September 26, 2015
Exelixis Investor Briefing:
METEOR Phase 3 Results
European Cancer Congress 2015
Vienna, Austria
Exelixis, Inc.
(NASDAQ: EXEL)
Forward-Looking Statements
This presentation, including any oral presentation accompanying it, contains forward-looking
statements, including, without limitation, statements related to: future clinical development of
cabozantinib and the availability of additional data from the METEOR trial; future regulatory filings,
potential approval, and launch of cabozantinib in RCC; and, continued development and clinical,
therapeutic and commercial potential of, and opportunities for, cabozantinib. These statements are
based on Exelixis’ current expectations, assumptions, estimates and projections about its business and
its industry and involve known and unknown risks, uncertainties and other factors that may cause
results, timing, levels of activity, performance or achievements to be materially different from any actual
results. Words such as “intend”, “potential,” “expect,” “will,” “anticipate,” “assume,” “plan,” or the
negative of such terms or other similar expressions, identify forward-looking statements, but the
absence of these words does not necessarily mean that a statement is not forward-looking. In addition,
statements that refer to expectations, projections or characterizations of future events or their timing are
forward-looking statements. Factors that might cause such a difference include, without limitation: risks
related to clinical trials and the regulatory approval pathway for cabozantinib; risks related to whether
Exelixis compounds demonstrate safety and efficacy; risks and uncertainties related to Exelixis’
compliance with applicable regulatory requirements, including healthcare fraud and abuse laws and
post-marketing requirements; market competition; changes in economic and business conditions; and
other factors discussed under the caption “Risk Factors” of Exelixis’ quarterly report on Form 10-Q filed
with the Securities and Exchange Commission (SEC) on August 11, 2015 and in Exelixis' other filings
with the SEC. The forward-looking statements made in this presentation, including any oral presentation
accompanying it, speak only as of the date on which the statements are made. Exelixis expressly
disclaims any duty, obligation or undertaking to release publicly any updates or revisions to any forwardlooking statements contained herein to reflect any change in Exelixis' expectations with regard thereto
or any change in events, conditions or circumstances on which any such statements are based.
2
Today’s Agenda
Introduction
Susan Hubbard, Investor Relations, Exelixis
METEOR Results Review
Toni Choueiri, M.D., Dana Farber Cancer Center
Panel Discussion
Toni Choueiri, M.D.
Gisela Schwab, M.D., EVP and CMO, Exelixis
Moderator: Peter Lamb, Ph.D., EVP and CSO, Exelixis
Q&A, All joined by:
Mike Morrissey, Ph.D., President and CEO, Exelixis
Press release and webcast (live and archived) available at www.exelixis.com
3
COMETRIQ® (cabozantinib capsules) Approval Status
The European Commission has granted COMETRIQ® (cabozantinib capsules) conditional
marketing authorization for the treatment of adult patients with progressive, unresectable
locally advanced or metastatic MTC. Similar to another drug approved in this setting, the
approved indication states that for patients in whom Rearranged during Transfection (RET)
mutation status is not known or is negative, a possible lower benefit should be taken into
account before individual treatment decisions.
•  Please refer to the latest approved European Summary of Product Characteristics for
full European Union prescribing information, including contraindication, special warnings
and precautions for use at www.sobi.com once posted.
COMETRIQ® is currently approved by the U.S. Food and Drug Administration for the
treatment of progressive, metastatic medullary thyroid cancer (MTC).
•  Please see full U.S. prescribing information, including Boxed WARNINGS, at
www.COMETRIQ.com/downloads/Cometriq_Full_Prescribing_Information.pdf
4
COMETRIQ® (cabozantinib capsules) Safety
Important Safety Information, including Boxed WARNINGS
WARNING: PERFORATIONS AND FISTULAS, and HEMORRHAGE
Serious and sometimes fatal gastrointestinal perforations and fistulas occur in COMETRIQtreated patients.
Severe and sometimes fatal hemorrhage occurs in COMETRIQ-treated patients.
COMETRIQ treatment results in an increase in thrombotic events, such as heart attacks.
Wound complications have been reported with COMETRIQ.COMETRIQ treatment results in
an increase in hypertension. Osteonecrosis of the jaw has been observed in COMETRIQtreated patients. Palmar-Plantar Erythrodysesthesia Syndrome (PPES) occurs in patients
treated with COMETRIQ. The kidneys can be adversely affected by COMETRIQ. Proteinuria
and nephrotic syndrome have been reported in patients receiving COMETRIQ. Reversible
Posterior Leukoencephalopathy Syndrome has been observed with COMETRIQ. Avoid
administration of COMETRIQ with agents that are strong CYP3A4 inducers or inhibitors.
COMETRIQ is not recommended for use in patients with moderate or severe hepatic
impairment. COMETRIQ can cause fetal harm when administered to a pregnant woman.
Adverse Reactions – The most commonly reported adverse drug reactions (≥25%) are
diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome (PPES), decreased weight,
decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension,
abdominal pain, and constipation. The most common laboratory abnormalities (≥25%) are
increased AST, increased ALT, lymphopenia, increased alkaline phosphatase, hypocalcemia,
neutropenia, thrombocytopenia, hypophosphatemia, and hyperbilirubinemia.
5
Abstract 4LBA
Cabozantinib versus everolimus in patients
with advanced renal cell carcinoma: results
of a randomized phase 3 trial (METEOR)
T. Choueiri, B. Escudier, T. Powles, P. Mainwaring, B. Rini, F. Donskov, H.
Hammers, T. Hutson, B. Roth, K. Peltola, J-L. Lee, D. Heng, M. Schmidinger,
A. Borgman-Hagey, C. Hessel, C. Scheffold, G. Schwab, N. Tannir, R. Motzer
for the METEOR investigators
Presented at the European Cancer Congress, Vienna, 26 September 2015
Introduction
•  Drugs targeting VEGF and its receptors, or the mammalian
target of rapamycin (mTOR), are standard therapies in RCC
•  Inactivation of the von Hippel-Lindau tumor suppressor protein
in clear cell RCC results in upregulation of VEGF, MET, and
AXL1
•  Increased MET and AXL expression has been associated with
poor prognosis and resistance to VEGFR inhibitors in RCC1,2
•  Resistance to targeted therapy represents a major challenge
to improving clinical outcomes of patients with RCC
1 Zhou
L et al., Oncogene, 2015
E et al., Mol Cancer Ther, 2014
2 Ciamporcero
Presented at the European Cancer Congress, Vienna, 26 September 2015
7
Cabozantinib
•  Cabozantinib is an oral small molecule inhibitor of tyrosine
kinases including MET, VEGF receptors, and AXL1
•  A single arm trial of cabozantinib demonstrated clinical activity
in heavily pretreated RCC patients2
•  The international, open-label phase 3 METEOR study
evaluated the efficacy and safety of cabozantinib compared to
everolimus in VEGFR TKI pretreated RCC patients
1 Yakes
FM et al., Mol Cancer Ther, 2011
TK et al., Ann Oncol, 2014
2 Choueiri
Presented at the European Cancer Congress, Vienna, 26 September 2015
8
Study Design
Cabozantinib
60 mg qd orally
Advanced RCC (N=650)
•  Clear cell histology
•  Measurable disease
•  Progression on prior VEGFR TKI within 6
months of enrollment
•  No limit to the number of prior therapies
•  Antibodies targeting PD-1/PD-L1 allowed
•  Brain metastases allowed if treated
Randomization 1:1
No cross-over allowed
Tumor assessment
by RECIST 1.1
every 8 weeks
Treatment until loss
of clinical benefit or
intolerable toxicity
Everolimus
10 mg qd orally
Stratification:
•  MSKCC1 risk groups: favorable, intermediate, poor
•  Number prior VEGFR-TKIs: 1, 2 or more
1 Motzer
R. et al., J Clin Oncol, 2004
Presented at the European Cancer Congress, Vienna, 26 September 2015
9
Statistical Design
•  Primary endpoint: progression-free survival (PFS)
– 
– 
– 
– 
Assessed by independent radiology review committee (IRC)
259 events to achieve 90% power
Among first 375 enrolled patients
Hypothesized 50% increase in PFS (hazard ratio = 0.667)
•  Secondary endpoints:
–  Overall survival (OS)
•  408 events among 650 planned patients
•  Interim analysis at the time of primary PFS analysis
–  Objective response rate (ORR) by IRC
Advanced
RCC
OS
Population
Randomization
1:1
PFS Population
N=First 375 Randomized
N=650
!
!!
Presented at the European Cancer Congress, Vienna, 26 September 2015
10
Patient Disposition
Screened N=922
Randomized (1:1) N=658
Cabozantinib n=330
Everolimus n=328
Received cabozantinib*!
Continuing treatment
Discontinued treatment
n=331
40%
60%
Received everolimus*‡
Continuing treatment
Discontinued treatment
n=322
21%
79%
PFS analysis
Interim OS analysis
Safety analysis
n=187
n=330
n=331
PFS analysis
Interim OS analysis
Safety analysis
n=188
n=328
n=322
* One patient randomized to everolimus received cabozantinib
‡ Five patients did not initiate treatment with everolimus
Primary endpoint analysis cut-off: 22 May 2015
Presented at the European Cancer Congress, Vienna, 26 September 2015
11
Baseline Characteristics
Characteristic*
Median age, years (range)
Male, %
Enrollment Region, %
Europe / North America
Asia-Pacific & Latin America
ECOG Performance Status, %
0
1
MSKCC risk group1, %
Favorable
Intermediate
Poor
Metastatic sites per IRC, %
Lung
Liver
Bone
Cabozantinib
(N=330)
Everolimus
(N=328)
63 (32‒86)
77
62 (31‒84)
73
51 / 36
14
47 / 37
16
68
32
!
45!
42!
12!
66
34
!
46!
41!
13!
58
25
23
61
30
19
* Characteristics were consistent with the PFS population
1 Motzer R. et al., J Clin Oncol, 2004
Presented at the European Cancer Congress, Vienna, 26 September 2015
12
Prior Therapies
Cabozantinib
(N=330)
Everolimus
(N=328)
Number of VEGFR TKIs, %
1
2 or more
71
29
70
30
VEGFR-TKI, %
Sunitinib
Pazopanib
Axitinib
Sorafenib
64
44
16
6
62
41
17
9
Other systemic therapy, %
Cytokines
Nivolumab
Bevacizumab
12
5
2
16
4
3
33
85
33
85
Characteristic*
Radiotherapy, %
Nephrectomy, %
* Prior therapies were consistent with the PFS population
Presented at the European Cancer Congress, Vienna, 26 September 2015
13
Progression-Free Survival
Independent Central Radiology Review
P r o g r e s s io n - f r e e S u r v iv a l ( % )
100
Median PFS
mo (95% CI)
No.$of$
Events$
7.4 (5.6-9.1)
3.8 (3.7-5.4)
121
126
80
!
Cabozantinib (N=187)
Everolimus (N=188)
60
Hazard ratio, 0.58 (95% CI 0.45-0.75, P<0.001)
40
20
0
0
No. at Risk
Cabozantinib
Everolimus
187
188
3
152
99
6
92
46
9
M o n th s
68
29
12
15
18
20
10
6
2
2
0
Presented at the European Cancer Congress, Vienna, 26 September 2015
14
Progression-free Survival in Subgroups
Independent Radiology Review Committee
Subgroup
Cabozantinib Everolimus
no. of patients (events)
Hazard Ratio (95% CI)
187 (121)
188 (126)
0.58 (0.45 - 0.75)
One
137 (87)
136 (95)
0.56 (0.42 - 0.75)
Two or more
50 (34)
52 (31)
0.67 (0.41 - 1.10)
Favorable
80 (51)
83 (56)
0.54 (0.37 - 0.79)
Intermediate
80 (49)
75 (47)
0.56 (0.37 - 0.84)
Poor
27 (21)
30 (23)
0.84 (0.46 - 1.53)
All patients
Prior VEGFR TKIs
MSKCC risk group
0 .2 5
0 .5
C a b o z a n tin ib B e tte r
1
2
4
E v e ro lim u s B e tte r
Presented at the European Cancer Congress, Vienna, 26 September 2015
15
Sunitinib as Only Prior VEGFR TKI
Post-hoc PFS Subset Analysis
P r o g r e s s io n - f r e e S u r v iv a l ( % )
100
!
Cabozantinib (N=76)
Everolimus (N=77)
80
Median PFS
mo (95% CI)
No.$of$
Events$
9.1 (5.6-11.2)
3.7 (1.9-4.2)
45
58
Hazard ratio, 0.41 (95% CI 0.28-0.61)
60
40
20
0
0
No. at Risk
Cabozantinib
Everolimus
3
6
9
12
15
M o n th s
76
77
63
36
41
15
32
11
8
3
2
0
Presented at the European Cancer Congress, Vienna, 26 September 2015
16
Tumor Response – PFS Population
Independent Radiology Review Committee
Objective response rate, %
95% CI
Cabozantinib
(N=187)
Everolimus
(N=188)
21
5
16‒28
2‒9
P value
< 0.001*
Best overall response, %
Complete response
0
0
Partial response
21
5
Stable disease
62
62
Progressive disease
14
27
Not evaluable or missing
3
6
* Cochran-Mantel-Haenszel test
The ORR was consistent in patients who received sunitinib as only prior VEGFR TKI
Presented at the European Cancer Congress, Vienna, 26 September 2015
17
Tumor Response – PFS Population
Independent Radiology Review Committee
Objective response rate, %
95% CI
Cabozantinib
(N=187)
Everolimus
(N=188)
21
5
16‒28
2‒9
P value
< 0.001*
Best overall response, %
Complete response
0
0
Partial response
21
5
Stable disease
62
62
Progressive disease
14
27
Not evaluable or missing
3
6
* Cochran-Mantel-Haenszel test
The ORR was consistent in patients who received sunitinib as only prior VEGFR TKI
Presented at the European Cancer Congress, Vienna, 26 September 2015
18
Best Target Lesion Change from Baseline
Independent Radiology Review Committee
80
84% (150/179) of cabozantinib treated
patients experienced tumor reduction
C h a n g e fro m B a s e lin e (% )
40
0
-4 0
-8 0
80
*!
59% (98/167) of everolimus treated
patients experienced tumor reduction
40
0
-4 0
* Increase of 188%
-8 0
Presented at the European Cancer Congress, Vienna, 26 September 2015
19
Kaplan-Meier Estimates of Overall Survival
Interim Analysis (49% Information Fraction)
100
C a b o z a n tin ib
O v e r a ll S u r v iv a l ( % )
80
60
E v e ro lim u s
40
Hazard ratio, 0.67 (95% CI 0.51-0.89, P=0.005)
20
(Medians cannot yet be estimated due to frequent early censoring)
0
0
3
6
9
12
15
18
21
24
M o n th s
No. at Risk
Cabozantinib
330
317
294
189
101
32
6
1
0
Everolimus
328
306
260
156
88
24
5
1
0
The interim boundary to reach significance (P=0.0019) was not reached
Survival follow up is continuing to the planned final analysis
Presented at the European Cancer Congress, Vienna, 26 September 2015
20
Exposure and Dose Reductions
Safety Population
Cabozantinib
(N=331)
Everolimus
(N=322)
7.6
4.4
(0.3‒20.5)
(0.21‒18.9)
44 mg
9 mg
Any dose reduction
60%
25%
Discontinued due to adverse event
9%
10%
Median duration of exposure – months
(range)
Median average daily dose
Dose reductions were used to adjust to the individual patient’s tolerability
Presented at the European Cancer Congress, Vienna, 26 September 2015
21
All-causality Adverse Events
Preferred Term, %
Cabozantinib (N=331)
All Grades
Grade 3/4
Everolimus (N=322)
All Grades Grade 3/4
Any adverse event*
Diarrhea
Fatigue
Nausea
Decreased appetite
PPE syndrome
Hypertension
Vomiting
Weight decreased
Constipation
Anemia
Cough
Dyspnoea
Rash
100
74
56
50
46
42
37
32
31
25
17
18
19
15
68
11
9
4
2
8
15
2
2
<1
5
<1
3
<1
>99
27
46
28
34
6
7
14
12
19
38
33
28
28
58
2
7
<1
<1
<1
3
<1
0
<1
16
<1
4
<1
Events of interest
Hyperglycaemia
Pneumonitis
GI Perforation
Fistula
5
0
<1
<1
<1
0
<1
<1
19
10
<1
0
5
2
<1
0
* Events reported in at least 25% of patients in either study group; PPE, palmar-plantar erythrodysesthesia
Presented at the European Cancer Congress, Vienna, 26 September 2015
22
All-causality Adverse Events
Preferred Term, %
Cabozantinib (N=331)
All Grades
Grade 3/4
Everolimus (N=322)
All Grades Grade 3/4
Any adverse event*
Diarrhea
Fatigue
Nausea
Decreased appetite
PPE syndrome
Hypertension
Vomiting
Weight decreased
Constipation
Anemia
Cough
Dyspnoea
Rash
100
74
56
50
46
42
37
32
31
25
17
18
19
15
68
11
9
4
2
8
15
2
2
<1
5
<1
3
<1
>99
27
46
28
34
6
7
14
12
19
38
33
28
28
58
2
7
<1
<1
<1
3
<1
0
<1
16
<1
4
<1
Events of interest
Hyperglycaemia
Pneumonitis
GI Perforation
Fistula
5
0
<1
<1
<1
0
<1
<1
19
10
<1
0
5
2
<1
0
* Events reported in at least 25% of patients in either study group; PPE, palmar-plantar erythrodysesthesia
Presented at the European Cancer Congress, Vienna, 26 September 2015
23
All-causality Adverse Events
Preferred Term, %
Cabozantinib (N=331)
All Grades
Grade 3/4
Everolimus (N=322)
All Grades Grade 3/4
Any adverse event*
Diarrhea
Fatigue
Nausea
Decreased appetite
PPE syndrome
Hypertension
Vomiting
Weight decreased
Constipation
Anemia
Cough
Dyspnoea
Rash
100
74
56
50
46
42
37
32
31
25
17
18
19
15
68
11
9
4
2
8
15
2
2
<1
5
<1
3
<1
>99
27
46
28
34
6
7
14
12
19
38
33
28
28
58
2
7
<1
<1
<1
3
<1
0
<1
16
<1
4
<1
Events of interest
Hyperglycaemia
Pneumonitis
GI Perforation
Fistula
5
0
<1
<1
<1
0
<1
<1
19
10
<1
0
5
2
<1
0
* Events reported in at least 25% of patients in either study group; PPE, palmar-plantar erythrodysesthesia
Presented at the European Cancer Congress, Vienna, 26 September 2015
24
All-causality Serious Adverse Events
Cabozantinib
(N=331)
Everolimus
(N=322)
40
43
Grade 3
24
26
Grade 4
3.0
4.0
Grade 5
6.6
7.8
0.3*
0.6‡
Any serious adverse event, %
Related
* One event of death not otherwise specified
‡ One event of aspergillus infection and one event of aspiration pneumonia
Presented at the European Cancer Congress, Vienna, 26 September 2015
25
METEOR Study Conclusions
•  Cabozantinib significantly improves PFS compared to
everolimus in RCC patients after prior VEGFR TKI therapy
•  Cabozantinib improved the objective response rate
•  Overall survival results at the interim analysis show a
strong trend favoring cabozantinib
•  Cabozantinib's safety profile is acceptable and tolerability is
similar to other TKIs in this population
•  Cabozantinib represents a potential new treatment option
for second or later line therapy for RCC
Presented at the European Cancer Congress, Vienna, 26 September 2015
26
Presented at the European Cancer Congress, Vienna, 26 September 2015
Acknowledgments
We are grateful to all METEOR patients and their caregivers.
The following Principal Investigators also participated in this study:
M. Aarts
T. Csoszi
P. Geertsen
S. Hussain
A. Martinez
J. Passos Coelho
J. Sarantopoulos
S. Tykodi
N. Agarwal
K. Cuff
D. George
N. Jensen
G. Marx
J. Perez Gracia
P. Schöffski
D. Vaena
L. Appleman
P. Czaykowski
D. Geynisman
F. Joly
T. Maurina
D. Pfister
T. Schnöller
U. Vaishampayan
O. Aren Frontera F. Dane
T. Gil
F. Kabbinavar
J. McCaffrey
J. Pikiel
W. Schultze-Seemann J. van Thienen
N. Basappa
I. Davis
H. Glen
J. Katolicka
R. McDermott
D, Pook
A. Sevinc
P. Van Veldhuizen
S. Begbie
U. De Giorgi
E. Gokmen
B. Keam
B. Melichar
E. Porfiri
D. Shaffer
E. Voog
L. Bergmann
M. De Santis
E. Grande
H. Kluger
J. Merchan
J. Randall
P. Singh
E. Winquist
G. Bjarnason
W. Demey
G. Gravis
J. Knox
J. Mikulas
B. Redman
G. Sonpavde
M. Wirth
R. Blom
R. Depenbusch
M. Gross Goupil
A. Koletsky
I. Mincik
M. Retz
D. Soulieres
M. Wojtukiewicz
F. Boccardo
P. deSouza
C. Gruellich
T. Kolevska
P. Nathan
S. Rha
N. Sousa
B. Wong
S. Bracarda
G. Doshi
V. Gruenwald
C. Kollmannsberger S. Negrier
S. Richey
W. Stadler
L. Wood
F. Carrozza
H. Drabkin
H. Gurney
E. Kopyltsov
D. Nosov
M. Rink
M. Staehler
J. Wright
D. Castellano
I. Duran
J. Hainsworth
T. Kuzel
L. Nott
F. Roila
C. Steer
W. Wynendaele
Y. Chang
R. Epstein
W. Hanna
B. Laguerre
T. Olencki
F. Rolland
C. Sternberg
R. Yildiz
S. Cheporov
E. Esteban Gonzalez
U. Harmenberg
J. Larkin
S. Osanto
C. Ryan
C. Suarez
P. Zalewski
C. Chevreau
R. Figlin
R. Hawkins
C. Lin
Y.Ou
R. Sabbatini
C. Szczylik
I. Chirivella
M. Fishman
T. Ho
W. Loidl
S. Oudard
M. Saez Medina
H. Tan
S. Chowdhury
X. Garcia del Muro Solans S. Hotte
A. MacDonald
S. Pal
P. Salman
M. Thomasson
L. Costa
J. Garcia Donas
E. Hovey
J. Malik
S. Park
W. Samlowski
P. Tomczak
B. Costello
L. Géczi
A. Hussain
P. Maroto
R. Passalacqua D. Santini
M. Troner
The METEOR study was supported by Exelixis, Inc.
Presented at the European Cancer Congress, Vienna, 26 September 2015
28
Panel Discussion
Dr. Toni Choueiri
Dr. Gisela Schwab
Moderator: Dr. Peter Lamb, Exelixis
Sunitinib as Only Prior VEGFR TKI
Post-hoc PFS Subset Analysis
P r o g r e s s io n - f r e e S u r v iv a l ( % )
100
!
Cabozantinib (N=76)
Everolimus (N=77)
80
Median PFS
mo (95% CI)
No.$of$
Events$
9.1 (5.6-11.2)
3.7 (1.9-4.2)
45
58
Hazard ratio, 0.41 (95% CI 0.28-0.61)
60
40
20
0
0
No. at Risk
Cabozantinib
Everolimus
3
6
9
12
15
M o n th s
76
77
63
36
41
15
32
11
8
3
2
0
Presented at the European Cancer Congress, Vienna, 26 September 2015
30
Kaplan-Meier Estimates of Overall Survival
Interim Analysis (49% Information Fraction)
100
C a b o z a n tin ib
O v e r a ll S u r v iv a l ( % )
80
60
E v e ro lim u s
40
Hazard ratio, 0.67 (95% CI 0.51-0.89, P=0.005)
20
(Medians cannot yet be estimated due to frequent early censoring)
0
0
3
6
9
12
15
18
21
24
M o n th s
No. at Risk
Cabozantinib
330
317
294
189
101
32
6
1
0
Everolimus
328
306
260
156
88
24
5
1
0
The interim boundary to reach significance (P=0.0019) was not reached
Survival follow up is continuing to the planned final analysis
Presented at the European Cancer Congress, Vienna, 26 September 2015
31
Activity of Cabozantinib, Everolimus, and Axitinib in
Patients who Have Received Prior Sunitinib Only
Cabozantinib Everolimus
Everolimus*
Axitinib* Sorafenib*
(METEOR)
(METEOR)
(RECORD-1)1,2
(AXIS)2
(AXIS)2
N=76
40% of PITT
N=77
41% of PITT
N=124
45% of ITT
N=194
54% ITT
N=195
54% of ITT
PFS (months)
9.1
3.7
3.9
4.8
3.4
ORR
22%
3%
1-2%
11%
8%
Discontinuation
due to AEs
9%
10%
14%
9%
13%
PITT, Primary Intent-to-Treat Population; ITT, Intent-to-Treat Population
*Data does not constitute substantial evidence as it reflects a cross-study comparison
1. Motzer et al, Cancer 2010
2. Package Inserts for everolimus and axitinib (accessed 13 May 2012); axitinib ODAC FDA Briefing
Document 7 Dec 2011
32
Second Line RCC Clinical Trial Data
PFS (months)
OS HR
Cabozantinib
Everolimus
Nivolumab*
(METEOR)
(METEOR)
(Checkmate-025)
7.4
3.8
4.6
0.67 (p=0.005)#
0.73 (p=0.002)
ORR (Investigator)
23%
6%
25%
ORR (IRC)
21%
5%
NA
PD as best response
14%
27%
35%
Discontinuation
due to AEs
9%
10%
8%
*Data does not constitute substantial evidence as it reflects a cross-study comparison
#The
significance boundary (P < 0.0019) was not met at the interim analysis
33
Progression Free Survival and Duration of
Therapy in METEOR
•  METEOR protocol allows treatment beyond progression if there is evidence
of clinical benefit
•  Median duration of therapy longer than median PFS for the PFS population
–  Mature data with 11 month minimum follow up vs 6 month minimum follow up
in OS population
Cabozantinib Everolimus
Nivolumab*
187
185
406
Minimum Follow up (Months)
11
11
14
Median Duration of Therapy (Months)
8.3
4.1
5.5
Median PFS (Months)
7.4
3.8
4.6
PFS Safety Population, N
*Data does not constitute substantial evidence as it reflects a cross-study comparison
34
All-Causality Adverse Events
Cabozantinib vs Axitinib
Preferred Term*, %
Diarrhea
Fatigue
Nausea
Decreased appetite
PPE syndrome
Hypertension
Vomiting
Weight decreased
Constipation
Dysgeusia
Stomatitis
Hypothyroidism
Dysphonia
Mucosal inflammation
Asthenia
Dyspnea
Cough
Aspartate aminotransferase increase
Anemia
Back pain
Event of interest
Proteinuria
*All-causality adverse events
Cabozantinib (n=331)
All Grades
Grade 3/4
74
11
56
9
50
4
46
2
42
9
37
15
32
2
31
2
25
<1
24
0
22
2
20
0
20
<1
19
<1
19
4
19
3
18
<1
18
2
17
5
17
2
12
2
Axitinib* (n=359)
All Grades
Grade 3/4
54
11
37
10
30
2
31
4
28
6
42
17
24
3
19
3
13
<1
11
15
1
20
<1
13
16
1
18
4
UKN
UKN
13
1
20
<1
35
<1
UKN
UKN
13
3
* AXIS trial; Rini et al. Lancet 2011; Motzer et al., Lancet Oncology 2013; Inlyta label
Additional Cabozantinib Development
•  CABOSUN – cabozantinib vs sunitinib in first line RCC
–  ALLIANCE/CALGB randomized Phase 2 trial, PFS is primary endpoint
–  Enrollment completed March 2015, data expected in 2016
•  Cabozantinib in combination with Checkpoint Inhibitors
–  Cabozantinib plus nivolumab or plus nivolumab and ipilimumab in patients with GU tumors
(including bladder, RCC)
–  NCI/CTEP Phase 1b trial now recruiting
•  CELESTIAL – cabozantinib vs placebo in second line HCC
–  Randomized, blinded Phase 3 study in HCC pts who have received prior sorafenib
–  OS is the primary endpoint, data anticipated in 2017
•  NSCLC, ongoing Phase 2 trials addressing different patient populations
–  EGFR WT ECOG/ACRIN randomized Phase 2 data presented at ASCO
–  Evidence for a PFS and OS benefit for cabozantinib or cabozantinib plus erlotinib vs erlotinib
–  Ongoing discussions regarding a potential Phase 3 study
36
Question & Answer Session
September 26, 2015
Exelixis Investor Briefing:
METEOR Phase 3 Results
European Cancer Congress 2015
Vienna, Austria
Exelixis, Inc.
(NASDAQ: EXEL)