kisqali® monaleesa-3 esmo data investor call

Kisqali® MONALEESA-3 ESMO Data Investor CallSusanne Schaffert, President of Novartis Oncology

Jeff Legos, Head for Oncology Global Development, Solid Tumors (a.i.)

October 1, 2019

Novartis AG

Investor Relations

Disclaimer

Novartis ESMO Investor Call I October 1, 20192

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Securities and Exchange Commission. Novartis is providing the information in this presentation as of this date and does not undertake any obligation to update any

forward-looking statements as a result of new information, future events or otherwise.


Susanne SchaffertPresident of Novartis Oncology

Q2 H1

Sales Growth vs PY Growth vs PY Sales Growth vs PYUSD million USD million cc USD million cc

109 nm1 215 nm1

349 23% 656 24%

340 25% 637 21%

111 94% 202 103%

284 26% 542 23%

58 nm1 103 nm1

Oncology BU 3606 9% 6927 9%

45

42

56

52

173

85

57

Novartis Oncology growing strongly, with sales up +9% in H1 2019

1. Not meaningful

Key growth drivers


Overview of Novartis presence at ESMO

1. Excludes IITs and third party

30Abstracts have

been accepted1

13Novartis brands /

compounds with data

being presented

5Oral

presentations

2Satellite

symposiums


MONALEESA-3 overall survival results further differentiate Kisqali®

1. Source: Zanotti et al. BMC Cancer (2017) 17:393.

Five-year survival rates in HR+ metastatic

breast cancer have improved by less than 5% in

25 years

Improved OS is the #1 treatment goal for the

majority of oncologists and patients1

MONALEESA-3 is the second Phase III trial in

which Kisqali® demonstrated a statistically

significant overall survival (OS) benefit of ~30%

OS benefit proven with multiple combination

partners and the largest number of patients,

incl. post-, pre- and peri-menopausal patients


Jeff LegosHead for Oncology Global Development,

Solid Tumors (a.i.)

MONALEESA-3 study design


Primary end point PFS (locally assessed per RECIST version 1.1)

Secondary end points Overall survival

Overall response rate

Clinical benefit rate

Time to response

Duration of response

Time to definitive deterioration of ECOG PS

Patient-reported outcomes

Safety

Pharmacokinetics

Ribociclib (600 mg/day; 3 weeks on/1 week off)

+

fulvestrant (500 mg)a n = 484

Placebo+

fulvestrant (500 mg)a n = 242Stratified by:

Presence/absence of

liver/lung metastases

Prior endocrine therapy

Random

ized 2

:1Men and post-menopausal

women with HR+/HER2− ABC

≤ 1 line of prior ET for

advanced disease

n = 726

a. Fulvestrant 500 mg intramuscularly every 28 days plus an additional dose on Cycle 1, Day 15. HER2, human epidermal growth factor receptor 2; HR, hormone receptor; ABC, advanced breast cancer; ET, endocrine therapy; PFS,

progression-free survival; RECIST, Response Evaluation Criteria in Solid Tumors; ECOG PS, Eastern Cooperative Oncology Group performance status. Slamon DJ, et al. J Clin Oncol. 2018;36:2465-247.

Patient dispositionMedian follow-up time was 39.4 months


Parameter, n (%)

RIB + FUL

n = 484

PBO + FUL

n = 242

All patients

n = 726

Patients treated 483 (99.8) 241 (99.6) 724 (99.7)

Treatment ongoinga 121 (25.0) 32 (13.2) 153 (21.1)

End of treatment 362 (74.8) 209 (86.4) 571 (78.7)

Reason for end of treatment

Progressive disease

Adverse event

Physician decision

Patient/guardian decision

Death

Protocol deviation

Technical issue

263 (54.3)

43 (8.9)

28 (5.8)

26 (5.4)

2 (0.4)

1 (0.2)

0

184 (76.0)

9 (3.7)

8 (3.3)

6 (2.5)

1 (0.4)

1 (0.4)

1 (0.4)

447 (61.6)

52 (7.2)

36 (5.0)

32 (4.4)

3 (0.4)

2 (0.3)

1 (0.1)

RIB, ribociclib; FUL, fulvestrant; PBO, placebo. a. At the time of data cutoff: 03 June 2019.

Overall survivalThe relative reduction in risk of death with RIB was 28%


RIB + FUL PBO + FUL

Events/N 167/484 108/242

OS, median

(95% CI), moNR (42.5-NR) 40.0 (37.0-NR)

HR (95% CI) 0.724 (0.568-0.924)

P value 0.00455

Landmark analysis

The P value of 0.00455 crossed the prespecified boundary to claim superior efficacy (P < 0.01129)

KM

estimate

RIB +

FUL

PBO +

FUL

36 months 67.0% 58.2%

42 months 57.8% 45.9%Ove

rall

su

rviv

al, %

RIB + FUL

PBO + FUL

FUL, fulvestrant; HR, hazard ratio; KM, Kaplan-Meier; NR, not reached; OS, overall survival; PBO, placebo; RIB, ribociclib.

Overall survival by line of therapyOS by line of therapy was consistent with overall population


First line Early relapse + second line

FUL, fulvestrant; HR, hazard ratio; KM, Kaplan-Meier; NR, not reached; OS, overall survival; PBO, placebo; RIB, ribociclib. a. This median value may not be estimated reliably due to the last patient on follow-up, who had an event at 45.1 months.

RIB + FUL PBO + FUL

Events/N 63/237 47/128

OS, median, mo Not reached 45.1a

HR (95% CI) 0.700 (0.479-1.021)

RIB + FUL

PBO + FUL

RIB + FUL

PBO + FUL

Ove

rall

su

rviv

al, %

Ove

rall

su

rviv

al, %

RIB + FUL PBO + FUL

Events/N 102/237 60/109

OS, median, mo 40.2 32.5

HR (95% CI) 0.730 (0.530-1.004)

Overall survival subgroup analysis


ECOG, Eastern Cooperative Oncology Group; ER,

estrogen receptor; ET, endocrine therapy; HR,

hazard ratio; PgR, progesterone receptor.

Solid line shows no effect point, and dotted line

shows overall treatment effect point. HR (95% CI) is

based on Cox proportional hazards model stratified

by lung and/or liver metastasis and previous ET per

IRT. Exception: For subgroup analyses related to

stratification factors, unstratified models are used.

Subgroups are based on CRF.

Progression-free survivalDescriptive analysis of PFS for overall population consistent with primary report;

Median PFS for RIB + FUL now reached in first line (33.6 months)


FUL, fulvestrant; HR, hazard ratio; PBO, placebo; PFS, progression-free survival; RIB, ribociclib.

Pro

gre

ssio

n-f

ree

su

rviv

al, %

First line

RIB + FUL

PBO + FUL

RIB + FUL PBO + FUL

Events/N 112/237 95/128

Median PFS, mo 33.6 19.2

HR (95% CI) 0.546 (0.415-0.718)

Overall population

RIB + FUL

PBO + FUL

Pro

gre

ssio

n-f

ree

su

rviv

al, %

RIB + FUL PBO + FUL

Events/N 283/484 193/242

Median PFS, mo 20.6 12.8

HR (95% CI) 0.587 (0.488-0.705)

Subsequent therapy after discontinuation


First subsequent therapy after discontinuation by typen (%)a

RIB + FULn = 484

n discontinued = 362

PBO + FULn = 242

n discontinued = 209

Any medication 295 (81.5) 177 (84.7)

Chemotherapy alone

Chemotherapy + hormone therapy/otherb

Hormone therapy alone

Hormone therapy + otherc

Targeted therapy alone

84 (23.2)

46 (12.7)

94 (26.0)

66 (18.2)

5 (1.4)

42 (20.1)

33 (15.8)

38 (18.2)

61 (29.2)

3 (1.4)

CDK4/6 inhibitors as any line of subsequent therapy after discontinuation were received by 11% of patients in the

RIB arm and 25% of patients in the PBO arm

a. For all rows, patients counted only once in each medication type, and categories are mutually exclusive except for CDK4/6 inhibitors; percentages are based on the number of patients who discontinued. b. Includes patients who received

chemotherapy + any nonchemotherapy. c. Includes patients who received hormonal therapy + other without chemotherapy.

Time to first chemotherapyTime to first chemotherapy was longer with RIB + FUL


RIB + FUL PBO + FUL

Events/N 182/484 115/242

TTC, median, mo NR 29.5

HR (95% CI) 0.696 (0.551-0.879)

Not Y

et

Rece

ive

d C

he

mo

the

rap

y, % RIB + FUL

PBO + FUL

Landmark analysis

KM

Estimate

RIB +

FUL

PBO +

FUL

36 months 57.4% 45.2%

42 months 56.4% 43.7%

FUL, fulvestrant; HR, hazard ratio; NR, not reached; PBO, placebo; RIB, ribociclib; TTC, time to first chemotherapy.

Safety summarySafety profile remains consistent with longer exposure

After approximately 40 months of follow-up, no new safety signals were observed

For this analysis, the rates of key grade 3/4 adverse events of special interest in the RIB

and PBO arms, respectively, were:

– Neutropenia, 57.1% and 0.8%

– Hepatobiliary toxicity, 13.7% and 5.8%

– Pulmonary disorders, 0.2% and 0%

No grade 3/4 pneumonitis or interstitial lung disease were observed in either arm

– QTc prolongation, 3.1% and 1.2%

No episodes of Torsades de Pointes were observed


PBO, placebo; PFS, progression-free survival; RIB, ribociclib.


Susanne SchaffertPresident of Novartis Oncology

Kisqali®: The only CDK4/6 to demonstrate consistently superior overall survival in two Phase III trials

18

In pre- and

peri-menopausal

women

First-line

treatment

With goserelin

plus aromatase

inhibitor

MONALEESA-3

In post-

menopausal

women

First- and

second-line

With

fulvestrant


MONALEESA-7

Kisqali® is unique in the CDK4/6 class on key pharmacokinetic parameters

CDK4 is a critical driver of HR+/HER2-

advanced breast cancer1,2

Kisqali® inhibits CDK4 8x more than

CDK63,6

Available drug penetrates tumor cells,

binds to, and inhibits CDK44,5

Kisqali® has the highest levels of drug

available to bind3


®

Pharmacokinetic differences among CDK4/6 inhibitors3,5,6

1. Yu Q, Sicinska E, Geng Y, et al. Requirement for CDK4 kinase function in breast cancer. Cancer Cell. 2006;9(1):23-32. 2. An H-X, Beckmann MW, Reifenberger G, Bender HG, Niederacher D. Gene amplification and overexpression of

CDK4 in sporadic breast carcinomas is associated with high tumor cell proliferation. Am J Pathol. 1999;154(1):113-118. 3. Kim S, Tiedt R, Loo A, et al. The potent and selective cyclin-dependent kinases 4 and 6 inhibitor ribociclib (LEE011) is

a versatile combination partner in preclinical cancer models. Oncotarget. 2018;9(81):35226-35240;(suppl). 4. Musteata FM. Monitoring free drug concentrations: challenges. Bioanalysis. 2011;3(15):1753-1768. 5. Chen P, Lee NV, Hu W, et

al. Spectrum and degree of CDK drug interactions predicts clinical performance. Mol Cancer Ther. 2016;15(10):2273-2281;(suppl tables). 6. Sammons SL, Topping DL, Blackwell KL. HR+, HER2- advanced breast cancer and CDK4/6

inhibitors: mode of action, clinical activity, and safety profiles. Curr Cancer Drug Targets. 2017;17(7):637-649.


Conclusions

In MONALEESA-3, Kisqali® achieved statistically significant OS benefit in

post-menopausal patients with HR+/HER2- advanced breast cancer1

OS benefit proven with multiple combination partners and the largest

number of patients, including post-, pre- and peri-menopausal patients3

Results build on MONALEESA-7, making Kisqali® the only CDK 4/6

inhibitor to demonstrate positive OS in two pivotal Phase III studies2

Comprehensive OS evidence expected to further differentiate Kisqali® as

the CDK4/6 inhibitor with consistently superior OS4

Expected Oncology pipeline milestonesSelect milestones through 2020


2019

INC280 in NSCLC US and Japan filings

Jakavi® in acute GvHD and

chronic GvHDPhase lll data readouts

PDR001 combination with

Tafinlar® + Mekinist® in

metastatic melanoma

Phase lll interim

analysis data readout

2020

Piqray® in HR+/HER2- ABC

with PIK3CA mutation

EU approval

177Lu-PSMA-617 in mCRPC Phase lll data readout

SEG101 in sickle cell disease US and EU approvals

ABL001 in CML, 3rd line Phase lll data readout

Appendix

Proven innovation track record in Breast Cancer for more than two decades


Established commercial infrastructure around the world

Deep understanding of disease landscape and patient needs

Trusted partner to oncologists, hospitals and payers

1997 2002 2007 2012 2017 2019

Other highlights across disease areas at ESMO 2019


Breast

Cancer

Kisqali®

(Ribociclib)

MONALEESA-7: Overall survival improvement observed with Robociclib + NSAI was associated

with QoL benefits.

CompLEEment-1: Interim Analysis confirms efficacy and safety of Ribociclib + Letrozole in a

broader HR+ HER2– ABC population (with visceral, bone and CNS metastasis; and male patients).

Piqray®

(Alpelisib)SOLAR-1: Clinical management of AEs optimizes patient outcomes on Alpelisib. Intra-study

comparison of first 50% patients enrolled versus the later 50% indicated notably lower

discontinuation rates of Grade 3+ AEs.

Melanoma Tafinlar® +

Mekinist®

(Dabrafenib +

Trametinib)

Analysis across all of Novartis Dabrafenib + Trametinib melanoma studies confirmed that pyrexia

is typically low-grade, occurs early during treatment, and can be effectively managed with

resolution in nearly all events.

Lung Canakinumab Satellite Symposium on removing the breaks on the immune system: Gearing up for tumor-

promoting inflammation inhibitors in NSCLC.

kisqali® monaleesa-3 esmo data investor call

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