SECOND AMENDMENT TO LOAN AND SECURITY
                                    AGREEMENT


     THIS SECOND AMENDMENT TO LOAN AND SECURITY AGREEMENT (the "Second
Amendment") is made and effective as of this 20th day of September, 2004
("Effective Date") by and between Exelixis, Inc., a Delaware corporation
("Exelixis"), and SmithKline Beecham Corporation, a Pennsylvania corporation,
doing business as GlaxoSmithKline ("GSK"). Exelixis and GSK are each referred to
herein by name or as a "Party" or collectively, as "Parties". All capitalized
terms used, but not specifically defined, herein shall have the same meaning
provided for such terms in the Loan Agreement.

     WHEREAS, Exelixis and GSK are parties to that certain Loan and Security
Agreement dated October 28, 2002 as amended by a First Amendment to Loan and
Security Agreement dated December 5, 2002 (the Loan and Security Agreement as
amended by such First Amendment, the "Loan Agreement");

     WHEREAS, Exelixis and GSK desire to amend certain covenants contained in
the Loan Agreement in furtherance of the Parties' ongoing collaboration; and

     WHEREAS, pursuant to Section 8.1 of the Loan Agreement, the Parties may
agree to amend the Loan Agreement by mutual written agreement of the Parties.

     NOW, THEREFORE, in consideration of the foregoing and of other good and
valuable consideration, the receipt and sufficiency of which are herby
acknowledged, GSK and Exelixis agree that Article 11 of the Loan Agreement shall
be amended in its entirety effective as of September 15, 2004 to read as
follows:


                                   ARTICLE 11
                               FINANCIAL COVENANTS

     Exelixis covenants and agrees that for the period from September 15, 2004
through March 31, 2005 Exelixis shall comply either with (a) the covenants set
forth in both Sections 11.1 and 11.2 or (b) the covenant set forth in Section
11.3. For the period from April 1, 2005 through the balance of the Term,
Exelixis shall comply with the covenants set forth in both Sections 11.1 and
11.2.
     11.1 Working Capital. Exelixis shall not cause or permit Working Capital to
be less than Twenty-Five Million Dollars ($25,000,000), the term "Working
Capital" meaning, as of the time of any determination thereof, the amount
determined in accordance with GAAP, by which the current assets of Exelixis
exceed its current liabilities.

     11.2 Tangible Net Worth. Exelixis shall not cause or permit Tangible Net
Worth to be less than Ten Million Dollars ($10,000,000), the term "Tangible Net
Worth" meaning, as of the time of any determination thereof, total stockholder
equity less good will and other intangible assets as reported by Exelixis in its
SEC Filings prepared in accordance with GAAP.

     11.3 Minimum Cash and Investments. Exelixis shall not cause or permit Cash
and Investments to be less than Fifty Million Dollars ($50,000,000). The term
"Cash and Investments" meaning, as of the time of any determination thereof,
total cash, cash equivalents and investments as reported by Exelixis in its SEC
Filings prepared in accordance with GAAP.

     All other conditions of the Loan Agreement, as amended and all other
writings submitted by Exelixis to GSK pursuant thereto, shall remain unchanged
and in full force and effect.

     This Second Amendment shall not constitute a waiver or modification of any
of GSK's rights and remedies or any of the terms, conditions, warranties,
representations, or covenants contained in the Loan Agreement, as amended,
except as specifically set forth above, and GSK hereby reserves all of its
rights and remedies pursuant to the Loan Agreement and applicable law.

     In WITNESS WHEREOF, the parties have executed this Second Amendment to Loan
and Security Agreement as of the date written above.


                              Exelixis, Inc.

                              By:  /s/  Frank Karbe
                                 --------------------
                              Name:     Frank Karbe
                              Title:    Senior Vice President &
                                        Chief Financial Officer

                              SmithKline Beecham Corporation

                              By:  /s/  Donald F. Parman
                                      -------------------------
                              Name:     Donald F. Parman
                              Title:    Vice President & Secretary