59 - Roche4cf03e98-fb44-4f1f... · •Primary endpoint CR by PET-CT by IRC after primary assessment...

59th ASH Annual Meeting, Atlanta

Roche Conference Call Wednesday, 13 December 2017

3

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Introduction

Karl Mahler Head of Investor Relations

Agenda

Welcome

Karl Mahler, Head of Investor Relations

Roche hematology portfolio: ASH update

Sandra Horning, M.D., Chief Medical Officer and Head Global Product Development

Hemlibra: Changing the standard of care in hemophilia A

Gallia Levy, M.D., Ph.D., Global Development Team Leader, Hemlibra

Q&A

Karl Mahler, Head of Investor Relations

5

Highlights from ASH

6

Venclexta

Polatuzumab vedotin

Emicizumab

Ph 3 MURANO sets a new

standard of care in R/R CLL

Ph 3 trials ongoing in 1L

CLL, AML, and MM: novel

combinations (idasanutlin)

Ph 2 results in R/R DLBCL show

strong benefit over Rituxan + benda

Moving into 1L DLBCL with

Ph 3 POLARIX trial

Updated data in Hemophilia A

patients with inhibitors shows bleed

rates continue to improve, q4w data

Positive results in patients

without inhibitors and for

monthly dosing

Data presented at ASH Future program developments

DLBCL=diffuse large B cell lymphoma; AML=acute myeloid leukemia; CLL=chronic lymphocytic leukemia, R/R = relapsed/refractory

Recognition for innovation 2013-present

7 Breakthrough designations for 4 NMEs in hematology

7

Rank Company #

1 Roche 18

2 Novartis 15

3 BMS 10

4 Merck 9

4 Pfizer 9

18 Breakthrough Therapy Designations

Source: http://www.focr.org/breakthrough-therapies as of October 2017; NME=new molecular entity; BR=bendamustin+Rituxan; DLBCL=diffuse large B cell lymphoma;

LDAC=low dose cytarabine; AML=acute myeloid leukemia; ECD=Erdheim-Chester disease; NSCLC=non-small cell lung cancer; PPMS=primary progressive multiple

sclerosis; HMA=hypomethylating agent; CLL=chronic lymphocytic leukemia; IPF=idiopathic pulmonary fibrosis

= BTDs in hematology

http://www.focr.org/breakthrough-therapies



Roche hematology portfolio: ASH update

Sandra Horning, M.D. Executive VP Chief Medical Officer and Head Global Product Development

Late-stage portfolio: Improving the standard of

care and new indications in malignant hematology

9

¹Datamonitor; incidence rates includes the 7 major markets (US, Japan, France, Germany, Italy, Spain, UK); CLL=chronic lymphoid leukemia; DLBCL (aNHL)=diffuse

large B-cell lymphoma; iNHL=indolent non-hodgkin`s lymphoma; AML=acute myeloid leukemia; MM=multiple myeloma; MDS=myelodysplastic syndrome; ALL=acute

lymphoblastic leukemia; Venclexta in collaboration with AbbVie; Gazyva in collaboration with Biogen; Polatuzumab vedotin in collaboration with Seattle Genetics; Rituxan

HYCELA (Rituxan SC) partnered with Halozyme, BTD for R/R CLL and R/R DLBCL

Incidence rates (330,000 pts1)

Ph III 1L (CLL14)

Ph III R/R (MURANO)

Ph III

Ph III

Polatuzumab

vedotin

+

Ph II R/R (GO29365)

Ph III 1L (POLARIX) +

Ph III Idasanutlin

Late-stage portfolio:

Polatuzumab vedotin in DLBCL

10 ¹Datamonitor; incidence rates includes the 7 major markets (US, Japan, France, Germany, Italy, Spain, UK); CLL=chronic lymphoid leukemia; DLBCL (aNHL)=diffuse


lymphoblastic leukemia; Gazyva in collaboration with Biogen; Polatuzumab vedotin in collaboration with Seattle Genetics


Polatuzumab

vedotin

Ph II R/R (GO29365)

Ph III 1L (POLARIX) +

11

Polatuzumab vedotin in R/R DLBCL

Compelling randomized Ph2 results

Overall Survival

Phase II update:

• Primary endpoint CR by PET-CT by IRC after primary assessment (6-8 weeks after end of treatment)

was 40% for Pola + BR vs 15% for BR (p=0.012)

• DOR, PFS, OS were positive with a PFS HR of 0.31 (p<0.0001) and a OS HR of 0.35 (p=0.0008)

• Safety profile in-line with that observed for BR

Sehn L. H. et al., ASH 2017; PET-CT=positron emission tomography-computed tomography; ORR=overall response rate; CR=complete remission;

PR=partial remission; SD=stable disease; PD=progressive disease; DOR=duration of response; PFS=progression free survival; OS=overall survival;

HR=hazard ratio; Pola=polatuzumab vedotin (in collaboration with Seattle Genetics); B=bendamustine; R=rituxan

12

Polatuzumab vedotin in R/R DLBCL

Ph3 study of polatuzumab + R-CHP started

Phase II update:

• PET-CT data show that Pola+BR improved responses in both ABC and GCB

• Based on these results BTD and PRIME status awarded by FDA and EMA

• Ph3 study (POLARIX) of Pola+R-CHP vs R-CHP in 1L DLBCL initiated (First-patient-in Nov 17)

OR and CR by PET-CT*

Sehn L. H. et al., ASH 2017; PET-CT=positron emission tomography-computed tomography; OR= overall response; CR=complete remission; INV=investigator;

IRC=independent review committee; Pola=polatuzumab vedotin (in collaboration with Seattle Genetics); B=bendamustin; R=rituxan

* at primary response assessment (6–8 weeks after Cycle 6 Day 1 or last dose of therapy); + conducted in subset with available data

Armitage J., Blood 2011;118:2-3

PET-CT as endpoint

Pretreatment Posttretreatment


Venclexta in CLL

13 ¹ Datamonitor; incidence rates includes the 7 major markets (US, Japan, France, Germany, Italy, Spain, UK); CLL=chronic lymphoid leukemia; DLBCL (aNHL)=diffuse


lymphoblastic leukemia; Venclexta in collaboration with AbbVie; Gazyva in collaboration with Biogen


Ph III 1L (CLL14)

Ph III R/R (MURANO) +

14

Venclexta in R/R CLL

MURANO supports new standard therapeutic option

Seymour J. et al., ASH 2017; INV=investigator; PFS=progression free survival; HR=hazard ratio; V=Venclexta in collaboration with

AbbVie

Trial design

Phase III interim results (MURANO):

• Primary PFS endpoint met (HR of 0.17) with benefit across all sub-groups, including high-risk patients

• Safety consistent with known safety profile of R/R CLL patients

INV assessed PFS

HR (95% CI)

0.17 (0.11-0.25)

P<0.0001

15 Seymour J. et al., ASH 2017; * descriptive P value; INV=investigator; IRC=independent review committee; ORR=overall response rate;

CR=complete remission; CRi=complete remission with incomplete marrow recovery; PR=partial remission; nPR=nodular partial remission;

SD=stable disease; PD=progressive disease; HR=hazard ratio; V=venclexta (in collaboration with AbbVie); R=rituxan; B=bendamustine

Venclexta in R/R CLL Strong response rates, encouraging OS

Response rates


• Investigator assessed ORR of 93.3% with 26.8% of patients showing a CR or CRi

• OS HR of 0.48 with a descriptive p-value of 0.0186

• Landmark 2Y OS at 91.9% for V+R vs 86.6% for B+R

Overall Survival (OS)

HR (95% CI)

0.48 (0.25-0.90)

P=0.0186*

16 16

MRD in CLL: Surrogate endpoint of depth of

remission and marker of durable disease control

MRD=minimal residual disease; PFS=progression free survival; OS=overall survival; F=fludarabine, C=cyclophosphamide; R=Rituxan

MRD as prognostic factor: CLL8 study in 1L CLL (FCR vs FC)

Venclexta in R/R CLL

MRD negativity rate maintained over time

17 Seymour J. et al., ASH 2017; MRD=minimal residual disease; V=venclexta (in collaboration with AbbVie); R=rituxan; B=bendamustine


• High rates of peripheral blood MRD negativity achieved

• Around 60% of patients on V+R achieved MRD negativity vs 5-10% for B+R

• Higher rates of peripheral blood MRD negativity were maintained for at least 18 months

indicating deep and long lasting responses

Minimal residual disease in peripheral blood

18 18

R/R CLL: Cross trial comparison

Venclexta to induce deep responses

1.Stilgenbauer S, et al. ASH 2015 LBA-6; 2. Seymour JF, et al. ASCO 2014 Abs 7015; 3.Roberts NEJM 2016; 4. Byrd ASCO 2017 P7510; 5.Brown, JCO 2013;

6.Seymour ASH 2017 LBA2; 7.Chanan-Khan Lancet Oncol. 2016; 8.Burger Lancet 2014; 9. Jain CCR 2017; 10. Furman NEJM 2014; 11. Robak, JCO 2010;

Cross-trial comparisons have inherent limitations. Therefore, any such comparison should be taken with its limitations in consideration. Different

trials can potentially include different patient populations and may have different methodologies for data collection/data analysis.

ORR=overall response rate; CR=complete remission; MRD=minimal residual disease; mPFS=medium progression free survival; mOS=medium overall

survival; HR=hazard ratio; VEN=Venclexta (in collaboration with AbbVie); Ibr=ibrutinib; Idela=idelalisib; B=bendamustine; R=rituxan; IRC=independent

review committee; PB=peripheral blood; NR=not reached; est=estimated from graph

Venclexta + Gazyva in 1L CLL

Ph1 study design

19 Flinn I. W. et al., ASH 2017; Gazyva dosing schedule: C1D1=Cycle 1 day 1; VEN=venclexta (in collaboration with AbbVie);

G=Gazyva (in collaboration with Biogen)

Phase I update (GP28331/NCT01685892):

• 6 cycles of VEN+G combination therapy followed by 6 months of VEN monotherapy

• 1 cycle of G completed prior to VEN ramp up phase; 6 patients were started on a different schedule

• Ph3 study (CLL14) ongoing; First-patient-in in Nov 2016

Study design

Venclexta + Gazyva in 1L CLL

Strong response rates and lasting MRD negativity

20 Flinn I. W. et al., ASH 2017; MRD=minimal residual disease; VEN=venclexta (in collaboration with AbbVie); G=Gazyva (in collaboration with Biogen);

ORR=overall response rates; CR=complete remission; CRi=complete remission with incomplete marrow recovery; PR=partial remission

MRD negativity in peripheral blood

Phase I interim results (GP28331/NCT01685892):

• 32 patients with 100% ORR (72% CR/CRi and 28% PR), including high-risk patients

• Highly durable MRD negativity rates

• Favorable benefit/risk profile in previously untreated CLL

Response rates


Venclexta in AML

21 ¹ Datamonitor; incidence rates includes the 7 major markets (US, Japan, France, Germany, Italy, Spain, UK); CLL=chronic lymphoid leukemia; DLBCL (aNHL)=diffuse


lymphoblastic leukemia; Venclexta in collaboration with AbbVie; Gazyva in collaboration with Biogen


Ph III

Venclexta + AZA/DEC in 1L elderly AML

Encouraging response rates and mOS

22

Phase Ib update (NCT02203773):

• ORR of 65%, compares favorably to historic results

• mOS of 17.5 months obtained for the 800mg VEN dose; not reached for the 400mg VEN dose

• 400mg VEN combination dose established due to best benefit-risk profile

• Ph3 study (NCT02993523) of VEN+AZA in 1L AML on-going (First-patient-in in Q1 17)

DiNardo C. D. et al., ASH 2017; AZA=azacitidine; DEC=decitabine; ORR=overall response rate; CR=complete remission; CRi=complete

remission with incomplete marrow recovery; DOR=duration of response; NR=not reached; VEN=Venclexta (in collaboration with AbbVie)

Overall Survival (OS)

23

20 Years of improving the standard of care

ADCC=antibody-dependent cellular cytotoxicity; ADCP=antibody-dependent cellular phagocytosis

Hemlibra: Changing the standard of care in

hemophilia A

Gallia Levy, M.D., Ph.D. Global Development Team Leader, Hemlibra

Hemlibra now approved in hemophilia A with

factor VIII inhibitors

Approved in US, updated data presented at ASH, data

currently under review by EMA (accelerated assessment)

Trial met primary endpoint and key secondary endpoints

HAVEN 1 Adult/adolescent inhibitor, QW dosing

Positive interim results

• Label contains no limitations

on age

• First treatment in hemophilia

to compare to prophylaxis

• Statistically significant

quality-of-life improvement

included in label.1

• Boxed warning and dosing

guidance important for

patient safety

FDA approval November 2017

3 months prior to PDUFA date

1 Physical Health Score of the Hemophilia-specific Quality of Life Score ,

HAVEN 2 Pediatric inhibitor, QW dosing

HAVEN 3 Non-inhibitor, QW/Q2W dosing

HAVEN 4 Inhibitor/Non-inhibitor Q4W dosing

✔

✔

Approved in US, updated data presented at ASH, data

currently under review by EMA (accelerated assessment)

25

15.7

1.8 0

2

4

6

8

10

12

14

16

18

Prior BPA

prophylaxis

Emicizumab

prophylaxis

Annualliz

ed b

leedin

g r

ate

1

88% reduction P<0.0001

HAVEN 1: Bleed rates have continued to

improve over time

Prophylactic

BPA’s

Prior

prophylactic

BPA

Emicizumab

NIS Haven1, Arm C

Treated bleeds with emicizumab prophylaxis

vs. prior BPA prophylaxis

HAVEN 1 intra-individual comparison

Mancuso M.E. et al., ASH 2017; ABR=Annualized bleeding rate; BPA=Bypassing agent; NIS=Non-interventional study, IQR = interquartile range 1Negative binomial model 2 Primary analysis data cutoff: Oct 25, 2016; Updated analysis data cutoff: Sep 8, 2017

Interval (weeks)

1-24 25-48 49-72

Mean ABR (95% CI)

Median ABR (IQR)

0 0 0 0.5

Calc

ula

ted A

BR

for

24 w

k inte

rval

HAVEN 1 emicizumab bleed rates over time

Treated bleeds with emicizumab prophylaxis over 24 wk intervals

1-24 25-48 49-72

Interval (weeks)

Proportion of patients with zero bleeds over 24 wk intervals Patients

with z

ero

ble

eds

for

24-w

eek inte

rval (%

)

88%

26

Nearly 10 months additional follow-up2

HAVEN 2: Ph3 update in pediatric patients with

inhibitors

Young G. et al., ASH 2017; ABR = Annualized Bleeding Rate, BPA = Bypassing agent, QOL= Quality of Life, IQR = interquartile range, 1Interim analysis data

cutoff: Oct 28, 2016; Updated analysis data cutoff: May 8, 2017, *Aged <12 years, † Primary efficacy results (ABR analysis) based only on patients aged < 12 yrs

on study for ≥12 wks, ‡ Negative binomial regression model

• 54/57 (94.7%) of children with zero treated bleeds on emicizumab prophylaxis

• Quality of life improvement seen in pediatric patients on emicizumab prophylaxis

• No thromboembolic or thrombotic microangiopathy events reported

40 additional patients and ~6m of additional follow-up confirm earlier analysis1

27

HAVEN 2: Ph3 update in pediatric patients with

inhibitors in intra-patient analysis

Young G. et al., ASH 2017; ABR = Annualized Bleeding Rate, BPA = Bypassing agent, QOL= Quality of Life, Interim analysis data cutoff: Oct 28, 2016; Updated

analysis data cutoff: May 8, 2017,

HAVEN 2 intra-individual comparison emicizumab prophylaxis vs prior BPA treatment

31.8

12.4

2.5

18.0

0

24.4

14.3

34.2 31.8

9.3

17.9

11.5 11.0

1.4 1.3 0 0 0 0 0 0 0 0 0 0 0 0

10

20

30

40

1 2 3 4 5 6 7 8 9 10 11 12 13

Patient

Calc

ula

ted

AB

R

(tre

ate

d b

leed

s)

Emicizumab Prophylaxis Prior BPA, episodic Prior BPA prophylaxis

99% reduction in treated bleeds vs. prior BPA treatment in intra-patient analysis

28

Hemlibra continues to build robust safety profile

29 surgeries1

1 Patients with planned surgeries, with the exception of minor procedures, were excluded from both studies. Unplanned emergency surgeries, in addition to minor

procedures, were performed in patients receiving emicizumab. Surgeries included: tooth extractions (6), CVAD procedures (13), other (10)

BPA = bypassing agent, TMA = thrombotic microangiopathy, aPCC = activated prothrombin complex concentrate, rVIIa = recombinant activated factor VII

19 No BPA

Prophylaxis

10 BPA

Prophylaxis

Surgical experience with inhibitor patients in

HAVEN1 and HAVEN2

3 Untreated

Bleed

2 Treated

bleeds

14 No

Bleeds

2 Treated

bleeds

8 No

Bleeds

Dosing guidance drove risk-mitigating changes

treatment of breakthrough bleeds

Investigator’s choice

74% 10% 11% 80% 20%

Pre-dosing

guidance

Post-dosing

guidance

59.1% 76.6% Breakthrough bleeds

treated with rFVIIa

Of those treated with

aPCC, low dose given <50U/kg/day

1.6% 40.0%

TMA/thrombosis events successfully mitigated when dosing guidance was followed in >200

patients with inhibitors to date

Callaghan M. U. et al., ASH 2017 Jarres R. K. et al., ASH 2017

29

HAVEN 3: Positive trial in non-inhibitor patients

• Met primary endpoint: reduction in treated bleeds vs. no prophylaxis (Arm A vs. C)

• Q2W dosing achieved: secondary endpoint met (Arm B vs. C)

• Intra-Patient Comparison: emicizumab prophylaxis superior to FVIII prophylaxis (Arm D)

• No new safety signals observed: no TMA or thrombotic events occurred in this study.

• Plan to submit for filing: data to be presented at an upcoming medical congress.

FVIII = factor VIII, TMA = thrombotic micro angiopathy

ARM A: Emicizumab 1.5mg/kg/wk maintenance

Screening Severe Hemophilia A

Pre-study episodic FVIII

Pre-study FVIII prophylaxis

R 2:2:1

ARM B: Emicizumab 3.0mg/kg/2wks maintenance

ARM C: No prophylaxis

ARM D: Emicizumab 1.5mg/kg/wk maintenance

24 w

eek p

rim

ary

eff

icacy

analy

sis

Em

iciz

um

ab

continuation

n=34

n=34

n=17

n=40-60 Intra-patient comparison

HAVEN3 Study Design: Adult and adolescent non-inhibitor patients

✔

✔

✔

30

Clinical data from weekly and monthly dosing

consistent with PK modeling

31

weekly

dosing

Modeled ABR

q2w

dosing

q4w

dosing

HAVEN 1/2/3 Data consistent with

PK modeling

HAVEN 3

Data consistent with

PK modeling

HAVEN 4 Preliminary data

consistent with PK

modeling

PK Modeling (plasma conc.)

✔

✔

Clin. Pharmacokinetics 2017 Dec 06, Selected phase III dosing regimens: repeated subcutaneous loading dose of 3 mg/kg once weekly for first 4 weeks followed

by subcutaneous maintenance doses of 1.5 mg/kg once weekly (a), 3 mg/kg every 2 weeks (b), and 6 mg/kg every 4 weeks (c).

HAVEN 4: Positive interim results for q4w dosing

HAVEN 4 PK run-in data

PK run-in cohort

(n=7)

Expansion cohort

(n=41)

PK, safety Efficacy, safety, PK/PD

• Hemlibra q4w prophylaxis showed a

clinically meaningful control of bleeding

• Preliminary findings are consistent with

results from previous studies of Hemlibra

dosed once weekly or every two weeks

• Levels of Hemlibra in the blood

(pharmacokinetics) are maintained in a

clinically effective range

• HAVEN 4 fully enrolled, interim results to

be presented at an upcoming meeting

HAVEN 4 positive interim results

✔

Jiménez-Yuste V. et al., ASH 2017, Dosing regimens: repeated subcutaneous loading dose of 3 mg/kg once weekly for first 4 weeks followed by subcutaneous

maintenance doses of 6 mg/kg every 4 weeks (c).

32

33

Appendix

34

Hematology pipeline progress in 2017

13 molecules in combination testing

* Venclexta in collaboration with AbbVie; Polatuzumab vedotin in collaboration with Seattle Genetics; Cotellic in collaboration with Exelixis; ChK1i in collaboration with

Array BioPharma; NHL=non-hodgkin`s lymphoma; CLL=chronic lymphoid leukemia; MM=multiple myeloma; MDS=myelodysplastic syndrom; AML=acute myeloid

leukemia

= progress in 2017

2x

2x

Indication Relapsed or refractory

FL and DLBCL 1L DLBCL

Phase/study Phase Ib/II Phase III

POLARIX

# of patients N=224 N=875

Design

PIb: Dose escalation

PhII: Polatuzumab vedotin plus BR vs. BR

PhII expansion: Polatuzumab vedotin plus Gazyva, non-

randomized

ARM A: Polatuzumab vedotin plus R-CHP

ARM B: R-CHOP

Primary

endpoint

Safety and response by PET/CT Progression-free survival

Status

FPI Q4 2014

Recruitment completed Q3 2016

Updated data presented at ASH 2016, ICML and EHA 2017

PRIME designation (Q2 2017) and Breakthrough Therapy

Designation granted (Q3 2017) for r/r DLBCL

FPI expected Q4 2017

CT Identifier

NCT02257567 NCT03274492

35

Polatuzumab vedotin (RG7596)

ADC targeting CD79b to treat B cell malignancies

In collaboration with Seattle Genetics

ADC=antibody–drug conjugate; DLBCL=diffuse large B cell lymphoma; FL=follicular lymphoma; ASH=American Society of Hematology;

ICML=international Conference on Malignant Lymphoma; EHA=European Hematology Association; BR=bendamustine and Rituxan; R-CHP=Rituxan,

cyclophosphamide, hydroxydoxorubicin, prednisone; R-CHOP=Rituxan, cyclophosphamide, doxorubicin, vincristine, and prednisone

Venclexta (venetoclax, RG7601, ABT-199)

Novel small molecule Bcl-2 selective inhibitor – CLL

36 Joint project with AbbVie, in collaboration with The Walter and Eliza Hall Institute

CLL=chronic lymphocytic leukemia

Indication Untreated CLL patients with

coexisting medical conditions Relapsed or refractory CLL

Relapsed or refractory CLL

with 17p deletion

Phase/study Phase III

CLL14

Phase III

MURANO Phase II

# of patients N=432 N=391 N=100

Design

ARM A: Venclexta plus Gazyva

ARM B: Chlorambucil plus Gazyva

ARM A: Venclexta plus Rituxan

ARM B: Rituxan plus bendamustine

Single-agent Venclexta

Primary

endpoint

Progression-free survival Progression-free survival Safety and maximum tolerated dose

(MTD)

Status

FPI Q4 2014



Study met primary endpoint at interim

analysis

Breakthrough designation granted by FDA

Q2 2015, priority review granted, US

approval Q2 2016

Approved in EU Q4 2016

CT Identifier NCT02242942 NCT02005471 NCT01889186


CLL=chronic lymphocytic leukemia; SLL=small lymphocytic lymphoma

ASH=American Society of Hematology; ASCO=American Society of Clinical Oncology; EHA=European hematology association


Novel small molecule Bcl-2 selective inhibitor – CLL

Indication Relapsed or refractory CLL Relapsed CLL and SLL Relapsed or refractory or

previously untreated CLL

Relapsed or refractory or

previously untreated CLL

Phase/study Phase II Phase Ib Phase Ib Phase Ib

# of patients N=120 N=50 N=100 N=90

Design

Venclexta after ibrutinib

therapy

Venclexta after idelalisib

therapy

Dose-escalation study in

combination with

MabThera/Rituxan

Venclexta in combination with

MabThera/Rituxan and

bendamustine

Venclexta in combination with

Gazyva

Primary

endpoint

Overall response rate Safety and maximum tolerated

dose

Safety and maximum tolerated

dose

Safety and maximum tolerated

dose

Status

FPI Q3 2014

Data presented at ASH 2015

Updated data presented at

ASCO 2016

Recruitment completed Q1

2015

Data presented at ASCO 2014

and EHA 2015

Updated data presented at

ASH 2015 and ASCO 2016

Breakthrough designation

granted by FDA Q1 2016

FPI Q2 2013


FPI Q1 2014


CT Identifier NCT02141282 NCT01682616 NCT01671904 NCT01685892

Indication Treatment-naïve AML not eligible for standard induction therapy

Phase/study Phase Ib Phase I/II Phase III


Design

Venclexta (dose escalation) plus

decitabine


azacitidine


decitabine plus posaconazole

Venclexta (dose escalation) plus low-dose

cytarabine

• ARM A: Venclexta plus azacitidine

• ARM B: Azacitidine

Primary

endpoint

Safety Safety, PK, PD and efficacy Percentage of participants with CR,

Overall survival

Status

FPI Q4 2014


Breakthrough designation granted by FDA

Q1 2016

Updated data presented at ASCO 2016

FPI Q1 2015

Initial data presented at ASCO 2016

Updated data presented at ASH 2016

FPI Q1 2017



AML=acute myelogenous leukemia; ASH=American Society of Hematology; ASCO=American Society of Clinical Oncology


Novel small molecule Bcl-2 selective inhibitor – AML

Indication Relapsed or refractory multiple myeloma

Phase/study Phase III

BELLINI Phase I Phase I


Design

ARM A: Venclexta plus bortezomib plus

dexamethasone

ARM B: Placebo plus bortezomib plus

dexamethasone

Patients receiving bortezomib and

dexamethasone as standard therapy:

Dose escalation cohort: Venclexta plus

bortezomib plus dexamethasone

Safety expansion cohort: Venclexta

plus bortezomib plus dexamethasone

Dose escalation cohort:

Venclexta dose escalation

Safety expansion cohort:

Venclexta expansion

Combination:

Venclexta plus dexamethasone

Primary

endpoint

Progression-free survival Safety and maximum tolerated dose Safety and maximum tolerated dose

Status

FPI Q3 2016 FPI Q4 2012



and ASH 2016

FPI Q4 2012



and ASH 2016



MM=multiple myleloma; ASCO=American Society of Clinical Oncology; ASH=American Society of Hematology


Novel small molecule Bcl-2 selective inhibitor – MM

Oncology development programs

Small molecules

40

Molecule Idasanutlin

(MDM2 antagonist, RG7388)

Indication Relapsed/refractory AML

MIRROS

Refractory AML

not eligible for cytotoxic therapy

Phase/study Phase III Phase I

# of patients N=440 N=140

Design

ARM A: Idasanutlin plus cytarabine

ARM B: Placebo plus cytarabine

Phase I (dose escalation)

ARM A: Cotellic1 plus Venclexta2

ARM B: Idasanutlin plus Venclexta2

Phase II (expansion)

ARM A: Cotellic1 plus Venclexta2

ARM B: Idasanutlin plus Venclexta2

Primary

endpoint

Overall survival Safety and efficacy

Status FPI Q4 2015 FPI Q1 2016

CT Identifier NCT02545283 NCT02670044

1 Cotellic in collaboration with Exelixis; 2 Joint project with AbbVie, in collaboration with The Walter and Eliza Hall Institute

AML=acute myeloid leukemia; ASCO=American Society of Clinical Oncology; ECC=European Cancer Congress; ESMO=European Society for Medical Oncology

41 41

Un-classified ABC GCB

~15% ~55% ~30%

Lenalidomide (RELEVANCE)

Ibrutinib (PHOENIX)

Polatuzumab vedotin backbone

* 46% of ABC patients are double positive (Hu S et l. Blood, 2013); Source: Roche internal data presented during REFORCE F2F Feb-2015; Johnson N et al, JCO 2012;

Hu S et al, Blood 2013; Iqbal J et al. Clin Can Res 2011; Iqbal J et al. JCO, 2006; Davis et al. Nature 2010; Haberman T et al, JCO 2006; Thieblemont C et al. JCO 2011

~50%

~50%

Elevated BCL-2

Double Positive

BCL-2 and myc* Double Hit

BCL-2

and myc

Increasing Segmentation in 1L DLBCL

Rituxan backbone

Doing now what patients need next

59 - Roche4cf03e98-fb44-4f1f... · •Primary endpoint CR by PET-CT by IRC after primary assessment...

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