Fourth Quarter and Full Year 2016
Financial Results
Monday, February 27, 2017
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: Exelixis’ plan to file a sNDA in first-line RCC in Q3 2017; anticipated data results from CELESTIAL in 2017; Exelixis’ plans to take steps for measured
resumption of discovery and in-licensing of assets in 2017; Exelixis’ intent to retire the Deerfield Notes in the July 2017 timeframe and related cash
savings; Exelixis belief that its debt repayment activities will substantially de-lever the company’s balance sheet; Exelixis’ guidance for 2017 total
operating expenses, including non-cash costs and expenses; Exelixis’ belief that significant growth opportunities remain in second and third-line
metastatic RCC; Exelixis’ plan to continue to expand prescriber base; potential future launches in other indications; potential expansion into first-line RCC
based on CABOSUN trial results; opportunities for the next wave of late-stage trials under Exelixis’ clinical collaboration with Bristol-Myers Squibb,
including a phase 3 study of cabozantinib with nivolumab, or with nivolumab and ipilimumab, in first-line RCC and potential other trials in Bladder Cancer
and HCC; the potential for Ipsen and Takeda to participate in future studies under Exelixis’ clinical collaboration with Bristol-Myers Squibb and the terms
of such participation; opportunities for the next wave of late-stage trials under Exelixis’ clinical collaboration with Roche, including a dose-ranging study of
cabozantinib and atezolizumab in solid tumors, and planned expansion cohorts; the potential for Takeda to participate in future studies under Exelixis’
clinical collaboration with Roche and the terms of such participation; the continued development of cobimetinib, including a pivotal phase 3 trial
(IMspire170) in braf wild-type advanced melanoma planned for this year, with first patient enrollment expected in Q2 2017; and opportunities ahead for
Exelixis, including Exelixis’ focus on critical activities planned for 2017 and commitment to disciplined expense management, with R&D tied to revenues
in 2017 and beyond. 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 “continue,” “planning,” “anticipating,” “intent,” “will,” “guidance,” “potential,”
“expected,” “guidance,” “focused,” “committed,” or the negative of such terms or other similar expressions, identify forward-looking statements. 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: the degree of market acceptance of CABOMETYX and COMETRIQ and the availability of
coverage and reimbursement for CABOMETYX and COMETRIQ; competition from other therapies; the risk that unanticipated developments could
adversely affect the commercialization of CABOMETYX or COMETRIQ; the level of costs and expenses associated with Exelixis’ commercialization,
research and development and other activities; Exelixis’ dependence on its relationships with its collaboration partners, including, the level of their
investment in the resources necessary to successfully commercialize cabozantinib in the territories where it is approved; the availability of data at the
referenced times; risks and uncertainties related to regulatory review and approval processes and Exelixis’ compliance with applicable legal and
regulatory requirements; Exelixis’ ability and the ability of its collaborators to conduct clinical trials of cabozantinib both alone and in combination with
other therapies sufficient to achieve a positive completion; risks related to the potential failure of cabozantinib, both along and in combination with other
therapies, to demonstrate safety and efficacy in clinical testing; Exelixis’ dependence on its relationship with Genentech/Roche with respect to
cobimetinib and Exelixis’ ability to maintain its rights under the collaboration; Exelixis’ dependence on third-party vendors; Exelixis’ ability to protect the
company’s intellectual property rights; market competition; changes in economic and business conditions, and other factors discussed under the caption
“Risk Factors” in Exelixis’ annual report on Form 10-K filed with the Securities and Exchange Commission (SEC) on February 27, 2017, and in Exelixis’
future 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 forward-looking 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, EVP, Public Affairs and
Investor Relations
Overview
Michael M. Morrissey, Ph.D., President and CEO
Financial Update
Chris Senner, EVP and CFO
Commercial Update
PJ Haley, SVP, Commercial
Development Update
Gisela Schwab, M.D., President, Product
Development and Medical Affairs & CMO
Partnered Programs
Update
Peter Lamb, Ph.D., EVP, Scientific Strategy & CSO
Q&A
All
3
Overview
Michael M. Morrissey, Ph.D.
President and CEO
Fourth Quarter 2016 Highlights
Strong performance of CABOMETYX
resulting in $51.9 million of cabozantinib
franchise product revenue
Continued success in monetizing
cabozantinib ex-US: $30 million in upfront
and milestones from Ipsen; Takeda deal with
$50 million upfront in Q1’17
Rapidly expanding development for
cabozantinib and cobimetinib, including:
–  cabozantinib + IO combination trials
–  three new cobimetinib pivotal trials over
past nine months
5
Exelixis in 2017
Planning supplemental NDA for cabozantinib in first-line renal cell
carcinoma (RCC)
Anticipating data from CELESTIAL phase 3 pivotal trial in advanced
hepatocellular cancer (HCC)
Entering 2017 in a very sound financial position, including healthy
cash balance and greatly reduced debt
Flexibility to further optimize the balance sheet, support cabozantinib’s
development (esp. IO combinations), and take steps for measured
resumption of discovery and in-licensing of assets
6
Financial Update
Chris Senner
EVP and CFO
Financial Highlights: Q4 2016
(in millions, except for per share amounts)
YoY
Delta
QoQ
Delta
Q4’15
Q3’16
Q4’16
Total revenues
$9.9 M
$62.2 M
$77.6 M
+683.8%
+24.8%
Cost of goods sold
$1.0 M
$2.5 M
$1.8 M
+80.0%
-28.0%
R&D expenses
$23.5 M
$20.3 M
$23.8 M
+1.3%
+17.2%
SG&A expenses
$17.1 M
$32.5 M
$13.0 M
-24.0%
-60.0%
Restructuring charge
$(0.1) M
$(0.2) M
$0.04 M
+140.0%
+120.0%
Total operating expenses
$41.5 M
$54.9 M
$38.7 M
-6.7%
-29.5%
Other income (expense): net
$(9.9) M
$(18.5 M)
$(3.8) M
-61.6%
-79.5%
Net income (loss) per share,
basic and diluted
$(0.18)
$(0.04)
$0.12
+166.7%
+400%
$253.3 M
$379.6M
$479.6 M
+89.3%
+26.3%
Ending cash*
* Includes cash and cash equivalents, short- and long-term investments
and long-term restricted cash and investments.
8
Financial Highlights: Fiscal Year 2016
(in millions, except for per share amounts)
FY 2015
FY 2016
Delta
$37.2 M
$191.5 M
+414.8%
$3.9 M
$6.5 M
+66.7%
R&D expenses
$96.4 M
$96.0 M
-0.4%
SG&A expenses
$57.3 M
$116.1 M
+102.6%
$1.0 M
$0.9 M
-10.0%
Total operating expenses
$158.6 M
$219.6 M
+38.5%
Other income (expense): net
$(40.3) M
$(42.1) M
+4.5%
Net income (loss) per share,
basic and diluted
$(0.77)
$(0.28)
-63.6%
Total revenues
Cost of goods sold
Restructuring charge
9
Q4 2016 Total Revenue
(See press release at www.exelixis.com for full details)
77.6
$80
$70
Royalty, License &
Contract Revenue
62.2
$60
25.7
Q4 2016 Notes
u 
Total revenues of $77.6M
u 
$51.9M in net product revenue,
including $44.7M in CABOMETYX
and $7.2M in COMETRIQ net
product revenues
v  Increase in net product revenues
vs. Q4 2015 primarily reflects
impact of CABOMETYX launch
u 
Total revenues for Q4 2016 include:
v  Two $10M milestones for Ipsen’s
first commercial sales of
CABOMETYX in Germany and
the United Kingdom
v  $1.0M of royalty revenues from
Ipsen and Roche
v  $4.7M of license revenues related
to amortization of upfront and
approval milestones from Ipsen
CABOMETYX
19.5
$50
(In Millions)
COMETRIQ
$40
36.3
4.6
$30
44.7
31.2
17.6
$20
$10
15.4
9.9
6.3
9.9
9.1
Q4 '15
Q1 '16
14.0
11.5
7.2
$0
Q2 '16
Q3 '16
Q4 '16
10
Q4 2016 R&D Expense
(See press release at www.exelixis.com for full details)
$35
28.9
$30
Q4 2016 Notes
$25
23.5
23.8
23.0
(In Millions)
20.3
$20
$15
u 
R&D expenses of $23.8M
u 
Decreases in share-based
compensation and allocation of
general corporate costs offset by
increases in personnel-related
expenses resulting from increase in
headcount predominantly associated
with buildout of Medical Affairs
$10
$5
$0
Q4 '15
Q1 '16
Q2 '16
Q3 '16
Q4'16
11
Q4 2016 SG&A Expense
(See press release at www.exelixis.com for full details)
$40
34.9
$35
35.8
Q4 2016 Notes
32.5
$30
u 
SG&A expenses of $13.0M
u 
Increases in personnel-related expenses
resulting from increase in headcount
connected with build-out of U.S.
commercial organization and outside
services to support CABOMETYX launch
and commercialization
u 
Offset by decrease in marketing costs
related to losses on our collaboration
with Genentech
u  SG&A expenses offset by
$23.1M recovery of net losses,
which had been recorded from
2013 through September 30, 2016
(In Millions)
$25
$20
17.1
$15
13.0
$10
$5
$0
Q4 '15
Q1 '16
Q2 '16
Q3 '16
Q4 '16
12
Cotellic + Zelboraf Promotional Expense Allocation Details
(See press release at www.exelixis.com for full details)
As announced in January 2017, Genentech unilaterally changed,
retroactively and prospectively, how it allocates promotion expenses
for the combination
–  Exelixis relieved of $18.7M of disputed costs previously recorded
–  Exelixis invoiced Genentech for expenses (plus interest) previously paid
During Q4 2016, Exelixis offset SG&A expenses for $23.1M recovery of
net losses recorded from 2013 through September 30, 2016
–  Including $13.3M of losses recognized and recorded prior to 2016
During Q4 and FY 2016, Exelixis recognized net gain of $0.6M and net
loss of $4.5M, respectively, for current U.S. activities as computed
under Genentech’s revised approach
13
Q4 and Full Year 2016 Financial Results (continued)
(See press release at www.exelixis.com for full details)
Other income (expense), net: ($3.8M) Q4 2016 // ($42.1M) FY 2016 vs.
($9.9M) Q4 2015 // ($40.3M) FY 2015
–  Decrease Q4 ‘16 vs.‘15 primarily due to reduction in interest expense as a result of
conversion/redemption of $287.5M in aggregate principal in 2019 Notes
–  FY ‘16 reduction in interest expense offset by $13.9M of loss associated with
conversion of 2019 Notes for ~54M shares of common stock
Net Income in Q4 2016: $35.1M or $0.12 per share, basic
Net Loss in FY 2016: ($70.2M) or ($0.28) per share, basic
–  Net loss in comparable periods: ($41.6M) or ($0.18) per share, basic in Q4 ‘15;
($161.7M) or ($0.77) per share, basic in FY ‘15
–  Decreases in net loss for Q4 and FY ‘16 primarily due to: increases in net product
and revenues; recovery of net losses previously recorded under collaboration with
Genentech; decrease in net interest expense
–  Offset by personnel costs and CABOMETYX launch/commercialization costs
Cash at December 31, 2016: $479.6M*
–  As compared to $253.3M at December 31, 2015
* Includes cash and cash equivalents, short- and long-term investments and long-term restricted cash and investments
14
Exelixis Debt Overview:
Recently Made Significant Progress in Addressing Balance Sheet
Retired 4.25% Convertible Senior Subordinated Notes due 2019
­  On 8/9 and 8/19/16, EXEL entered into exchange agreements with several
holders of the notes
•  Exchanged ~$239.4 million in notes for ~45.1 million shares of the
Company’s common stock
­  On 8/24/16, EXEL called for redemption ~$48.1 million of the notes, representing
all remaining notes outstanding.
­  Redemption closed on 11/2/16
$204.9 Million in Debt Remains Outstanding as of 12/31/16
­  Deerfield Notes
•  Principal amount borrowed (7/1/15): $100 million
•  Total due at maturity (7/1/18): $124.9 million
•  Carrying balance (as of 12/31/16): $109.8 million
•  Interest expense is 15%, 7.5% in cash and 7.5% paid in kind
•  Prepayments prior to 7/1/17 subject to a 5% penalty along with all accrued
and unpaid interest through 7/1/17
•  Prepayment after 7/1/17 only subject to 5% penalty and accrued interest
­  Silicon Valley Bank Loan
•  $80.0 million,1% interest, Term Loan, entered into June 2010, due May 2017
•  Total due (as of 12/31/16): $80.0 million
15
Balance Sheet Update
(See press release at www.exelixis.com for full details)
As reflected in the 10K, the Deerfield Notes have now been classified
as a “Current Liability,” given our ability and intent to retire them in
July 2017 timeframe
Retiring the Deerfield Notes one year prior to their maturity date will
save ~$12M, net of termination fee, over Notes’ remaining life
With May 2017 maturation of Silicon Valley Bank loan and early
retirement of Notes, we will have substantially de-levered our
balance sheet
16
2017 Financial Guidance
(See press release at www.exelixis.com for full details)
Total costs and operating expenses of $290-310M in 2017
–  Includes ~$25M of non-cash costs and expenses related to stock-based
compensation
17
Commercial Update
PJ Haley
SVP, Commercial
Cabozantinib Franchise Q4’16 Net Revenue: $51.9M
CABOMETYX Net Revenue ($M)
~45%
Growth
$44.7
$31.2
Q3
Q4
Demand:
−  Product volume growth ~40%
−  New patient starts growth ~20%
*Sources: Exelixis internal data
19
CABOMETYX: Expanding Customer Base
Customer Segment Growth
CABOMETYX
Volume
~25%
Growth
~60%
Growth
Q3 '16
Q4 '16
Academic
Community
§  ~ 60% prescriber growth (specialty pharmacies)
§  ~ 50% growth in purchasing outlets (specialty distributors)
*Sources: Exelixis internal data
20
CABOMETYX: Growth in New Patient Share
Estimated 2L+ New Patient Share*
27%
30%
25%
22%
20%
20%
18%
15%
10%
5%
0%
Q3
Q4
CABOMETYX
INLYTA
§  23% growth in new patient share
§  Increasing utilization in second line mRCC
§  Share gain from immunotherapy and oral agents
*Sources:
IMS National Prescription Audit™” NRx data ending 12/30/2016
Decision Resources Group Renal Cell Carcinoma Epidemiology (2016)
Exelixis internal data
21
Impact on Competition
IMS Rolling 4 Week NRx Volume
+26%
Q/Q NRx
Volume Growth
-10%
Q/Q NRx
Volume Growth
CABOMETYX
Launch
04/30/16
05/31/16
06/30/16
07/31/16
08/31/16
CABOMETYX R4WK NRX
NRx = New Prescriptions
Source: IMS National Prescription Audit™” NRx data ending 12/30/2016
09/30/16
10/31/16
11/30/16
12/31/16
INLYTA R4WK NRX
22
Conclusions
Significant growth opportunities remain
–  Second and third-line metastatic RCC
–  Continue to expand prescriber base
Pleased with refill rates and persistency
CABOMETYX competing and being differentiated in the marketplace
Launch readiness preparations underway for potential future
indications
23
Development Update
Gisela Schwab, M.D.
President, Product Development and
Medical Affairs & CMO
Potential Expansion into First-Line RCC: CABOSUN Trial
CABOSUN (Phase 2)
ARM
o  Trial conducted by
The Alliance cooperative
group under NCI-CTEP IND
o  157 patients with previously
untreated advanced RCC,
classified as poor or
intermediate risk by IMDC
A
cabozantinib
60 mg daily
N = 157
1:1 randomization
o  Patients stratified by
presence of bone
metastases, risk category
ARM
B
sunitinib
50 mg daily
4 weeks on,
2 weeks off
Endpoints
•  Primary:
Progression-Free Survival
•  Secondary:
Overall Survival
CABOSUN’s population of
poor- and intermediate-risk
patients represents 80% of the
first-line RCC population.1
Objective Response Rate
Study initiated in July 2013.
1. Ko et al., British Journal of Cancer (2014) 110, 1917–1922 | doi: 10.1038/bjc.2014.25
25
CABOSUN Efficacy Results
ORR* (95%CI)
Cabozantinib
Sunitinib
(N=79)
(N=78)
46% (34-57%)
18% (10-28%)
Arm
Median PFS (95% CI), mo*
HR (95% CI)
Cabozantinib
Sunitinib
8.2 (6.2, 8.8)
5.6 (3.4, 8.1)
0.66 (0.46-0.95)
p-value (one-sided) = 0.012
Arm
Median OS (95% CI), mo
HR (95% CI)
Cabozantinib
Sunitinib
30.3
21.8
(14.6, 35.0)
(16.3, 27.0)
0.80 (0.50, 1.26)
* Investigator assessed
Full citation: DOI: 10.1200/JCO.2016.70.7398 Journal of Clinical Oncology - published online before print November 14, 2016
26
CABOSUN Filing Update
Targeting Q3 2017 for supplemental NDA filing
Activities were contingent upon receipt of CABOSUN data from The
Alliance for Clinical Trials in Oncology
Making good progress on work needed to support filing
–  Source data verification
–  Programming work, and preparation of data sets and analyses
–  Collection of imaging scans from Alliance sites for central independent
radiology read following IRB approval at all sites
27
CELESTIAL: Phase 3 Trial of Cabozantinib in Advanced HCC
Continues to Enroll; Data Expected in 2017
CELESTIAL
o  Patients with advanced
hepatocellular cancer
(HCC) who have received
prior sorafenib
o  Randomized, double-blind,
placebo controlled global
trial; no crossover permitted
ARM
A
60 mg daily
Targeted enrollment: 760 patients
2:1 randomization
ARM
B
Endpoints
Cabozantinib
Placebo
Once daily
As announced in Sept. 2016, at first interim
analysis, scheduled for when 50% of events for
primary endpoint had occurred, IDMC
recommended study continue without changes.
•  Primary: Overall survival
•  Secondary and Exploratory: Objective response rate, progression-free
survival, patient-reported outcomes, biomarkers, safety
Study initiated in September 2013.
28
Strong Rationale for Combining Cabozantinib
with Immunotherapy
In preclinical models cabozantinib promotes an immune permissive
environment
–  Increases tumor MHC class 1 expression, increases T-cell mediated killing
–  Increases levels of circulating and tumor infiltrating cytotoxic T-cells
–  Decreases number and/or function of immune-suppressive cells (Tregs,
MDSCs)
Multiple cabozantinib targets are implicated in promoting tumor
immune-suppression
–  VEGFRs, MET, AXL, MER, TYRO3
Patients dosed with cabozantinib show reduced levels of circulating
immune suppressive cells and increased levels of T-cells
–  Reduced Tregs, CD14+ monocytes
–  Increased CD8+ T-cells
29
Encouraging Results in Phase 1b Trial Evaluating
“CaboNivoIpi” in Advanced Genitourinary Cancers
ESMO 2016: CaboNivo treatment associated with 43 percent
objective response rate (ORR) in 23 evaluable patients
–  Four of six (67 percent) urothelial carcinoma patients achieved response
–  Acceptable safety and tolerability profile
–  Recommended phase 2 dose for doublet regimen identified for ongoing
expansion cohorts in RCC and bladder cancers
ASCO GU 2017: Continued antitumor activity for CaboNivo and
CaboNivoIpi, with 38 and 18 percent ORRs, respectively
–  Acceptable safety and tolerability profiles for both regimens
–  Recommended phase 2 dose for triplet regimen identified
30
Compelling Opportunities for Next Wave of Late-Stage Trials:
Clinical Collaboration with Bristol-Myers Squibb
First Trial
Potential Other Trials
Phase 3 study of cabozantinib with nivolumab, or
with nivolumab and ipilimumab, in first-line RCC
Bladder Cancer
HCC
Others
Funding Source
Exelixis and BMS to share costs;
Ipsen to opt in to funding of 1L RCC trial
Exelixis Partner
Involvement
Ipsen and Takeda can participate in future
studies, have access to results for filing in their
territories if they opt in to funding obligations
31
Compelling Opportunities for Next Wave of Late-Stage Trials:
Clinical Collaboration with Roche
Trial Details
Planned Expansion
Cohorts
Dose-ranging study of cabozantinib and
atezolizumab in solid tumors
Previously treated advanced RCC
Previously treated bladder cancer
Previously untreated bladder cancer (cisplatinum
eligible and ineligible)
Funding Source
Exelixis to sponsor; Roche to provide
atezolizumab; Ipsen to contribute funding
Exelixis Partner
Involvement
Takeda can participate, have access to results
for potential future development/regulatory
submissions if it opts in to funding obligations
32
Additional Planned Studies through NCI-CTEP and
Investigator Sponsored Programs
Multiple study proposals under advanced review for phase 2 studies
combining cabozantinib with immune checkpoint inhibitors
Indications include:
–  NSCLC
–  Triple negative breast cancer
–  Endometrial cancer
–  Other tumor types
33
Broad Clinical Development Program for Cabozantinib
Single and combination studies, including with IO, sponsored by Exelixis and its collaborators
Not a full list of studies: see ClinicalTrials.gov for comprehensive list of all cabozantinib clinical trials
Indication
Combination Regimen
Status Update
Progressive, Metastatic Medullary Thyroid Cancer (MTC)
Approved in US and EU; Post-marketing study EXAMINER ongoing
Renal Cell Carcinoma (RCC)
Second-line
Approved in US and EU
First-line (intermediate- or poor-risk classification)
Preparing to file sNDA in 2017 based on results from CABOSUN† trial
First-line
+ nivolumab +/- ipilimumab
Phase 3 pivotal trial expected to begin in 2017, co-sponsored with Bristol-Myers Squibb
Hepatocellular Carcinoma
Second-line
Phase 3 (CELESTIAL), data anticipated in 2017
Non-Small Cell Lung Cancer
EGFR wild-type
Phase 2†
Molecular alterations in RET, ROS1, MET, AXL, or NTRK1 Phase 2*
Genitourinary Tumors, including Bladder and Urothelial Cancers
Genitourinary tumors
+ nivolumab +/- ipilimumab
Phase 1†
Advanced solid tumors
+ atezolizumab
Phase 1B* trial to begin in 2017, planned cohorts in RCC and urothelial carcinoma
Signal Search Opportunities to Inform Potential Development
Pancreatic neuroendocrine and carcinoid tumors
Phase 2*
Endometrial cancer
Phase 2†
Differentiated thyroid cancer
Phase 2*
Metastatic gastrointestinal stromal tumor
Phase 2 (CABOGIST)§
Breast cancer with brain metastases
+/- trastuzumab
Phase 2*
Metastatic, hormone-receptor-positive breast cancer
+ fulvestrant
Phase 2*
Metastatic, triple negative breast cancer
Phase 2*
Soft-tissue sarcomas
Phase 2†
High-grade uterine sarcomas
Phase 2§
Relapsed osteosarcoma or Ewing sarcoma
Phase 2†
Colorectal cancer
+/- panitumumab
* Trial conducted through Exelixis' Investigator-Sponsored Trial program.
† Trial conducted through collaboration with NCI’s Cancer Therapy Evaluation Program.
§ Trial sponsored by the European Organisation for Research and Treatment of Cancer (EORTC).
Phase 1*
34
Partnered Programs Update
Peter Lamb, Ph.D.
EVP, Scientific Strategy & CSO
Cobimetinib: Subject of a Broad Development Program
Cobimetinib: a selective inhibitor of MEK,
a component of the RAS/RAF/MEK/ERK
pathway activated in wide variety of tumors
–  Discovered by Exelixis
–  Licensed to and being investigated in
combination with numerous other
compounds by Genentech, a member of
the Roche Group
Approved to treat forms of advanced melanoma
in multiple territories, including the U.S. and EU,
Canada, Australia and Brazil
A second source of revenue for Exelixis
–  U.S. profit share with initial 50/50 split of profits and losses
–  U.S. co-promotion, with Exelixis fielding 25% of sales team
–  Ex-U.S., low double-digit royalty on sales
36
Rationale for Combining Cobimetinib with IO Agents
MEK inhibition:
ü Increases tumor expression of MHC class 1
ü Protects T-cells from apoptosis due to chronic stimulation
ü Inhibits MDSC differentiation and trafficking
Combination of a MEK inhibitor with anti-PD-L1 antibody yields durable
responses in a KRAS mutant colon cancer model
•  Similar data with cobimetinib
Provides compelling rationale
for ongoing cobimetinib/atezolizumab
combination trial in KRAS mutant CRC,
NSCLC and melanoma
Ebert et al. 2016 Immunity v44, 1
37
Activity in Ph 1b Trials of Cobimetinib*/Atezolizumab in
Solid Tumors Has Led to Three Ph 3 Studies Planned or Initiated
Cobi / Atezo
20 mg cobia PO QD
800 mg atezo IV Q2W
Cohort Expansion
IMblaze370
Colorectal Carcinoma
Phase 3 mCRC
NSCLC
40 mg cobia PO QD
800 mg atezo IV Q2W
Solid Tumors (biopsy)
60 mg cobia PO QD
800 mg atezo IV Q2W
Metastatic Melanoma
IMspire170
Phase 3 BRAF WT
Metastatic Melanoma
Metastatic Melanoma
BRAF V600
IMspire150 TRILOGY
Phase 3 BRAF V600
Metastatic Melanoma
Cobi / Vem / Atezo
60 mg cobia PO QD
720 mg vem PO BID
800 mg atezo IV Q2W
acobi
administered on a 21 day on / 7 day off schedule
* Cobimetinib is the subject of an ongoing collaboration with Genentech, a member of the Roche Group.
38
Phase 3 Trial of Cobimetinib*/Atezolizumab in Metastatic
Colorectal Adenocarcinoma Now Enrolling (NCT02788279)
IMblaze370 (Ph 3)
ARM
A
Cobimetinib
Atezolizumab
o  Unresectable metastatic
colorectal cancer
o  Must have received at least
2 regimens in metastatic
setting (not including
maintenance)
ARM
B
N = 360
o  Wild-type RAS capped at
50%; MSI-High capped at
approximately 5%
ARM
C
Atezolizumab
Regorafenib
Genentech-sponsored study initiated in Q2 2016.
Endpoints
•  Primary: Overall Survival
•  Secondary: Investigator-assessed PFS, ORR, DOR, Safety, Quality of Life
* Cobimetinib is the subject of an ongoing collaboration with Genentech, a member of the Roche Group.
39
Cobimetinib*/Atezolizumab Phase 1 Trial: Data in BRAF Wild-Type Melanoma
at SMR (Infante et al; Oral Presentation, Monday, Nov. 7, 2016)
Primary objective: to evaluate the safety and clinical activity of the
combination
Investigators reported combination was well tolerated
–  Treatment-related Grade 3-4 AEs occurred in 59 percent of patients; no treatmentrelated grade 5 AEs were reported
Encouraging anti-tumor activity observed
–  Among 20 non-ocular melanoma patients, ORR of 45 percent with 9 partial responses,
including 5 in BRAF wild-type patients
–  Median PFS of 12 months across all non-ocular melanoma patients (15.7 months in
BRAF wild-type)
–  With median follow-up of 18.9 months, median OS not reached
Genentech/Roche-sponsored pivotal phase 3 trial (IMspire170) in
BRAF wild-type advanced melanoma planned for this year
–  Cobimetinib plus atezolizumab versus pembrolizumab
–  First patient enrollment expected in Q2 2017, per Roche FY 2016 results call
* Cobimetinib is the subject of an ongoing collaboration with Genentech, a member of the Roche Group.
40
Cobimetinib*/Vemurafenib/Atezolizumab Phase 1 Trial: Triple Combination
Data at SMR (Sullivan et al; Oral Presentation, Monday, Nov. 7, 2016)
Primary objective: to evaluate the safety and tolerability of the triple
combination in previously untreated patients with BRAF V600 mutationpositive advanced melanoma
Investigators reported triple-combination was generally well tolerated
–  Grade 3-4 AEs seen in 40% of patients during triple combination period; all resolved after
appropriate intervention
Promising antitumor activity observed
–  Responses seen in 24 of 29 (83%) evaluable patients: 3 complete responses and 21 partial
responses
–  Median PFS was not estimable due to limited follow-up time, majority of patients continued
to respond at the time of data cutoff
Genentech/Roche-sponsored pivotal, placebo-controlled phase 3 trial
enrolling as of January 2017, with details on ClinicalTrials.gov
–  IMspire150 TRILOGY (NCT02908672) expected to enroll ~500 patients with previously
untreated BRAF V600 mutation-positive advanced melanoma
–  Primary endpoint: PFS by investigator; secondaries include PFS by IRC, OS, and ORR
* Cobimetinib is the subject of an ongoing collaboration with Genentech, a member of the Roche Group.
41
IMspire150 TRILOGY: A Phase III Study of Atezo + Cobi +
Vem in BRAF V600 Mutant Melanoma (NCT02908672)
IMspire150 TRILOGY (Ph 3)
Previously untreated
advanced melanoma
o  BRAF V600 mutation
o  ECOG PS 0-1
o  Measurable disease
N = 500
Key Study Objectives
Vemurafenib
960mg BIDa
Cobimetinib
60mg QDb
28 days
Vemurafenib
960mg BIDa
Cobimetinib
60mg QDb
Atezolizumab 840mg q2w
Vem 720mg BID + Vem
Placebo 240mg BID
Cobi 60mg QDb
Treatment until PD
or toxicity
Placebo q2w
Vemurafenib 960mg BID
Cobimetinib 60mg QDb
First patient enrolled in
January 2017
•  Primary: Investigator-assessed PFS
•  Secondary: PFS (IRF-assessed), OS, ORR, DOR, Safety, PK
aVemurafenib
dose will decrease to 720mg BID + placebo 240mg BID beginning day 22 of vem+cobi doublet treatment phase
administered on 21 days on/7 days off schedule.
IRF = independent review facility; PK = pharmacokinetics
bCobimetinib
42
Cobimetinib Triple-Negative Breast Cancer Data at ESMO
2016 Congress (Miles et al, Poster Presentation, Mon, Oct. 10 2016 )
Abstract 286-P: First-line cobimetinib + paclitaxel in triple-negative breast cancer
(Phase 2 COLET trial, NCT02322814)
• 
8 of 16 patients (50%) achieved a tumor response
• 
Combination was tolerable with no new safety signals
• 
Randomized phase 2 portion of trial now enrolling (paclitaxel vs. cobi+paclitaxcel),
including new cohorts of cobimetinib + paclitaxel + atezolizumab and cobimetinib + nabpaclitaxel +atezolizumab
Cobimetinib is the subject of a worldwide collaboration with Genentech, a member of the Roche Group.
43
Closing
Michael M. Morrissey, Ph.D.
President and CEO
Progress in 2016 Creates Opportunities Ahead
Steadfast and focused on critical activities planned for 2017
Moving science and business forward with focus, urgency
Committed to disciplined expense management, R&D tied to
revenues in 2017 and beyond
45
Q&A Session
Fourth Quarter and Full Year 2016
Financial Results
Monday, February 27, 2017
Exelixis, Inc.
(NASDAQ: EXEL)