[ * ] = Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.
Exhibit 10.52

First Amendment to the Collaboration Agreement
This first amendment (the “Amendment) to the Collaboration Agreement dated
December 22, 2006 (the “Agreement”) between Exelixis, Inc. (“Exelixis”) and
Genentech, Inc. (“Genentech”) is made and entered into by Exelixis and Genentech
effective March 13, 2008 (the “Amendment Effective Date”). All capitalized terms
not expressly defined in this Amendment shall have the meaning assigned to them
in the Agreement.
Whereas, Exelixis and Genentech are parties to the Agreement; and
Whereas, Exelixis and Genentech wish to make certain amendments to the
Agreement;
Now, therefore, in consideration of the foregoing premises the Parties do hereby
agree to amend the Agreement, effective as of the Amendment Effective Date, as
follows:
1.
The following new Sections 1.75 through 1.77 are hereby added to the end of
Article 1 of the Agreement:

1.75    “Development Plan Activities” means the activities directed toward
achieving the primary, secondary, and exploratory objectives listed under the
heading “Development Plan Activities” in Exhibit D.
1.76     “Opt-In Date” means the date on which Exelixis receives Genentech’s
written notification of its decision to exercise its Opt-In right pursuant to
Section 3.4(b).
1.77    “Transfer Date” means the date on which Exelixis notifies Genentech of
the first occurrence of [ * ] MTD has been established consistent with the
Development Plan Activities[ * ].
2.
Section 2.1(d) of the Agreement is hereby amended and restated as follows:

“(d) Decision Making. The JSC shall make decisions unanimously, with each
Party’s representatives collectively having one (1) vote and at least one (1)
representative from each Party present. In the event the JSC cannot reach an
agreement regarding a decision within the JSC’s authority for a period of [ * ],
then, except as otherwise set forth in this Section 2.1(d) below, for the
Collaboration: (i) Exelixis shall make the final determination in its sole
discretion if such decision is regarding the [ * ] of Collaboration Compound(s)
prior to [ * ], provided that Genentech shall make the final determination in
its sole discretion if such decision is regarding whether Exelixis [ * ] with
respect to [ * ]; and (ii) Genentech shall make the final determination in its
sole discretion if such decision is regarding the [ * ] of Licensed Product(s) [
* ] (although notwithstanding Genentech’s sole discretion under this Section,
Genentech continues to be subject to [ * ]). Notwithstanding the foregoing, [ *
], Exelixis shall have final decision making authority for all matters relating
to: (x) [ * ]; and (y) [ * ]. [ * ], Genentech will have final decision making
authority for all matters related to the [ * ]. When either Party makes final
determinations under this Section, that final determination shall be consistent
with the terms of this Agreement. Disputes regarding matters not within the
responsibilities of the JSC shall be resolved pursuant to Section 15.3.”
3.
Section 2.2(d) of the Agreement is hereby amended by replacing the phrase [ * ]
with [ * ], and by replacing the phrase [ * ] with [ * ].

4.
Section 3.1 of the Agreement is hereby amended and restated as follows:

1.

--------------------------------------------------------------------------------

“3.1    DC, TCP and Development Plan Activities. The Parties have agreed on the
DC and TCP, which are attached as Exhibit B and Exhibit C to this Agreement,
respectively. The Parties have also agreed on the Development Plan Activities
described in Exhibit D to this Agreement. The DC, TCP and Development Plan
Activities may be amended only by the Parties’ mutual written agreement. The
Parties agree that the Existing Compound meets the DC and TCP. For other
Collaboration Compounds, the JSC shall determine whether such Collaboration
Compound has met the DC or TCP based on meeting all of the objective criteria
set forth in Exhibit B or Exhibit C, respectively.”
5.
Section 3.2(a) of the Agreement is hereby amended and restated as follows:

“(a)    Development by Exelixis for Existing Compound. Exelixis shall, at its
expense, use Diligent Efforts to conduct the Development Plan Activities,
including the Initial Phase I Trial, as set forth on Exhibit D, as amended,
until the Transfer Date. Except as expressly set forth in the Agreement, as
amended, including, without limitation, in Section 3.5(c), 4.1(a), and 4.1(b),
after the Transfer Date, Exelixis shall have no obligation to conduct any
further development activities with respect to the Existing Compound, [ * ]
pursuant to the terms of the Agreement.”
6.
The second sentence of Section 3.2(d) of the Agreement is hereby amended by: (1)
replacing the phrase [ * ] with the phrase [ * ] and (2) replacing the phrase [
* ] with the phrase [ * ].

7.
Section 3.2(d) of the Agreement is amended by adding the following to the end of
such section:

“[ * ], Exelixis will provide Genentech with [ * ] updates, including, without
limitation, copies of the data generated by Exelixis pursuant to Section 3.2(a)
(as amended), on the Initial Phase I Trial and other information and data
generated in connection with the Development Plan Activities. In addition, [ *
], Genentech’s representatives on the JPT, or, in place of such representatives,
an equivalent number of Genentech’s designees, [ * ]: (i) [ * ]; and (ii) [ * ].
[ * ], if Genentech has [ * ] with: (1) [ * ]; or (2) [ * ], then Exelixis’
representatives on the JPT, or, in place of such representatives, an equivalent
number of Exelixis’ designees, may [ * ].”
8.
Section 3.2(f) of the Agreement is hereby amended and restated as follows:

“(f) Regulatory. Exelixis shall file and own all INDs for Collaboration
Compounds that are the subjects of clinical trials to be carried out by Exelixis
under this Agreement, subject to Section 3.5(b), and shall be responsible for
the filing of any additional necessary regulatory documents in the Profit-Share
Territory for such Collaboration Compounds during the period [ * ] for those
Collaboration Compounds. If Genentech exercises its Opt-In right pursuant to
Section 3.4 then Exelixis shall [ * ], and [ * ] for, any additional regulatory
documents or filings, including any NDAs, with respect to any Licensed Product.”
9.
Section 3.4(a) of the Agreement is hereby amended and restated as follows:

“(a)    Performance of Development Plan Activities.” Exelixis shall use Diligent
Efforts in performance of the Development Plan Activities set forth on Exhibit
D, including [ * ]. Exelixis will notify Genentech promptly after [ * ] MTD for
the Existing Compound is established consistent with the Development Plan
Activities[ * ].”
10.
Section 3.4(b)(i) of the Agreement is hereby amended and restated as follows:

2

[ * ] = Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

--------------------------------------------------------------------------------

“(i)    Genentech shall notify Exelixis in writing of its decision as to whether
it will exercise its right to obtain a license for the development and
commercialization of Licensed Product(s) containing any Collaboration Compound
(“Opt-In”) by [ * ] (the “Initial Opt-In Expiration Date”).”
11.
Section 3.4(b)(ii) of the Agreement is hereby amended and restated in its
entirety as follows: “If, as of the Initial Opt-In Expiration Date, Genentech
notifies Exelixis in writing of its decision to exercise its Opt-In right with
respect to such Existing Compound, then: (A) Genentech shall obtain a license,
pursuant to Section 7.1, to develop and commercialize such Existing Compound and
any other Collaboration Compounds; and (B) all [ * ] Existing Compound will [ *
], but will [ * ]; provided, however, that Exelixis shall [ * ], under this
Agreement. The Parties shall conduct further development activities and
commercialization activities with respect to such Collaboration Compounds and
the associated Licensed Products pursuant to this Agreement, with Genentech
being the Party responsible for the further clinical development (after the
Transfer Date) of all Collaboration Compound(s) and the commercialization of any
Licensed Product(s) containing such Collaboration Compound(s).

12.
Section 3.4(b)(iv) is hereby added to the Agreement to read as follows:

“(iv)    If Genentech exercises its Opt-In right pursuant to Section, 3.4(b)(ii)
and subsequently [ * ], to either (1) [ * ], or (2) [ * ], then [ * ], the [ * ]
under this Agreement regarding [ * ], but will [ * ], and the [ * ]. Thereafter
Genentech shall use reasonable efforts [ * ], and the Parties shall [ * ]. If
Genentech [ * ].”
13.
Section 3.5(a) of the Agreement is hereby amended and restated in its entirety
as follows:

“(a)    Effect of Opt-In; Protocol Amendment; Creation of Development Plan.
Promptly after Exelixis receives Genentech’s notice of its decision to Opt-In
pursuant to Section 3.4, Exelixis shall provide Genentech with a copy of the
protocol for the Initial Phase I Trial. Should Genentech want to amend this
protocol, Genentech will provide Exelixis with the terms of such amendment for
review (the “Protocol Amendment”). The Parties understand and agree that any
Protocol Amendment shall not [ * ]. Exelixis will provide, and Genentech will
reasonably consider, any comments to the Protocol Amendment within [ * ] of
receipt thereof. Provided the Parties mutually agree on such Protocol Amendment,
such agreement not to be unreasonably withheld by either Party, Exelixis will
file such amendment for Regulatory Approval. [ * ], each Party will use Diligent
Efforts to transfer the conduct of the Initial Phase I Clinical Trial to
Genentech so as to minimize any disruptions thereto. Thereafter, Genentech shall
provide to Exelixis, through the JPT or JSC, a plan for the further development
of that Collaboration Compound and the associated Licensed Product which shall
be incorporated herein by reference (the “Development Plan”). Genentech has
final decision-making authority regarding any Development Plan; the Development
Plan shall reflect Genentech’s responsibility for the further clinical
development (after the Transfer Date) of Collaboration Compound(s) in the
Profit-Share Territory. Genentech may amend or update the Development Plan [ *
], and shall provide such updated Development Plan to [ * ] at scheduled
meetings of the JSC, but no more frequently than annually. The Development Plan
is [ * ].”
14.
Section 3.5(c) of the Agreement is amended and restated to read in its entirety
as follows:

“(c)    Technical Assistance and Transfer. Exelixis shall transfer to Genentech
the Information and documents described in subsections (i) -(iii) below;
provided, however, that except for those documents expressly set forth on
Exhibit D-1, Exelixis shall not have any obligation to transfer or provide
copies of any Information or documents pursuant to subsections (i) and (ii)
below that are [ * ] (e.g., [ * ]).

3

[ * ] = Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

--------------------------------------------------------------------------------

(i)    Within [ * ], Exelixis shall, [ * ], transfer (or provide copies of, as
applicable) to Genentech (or a Third Party designated by Genentech) the
Information associated with [ * ], the Parties will meet and discuss in good
faith the technical assistance from Exelixis reasonably required for Genentech
to [ * ], and the commercially reasonable terms under which such technical
assistance would be provided.
(ii)    Within [ * ], Exelixis shall, [ * ], disclose (and provide copies, as
applicable) to Genentech the “Priority” documents identified on Exhibit D-1.
Within [ * ], Exelixis shall, [ * ], disclose (and provide copies, as
applicable) to Genentech the “Other” documents identified on Exhibit D-1. In
addition, within [ * ], Exelixis shall, [ * ] disclose (and provide copies, as
applicable) to Genentech any other Information, including [ * ].
(iii)    [ * ], Exelixis shall transfer to Genentech: (1) [ * ], with respect to
Collaboration Compounds, [ * ]; (2) [ * ] with respect to any Collaboration
Compound; (3) [ * ]; and (4) [ * ], all [ * ] such Collaboration Compounds.”
15.
Section 3.5(d) is amended and restated to read in its entirely as follows:

“(d)    Development Costs. If Genentech exercises its Opt-In rights under
Section 3.4(b) or Section 3.4(c); then[ * ] Genentech shall bear one hundred
percent (100%) of the Development Costs with respect to a Collaboration Compound
and with respect to the associated Licensed Product incurred after the Transfer
Date.”
16.
Section 4.1(a) of the Agreement is hereby amended and restated as follows:

“(a)    Exelixis shall be the Party responsible, [ * ], for the Manufacture of
Collaboration Compound(s) to supply the Development Activities [ * ] or pursuant
to an Exelixis Work Plan, either by itself or through one or more Third Parties
(subject to Section [ * ]). Notwithstanding anything to the contrary in the
Agreement, if [ * ], then Exelixis will be responsible, at [ * ]. In addition,
within [ * ], at [ * ], Exelixis shall provide Genentech with [ * ] in
accordance with the terms of this Agreement.”
17.
Section 4.1(b) of the Agreement is hereby amended and restated as follows:

“(b)    Except as otherwise agreed by the Parties, including as may be agreed
pursuant to Section 3.5(c)(i), following the Opt-In Date Exelixis shall be
relieved from any Manufacturing obligations for any Collaboration Compound,
except for: (1) the requirement to provide Collaboration Compound for the
Initial Phase I Clinical Trial as set forth in Section 4.1(a) above; (2) the
requirement to [ * ]; and (3) the obligation to provide those quantities of
Collaboration Compounds needed for Exelixis to perform Back-Up Work under an
Exelixis Work Plan. Upon being relieved of its Manufacturing obligations,
Exelixis shall, [ * ], use Diligent Efforts to transfer the
Manufacturing-related activities for those Collaboration Compounds for which it
no longer has Manufacturing obligations to Genentech, pursuant to a mutually
agreeable transfer plan. In addition to the transfer of documents and
Information as set forth under Section 3.5(c), such transfer shall include [ *
]. Where Genentech has taken over the responsibility for the Manufacture of any
Collaboration Compound(s) and related Licensed Product(s), Genentech may carry
out such responsibilities either by itself or through one or more Third Parties.
Other than costs pursuant to carrying out the Manufacturing-related activities
under the technological transfer consistent with Section 3.5(c) (which costs are
borne by [ * ] pursuant to Section 3.5(c)), Fully Burdened Manufacturing Costs
(as defined in the Financial Appendix, and expressly including Third Party
suppliers) incurred by Genentech (including in connection with engaging Third
Party suppliers) for Collaboration Compound(s) and/or Licensed Product(s) with
be borne as follows: (i) if the product is for use in [ * ] (including [ * ]),
such Fully Burdened Manufacturing Costs shall be deemed [ * ] and shall be borne
[ * ]; (ii) if the product is for [ * ], such Fully Burdened

4

[ * ] = Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

--------------------------------------------------------------------------------

Manufacturing Costs shall be borne [ * ]; and (iii) if the product is for [ * ],
such Fully Burdened Manufacturing Costs shall be [ * ] and [ * ]”
18.
Section 7.1(e) of the Agreement is hereby amended by inserting the following
phrase at the end of subsection (i)(2): “, including without limitation the
Initial Phase I Trial (as set forth on Exhibit D)”

19.
Section 8.2(a) of the Agreement is hereby amended and restated in its entirety
as follows:

“(a) if Genentech exercises its Opt-In right pursuant to Section 3.4(b), as
amended, (i.e. with respect to an Existing Compound and all other Collaboration
Compounds), Genentech shall make the following payments to Exelixis: (i)
$3,000,000 within [ * ] of the Opt-In Date, and (ii) $7,000,000 within [ * ]
following the enrollment of the first human subject in the first Phase II
Clinical Trial for a Licensed Product containing the Existing Compound. For
clarity, if Genentech [ * ]; provided, however, that Genentech shall [ * ] under
this Agreement. Further, if Genentech [ * ], [ * ] Existing Compound.”
20.
The second sentence of Section 10.1(b) is hereby amended by inserting the phrase
“; provided, however, that [ * ] shall have the right to use such Confidential
Information of [ * ] to [ * ], under this Agreement.” at the end of such
sentence.

21.
Exhibit D is hereby amended and restated in its entirety, as described in the
attached Appendix.

22.
Except as expressly and unambiguously stated herein, no other changes are made
to the Agreement or Genentech’s rights following an Opt-In, and all other terms
and conditions of the Agreement shall remain in full force and effect. In the
event of a conflict between the provisions hereof and the Agreement, the
provisions of this Amendment shall control. The Agreement and this Amendment
contains the entire understanding between the Parties hereto with respect to the
subject matter hereof and supersedes and terminates all prior agreements,
understandings and arrangements between the Parties, whether written or oral
with respect to such subject matter.

Signature page follows.

5

[ * ] = Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

--------------------------------------------------------------------------------

Accepted and Agreed:
GENENTECH, INC. By:
By:     Ashraf Hanna    
Title:     VP Alliance Management    
Date:     March 13, 2008    

EXELIXIS, INC.
By:     /s/ George A. Scangos, PhD    
Title:     President & CEO    
Date:     March 13, 2008    

6

[ * ] = Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

--------------------------------------------------------------------------------

Appendix
Exhibit D
o
[ * ]

The patient population for this study will be cancer patients with advanced
solid tumors. Entry criteria are summarized below:
Inclusion Criteria for subjects in the Phase I Clinical Trial:
•
The subject has a histologically confirmed solid tumor that is metastatic or
unresectable, and for which standard curative or palliative measures do not
exist or are no longer effective, and there are no therapies known to prolong
survival.

•
The subject has disease that is assessable by tumor marker, physical, or
radiologic means.

•
The subject is ³18 years old.

•
The subject’s weight is ³55 kg and £120 kg.

•
The subject has an Eastern Cooperative Oncology Group (“ECOG”) performance
status £2.

•
The subject has organ and marrow function as follows: absolute neutrophil count
(“ANC”) ³1500/mm3, platelets ³100,000/ mm3, hemoglobin ³9 g/dL, bilirubin £1.5
mg/dL, serum creatinine £1.5 mg/dL or creatinine clearance ³60 mL/min, and
alanine aminotransferase (“ALT”) and aspartate aminotransferase (“AST”) £2.5
times the upper limit of normal if no liver involvement, or £5 times the upper
limit of normal with liver involvement.

•
The subject is capable of understanding and complying with the protocol and has
signed the informed consent document.

•
Sexually active subjects (male and female) must use medically acceptable methods
of contraception during the course of the study.

•
Female subjects of childbearing potential must have a negative pregnancy test at
screening.

•
If a subject has received more than three prior regimens of cytotoxic
chemotherapy, more than two biologic regimens, or more than 3000 cGy to ³25% of
his or her bone marrow, the sponsor must determine subject suitability before
enrollment.

•
The subject has had no other diagnosis of malignancy (unless non-melanoma skin
cancer or a malignancy diagnosed ³5 years ago, and has had no evidence of
disease for 5 years prior to screening for this study).

Exclusion Criteria or subjects in the Phase I Clinical Trial:
•
The subject has received anticancer treatment (e.g., chemotherapy, radiotherapy,
cytokines, or hormones) within 30 days (6 weeks for nitrosoureas or mitomycin C)
before the first dose of study drug.

•
The subject has received radiation to ³25% of his or her bone marrow within 30
days of study entry.

•
The subject has not recovered to grade £1 from adverse events (“AEs”) or to
within 10% of baseline values due to investigational or other agents
administered more than 30 days prior to study enrollment.

•
The subject has received another investigational agent within 30 days of the
first dose of study drug.

•
The subject has known brain metastases.

•
The subject has an uncontrolled intercurrent illness including, but not limited
to, ongoing or active infection, symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
that would limit compliance with study requirements.

•
The subject is pregnant or breastfeeding.

•
The subject is known to be positive for the human immunodeficiency virus
(“HIV”).

•
The subject has an allergy or hypersensitivity to components of the formulation.

•
The subject is unable or unwilling to abide by the study protocol or cooperate
fully with the investigator or designee.

7

[ * ] = Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

--------------------------------------------------------------------------------

The dose for the first cohort will be selected based on published FDA
guidelines, referenced as follows: “General Guide for Starting Dose Selection
for a Cytotoxic Agent in Cancer Patients”
(www.fda.gov/cder/cancer/docs/doseflow.pdf).
For the initial cohorts in study, XL518 drug substance will be provided in
powder form accompanied by a pharmaceutically appropriate aqueous vehicle for
oral administration as a solution and/or suspension (“PIB”). A solid oral dosage
form will be developed and introduced in the Phase 1 clinical trial with
appropriate PK and safety monitoring.
Following the initial cohort, additional subjects will be enrolled and receive
higher doses of XL518 in order to establish MTD as outlined below.
[ * ]

8

[ * ] = Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.

--------------------------------------------------------------------------------

Appendix
Exhibit D-1
Documents to be provided to Genentech by Exelixis [ * ] following a Genentech
Opt-In:
o
[ * ]

9

[ * ] = Certain confidential information contained in this document, marked by
brackets, has been omitted and filed separately with the Securities and Exchange
Commission pursuant to Rule 24b-2 of the Securities Exchange Act of 1934, as
amended.