Post on 18-Apr-2018
Novartis ACZ885 (canakinumab) –
CANTOS study results
Investor call
Vas Narasimhan MD, Global Head of Drug Development & Chief Medical Officer
Jay Bradner MD, President, Novartis Institutes for BioMedical Research
August 27, 2017
Global Drug Development
Global Drug Development
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CANTOS results | August 27, 2017 | Investor presentation 2
Global Drug Development
Anti-inflammatory therapy with ACZ885 targeting the IL-1β innate immunity pathway may
markedly impact early/undetected lung cancers and lung cancer mortality
• It has been hypothesized that inhibition of IL-1β might reduce cancer invasiveness, metastasis,
and angiogenesis
• Incident cancers and cancer deaths was prospective, blinded safety analysis adjudicated by an
independent Oncology monitoring committee as agreed with FDA in 2010
• Dose dependent 51% RRR in total cancer mortality (p=0.0009, 300mg); 77% RRR in lung
cancer mortality (p=0.0002, 300mg); 67% RRR in incident lung cancers (p=0.00008, 300mg)
• 37% RRR trend in cancer mortality, excluding lung cancer
Summary of CANTOS findings in CV risk
reduction1 and cancer therapy
2
CANTOS study demonstrated ACZ885 is the first anti-inflammatory therapy to demonstrate
reduced risk of major cardiovascular events, particularly in sub-group hsCRP3 responders
• 15% relative risk reduction (RRR) in MACE4 (p=0.02415,150mg)
• Effect driven by 24% RRR of fatal or non-fatal heart attack
• Subgroup of patients achieving a reduction of hsCRP below 1.8 mg/L after 1st dose (at 3 months)
show 27% RRR for MACE, with NNT6 of 50 at year 2 and 30 at 3.7 years
1. Ridker P. et al., Anti-Inflammatory Therapy with Canakinumab for Atherosclerotic Disease, NEJM 2017 2. Ridker P. et al, Effects of Interleukin-1 Inhibition with
Canakinumab on Incident Lung Cancer: Results from a Randomized Clinical Trial, LANCET 2017 3. High sensitivity C-reactive protein 4. CV death, non-fatal MI, or
non-fatal stroke 5. adjusted for multiplicity; All other p-values are unadjusted 6. NNT: Number needed to treat to prevent one MACE event
CANTOS results | August 27, 2017 | Investor presentation 3
Global Drug Development
Agenda
CANTOS results | August 27, 2017 | Investor presentation 4
• CANTOS Cardiovascular results
• CANTOS Cancer results
• Ilaris® as Anti-Cancer Therapy
• Planned next steps
Global Drug Development
Inflammation is the hallmark of atherosclerosis,
leading to MI and other CV events
Interleukin-1β
is instrumental in driving
atherosclerosis
ACZ885 (canakinumab),
a human mAb, selectively
blocks the IL-1β
inflammatory pathway
Ridker PM. Circ Res 2016;118:145-156
CANTOS results | August 27, 2017 | Investor presentation 5
Global Drug Development
Additional LDL Reduction
IMPROVE-IT : Ezetimibe 6% RRR
FOURIER/SPIRE: PCSK9 Inhibition q2 weeks 15% RRR
Known Cardiovascular Disease LDL 150 mg/dL (3.8 mmol/L)
hsCRP 4.5mg/L
Additional Inflammation Reduction
No Prior Proof of Concept
High Intensity Statin
LDL 70 mg/dL (1.8 mmol/L) hsCRP 3.8 mg/L
LDL 110 mg/dL (2.8 mmol/L) hsCRP 1.8 mg/L
“Residual Cholesterol Risk” “Residual Inflammatory Risk”
CANTOS study targets unique patient
population
CANTOS results | August 27, 2017 | Investor presentation 6
Global Drug Development
CANTOS study design
Myocardial infarction at least 30 days prior to randomization
on standard therapies and elevated hsCRP (≥ 2 mg/L)
Primary Endpoint
• Time to first major cardiovascular event (MACE: CV death, non-fatal MI, or non-fatal stroke) of at least one
ACZ885 dose compared to Placebo
Key Secondary Endpoints
• Time to first event of MACE or hospitalization for unstable angina requiring unplanned revascularization
• Time to new onset diabetes among those with pre-diabetes at randomization
Secondary Endpoints
• Time to all cause mortality
• Time to first occurrence of all cause mortality, non-fatal stroke, or non-fatal MI
Key Exploratory Endpoints
• DVT/PE1, stent thrombosis, hospitalizations for CHF2, PCI/CABG3 and biomarkers
Randomized
Canakinumab 50 mg
SC q3 months
Randomized
Canakinumab 150 mg
SC q3 months
Randomized
Canakinumab 300 mg
SC q3 months
Randomized
Placebo
SC q3 months
1. Deep Vein Thrombosis/Pulmonary Embolism 2. Chronic Heart Failure 3. Percutaneous Coronary Intervention/Coronary Artery Bypass Graft
CANTOS results | August 27, 2017 | Investor presentation 7
Global Drug Development
CANTOS study well-conducted with impact on
biomarkers without impact on lipids
• Baseline demographics for age, sex, time since prior MI, smoking status, type 2
diabetes, and dyslipidemia comparable across groups
• Patients well managed at baseline for LDL-C and blood pressure:
–Over 90% on lipid lowering agents, anti-thrombotics, and anti-ischemics
–Over 80% on beta blockers and RAAS blockers
• Dose dependent reductions in hsCRP and IL-6
• No meaningful changes in LDL-C, HDL-C, and Triglycerides
CANTOS results | August 27, 2017 | Investor presentation 8
Global Drug Development
Primary endpoint: Statistically significant 15%
reduction of MACE driven by fatal/non-fatal MI
Primary efficacy endpoint (MACE)
Multiplicity adjusted
p-values
p=0.031
p=0.024*
p=0.030
* Statistically significant 1-sided P-value≤ 0.0245 (adjusted according to the Multiple Testing Procedure and accounting for the 2 efficacy IAs)
CANTOS results | August 27, 2017 | Investor presentation 9
Global Drug Development
Benefit apparent within first year of treatment
and sustained throughout trial duration
Primary endpoint (MACE):
HR 0.85 (0.74, 0.98); RRR 15%
3.7 year median follow-up
CANTOS results | August 27, 2017 | Investor presentation 10
Global Drug Development
Consistent benefit across pre-specified
baseline subgroups
Primary endpoint; Canakinumab 150 mg (1/2)
Favours
Canakinumab 150mg
Favours
Placebo
CANTOS results | August 27, 2017 | Investor presentation 11
Global Drug Development
Consistent benefit across pre-specified
baseline subgroups
Primary endpoint; Canakinumab 150 mg (2/2)
Favours
Canakinumab 150mg
Favours
Placebo
CANTOS results | August 27, 2017 | Investor presentation 12
Global Drug Development
Pre-specified sub-group analysis of patients
achieving hsCRP of 1.8 mg/L after 1st
dose at
month 3 show 27% RRR for MACE*
CANTOS results | August 27, 2017 | Investor presentation 13
* Values for 3 point MACE (primary endpoint) or 4 point MACE (MACE + urgent revascularization) similar – graph above for MACE + urgent revascularisation
0 1 2 3 4 5
Follow-up Years
0.00
0.05
0.10
0.15
0.20
0.25
Cum
ulat
ive
Inci
denc
e
Confirmed MACE+Urgent Revasc by Median 3 Month hsCRP
Placebo>=1.8 mg/L<1.8 mg/L
Placebo
Canakinumab hsCRP reduction < median)
Canakinumab hsCRP reduction > median)
HR (95%CI) P
1.0 (referent) (referent)
0.95 (0.84-1.08) 0.47
0.73 (0.63-0.83) 0.0001
Cu
mu
lati
ve
in
cid
en
ce
(%
)
HR 0.73
95%CI 0.63-0.83
P=0.0001 for those with reductions
in hsCRP > median
at 3-months (1.8 mg/L)
Follow-up years
Global Drug Development
Key secondary endpoint met at 150 mg dose
36% RRR for urgent revascularization component
Treatment N n (n/100py)
Hazard ratio vs.
Placebo (95% CI)
Adjusted
P-value
MACE or unstable
angina requiring
unplanned
revascularization
Canakinumab 300 mg 2263 348 ( 4.25) 0.82 ( 0.72, 0.94) 0.0648
Canakinumab 150 mg 2284 352 ( 4.29) 0.83 ( 0.73, 0.95) 0.0241*
Canakinumab 50 mg 2170 344 ( 4.56) 0.90 ( 0.79, 1.03) 0.1895
Placebo 3344 601 ( 5.13)
* Statistically significant 1-sided P-value≤ 0.0245 (adjusted according to the Multiple Testing Procedure and accounting for the 2 efficacy IAs)
Treatment N n (n/100py)
Hazard ratio vs.
Placebo (95% CI)
Unstable angina
requiring unplanned
revascularization
Canakinumab 300 mg 2263 34 ( 0.40) 0.58 ( 0.39, 0.86)
Canakinumab 150 mg 2284 38 ( 0.44) 0.64 ( 0.44, 0.94)
Canakinumab 50 mg 2170 38 ( 0.48) 0.71 ( 0.48, 1.05)
Placebo 3344 85 ( 0.69)
17% RRR in composite of MACE + hospitalization for unstable angina requiring unplanned
revascularization
36% RRR for hospitalization for unstable angina requiring unplanned revascularization
CANTOS results | August 27, 2017 | Investor presentation 14
Global Drug Development
Preliminary NNT1 for both, overall population and
hsCRP responders, compares favorably to recent
benchmarks
Endpoint MACE (MI, Stroke,
CV death)
CANTOS
150mg2
All patients
CANTOS 150mg
hsCRP responders
(<1.5 mg/L) FOURIER3
2 years 78 50 74
3.7 years 46 30 N/A
1. NNT: Number needed to treat to prevent one MACE event
2. Calculated using Hazard Ratio approach
3. N Engl J Med 2017; 376:1713-1722
CANTOS results | August 27, 2017 | Investor presentation 15
* lung cancer incidence and mortality benefit with 300 mg confirmed for both groups
Global Drug Development
Adverse event and tolerability profile
Generally comparable to placebo
Can. 300 mg
N=2263
n (%)
Can. 150 mg
N=2285
n (%)
Can. 50 mg
N=2170
n (%)
Placebo
N=3348
n (%)
Subjects with at least one AE 1987 (87.8) 1970 (86.2) 1872 (86.3) 2914 (87.0)
Subjects with at least one SAE 836 (36.9) 812 (35.5) 741 (34.1) 1203 (35.9)
AEs suspected to be related to study
drug 355 (15.7) 350 (15.3) 267 (12.3) 474 (14.2)
Subjects who permanently
discontinued study drug due to AEs 175 (7.7) 164 (7.2) 142 (6.5) 244 (7.3)
Discontinued due to SAEs 135 (6.0) 130 (5.7) 117 (5.4) 197 (5.9)
Discontinued due to non-serious AEs 40 (1.8) 34 (1.5) 25 (1.2) 47 (1.4)
AEs leading to study treatment
interruption 268 (11.8) 270 (11.8) 228 (10.5) 399 (11.9)
CANTOS results | August 27, 2017 | Investor presentation 16
Global Drug Development
Canakinumab SC q 3 months
Adverse Event (%) Placebo
(N=3347)
50 mg
(N=2170)
150 mg
(N=2284)
300 mg
(N=2263)
P-trend
Any SAE 12.0 11.4 11.7 12.3 0.43
Leukopenia 0.24 0.30 0.37 0.52 0.002
Any infection 2.86 3.03 3.13 3.25 0.12
Fatal infection 0.18 0.31 0.28 0.34 0.09/0.02
Injection site
reaction
0.23 0.27 0.28 0.30 0.49
Any Malignancy 1.88 1.85 1.69 1.72 0.31
Fatal Malignancy 0.64 0.55 0.50 0.31 0.0007
Arthritis 3.32 2.15 2.17 2.47 0.002
Osteoarthritis 1.67 1.21 1.12 1.30 0.04
Gout 0.80 0.43 0.35 0.37 0.0001
ALT > 3x normal 1.4 1.9 1.9 2.0 0.19
Bilirubin > 2x normal 0.8 1.0 0.7 0.7 0.34
Select safety topics of interest1
1. Based on known or potential risks of canakinumab
CANTOS results | August 27, 2017 | Investor presentation 17
Global Drug Development
Summary of CANTOS cardiovascular results
CANTOS study demonstrated ACZ885 is the first anti-inflammatory therapy to
demonstrate reduced risk of major cardiovascular events, particularly in sub-
group of hsCRP responders
• 15% relative risk reduction (RRR) in MACE (p=0.0241,150mg)
• Effect driven by 24% RRR of fatal or non-fatal heart attack; a 10% RRR of
cardiovascular death and neutral effect on risk of stroke
• Subgroup of patients achieving a reduction of hsCRP below 1.8 mg/L after 1st dose
(at 3 months) show 27% RRR for MACE, with NNT of 50 at year 2 and 30 at 3.7
years
CANTOS results | August 27, 2017 | Investor presentation 18
Global Drug Development
Agenda
CANTOS results | August 27, 2017 | Investor presentation 19
• CANTOS Cardiovascular results
• CANTOS Cancer results
• Ilaris® as Anti-Cancer Therapy
• Planned next steps
Global Drug Development
IL-1β promotes cancer progression*
IL-1β
Angiogenesis Invasion Metastasis Immune suppression
Killer T-cells
NK cells
Dendritic cells
CANTOS results | August 27, 2017 | Investor presentation 20
* Dinarello CA. Why not treat human cancer with interleukin1 blockade? Cancer Metastasis Rev 2010; 29: 317–29.
* Lewis AM. Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment J Transl
Med. 2006; 4: 48
Global Drug Development
Incident cancers were adjudicated and analyzed
in a prospective and blinded fashion as part of
safety evaluation
• In agreement with FDA in 2010, incident cancers were adjudicated by a
blinded independent Oncology monitoring committee
• Data on incident cancers including cancer deaths were collected as
serious adverse events and analyzed in a prospective fashion
• In the study design:
– History of cancer was an exclusion criteria to study enrolment; baseline CT scans were not
conducted
– Diagnosis of cancer led to a discontinuation of treatment as per protocol
– Statistical analysis of cancer incidence and cancer deaths was pre-planned
CANTOS results | August 27, 2017 | Investor presentation 21
Global Drug Development
Baseline demographics of cancer diagnoses
High hsCRP and history of or active smoking predicted higher risk for lung cancer
No
incident cancers
Incident
non-lung cancers
Incident
lung cancers
Placebo
(N=3113)
Canakinuma
b
(N=6286)
Placebo
(N=179)
Canakinuma
b
(N=377)
Placebo
(N=61)
Canakinum
ab
(N=69)
Age (yr) 61.0 61.0 67.0 66.0 66.0 64.0
Female sex (%) 26.3 25.8 22.3 22.5 14.8 26.1
Smoking status (%)
Current smoking 22.3 23.6 25.7 24.7 45.9 42.0
Past smoking 48.0 46.5 55.4 48.8 50.8 53.6
Never smoker 29.7 29.9 19.0 26.5 3.3 4.3
hsCRP (mg/L) 4.1 4.2 4.3 4.4 6.8 6.0
CANTOS results | August 27, 2017 | Investor presentation 22
Global Drug Development
Dose dependent risk reduction with canakinumab
in all fatal cancer incidence of 51% (300mg)
Cumulative incidence all fatal cancers
Follow-up years
CANTOS results | August 27, 2017 | Investor presentation 23
Global Drug Development
Dose dependent risk reduction with canakinumab
in lung cancer incidence of 67% (300 mg)
Cumulative incidence lung cancer
Follow-up years
CANTOS results | August 27, 2017 | Investor presentation 24
Global Drug Development
Dose dependent risk reduction with canakinumab
in lung cancer mortality incidence of 77% (300mg)
Cumulative incidence lung cancer mortality
Follow-up years
CANTOS results | August 27, 2017 | Investor presentation 25
Global Drug Development
Summary of CANTOS lung cancer
results
CANTOS results | August 27, 2017 | Investor presentation 26
Canakinumab Dose (SC q 3 months)
P-value for
trend across
doses Clinical Outcome
Placebo
(N=3344)
50mg
(N=2170)
150mg
(N=2284)
300mg
(N=2263)
All doses
(N=6717 )
Any Cancer (all)
Incident rate, (N) 1.88 (231) 1.85 (144) 1.69 (143) 1.72 (144) 1.75 (431) 0.31
Hazard ratio 1.00 0.99 0.90 0.91 0.93
95 % CI (referent) 0.80-1.22 0.73-1.11 0.74-1.12 0.79-1.09
P (referent) 0.91 0.31 0.38 0.38
Any Cancer (fatal)
Incidence rate, (N) 0.64 (81) 0.55 (44) 0.50 (44) 0.31 (27) 0.45 (115) 0.0007
Hazard ratio 1.00 0.86 0.78 0.49 0.71
95% CI (referent) 0.59-1.24 0.54-1.13 0.31-0.75 0.53-0.94
P (referent) 0.42 0.19 0.0009 0.016
Lung Cancer (all)
Incidence rate, (N) 0.49 (61) 0.35 (28) 0.30 (26) 0.16 (14) 0.27 (68) <0.0001
Hazard ratio 1.00 0.74 0.61 0.33 0.55
95% CI (referent) 0.47-1.17 0.39-0.97 0.18-0.59 0.39-0.78
P (referent) 0.20 0.034 <0.0001 0.0007
Lung Cancer (fatal)
Incidence rate, (N) 0.30 (38) 0.20 (16) 0.19 (17) 0.07 (6) 0.15 (39) 0.0002
Hazard ratio 1.00 0.67 0.64 0.23 0.51
95% CI (referent) 0.37-1.20 0.36-1.14 0.10-0.54 0.33-0.80
P (referent) 0.18 0.13 0.0002 0.0026
Global Drug Development
Trend of up to 37% risk reduction for fatal –
non-lung – cancers also observed
CANTOS results | August 27, 2017 | Investor presentation 27
Canakinumab Dose (SC q 3 months)
P-value for
trend across
doses Clinical Outcome
Placebo
(N=3344)
50mg
(N=2170)
150mg
(N=2284)
300mg
(N=2263)
All doses
(N=6717 )
Non-Lung Cancer (all)
Incident rate, (N) 1.46 (179) 1.55 (121) 1.44 (122) 1.60 (134) 1.53 (377) 0.54
Hazard ratio 1.00 1.08 0.99 1.10 1.05
95 % CI (referent) 0.85-1.36 0.78-1.24 0.88-1.37 0.88-1.26
P (referent) 0.54 0.91 0.42 0.58
Non-Lung Cancer (fatal)
Incidence rate, (N) 0.39 (49) 0.38 (30) 0.34 (30) 0.24 (21) 0.32 (81) 0.06
Hazard ratio 1.00 0.96 0.88 0.63 0.82
95% CI (referent) 0.61-1.51 0.56-1.39 0.38-1.04 0.58-1.17
P (referent) 0.86 0.60 0.07 0.28
Global Drug Development
Novartis has rigorously assessed the
cancer findings in CANTOS
• CANTOS patients were at high risk for CV disease and lung cancer with
overlapping risk factors
• Biological basis and experimental data support role for IL-1β in lung cancer
biology
• Dose response in cancer findings
• Robust effect size and reasonable number of events in cancer findings
• Statistical considerations:
– Oncology finding is robust even after assessing for multiplicity adjustments
– Finding was a per protocol analysis
– Novartis has reanalyzed the data in a blinded manner and confirmed the result
CANTOS results | August 27, 2017 | Investor presentation 28
Global Drug Development
Effect of Canakinumab likely due to
treatment of undetected cancers
• Patients who developed lung cancer during follow-up were 65 years of age on
average on study entry and more than 90% were current or past smokers – and
therefore at high risk for existing cancers
• Average follow-up time is unlikely to be adequate to demonstrate a reduction
in new cancers
• Canakinumab likely reduced the rate of progression, invasiveness, and
metastatic spread of lung cancers that were existing but undiagnosed at trial
entry
• Result consistent with prior trial results showing effects of long-term treatment
with NSAIDS1 in adenocarcinomas. Canakinumab effect seen after first doses
unlike prior studies
• Analysis ongoing of non-lung cancer cases
1. Non-steroidal anti-inflammatory drugs
CANTOS results | August 27, 2017 | Investor presentation 29
Global Drug Development
Summary of CANTOS Oncology findings
Anti-inflammatory therapy with ACZ885 targeting the IL-1β innate immunity
pathway may markedly impact early/undetected lung cancers and lung cancer
mortality
• In pre-clinical models for over a decade, IL-1β inhibition demonstrated to reduce cancer
invasiveness, metastasis, and angiogenesis.
• Incident cancers and cancer deaths were prospective, blinded safety analyses in the CANTOS
study, adjudicated by an independent Oncology monitoring committee, as agreed with FDA in
2010
• Dose dependent 51% RRR in total cancer mortality (p=0.0009, 300mg); 77% RRR in lung
cancer mortality (p=0.0002, 300mg);
67% RRR in incident lung cancers (p=0.00008, 300mg)
• 37% RRR trend in cancer mortality excluding lung cance
CANTOS results | August 27, 2017 | Investor presentation 30
Global Drug Development
Agenda
CANTOS results | August 27, 2017 | Investor presentation 31
• CANTOS Cardiovascular results
• CANTOS Cancer results
• Ilaris® as Anti-Cancer Therapy
• Planned next steps
Global Drug Development
Novartis Immuno-Oncology
CAR-T Immune Checkpoint Myeloid Cells
CSF-1
IL-17
TGFβ
STING
TIM3
c-MET
Porcupine
Adenosine
mTOR
IAP
PD-L1
CANTOS results | August 27, 2017 | Investor presentation 32
Global Drug Development
Taking aim at Myeloid cells in cancer
CANTOS results | August 27, 2017 | Investor presentation 33
Global Drug Development
Inflammasome activation in cancer
CANTOS results | August 27, 2017 | Investor presentation 34
Global Drug Development
IL-1β promotes cancer progression*
IL-1β
Angiogenesis Invasion Metastasis Immune suppression
Killer T-cells
NK cells
Dendritic cells
CANTOS results | August 27, 2017 | Investor presentation 35
* Dinarello CA. Why not treat human cancer with interleukin1 blockade? Cancer Metastasis Rev 2010; 29: 317–29.
* Lewis AM. Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment J Transl
Med. 2006; 4: 48
Global Drug Development
Hypothesis Inhibition of IL-1β with canakinumab will block the
tumor-promoting effects of myeloid cells in the tumor
microenvironment, so as to inhibit cancer cell growth
and metastasis, and to promote protective immune
response augmented by PD-1 inhibition with PDR001
Study PDR001X2103 A Phase 1b, open-label, multi-center study to
characterize the safety, tolerability and
pharmacodynamics (PD) of PDR001 in combination
with CJM112, EGF816, Ilaris® (canakinumab) or
Mekinist® (trametinib)
First patient enrolled Aug 2016
Active sites in Spain, France, Belgium, USA,
Singapore, and Canada
IL-1β inhibition as cancer therapy:
Ilaris® + PDR001 in solid tumors
CANTOS results | August 27, 2017 | Investor presentation 36
Global Drug Development
Dose dependent risk reduction with canakinumab
in fatal lung cancer incidence of up to 77%
Follow-up Years
Cumulative incidence fatal lung cancer
CANTOS results | August 27, 2017 | Investor presentation 37
Global Drug Development
Target (Compound)
FIH Trial
Initiated
IO with
targeted
agent2
cMET (INC280) + PD-1 ✓
Porcupine (WNT974) +
PD-1 ✓
HDAC (Farydak®) + PD-1 ✓
mTOR (Afinitor®) + PD-1 ✓
IAP inh (LCL161) + PD-1 ✓
MEK (Mekinist®) + PD-1 ✓
TEC (EGF816) + PD-1 ✓
B/CRAF (LXH254) + PD-1 ✓
FGFR4 (FGF401) + PD-1 2017
Target (Compound)
FIH Trial
Initiated
IO / IO
LAG3 (LAG525) + PD-1 ✓
TIM3 (MBG453) + PD-1 ✓
GITR (GWN323) + PD-1 ✓
CSF-1 (MCS110) + PD-1 ✓
Adenosine R (NIR178) + PD-1 ✓
Het IL-15 (NIZ985) + PD-1 2017
IL-17 (CJM112) + PD-1 ✓
IL-1 (Ilaris®) + PD-1 ✓
TGFβ (NIS793) + PD-1 ✓
PD-L1 (FAZ053) + PD-1 ✓
STING (MIW815)1 + PD-1 2017
IO with
chemo CSF-1 (MCS110) + carbo/gem ✓
1. Collaboration / licensing with Aduro
2. Excludes IO targeted agent partner studies
First-in-class combination therapies
21 exploratory IO combination studies in 2017
CANTOS results | August 27, 2017 | Investor presentation 38
Global Drug Development
Agenda
CANTOS results | August 27, 2017 | Investor presentation 39
• CANTOS Cardiovascular results
• CANTOS Cancer results
• Ilaris® as Anti-Cancer Therapy
• Planned next steps
Global Drug Development
Novartis plans to pursue filing of CV indication,
discuss Oncology data inclusion in CV label, and
initiate Oncology phase 3 trials
CV filing planned
for Q4 2017
Proposal to
include Oncology
data in CV label
Oncology
Phase 3 programs
Novartis plans to meet
FDA and EMA in the
October timeframe
Subgroup of hsCRP
responders at 3 months
to be fully analyzed and
used in discussions with
regulators and payers
FDA oncology division
to review CANTOS
data set
Plan to discuss with
regulators appropriate
inclusion of CANTOS
oncology findings in
labeling for ACZ885
Phase 3 studies in NSCLC
expected to start in Q1
2018
Additional phase 3 and
phase 1b studies in other
inflammation driven
cancers as mono or in
combination
CANTOS results | August 27, 2017 | Investor presentation 40
Q&A