[*] = 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 10.40
Amendment #3
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, will be amended to add:

“Quality Technical Agreement or QTA” means the agreement setting forth in detail
the quality assurance arrangements and procedures for the manufacture and supply
of the Investigational Agent.”

“Regulatory Authority” means any governmental authority that has responsibility
in its applicable jurisdiction over the testing, development, manufacture, use,
storage, import, transport, promotion, marketing, distribution, offer for sale,
sale, or other commercialization of pharmaceutical products in a given
jurisdiction, including but not limited to the FDA and EMA.”
2.
The second sentence of Section 3.8.1 is hereby deleted in its entirety and
replaced with the following:

“Investigational Agent should be suitable for shipment to all countries and
sites participating in DCTD-sponsored clinical trials approved under this CRADA.
Investigational Agent will be provided in accordance with the Quality Technical
Agreement.”
3.
Section 3.8.2 is hereby deleted in its entirety and replaced with the following:

“DCTD will provide updated forecasts of amounts of Investigational Agent
anticipated for ongoing and anticipated clinical studies under mutually agreed
upon Protocol(s) and, in any event, will notify Collaborator of the quantity of
Investigational Agent required to maintain adequate supply for each clinical
study to be conducted under such Protocol(s) at least [*] before the date on
which Collaborator is required to supply such Investigational Agent for use in
such studies. NCI NSC (National Service Center) numbers are required to be on
the drug product label provided by Collaborator to DCTD only. Investigational
Agent provided by Collaborator directly to clinical sites outside of the United
States are not required to be labeled with the NCI NSC numbers additional
labeling and/or other information may be added by the NCI Pharmaceutical
Management Branch (PMB) on the label of Investigational Agent for all
DCTD-sponsored clinical trials. DCTD is responsible for ensuring that
appropriate quality standards and regulatory requirements are met for all such,
additional labeling and/or other information, as further detailed in the Quality
Technical Agreement.”
4.
Collaborator contact in Section 3.9 shall be replaced with “[*].”

[*] = 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.

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

5.
Section 4.5 is hereby deleted in its entirety and replaced with the following:

“Annual Reports. DCTD will provide to Collaborator a copy of the Annual Report,
or such portion containing Protools using Collaborator’s Investigational Agent
concurrently with the submission of the Annual Report to the FDA. Such Annual
Reports will be CRADA Data, and will be kept confidential by the Parties in
accordance with Article 8.”
6.
All instances of “FDA” in Sections 3.9 and 3.11shall be replaced with “FDA
and/or other Regulatory Authority”.

7.
Instances of “21 CFR 312.33” shall be replaced with “21 CFR 312.33, and any
applicable local regulatory regulations or guidances”.

Signatures begin on next page

[*] = 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 TO:

For the National Cancer Institute
/s/ James H. Doroshow
 
5/16/2018
James H. Doroshow, M.D.
 
Date
Deputy Director, NCI
 
 

For Collaborator:
Exelixis Inc.
/s/ Gisela M. Schwab
 
5/29/2018
Gisela M. Schwab, M.D.
President, Product Development and Medical Affairs, CMO
 
Date

[*] = 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.