2014 cobimetinib + Zelboraf m. melanoma Filed December 2014 Lucentis diabetic retinopathy February 2015 Status as of April 22, 2015

Japan-Chugai

Bonviva osteoporosis (oral) Filed February 2015

Cancer immunotherapy pipeline overview

8

Phase II

(1NME + 3 Als)

PD-L1 MAb bladder cancer 1/2L RCC RG7446 emactuzumab (RG7155 CSF-1R) PVNS/s. tumors

Phase III

(1NME + 6AIs)

PD-L1 MAb NSCLC 2L RG7446

PD-L1 MAb bladder cancer 2L RG7446

PD-L1+chemo NSCLC non-sq 1L RG7446

NSC RG7446 PD-L1+chemo+Avastin NSCLC non-sq 1L PD-L1+chemo NSCLC sq 1L RG7446

PD-L1 MAb Dx+ NSCLC sq 1L RG7446

PD-L1 MAb Dx+ NSCLC non-sq 1L RG7446

*external collaborations: INCB- Incyte INCB024360; CDX-1127- Celldex CD27 MAb

Phase I

(7 NMEs + 9 AIs)

PD-L1+Zelboraf+/-cobimetinib melanoma PD-L1+Avastin+chemo solid tumors

PD-L1 MAb+Tarceva NSCLC EGFR+ PD-L1 MAb+cobimetinib solid tumors PD-L1 MAb solid tumors

CEA IL2v solid tumors

PD-L1 MAb+ipi/IFN solid tumors

OX40 MAb solid tumors RG7446 RG7446 RG7446 RG7446 RG7446 RG7813 RG7446 RG7888

CEA CD3 TCB solid tumors RG7802 CD40 iMAb+PD-L1 MAb solid tumors RG7876

PD-L1 MAb+Gazyva lymphoma RG7446

emactuzumab RG7155 (CSF-1R) + PDL1 s.tumors

IDO inh solid tumors RG6078

CEA IL2v + PD-L1 MAb solid tumors RG7813 PD-L1 MAb + IDO inh solid tumors *INCB PD-L1 MAb + varlilumab solid tumors *CDX

9

Pipeline summary

Marketed products additional indications

Global Development late-stage trials

pRED (Roche Pharma Research & Early Development)

gRED (Genentech Research & Early Development)

Roche Group Q1 2015 results

Diagnostics

10

Indication Front-line metastatic _{ovarian cancer}

Phase/study _GOG-0218 Phase III Phase III _ICON7

# of patients N=1,873 N=1,528

Design ARM A: Paclitaxel and carboplatin for 6 cycles plus 5 cycles

of concurrent placebo followed by placebo alone for up to 22 cycles (15 months)

ARM B: Paclitaxel and carboplatin for 6 cycles plus 5 cycles

of concurrent Avastin followed by placebo alone for up to 22 cycles (15 months)

ARM C: Paclitaxel and carboplatin for 6 cycles plus 5 cycles

of concurrent Avastin followed by Avastin alone for up to 22 cycles (15 months)

ARM A: Paclitaxel and carboplatin for 6 cycles

ARM B: Paclitaxel and carboplatin plus concurrent Avastin for

6 cycles followed by Avastin alone for up to 18 cycles (12 months)

Avastin dose 15 mg/kg q3 weeks 7.5 mg/kg q3 weeks

Primary endpoint

Progression-free survival Progression-free survival

Status Study met its primary endpoint in Q1 2010

Data presented at ASCO 2010 and 2011 Results: NEJM 2011 Dec 29;365(26):2484-96

Study met its primary endpoint Q3 2010 Data presented at ESMO 2010 and ASCO 2011 Results: NEJM 2011 Dec 29;365(26):2473-83 OS data presented at ECC 2013

 EMA approval granted Q4 2011  Re-evaluate FDA submission in 2015

Avastin

Ovarian cancer clinical development programme

11

Indication Stage IVB, recurrent or persistent cervical cancer Newly diagnosed glioblastoma

Phase/study _GOG-240 Phase III Phase III _AVAglio

# of patients N=452 N=920

Design ARM A: Paclitaxel, cisplatin

ARM B: Paclitaxel, cisplatin plus Avastin ARM C: Paclitaxel, topotecan

ARM D: Paclitaxel, topotecan plus Avastin

ARM A: Concurrent radiation and temozolomide

plus placebo; followed by maintenance TMZ plus placebo for 6 cycles; then placebo until disease progression

ARM B: Concurrent radiation and TMZ plus

Avastin; followed by maintenance TMZ plus Avastin for 6 cycles; then Avastin (15mg/kg q3

weeks) monotherapy until disease progression

Avastin dose

15 mg/kg q3 weeks 10 mg/kg q2 weeks or 15 mg/kg q3 weeks

Primary endpoint

Overall survival Progression-free survival Overall survival

Status Study met its primary endpoint Q1 2013

Results published in NEJM Feb. 2014; 370(8):734-43 Filed globally Q2 2014

FDA approval granted Q3 2014 Approved in EU Q1 2015

Co-primary endpoint of PFS met Q3 2012 Overall survival data presented at ASCO 2013 Filed in EU Q1 2013

Negative CHMP opinion Q3 2014 US filing pending

Avastin

Cervical and brain cancer clinical development

programmes

TMZ=temozolomide

Indication _{lung cancer}Adjuvant First-line HER2-negative metastatic _{breast cancer} Relapsed platinum-sensitive _{ovarian cancer}

Phase/study _{ECOG 1505} Phase III _MERiDiAN Phase III Phase III _OCEANS

# of patients N=1,500 N=480 N=484

Design ARM A: Cisplatin plus vinorelbine,

docetaxel, gemcitabine or pemetrexed

ARM B: Cisplatin plus vinorelbine,

docetaxel, gemcitabine or pemetrexed plus Avastin up to 12 months

ARM A: Paclitaxel + Avastin ARM B: Paclitaxel + Placebo

ARM A: Carboplatin, gemcitabine,

and concurrent placebo for 6-10 cycles, followed by placebo alone until disease progression

ARM B: Carboplatin, gemcitabine,

and concurrent Avastin for 6-10 cycles, followed by Avastin alone until disease progression.

Avastin dose

15 mg/kg q3 weeks 10 mg/kg q2 weeks 15 mg/kg q3 weeks

Primary endpoint

Overall survival PFS in ITT

PFS in patients with high plasma

VEGF-A

Progression-free survival

Status Recruitment completed Q4 2013

Trial stopped for futility Q1 2015

Co-primary endpoints met Q1 2015 Data to be presented in 2015

Study met its primary endpoint Q1

2011

EMA approval granted Q4 2012 Final data presented at SGO 2014 Re-evaluate FDA submission in 2015

12

Avastin

Lung, breast and ovarian cancer development

programmes

Erivedge

A novel small molecule inhibitor of the hedgehog

signaling pathway

13

Phase/study Phase II _STEVIE Phase II

# of patients N=1,200 N=129

Design Single ARM: 150 mg Erivedge

orally once daily

ARM A: Erivedge 150mg daily ARM B: placebo

Primary endpoint

Safety: Incidence of adverse events Change in forced vital capacity (FVC)

Status FPI Q2 2011 FPI pending in anticipation of trial design

amendment to incorporate new standard of care Esbriet

Esbriet

Small molecule with activity in fibrotic diseases

14

Indication Systemic sclerosis-related interstitial lung disease (SSc-ILD)

Phase/study Phase II _LOTUSS

# of patients N=63

Design Open-label, randomized, parallel-group, safety and tolerability study

2 week vs. 4 week dose titration regimens

Primary endpoint

Safety

Status LPI Q3 2014

Data to be presented at ATS 2015

Gazyva/Gazyvaro

Type II, glycoengineered anti-CD20 monoclonal antibody

15

Previously untreated or

relapsed/refractory chronic lymphocytic leukemia

Diffuse large B-cell lymphoma (DLBCL)

Phase/study Phase III _GREEN Phase III _GOYA

# of patients N=800 N=1,418

Design Single-arm cohort study: Gazyva alone or in

combination with different chemotherapy regimens (FC, Bendamustin or Clb), investigation of different strategies to reduce IRRs

ARM A: Gazyva 1000mg IV plus CHOP ARM B: MabThera/Rituxan plus CHOP

Primary endpoint

Safety in combination with different

chemotherapy regimens

Progression-free survival

Status FPI Q4 2013

Initial safety data presented at ASH 2014

Recruitment completed Q2 2014

Trial continues after interim analysis in 2015 Final data expected in 2016

In collaboration with Biogen Idec

ASH=American Society of Hematology

Gazyva/Gazyvaro

Type II, glycoengineered anti-CD20 monoclonal antibody

16

In collaboration with Biogen Idec

CHOP=Cyclophosphamide, Doxorubicin, Vincristine and Prednisone; CVP=Cyclophosphamide, Vincristine and Prednisolone

Induction and maintenance study

Phase III GALLIUM

Induction and maintenance study

# of patients N=411 N=1,401

Design ARM A: Gazyva 1000mg IV plus bendamustine

followed by Gazyva mainteinance

ARM B: bendamustine

ARM A: Gazyva 1000mg IV plus chemotherapy

followed by Gazyva maintenance

ARM B: MabThera/Rituxan plus chemotherapy

followed by MabThera/Rituxan maintenance

Chemotherapy:

For follicular lymphoma: CHOP, CVP or

bendamustine

For non-follicular lymphoma: physician’s choice Primary

endpoint

Progression-free survival Progression-free survival

Status Trial stopped at interim for efficacy Q1 2015

Data to be presented at ASCO 2015 Expect global filing in 2015

Recruitment completed Expect data in 2017

Kadcyla

Evaluating new treatment options in HER2-positive

early breast cancer

17

Phase/study _KRISTINE Phase III _KATHERINE Phase III Phase III _KAITLIN

# of patients N=432 N=1,484 N=2,500

Design Before surgery patients will

receive 6 cycles of:

ARM A: Herceptin plus Perjeta

plus docetaxel plus carboplatin

ARM B: Kadcyla plus Perjeta

After surgery patients will receive:

ARM A: Herceptin plus Perjeta ARM B: Kadcyla plus Perjeta

ARM A: Kadcyla 3.6mg/kg q3w ARM B: Herceptin

Following surgery and

antracycline-based therapy:

ARM A: Herceptin 6mg/kg q3w

plus Perjeta 420 mg/kg q3w plus chemo

ARM B: Kadcyla 3.6mg/kg q3w

plus Perjeta 420mg/kg q3w plus chemo

Primary endpoint

Pathologic Complete Response

(pCR)

Invasive disease-free survival

(IDFS)

Invasive disease-free survival

(IDFS)

Status FPI Q2 2014 FPI Q1 2013 FPI Q1 2014

18

Previously untreated HER2 pos. metastatic breast

cancer

Previously treated locally advanced or metastatic HER2-positive gastric

cancer

HER2-positive advanced (2L+) NSCLC

Phase/study _MARIANNE Phase III Phase II/III _GATSBY Phase II

# of patients N=1,092 N=412 N=40

Design ARM A: Herceptin plus taxane

ARM B: Kadcyla 3.6mg/kg q3w plus

Perjeta

ARM C: Kadcyla 3.6 mg/kg q3w

plus placebo

ARM A: Kadcyla 3.6mg/kg q3w ARM B: Kadcyla 2.4mg/kg weekly ARM C: docetaxel or paclitaxel

Single-agent Kadcyla 3.6 mg/kg

Primary endpoint

Progression-free survival assessed

by IRF

Phase II: Dose-finding Phase III: Overall survival

Overall response rate and safety

Status Study met non-inferiority endpoint,

showing similar progression-free survival (PFS) among the three arms Q4 2014

Study did not meet PFS superiority

endpoint for Kadcyla-containing regimens Q4 2014

Data to be presented at ASCO 2015

Recruitment completed Q1 2015 Data expected in 2015

FPI Q4 2014

Kadcyla

Evaluating new treatment options in HER2-positive

breast and gastric cancer

In collaboration with ImmunoGen, Inc.

19

Indication Previously untreated chronic lymphocytic leukemia

Phase/study

Phase Ib SAWYER

Subcutaneous study Study being conducted ex-US

# of patients N=225

Design Two-stage design:

- Stage 1 (dose-finding, N=55)

- Stage 2 (N=170): CLL dose confirmation:

ARM A: MabThera IV plus chemotherapy

(fludarabine and cyclophosphamide)

ARM B: MabThera 1600mg SC plus chemotherapy (fludarabine and

cyclophosphamide)

Primary endpoint

Part 1: PK (dose selection)

Part 2: PK of MabThera IV versus MabThera SC (arm A vs. arm B)

Status Stage 2 data confirmed non-inferior PK and comparable safety/efficacy of

MabThera 1600mg SC vs. MabThera IV

Presented at ASH 2014 Filed in EU Q4 2014

MabThera/Rituxan

Oncology development programme

Subcutaneous MabThera : applies Enhanze technology, partnered with Halozyme

ASH=American Society of Hematology

Perjeta

First in a new class of HER dimerization inhibitors

20

Indication Neoadjuvant HER2-positive breast cancer Adjuvant HER2-positive breast _cancer

Phase/ study _NEOSPHERE Phase II _TRYPHAENA Phase II _APHINITY Phase III

# of patients N=417 N=225 N=4,803

Design ARM A: Herceptin plus docetaxel

ARM B: Perjeta (840mg loading,

420mg q3w) plus Herceptin and docetaxel

ARM C: Perjeta plus Herceptin ARM D: Perjeta plus docetaxel

ARM A: FEC followed by Taxane

with Herceptin and pertuzumab (H+P given concurrently)

ARM B: FEC followed by Taxane

with Herceptin + pertuzumab (H+P given sequentially)

ARM C: TCH + pertuzumab (H+P

given concurrently)

ARM A: Perjeta (840mg loading,

420 q3w) plus Herceptin for 52 weeks plus chemotherapy (6-8 cycles)

ARM B: placebo plus Herceptin (52

weeks) plus chemotherapy (6-8 cycles)

Primary endpoint

Pathologic complete response

(pCR)

Safety Invasive disease-free survival (IDFS)

Status Positive data presented at SABCS

2010

Biomarker data presented SABCS

2011

Survival data to be presented at

ASCO 2015

Positive safety and efficacy data

presented at SABCS 2011

Recruitment completed Q3 2013 Expect data in 2016

 FDA approval granted Q3 2013  Filed in EU Q3 2014

FEC = Fluorouracil, Epirubicin, and Cyclophosphamide; TCH = Docetaxel, Carboplatin, Herceptin;

SABCS=San Antonio Breast Cancer Symposium; ASCO=American Society of Clinical Oncology

Perjeta

First in a new class of HER dimerization inhibitors

21

Design ARM A: Herceptin plus

Xeloda

ARM B: Perjeta plus

Herceptin and Xeloda

ARM A: Perjeta (840mg

loading, 420mg q3w) plus Herceptin and

chemotherapy

ARM B: placebo plus

Herceptin and chemotherapy

Neoadjuvant treatment:

ARM A: ddAC q2w x4 cycles followed by

weekly paclitaxel for 12 weeks, with P+H x4 cycles

ARM B: FEC+P+H x4 cycles followed by

docetaxel+P+H x4 cycles Adjuvant treatment:

P+H q3w to complete 1 year of HER2 therapy Hormonal and radiation therapy as indicated Primary

endpoint

Progression-free survival Overall survival Safety

Status Recruitment completed Q3

2013

Expect data in 2015

FPI Q2 2013 FPI Q3 2014

Zelboraf

A selective novel small molecule that inhibits mutant

BRAF

22

Phase/study Phase III _BRIM8

# of patients N=725

Design 52-week treatment

ARM A: Zelboraf 960mg bid ARM B: Placebo

Primary endpoint

Disease-free survival

Status FPI Q3 2012

In collaboration with Plexxikon, a member of Daiichi Sankyo Group

23

Indication Systemic sclerosis Giant Cell Arteritis

Phase/study Phase II faSScinate Proof-of-concept study Phase III GiACTA # of patients N=86 N=250

Design Blinded 48-week treatment with weekly dosing:

ARM A: Actemra SC 162mg ARM B: Placebo SC

Open-label weekly dosing at weeks 49 to 96:

Actemra SC 162mg

Part 1: 52-week blinded period

ARM A: Actemra SC 162mg qw + 26 weeks

prednisone taper

ARM B: Actemra SC 162mg q2w + 26 weeks

prednisone taper

ARM C: Placebo+ 26 weeks prednisone taper ARM D: Placebo+ 52 weeks prednisone taper Part II:

104-week open label extension – patients in remission

followed off of the study drug; Patients with active disease receive open label Actemra SC 162mg qw

Primary endpoint

Change in modified Rodnan skin score (mRSS) at week

24

Safety

Proportion of patients in sustained remission at week 52

Status 48 week data presented at ACR 2014

Primary and all key secondary endpoints showed trend

for improved efficacy

FPI Q3 2013

Actemra/RoActemra

Interleukin 6 receptor inhibitor

In collaboration with Chugai

24

24

Pipeline summa

ry

Marketed products additional indications

Global Development late-stage trials

pRED (Roche Pharma Research & Early Development)

gRED (Genentech Research & Early Development)

Roche Group Q1 2015 results

Diagnostics

Alectinib (ALK inhibitor, RG7853, AF802)

New CNS-active inhibitor of anaplastic lymphoma kinase

25

In collaboration with Chugai

Indication Treatment naïve ALK-positive _{advanced NSCLC} ALK-positive crizotinib-naïve _{advanced NSCLC}

Phase/study Phase III _ALEX

Phase I/II AF-001JP

Japanese study

# of patients N=286 N=70

Design ARM A: alectinib 600mg BID

ARM A: crizotinib 250mg BID

Part 1: Dose escalation monotherapy Part 2: Monotherapy, dose selected

based on the results of Part 1

Primary endpoint

Progression-free survival Phase I: Determination of

recommended dose

Phase II: Safety and efficacy

Status FPI Q3 2014 Results published in Lancet Oncology

2013 Jun;14(7):590-8

Approved in Japan with brand name

Alectinib (ALK inhibitor, RG7853, AF802)

New CNS-active inhibitor of anaplastic lymphoma kinase

26

In collaboration with Chugai

ECC=European Cancer Congress; ASCO=American Society of Clinical Oncology

Indication ALK-positive advanced NSCLC after _{progression on crizotinib treatment} ALK-positive advanced NSCLC after _{progression on crizotinib treatment}

Phase/study Phase I/II AF-002JG/NP28761 US study Phase I/II ACCALIA/NP28673

# of patients _{Phase II: N=85} Phase I: N=36 N=130

Design Part 1: Dose escalation monotherapy

Part 2: Monotherapy, dose selected based on the

results of Part 1

Part 1: Dose escalation monotherapy

Part 2: Monotherapy, dose selected based on the

results of Part 1

Primary endpoint

Phase I: Determination of recommended dose Phase II: Safety and efficacy

Phase I: Determination of recommended dose Phase II: Safety and efficacy

Status Phase I data presented at ECC 2013

Phase I full cohort including CNS data published

in Lancet Oncology 2014, Sept.15(10):1119-28

Phase II FPI Q3 2013

Primary analysis positive Q1 2015 Data to be presented at ASCO 2015

Phase II FPI Q3 2013

Primary analysis positive Q4 2014 Updated analysis in Q1 2015 Data to be presented at ASCO 2015

Expect global filing in 2015

Anti-PDL1 (MPDL3280A, RG7446)

Novel approach in cancer immunotherapy

27

Indication 1L non-squamous NSCLC _{PD-L1-selected patients} 1L non-squamous NSCLC 1L non-squamous NSCLC

Phase/study Phase III Phase III Phase III

# of patients N=400 N=1200 N=550

Design ARM A: RG7446 monotherapy

ARM B: carboplatin or cisplatin + pemetrexed ARM A: RG7446 + Avastin + paclitaxel + carboplatin ARM B: RG7446 + paclitaxel + carboplatin

ARM C: Avastin + paclitaxel

+ carboplatin ARM A: RG7446 + nab-paclitaxel + carboplatin ARM B: nab-paclitaxel + carboplatin Primary endpoint

Progression-free survival Progression-free survival Progression-free survival

Anti-PDL1 (MPDL3280A, RG7446)

Novel approach in cancer immunotherapy

28

Indication _{PD-L1-selected patients}1L squamous NSCLC 1L squamous NSCLC

Phase/study Phase III Phase III

# of patients N=400 N=1200

Design ARM A: RG7446 monotherapy

ARM B: gemcitabine + cisplatin or carboplatin ARM A: RG7446 + nab-paclitaxel + carboplatin ARM B: RG7446 + paclitaxel + carboplatin ARM C: nab-paclitaxel + carboplatin Primary endpoint

Progression-free survival Progression-free survival

Anti-PDL1 (MPDL3280A, RG7446)

Novel approach in cancer immunotherapy

29

Locally advanced or metastatic NSCLC PD-L1 positive Locally advanced or metastatic NSCLC PD-L1 positive Locally advanced or metastatic NSCLC (2nd_/3rd _line)

Non-small cell lung cancer

Phase/study Phase III _OAK Phase II _FIR Phase II _{BIRCH POPLAR} Phase II Phase I

# of patients N=1100 N=130 N=635 N=287 N=32

Design ARM A: RG7446

1200mg q3w

ARM B: docetaxel

Single arm study RG7446 1200mg q3w

Single arm study RG7446 1200mg q3w ARM A: RG7446 1200mg q3w ARM B: docetaxel RG7446 plus Tarceva1 Primary endpoint

Overall survival Overall response rate Objective response

rate

Overall survival Safety

Status FPI Q1 2014 Recruitment

completed Q2 2014 Data to be presented at ASCO 2015 Recruitment completed Q4 2014 Readout in 2015 Recruitment completed Q2 2014 Data to be presented at ASCO 2015 FPI Q1 2014

1_{Tarceva is a registered trademark of OSI Pharmaceuticals, LLC, a subsidiary of Astellas US, LLC} ASCO=American Society of Clinical Oncology

Anti-PDL1 (MPDL3280A, RG7446)

Novel approach in cancer immunotherapy

30

Previously Untreated Metastatic Triple Negative

Breast Cancer Locally advanced or metastatic urothelial bladder cancer Locally advanced or metastatic urothelial bladder cancer

Phase/study Phase III Phase III Phase II

# of

patients N=350 N=767 N=400

Design ARM A: RG7446 +

nab-paclitaxel

ARM B: placebo +

nab-paclitaxel

Patients who progressed on at least one platinum-containing regimen will receive: ARM A: RG7446 1200mg q3w ARM B: chemotherapy (vinflunine, paclitaxel or docetaxel) RG7446 1200mg q3w Cohort 1: Treatment-naive and cisplatin-ineligible patients

Cohort 2: Patients with

disease progression following or during platinum-containing treatment Primary endpoint

Progression-free survival Overall survival Objective response rate

Status Expect FPI H2 2015 FPI Q1 2015 Recruitment completed Q1

2015

Anti-PDL1 (MPDL3280A, RG7446)

Novel approach in cancer immunotherapy

31

Indication Untreated advanced renal cell carcinoma

Phase/study Phase III Phase II

# of patients N=550 N=300

Design ARM A: RG7446 plus Avastin

ARM B: sunitinib

ARM A: RG7446 plus Avastin ARM B: RG7446; following PD:

RG7446 plus Avastin

ARM C: sunitinib; following PD:

RG7446 plus Avastin

Primary endpoint

Progression free survival Progression free survival

Status Expect FPI Q2 2015 Recruitment completed Q1 2015

Anti-PDL1 (MPDL3280A, RG7446)

Novel approach in cancer immunotherapy

32

Indication Solid tumors Solid tumors Solid tumors _{metastatic solid tumors} Locally advanced or

Phase/study Phase I Phase I Phase I Phase I

# of patients N=160 N=110 N=360 N=200

Design Part 1: sequential

administration of RG7446 and RG7876 (CD40 iMAb)

Part 2: concomitant

administration of RG7446 and RG7876

Part 3: study drugs

schedule in specific indication per Part 2

RG7446 in combination with RG7155 (anti-CSF1R)

Part 1: dose escalation Part 2: expansion

Stage 1: Dose escalation

of RG7446 plus RG7888 (anti-OX40) Stage 2: Expansion RG7446 plus RG7888 (anti-OX40) ARM A: RG7446 plus ipilimumab ARM B: RG7446 plus interferon alpha-2b Primary endpoint

Safety Safety Safety Safety

Anti-PDL1 (MPDL3280A, RG7446)

Novel approach in cancer immunotherapy

33

Indication Solid tumors Relapsed/Refractory follicular _{lymphoma and DLBCL}

Phase/study Phase I Phase I

# of patients N=180 N=52

Design ARM A: RG7446 + Avastin

ARM B: RG7446 + Avastin + FOLFOX ARM C: RG7446 + carboplatin + paclitaxel ARM D: RG7446 + carboplatin+ pemetrexed ARM E: RG7446 + carboplatin+ nab-paclitaxel ARM F: RG7446 + nab-paclitaxel

Stage 1: safety evaluation

RG7446 plus Gazyva Stage 2: expansion RG7446 plus Gazyva Primary endpoint Safety/PK Safety Status FPI Q2 2012

Chemo combination data in NSCLC

to be presented at ASCO 2015

Anti-PDL1 (MPDL3280A, RG7446)

Novel approach in cancer immunotherapy

34

Indication Solid tumors _{melanoma BRAF mutation positive} Previously untreated metastatic

Phase/study Phase I Phase I

# of patients N=180 N=44

Design ARM A: RG7446 + Avastin

ARM B: RG7446 + Avastin + FOLFOX ARM C: RG7446 + carboplatin + paclitaxel ARM D: RG7446 + carboplatin+

pemetrexed

ARM E: RG7446 + carboplatin+

nab-paclitaxel

ARM F: RG7446 + nab-paclitaxel

Dose-finding study of RG7446 + Zelboraf1

and RG7446 + Zelboraf1 _{+ cobimetinib}2 combinations

Primary endpoint

Safety/PK Safety/PK

Status FPI Q2 2012

Chemo combination data in NSCLC to be

presented at ASCO 2015

FPI Q4 2012

1_{Zelboraf in collaboration with Plexxikon, a member of Daiichi Sankyo Group;} 2_{Cobimetinib in collaboration with Exelixis}

Anti-PDL1 (MPDL3280A, RG7446)

Novel approach in cancer immunotherapy

35

ASCO=American Society of Clinical Oncology; ECC=European Cancer Congress; AACR=American Association for Cancer Research ESMO=European Society for Medical Oncology

Indication

Previously untreated metastatic melanoma BRAF

mutation positive

Solid tumors _{melanoma BRAF mutation positive} Previously untreated metastatic

Phase/study Phase I Phase I Phase I

# of patients N=44 N=90 N=344

Design Dose-finding study of RG7446 +

Zelboraf1 _{and RG7446 +} Zelboraf1 _{+ cobimetinib}2 combinations ARM A: Dose-finding – RG7446 plus cobimetinib ARM B: Dose-expansion - RG7446 plus cobimetinib

Dose escalation study

Primary endpoint

Safety/PK Safety Safety/PK

Status FPI Q4 2012 FPI Q4 2013 FPI Q2 2011

Initial efficacy data presented at

ASCO 2013

Updated data presented at ECC

2013

Data from bladder cohort presented

at ASCO and ESMO 2014

Data from TNBC cohort presented

at AACR 2015

Updated lung and bladder data to

Cobimetinib (RG7421, GDC-0973)

Selective small molecule inhibitor of

mitogen-activated protein kinase kinase

36

Phase/study Phase III _coBRIM Phase II

# of patients N=495 N=112

Design ARM A: Zelboraf1 plus cobimetinib

ARM B: Zelboraf1 plus placebo

ARM A: cobimetinib plus paclitaxel ARM B: placebo plus paclitaxel

Primary endpoint

Progression-free survival Progression-free survival, safety

Status Primary endpoint met Q3 2014

Data presented at ESMO and SMR 2014 Results published NEJM 2014 Nov

13;371(20):1867-76

Filed in EU Q3 2014 Filed in US Q4 2014

Priority review granted Q1 2015 Updated data to be presented at ASCO

2015

FPI Q1 2015

In collaboration with Exelixis

1_{Zelboraf In collaboration with Plexxikon, a member of Daiichi Sankyo Group;}

Cobimetinib (RG7421, GDC-0973)

Selective small molecule inhibitor of

mitogen-activated protein kinase kinase

37

In collaboration with Exelixis

1_{Zelboraf In collaboration with Plexxikon, a member of Daiichi Sankyo Group}

Indication Locally advanced or _{metastatic tumors}

Previously untreated metastatic melanoma BRAF

mutation positive

Locally advanced or metastatic tumors with

mutant KRAS

Phase/study Phase I Phase I Phase I

# of patients N=90 N=44 N=50

Design ARM A: Dose-finding -

cobimetinib plus RG7446 (anti-PDL1)

ARM B: Dose-expansion -

cobimetinib plus RG7446 (anti-PDL1)

Dose-finding study of

RG7446+Zelboraf1 _and RG7446+Zelboraf+ cobimetinib combinations

Dose finding of cobimetinib

plus RG7597 (anti-HER3/EGFR DAF)

Primary endpoint

Safety Safety/PK Safety

Polatuzumab vedotin (RG7596)

Antibody drug conjugate targeting CD79b for the

treatment of B-cell malignancies

38

Indication Non-Hodgkin's lymphoma Non-Hodgkin’s lymphoma Relapsed or Refractory follicular _{lymphoma and DLBCL}

Phase _ROMULUS Phase II Phase Ib/II Phase Ib/II

# of patients N=228 N=90 N=224

Design ARM A: pinatuzumab vedotin plus

Rituxan

ARM B: polatuzumab vedotin plus

Rituxan

ARM C: polatuzumab vedotin plus

Gazyva

PhIb: dose escalation PhII: polatuzumab vedotin in

combinaiton with Rituxan or Gazyva and CHP non-randomized

PIb: dose escalation

PhII: polatuzumab vedotin + BR vs.

BR

PhII expansion: polatuzumab vedotin

+Gazyva non-randomized

Primary endpoint

Safety and anti-tumor activity Safety Safety and response by PET/CT

Status Recruitment in arms A&B completed

Q1 2014

Updated data presented at ASH

2014

FPI in Gazyva arm C Q1 2015 Updated data to be presented at

ASCO 2015

FPI Q4 2013 FPI Q4 2014

In collaboration with Seattle Genetics

ASH=American Society of Hematology; ASCO=American Society of Clinical Oncology BR=bendamustine and Rituxan; CHP=Cyclophosphamide, Hydroxydoxorubicin, Prednisone

Taselisib (RG7604, GDC-0032)

Mutant-selective PI3 kinase inhibitor

39

HER2-negative ER-positive metastatic breast caner patients who progressed after aromatase

inhibitor therapy

Neoadjuvant HER2-negative ER-positive breast cancer

Phase _SANDPIPER Phase III _LORELEI Phase II

# of patients N=600 N=330

Design ARM A: taselisib plus Fulvestrant

ARM B: placebo plus Fulvestrant

ARM A: taselisib plus letrozole ARM B: placebo plus letozole

Primary endpoint

Progression-free survival Response rate and pCR

Taselisib (RG7604, GDC-0032)

Beta isoform sparing PI3 kinase inhibitor targeting

commonly mutated oncogene

40

HER2-negative HR-positive locally recurrent or metastatic

breast cancer

PI3KCAmut-pos. 2L squamous NSCLC

Lung Master Protocol

Phase Phase I/II Phase I _Lung-MAP Phase II

# of patients N=320 N=65 N=120

Design Phase I

taselisib

taselisib plus letrozole or

fulvestrant

Phase II

taselisib (multiple doses) plus

letrozole or fulvestrant

taselisib plus docetaxel taselisib plus paclitaxel

taselisib vs. chemo

Primary endpoint

Safety/PK/efficacy Safety Progression-free survival

Status Recruitment completed Q2 2014

Updated data presented at SABCS

2014

FPI Q2 2013 FPI Q2 2014

Venetoclax (RG7601, ABT-199/GDC-0199)

Novel small molecule Bcl-2 selective inhibitor

41

Untreated CLL patients with coexisting medical

conditions

Relapsed or Refractory CLL Relapsed or Refractory CLL _{with 17p deletion}

Phase/study Phase III _{CLL14 MURANO} Phase III Phase II

# of patients N=432 N=370 N=100

Design ARM A: venetoclax plus

Gazyva

ARM B: chlorambucil plus

Gazyva

ARM A: venetoclax plus

Rituxan

ARM B: Rituxan plus

bendamustine

Single-agent venetoclax

Primary endpoint

Progression-free survival Progression-free survival Safety/MTD

Status FPI Q4 2014 FPI Q1 2014 Recruitment completed Q2

2014

Data expected in 2015

Joint project with AbbVie in collaboration with WEHI (The Walter and Eliza Hall Institute)

CLL=Chronic Lymphocytic Leukemia; NHL=Non-Hodgkin's Lymphoma; SLL=Small Lymphocytic Lymphoma ASCO=American Society of Clinical Oncology

42

Indication Relapsed or Refractory _CLL Relapsed CLL and SLL

Relapsed or Refractory or previously untreated CLL Relapsed or Refractory or previously untreated CLL Phase/stud

y Phase II Phase Ib Phase Ib Phase Ib # of

patients N=40 N=50 N=70 N=74

Design venetoclax after ibrutinib

therapy

venetoclax after idelalisib

therapy Dose-escalation study in combination with MabThera/Rituxan venetoclax in combination with MabThera/Rituxan and bendamustine venetoclax in combination with Gazyva Primary endpoint

Overall response rate Safety/MTD Safety/MTD Safety/MTD

Status FPI Q3 2014 Recruitment completed

Q1 2015

Data presented at ASCO

2014

FPI Q2 2013 FPI Q1 2014

Joint project with AbbVie in collaboration with WEHI (The Walter and Eliza Hall Institute)

CLL=Chronic Lymphocytic Leukemia; NHL=Non-Hodgkin's Lymphoma; SLL=Small Lymphocytic Lymphoma ASCO=American Society of Clinical Oncology

Venetoclax (RG7601, ABT-199/GDC-0199)

43

Relapsed or Refractory follicular non-Hodgkin’s

lymphoma

Front-line DLBCL Relapsed or Refractory _NHL Relapsed or Refractory _{CLL and NHL}

Phase/study _CONTRALTO Phase II Phase I/II _CAVALLI Phase I Phase I

# of patients N=156 N=230 N=40 N=211

Design ARM A: venetoclax plus

Rituxan

ARM B: venetoclax plus

Rituxan plus bendamustine

ARM C: Rituxan plus

bendamustine Dose finding: ARM A: venetoclax+R-CHOP ARM B: venetoclax+G-CHOP Expansion: venetoclax+R/G-CHOP Dose escalation of venetoclax in combination with Rituxan and

bendamustine

Dose-escalation study

Primary endpoint

Overall response rate Safety and efficacy Overall response rate Safety/PK/Response rate

Status FPI Q4 2014 FPI Q2 2014 FPI Q2 2012

Study resumed Q3 2013

FPI Q2 2011

Updated CLL, SLL and NHL

(DLBCL and FL) data presented at ASCO 2014 Joint project with AbbVie in collaboration with WEHI (The Walter and Eliza Hall Institute)

ASCO=American Society of Clinical Oncology

Venetoclax (RG7601, ABT-199/GDC-0199)

44

Indication Relapsed or refractory multiple myeloma Acute myelogenous leukemia (AML)

Phase/study Phase I Phase I Phase II Phase Ib

# of patients N=30 N=30 N=54 N=89

Design Patients receiving

Bortezomib and Dexamethasone as standard therapy:

Dose escalation cohort:

venetoclax+bortezomib+de xamethasone

Safety expansion cohort:

venetoclax+bortezomib+de xamethasone

Dose escalation cohort Safety expansion cohort

Dose escalation of venetoclax venetoclax (dose escalation) +decitabine venetoclax (dose escalation) +azacitidine Primary endpoint

Safety/MTD Safety/MTD Overall response rate Safety

Status FPI Q4 2012 FPI Q4 2012 FPI Q4 2013

Data presented at ASH

2014

FPI Q4 2014

Joint project with AbbVie in collaboration with WEHI (The Walter and Eliza Hall Institute)

Venetoclax (RG7601, ABT-199/GDC-0199)

Factor IXa/X bispecific (RG6013, ACE910)

Factor VIII mimetic for treatment of hemophilia A

45

In collaboration with Chugai

ASH=American Society of Hematology

Indication Hemophilia A

Phase/study _{Study in Japan} Phase I _{Study in Japan} Phase I/II

# of patients N=82 N≈18

Design Enrolled 64 HVs and 18 patients Extension study in patients from

phase 1

Primary endpoint

Exploratory efficacy and safety Exploratory efficacy and safety

Status Recruitment completed Q2 2014

Data presented at ASH 2014

Bitopertin (GlyT-1, RG1678)

A small molecule first-in-class glycin reuptake inhibitor

(GRI)

46

Indication Obsessive-compulsive disorder

Phase/study _SKYLYTE Phase II

# of patients N=99

Design 16-week treatment period

Background therapy of selective serotonin reuptake inhibitors

(SSRI)

•ARM A: bitopertin daily (30 mg) •ARM B: bitopertin daily (10 mg) •ARM C: placebo

Primary endpoint

Change in total score on Yale-Brown Obsessive Compulsive

Scale

Gantenerumab (RG1450)

Fully human monoclonal antibody against amyloid-beta

47

Indication Prodromal Alzheimer’s Disease Mild Alzheimer’s Disease

Phase/study _{SCarlet RoAD} Phase II/III _{Marguerite Road} Phase III

# of patients N=799 N=1,000

Design 104-week subcutaneous treatment period

ARM A: gantenerumab (225 mg) ARM B: gantenerumab (105 mg) ARM C: placebo

104-week subcutaneous treatment period ARM A: gantenerumab

ARM B: placebo Primary

endpoint

Change in CDR-SOB at 2 years

Sub-study: change in brain amyloid by PET

at 2 years

Change in ADAS-Cog and ADCS-ADL at 2

years (co-primary)

Status Phase I PET data: Archives of Neurology

2012 Feb;69(2):198-207

Enrollment completed Q4 2013 Dosing stopped due to futility Q4 2014

FPI Q1 2014

In collaboration with Morphosys

Etrolizumab (RG7413)

A humanized monoclonal antibody against beta 7

integrin

48

Indication Ulcerative colitis patients who are TNF naïve

Phase/study Phase III HIBISCUS I Induction study Phase III HIBISCUS II Induction study Phase III GARDENIA

Sustained remission study

# of patients N=350 N=350 N=720

Design ARM A: etrolizumab 105mg SC q4w

+ adalimumab placebo

ARM B: etrolizumab placebo +

adalimumab

ARM C: etrolizumab placebo +

adalimumab placebo

ARM A: etrolizumab 105mg SC q4w

+ adalimumab placebo

ARM B: etrolizumab placebo +

adalimumab

ARM C: etrolizumab placebo +

adalimumab placebo

Time on treatment 54 weeks

ARM A: etrolizumab 105mg SC q4w + placebo IV ARM B: placebo SC q4w + adalimumab SC Primary endpoint

Induction of remission compared with

placebo as determined by the Mayo Clinic Score (MCS) at week 10

Induction of remission compared with

placebo as determined by the Mayo Clinic Score (MCS) at week 10

Proportion of patients in sustained

clinical remission as determined by Mayo Clinic Score (MCS) at weeks 10, 30 and 54

Etrolizumab (RG7413)

A humanized monoclonal antibody against beta 7

integrin

49

UC patient who are TNF naïve and refractory or intolerant to immunosuppressant and/or corticosteroid

treatment

UC patient who are refractory or intolerant of TNF inhibitors Phase/study Phase III LAUREL Maintenance study Phase III HICKORY

Induction and maintenance study

# of patients N=350 N=800

Design Induction phase:

ARM A: open label etrolizumab 105mg SC q4w

Maintenance study:

ARM B: etrolizumab 105mg SC q4w ARM C: placebo

Cohort 1 (open-label):

ARM A: etrolizumab induction + placebo maintenance ARM B: etrolizumab induction + maintenance

Cohort 2 (blinded):

ARM A: etrolizumab induction + maintenance ARM B: placebo induction + maintenance Primary

endpoint

Maintenance of remission (at week 62) among randomized

patients in remission at Week 10 as determined by the Mayo Clinic Score (MCS)

Clinical Remission (Mayo Clinic Score, MCS) at Week 14 Remission maintenance (by MCS, at Week 66) among

patients with remission at Week 14

Status FPI Q3 2014 FPI Q2 2014

Etrolizumab (RG7413)

A humanized monoclonal antibody against beta 7

integrin

50

Indication Moderate to severe ulcerative colitis Moderate to severe ulcerative colitis

Phase/study

Phase II SPRUCE

Open label extension study

Phase III COTTONWOOD

Open label extension study

# of patients N=116 N=2,600

Design Patients who were enrolled in EUCALYPTUS

study and meet enrollment criteria will receive etrolizumab 105 sc q4w

Patients who were previously enrolled in

etrolizumab phase III studies and meet enrollment criteria will receive etrolizumab 105 sc q4w

Primary endpoint

Safety Long-term efficacy as determined by partial

Mayo Clinic Score (pMCS)

Incidence of adverse events

Etrolizumab (RG7413)

A humanized monoclonal antibody against beta 7

integrin

51

Indication Moderately to severely active Crohn's _disease Moderately to severely active Crohn's _disease

Phase/study _BERGAMOT Phase III Phase III _JUNIPER

# of patients N=1,250 N=1,250

Design ARM A: etrolizumab SC 210 mg (induction

only)

ARM B: etrolizumab SC 105 mg and

maintainance

ARM C: placebo

Etrolizumab SC 105mg q4w

Primary endpoint

Induction and maintenance of clinical

remission

 Safety

HCV: Danoprevir (RG7227)

IFN-based triple regimen for treatment-naïve patients of

Asian origin conducted in China

52

Phase/study _DAPSANG Phase II

# of patients N=61

Design Without cirrhosis:

ARM A: Danoprevir 125 mg bid + Ritonavir 100mg bid+ Pegasys + Copegus for

12 weeks

With compensated cirrhosis:

ARM B: Danoprevir 125 mg bid + Ritonavir 100mg bid+ Pegasys + Copegus for

24 weeks

Primary

endpoint Safety

Status Recruitment completed Q4 2013

Results presented at APASL 2015

In collaboration with Ascletis

53

Indication Geographic atrophy (GA) secondary to age-related macular degeneration

Phase/study _CHROMA Phase III Phase III _SPECTRI Phase II

# of patients N=936 N=936 N=100

Design ARM A: lampalizumab 10mg q4w

ARM B: lampalizumab 10mg q6w ARM C: placebo ARM A: lampalizumab 10mg q4w ARM B: lampalizumab 10mg q6w ARM C: placebo ARM A: lampalizumab 10mg q2w ARM B: lampalizumab 10mg q4w ARM C: placebo Primary endpoint

Primary: change in GA area Secondary: change in BCVA and in

additional measures of visual function

Primary: change in GA area Secondary: change in BCVA and in

additional measures of visual function

Change in GA area

Status FPI Q3 2014

Design presented at EURETINA

2014

Fast track designation received Q4

2014

FPI Q3 2014

Design presented at EURETINA

2014

Fast track designation received Q4

2014

FPI Q4 2014

EURETINA=European Society of Retina Specialists

Lampalizumab (RG7417)

Antibody fragment to selectively block activation of

alternative complement pathway

Lebrikizumab (RG3637)

A humanized monoclonal antibody designed to

bind specifically to IL-13

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Indication _{asthma is uncontrolled with inhaled corticosteroids and a second controller medication} Adult patients whose

Phase/study _{LAVOLTA I} Phase III _{LAVOLTA II} Phase III

# of

patients N=1,050 N=1,050

Design Subcutaneous lebrikizumab q4w on top of SOC for

52 weeks safety follow-up

ARM A: lebrikizumab high dose ARM B: lebrikizumab low dose ARM C: placebo

Patients will be tested for periostin level

Subcutaneous lebrikizumab q4w on top of SOC for

52 weeks safety follow-up

ARM A: lebrikizumab high dose ARM B: lebrikizumab low dose ARM C: placebo

Patients will be tested for periostin level

Primary endpoint

Rate of asthma exacerbations during the 52-week

placebo-controlled period

Rate of asthma exacerbations during the 52-week

placebo-controlled period

Status Enrollment completed Q4 2014

Expect data in 2016

Enrollment completed Q4 2014 Expect data in 2016