EXELIXIS, INC (NASDAQ: EXEL)

Q1 2014 Financial Results May 1, 2014

Today’s Agenda

Introduction Susan Hubbard, Investor Relations

Overview Mike Morrissey, President and CEO

Financials Frank Karbe, EVP and CFO

Cabozantinib Gisela Schwab, EVP and CMO

Cobimetinib Peter Lamb, EVP and CSO

Commercial Update Scott Garland, EVP and CCO

Q&A All

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Press release and webcast (live and archived) available at www.exelixis.com

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Forward-Looking Statements

This presentation, including any oral presentation accompanying it, contains forward-looking statements, including, without limitation, statements related to: the continued development and clinical, therapeutic and commercial potential of, and opportunities for, cabozantinib and cobimetinib; anticipated developments in, and the expected timing of, various trials, including expected top-line results from four pivotal trials in 2014; Exelixis’ strategy for advancing the cabozantinib development program; the designs, plans and goals for ongoing and planned clinical trials of cabozantinib; future potential regulatory filings; the commercialization of COMETRIQ® (cabozantinib) in the approved medullary thyroid indications and in new indications if approved for use in such indications; future data presentations; Exelixis’ expectations for revenue growth and future product sales; Exelixis' financial guidance and outlook for 2014; the length of Exelixis’ financial runway; Exelixis’ goals to bring new therapies to patients with cancer and build value for investors; and Exelixis’ top priorities for 2014. 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 Exelixis’ or its industry’s results, levels of activity, performance or achievements to be materially different from any future results, levels of activity, performance or achievements expressed or implied in, or contemplated by, the forward-looking statements. Words such as “expect,” “believe,” “anticipate,” “potential,” “will,” “may” “should,” “would,” “could,” “focus,” “build,” “opportunity,” “continue,” “advance,” “expanding,” “hope,” “look forward,” “plans,” “priorities,” “strategy,” “preparation,” “objective,” “goals,” “progress,” “outlook,” “guidance,” “remains,” “promising,” “encouraging,” 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, any statements that refer to expectations, projections or other characterizations of future events or circumstances are forward-looking statements. Exelixis’ actual results and the timing of events may differ significantly from the results discussed in the forward-looking statements. Factors that might cause such a difference include, without limitation: the availability of data at the expected times; risks related to the potential failure of cabozantinib or cobimetinib to demonstrate safety and efficacy in clinical testing; the uncertain timing and level of expenses associated with the development of cabozantinib; Exelixis' ability to conduct clinical trials of cabozantinib sufficient to achieve a positive completion; Exelixis' dependence on its relationship with Roche/Genentech for the development of cobimetinib and Exelixis’ ability to maintain its rights under the collaboration; the uncertainty of regulatory approval processes; the risk that unanticipated developments could adversely affect the commercialization of COMETRIQ®; the degree of market acceptance of COMETRIQ and the availability of coverage and reimbursement for COMETRIQ; risks and uncertainties related to Exelixis' compliance with applicable regulatory requirements, including healthcare fraud and abuse laws and post-marketing requirements; Exelixis' dependence on third-party vendors; the sufficiency of Exelixis' capital and other resources; 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 May 1, 2014 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 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.

Overview Michael Morrissey, President & CEO

Exelixis Q1 2014 Highlights

Key regulatory milestone: E.U. approval for COMETRIQ®

•  Indicated for adult patients with progressive, unresectable locally advanced or metastatic medullary thyroid cancer (MTC)

•  Testament to in-house global regulatory capabilities

COMET-1 to proceed to final analysis •  No change to development plans •  Anticipate top-line data from both COMET-1 and -2 this year

Cobimetinib presentations at EADO and ASCO 2014 with data from phase 1 trial with vemurafenib (BRIM7)

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Financial Update Frank Karbe, EVP and CFO

Q1 2014 Financial Results (See press release at www.exelixis.com for full details)

Net Revenue: $4.9M, all from COMETRIQ sales •  Decrease of $4.8M vs. Q1’13 due to contract and license revenue of $7.8M

in Q1 last year •  Net revenue from sale of COMETRIQ year-over-year (YoY) increased by

$3M, reflecting launch at end of Jan. 2013 R&D Expenses: $54.8M

•  Increase of $22.1M vs. Q1’13 predominantly due to increase in clinical trial expenses, primarily related to METEOR start-up

SG&A Expenses: $14.7M •  Increase of $4.1M vs. Q1’13 mainly driven by higher personnel expenses

(expansion of sales force, higher stock-based compensation, cobimetinib)

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Q1 2014 Financial Results (See press release at www.exelixis.com for full details) Total Costs and Expenses: $69.9M

•  Increase of $26.2M vs. Q1’13 reflects increased R&D and SG&A expenses

Other Income (Expense): Net Expense of ($9.6M) •  Decrease of $1.1M vs. Q1’13 associated with mark-to-market valuation of

new Deerfield Warrants issued in Q1 2014 •  $7.0M of interest expense reflects non-cash charges

Quarter-End Cash: $408M* •  Includes net proceeds of ~$76M from stock offering in Q1 2014 •  Also reflects second and final $10M early debt repayment under Deerfield

notes, as well as $7.5M purchase of comparator drug for METEOR

Financial Guidance for FY2014 unchanged •  Total Costs and Expenses: $250-280M •  Year-end cash >$200M

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* Includes cash and cash equivalents, short- and long-term investments and short- and long-term restricted cash and investments

Cobimetinib: Corporate Collaboration with Genentech/Roche

United States: profit-share agreement with multiple tiers •  Entitled to 50% of first $200M in actual sales, decreasing to 30% of

actual sales above $400M

Ex-U.S.: royalties on net sales •  Entitled to low double-digit royalties

Co-promotion: Exelixis entitled to field up to 25% of U.S. sales force Exelixis not responsible for any development expenses

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Cabozantinib Development Update Gisela Schwab, EVP and CMO

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Focused on Expanding the Cabozantinib Opportunity

Phase 3 Pivotal Trials

•  COMET-1 (CRPC; OS)

•  COMET-2 (CRPC; Pain Palliation)

•  METEOR (RCC)

•  CELESTIAL (HCC)

•  EXAM (MTC)

EXELIXIS RESOURCES

Phase 1 and 2 Clinical Trials

•  National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP)

•  Investigator-Sponsored Trial (IST) Program

PARTNERSHIPS

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Cabozantinib: Castration-Resistant Prostate Cancer (CRPC)

Two randomized phase 3 pivotal trials of cabozantinib in CRPC •  COMET-1: vs. prednisone; overall survival (OS) endpoint

•  COMET-2: vs. mitoxantrone/prednisone; pain palliation endpoint

•  Potential to differentiate cabozantinib from other agents if successful

IDMC recommended COMET-1 proceed to final analysis

•  Recommended study continue unchanged; study remains blinded

•  Exelixis and CRO partner fully prepared for data read-out in 2014

•  Preparations for potential regulatory filings continue as well

Note: Cabozantinib is not approved for use under investigation in these trials.

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Cabozantinib: Castration-Resistant Prostate Cancer (CRPC)

Demonstrable activity in CRPC from phase 2 experience (n=144) •  Median OS of 10.8 months in patient population similar to COMET-1

•  Clinical meaningful pain relief in 57% of patients; reduction or discontinuation of narcotic analgesics in 55%

•  Bone scan response in 63%; reduction in measurable disease in 80%

•  Most common grade 3/4 AEs: fatigue (22%) and hypertension (14%)

Statistically significant and clinically meaningful improvements in OS have been seen at the final analysis in other large, randomized Phase 3 studies

•  Of six trials that resulted in approval, only three met endpoint at interim

•  Docetaxel (TAX327), sipuleucel-T (IMPACT), cabazitaxel (TROPIC) showed OS benefit at final analysis and were approved

Note: Cabozantinib is not approved for use under investigation in these trials.

Earlier-stage CRPC: combination randomized phase 2 trial with abiraterone started Q4’13, well underway

CELESTIAL: phase 3 trial in advanced hepatocellular cancer (HCC)

•  Versus placebo in 760 patients previously treated with sorafenib; OS endpoint

•  Enrolling on multiple continents; top line data expected 2016/17

METEOR: phase 3 pivotal trial in metastatic renal cell cancer (RCC)

•  Versus everolimus in 650 patients who have received and progressed on/after at least one prior VEGFR tyrosine kinase inhibitor; PFS endpoint, OS secondary endpoint

•  Top-line data expected in 2015; ~90% of sites now activated, reflecting a high level of interest due to early phase data with cabozantinib in RCC, the design of the phase 3 study, and a limited number of active competitive studies

Other Ongoing Studies of Cabozantinib

14 Note: Cabozantinib is not approved for use under investigation in these trials.

2014 Top-line data from COMET-1 and COMET-2 in CRPC

2015 Top-line data from METEOR in RCC

2016/17 Top-line data from CELESTIAL in HCC

Anticipated Cabozantinib Clinical Trial Milestones

15 Note: Cabozantinib is not approved for use under investigation in these trials.

Cabozantinib: Other Development Updates

MTC: Approval in the European Union •  Indicated for the treatment of adult patients with progressive, unresectable

locally advanced or metastatic MTC

•  European Commission maintained orphan drug status for COMETRIQ in MTC in Europe

Planned presentations at ASCO 2014, Chicago, May 30 – June 3, 2014

•  Nine abstracts selected for presentation

•  Trials in progress for RCC and HCC studies, plus data from IST and NCI-CTEP programs

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Cobimetinib Development Update Peter Lamb, EVP and CSO

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Competitive Landscape: RAF/MEK Combination in Metastatic Melanoma (MM), GSK Compounds

January 2014: accelerated approval for dabrafenib (RAF) and trametinib (MEK) combo in unresectable or MM with BRAF V600 E or K mutation

•  Based on phase 1/2 data looking in part at combination vs. dabrafenib alone •  IRC assessed PFS 9.2 mos for combo vs. 7.3 mos dabrafenib alone •  Overall response rate (ORR): 57% for combination versus 46% dabrafenib •  Both agents previously approved as single agents in same population

March 2014: top-line data for phase 3 trial comparing dabrafenib/trametinib vs. dabrafenib alone in same patient population

•  IRC-audited data: PFS 10.1 mos for combo vs. 9.5 mos dabrafenib alone •  ORR: 61% for combination vs. 47% dabrafenib alone

“Dear Healthcare Professional” letter sent to alert physicians to findings; more detailed data expected at ASCO

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Cobimetinib Development Program

BRIM7: phase 1b dose escalation study evaluating safety, tolerability of cobimetinib plus vemurafenib in advanced BRAF-mutated melanoma

•  Cohorts that met criteria for maximum-tolerated dose expanded and included BRAF inhibitor-naïve and vemurafenib-progressing patients

BRIM7 data presented at ESMO, Fall 2013: ORR of 85% in BRAF inhibitor-naïve patients; median PFS not reached with median follow-up of 10 months

•  Update on BRIM7 expected at EADO meeting, Vilnius, May 7, 2014

•  Updated data also expected during oral presentation at ASCO, Chicago, June 2, 2014

Genentech guiding top-line data from coBRIM, phase 3 pivotal trial in previously untreated patients with BRAF-mutated melanoma, expected this year

Commercial Update Scott Garland, EVP and CCO

Commercial Update

Total net COMETRIQ revenues of $4.9M in Q1 2014 •  13% increase vs. Q4’13 •  Essentially all sales came from United States: net $4.8M,

11% increase vs. Q4’13

7.5 months ave. treatment duration for active COMETRIQ MTC patients •  Continues to climb month-over-month •  ~25% of patients on drug for one year or longer •  Generally consistent with what was seen in clinical studies

Preparing for E.U. commercial launch with SOBI •  Reimbursement in Europe takes time •  Expect SOBI to purchase a small amount of commercial product in Q2 14 •  Will provide quarterly updates on SOBI’s progress in rolling out

Cometriq across the E.U.

Productive conversations with Genentech re: cobimetinib co-promotion

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Closing Michael Morrissey, President and CEO

Top Priorities for Exelixis in 2014

Top-line data readouts from the COMET studies Preparing for regulatory filings, assuming positive COMET data Expediting enrollment in METEOR, phase 3 pivotal trial in metastatic renal cell carcinoma Planning commercial build-out supporting prostate cancer in the U.S. and E.U., pending positive COMET data

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Question & Answer Session

EXELIXIS, INC (NASDAQ: EXEL)

Q1 2014 Financial Results May 1, 2014