Exhibit 10.46

Amendment #1
Cooperative Research and Development Agreement #11-1-00006
“Clinical Development of Exelixis Inc.’s Proprietary Cabozantinib (XL184), a MET
and
Vascular Endothelial Growth Factor Receptor 2 (VEGFR2)/Kinase Insert Domain
Receptor (KDR) inhibitor, as an Anti-Cancer Agent”

The purpose of this amendment is to change certain terms of the above-referenced
Cooperative Research and Development Agreement (CRADA). These changes are
reflected below, and except for these changes, all other provisions of the
original CRADA remain in full force and effect. Two originals of this amendment
are provided for execution; one is to remain with the National Cancer Institute
and the other is to remain with the Collaborator.
The aforementioned CRADA shall be amended as follows:
1.
Article 2, Definitions, “Test Article” is hereby amended as follows where
underlining denotes addition:

"Test Article" means, in accordance with 21 C.F.R. § 50.3(j), any drug
(including a biological product), medical device, food additive, color additive,
electronic product, or any other article subject to regulation under the Federal
Food, Drug, and Cosmetic Act that is intended for administration to humans or
animals, including a drug or biologic as identified in the Research Plan, that
is used within the scope of the Research Plan. The Test Article may also be
referred to as Investigational Agent, Study Material, or Study Product. For this
Agreement, Test Article, Investigational Agent, Study Material or Study Product
means XL184 (cabozantinib) provided by or on behalf of Collaborator. For purpose
of this CRADA, Investigational Agent shall also include pharmacokinetic and
pharmacodynamics kits (Kits), and related support services, provided by or on
behalf of the Collaborator.

2.
Article 3.8, Investigational Agent Information and Supply is hereby amended as
follows where underlining denotes addition:

3.8.8 Collaborator, or its vendor, will provide Kits directly to the sites in
support of the Protocols. The Protocol will contain specific information on the
use of the Kits.

SIGNATURES BEGIN ON NEXT PAGE

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ACCEPTED AND AGREED TO:

For the National Cancer Institute
/s/ JAMES H. DOROSHOW, M.D.
 
3/20/2013
James H. Doroshow, M.D.
Deputy Director, NCI
 
Date

For Collaborator:
Exelixis Inc.

/s/ GISELA M. SCHWAB, M.D.
 
4/16/2013
EVP and CMO
 
Date