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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
This presentation contains forward-looking statements within the meaning of the United States Private Securities Litigation Reform Act of 1995 that can generally
be identified by words such as “potential,” “expected,” “will,” “planned,” “pipeline,” “outlook,” “build,” or similar expressions, or by express or implied discussions
regarding Kisqali® and other approved and potential new products, potential new indications for Kisqali® and other approved products, potential product launches,
or regarding potential future revenues from such products; or regarding the development or adoption of potentially transformational technologies and business
models; or regarding potential future sales or earnings of the Group or its divisions or potential shareholder returns; or by discussions of strategy, plans,
expectations or intentions. Such forward-looking statements are based on the current beliefs and expectations of management regarding future events, and are
subject to significant known and unknown risks and uncertainties. Should one or more of these risks or uncertainties materialize, or should underlying assumptions
prove incorrect, actual results may vary materially from those set forth in the forward-looking statements. You should not place undue reliance on these
statements. In particular, our expectations could be affected by, among other things: global trends toward healthcare cost containment, including ongoing
government, payor and general public pricing and reimbursement pressures and requirements for increased pricing transparency; regulatory actions or delays or
government regulation generally, including potential regulatory actions or delays with respect to the development of the products described in this presentation; the
uncertainties inherent in the research and development of new healthcare products, including clinical trial results and additional analysis of existing clinical data;
our ability to obtain or maintain proprietary intellectual property protection; safety, quality or manufacturing issues; the inherent uncertainties involved in predicting
shareholder returns; uncertainties regarding actual or potential legal proceedings, including, among others, product liability litigation, disputes and litigation with
business partners or business collaborators, government investigations generally, litigation and investigations regarding sales and marketing practices, and
intellectual property disputes; uncertainties involved in the development or adoption of potentially transformational technologies and business models; general
political, economic and trade conditions, including uncertainties regarding the effects of ongoing instability in various parts of the world; uncertainties regarding
future global exchange rates; uncertainties regarding future demand for our products; uncertainties regarding potential significant breaches of data security or data
privacy, or disruptions of our information technology systems; and other risks and factors referred to in Novartis AG’s current Form 20-F on file with the US
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.
Novartis ESMO Investor Call I October 1, 20193
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
Novartis ESMO Investor Call I October 1, 20194
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
Novartis ESMO Investor Call I October 1, 20195
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
Novartis ESMO Investor Call I October 1, 20196
Jeff LegosHead for Oncology Global Development,
Solid Tumors (a.i.)
MONALEESA-3 study design
Novartis ESMO Investor Call I October 1, 20198
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
Novartis ESMO Investor Call I October 1, 20199
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%
Novartis ESMO Investor Call I October 1, 201910
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
Novartis ESMO Investor Call I October 1, 201911
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
Novartis ESMO Investor Call I October 1, 201912
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)
Novartis ESMO Investor Call I October 1, 201913
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
Novartis ESMO Investor Call I October 1, 201914
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
Novartis ESMO Investor Call I October 1, 201915
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
Novartis ESMO Investor Call I October 1, 201916
PBO, placebo; PFS, progression-free survival; RIB, ribociclib.
Novartis ESMO Investor Call I October 1, 201917
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
Novartis ESMO Investor Call I October 1, 2019
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
Novartis ESMO Investor Call I October 1, 201919
®
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.
Novartis ESMO Investor Call I October 1, 201920
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
Novartis ESMO Investor Call I October 1, 201921
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
Novartis ESMO Investor Call I October 1, 201923
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
Novartis ESMO Investor Call I October 1, 201924
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.