[ * ] = 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 10.18

 

SECOND AMENDMENT TO

COLLABORATION AGREEMENT

 

This Second Amendment to Collaboration Agreement (“Amendment”) is entered into
as of July 6, 2001 (“Amendment Date”) by and between Rigel Pharmaceuticals,
Inc., a Delaware corporation (“Rigel”) having offices at 240 East Grand Avenue,
South San Francisco, CA 94080, and Novartis Pharma AG, a Swiss corporation
(“Novartis”) having offices at Lichtstrasse 35, CH-4058, Basel, Switzerland.
Rigel and Novartis are referred to herein collectively as the “Parties,” and
each individually as a “Party.”

 

Recitals

 

Whereas, Rigel has, as of the Amendment Date, conducted significant research
regarding the role of endothelial cell function in angiogenesis (some of which
research Rigel has conducted pursuant to a collaborative program with Cell
Genesys, Inc., a Delaware corporation (“Cell Genesys”), and has substantial
expertise in the discovery of intracellular target molecules that modulate human
disease states, which expertise is applicable to further research on endothelial
cell function in angiogenesis;

 

Whereas, Novartis is engaged in the research, development, marketing and
manufacture of pharmaceutical compounds useful in treating or preventing human
diseases and conditions, including diseases and conditions which may affect or
be affected by angiogenesis, and therefore desires to have access to the results
of Rigel’s research up to the Amendment Date in such area, as well as to
cooperate with Rigel and employ Rigel technology to pursue further research in
such area;

 

Whereas, Rigel and Novartis are parties to that certain Collaboration Agreement
dated May 26, 1999 as amended by a First Amendment dated 18 May, 2001 (referred
to as the “Collaboration Agreement”) pursuant to which Novartis may have access
to up to five (5) collaborative research projects with Rigel, as more completely
described in the Collaboration Agreement, and in connection with research
surrounding such process that Rigel has ongoing under its collaboration with
Cell Genesys in order to benefit from the synergies and efficiencies of a
combined research program;

 

Whereas, the Parties wish to conduct their further research regarding
endothelial cell function in angiogenesis as a Joint Project within the
framework of their existing collaboration pursuant to the Collaboration
Agreement;

 

Whereas, the Parties have, as of the Amendment Date, initiated three (3)
collaborative projects pursuant to the Collaboration Agreement, of which two (2)
have been Joint Projects (as defined by the Collaboration Agreement) and one (1)
has been an At-Novartis Projects (as defined by the Collaboration Agreement);

 

Whereas,  the Collaboration Agreement provides for the Parties to conduct a
maximum of three (3) At-Novartis Projects; and

 

[Signature Page]

 

Whereas, the Parties wish to amend the Collaboration Agreement as provided
herein to accommodate conducting a collaborative project relating to endothelial
cell function in angiogenesis as a Joint Project pursuant to the Collaboration
Agreement in conjunction and consistent with Rigel’s research for and
responsibilities to Cell Genesys, as well as to provide for Rigel to be
compensated for its prior work outside the scope of the Collaboration Agreement
in such area of research.

 

Now, Therefore, in consideration of the foregoing and the covenants and promises
contained in this Amendment, the Parties agree as follows:

 

ARTICLE 1

 

DEFINITIONS

 

1.1          Terms Defined in Collaboration Agreement.  Any initially
capitalized terms not otherwise defined herein shall have the meanings given in
the Collaboration Agreement.

 

1.2          Additional Defined Terms.  As used herein and in the Collaboration
Agreement, the following terms shall have the following meanings:

 

(a)           “Angiogenesis Project” shall mean the Program of Research directed
to the identification of Novel Validated Targets involved in endothelial cell
function as part of the angiogenesis process, as such Program of Research is
more fully described in Exhibit A.

 

(b)           “CG Agreement” shall mean that certain License and Research
Agreement made effective by and between Rigel and Cell Genesys as of September
2, 1999, as first amended and restated by such parties on March 26, 2001 and
subsequently amended and restated by such parties effective July 1, 2001, a
partially redacted copy of the signed CG Agreement being appended to this
Amendment as Exhibit C.

 

(c)           “Novel Validated Angiogenesis Project Target” shall mean a Novel
Validated Target identified in the Angiogenesis Project.

 

1.3          Research Period. The Collaboration Agreement is hereby amended to
replace the definition of “Research Period” in its entirety with the following:

 

““Research Period” shall mean, for each Joint Project and At-Novartis Project
other than the Angiogenesis Project, five years commencing as of the
corresponding Commencement Date, subject to earlier termination as permitted
hereby.

 

With respect to the Angiogenesis Project, the Research Period shall mean three
(3) years after its Commencement Date.”

 

ARTICLE 2

 

NUMBER OF PROJECTS; ANGIOGENESIS PROJECT; RIGHTS IN NOVEL

VALIDATED ANGIOGENESIS TARGETS

 

2.1          Number of Projects.  The Collaboration Agreement is hereby amended
to replace the text of Section 2.1 thereof in its entirety with the following:

 

“Novartis may have access to up to five (5) Programs of Research of which at
least three (3) will be Joint Projects and no more than two (2) will be
At-Novartis Projects.”

 

2.2          Angiogenesis Project.  The Collaboration Agreement is hereby
amended to insert, after Section 2.5 thereof, a Section 2.6 entitled
“Angiogenesis Project” having the following as its text:

 

“The Program of Research constituting the Angiogenesis Project is as described
at Exhibit A to this Second Amendment. The Angiogenesis Project shall be
conducted as a Joint Project as provided in Section 4.1 of the Agreement and is
one of the Programs of Research referred to in Section 2.1 of the Agreement;
provided, that Novartis acknowledges that the Program of Research for the
Angiogenesis Project may describe, and the Angiogenesis Project may therefore
include, research that is also covered by the CG Agreement.  The number of FTEs
for each of the first three years of the Angiogenesis Project are set forth in
Exhibit B, row B-4.”

 

2.3          Discretionary Termination of Research Period: Section 4.5.1 of the
Collaboration Agreement is hereby amended to insert the phrase “if applicable”
immediately after the phrases “given Joint Project” and “such Joint Project” in
the sixth and eighth lines, respectively, of such Section.

 

2.4          Exclusivity Term: Section 5.2 of the Collaboration Agreement is
hereby amended to insert the phrase “and, with respect to the Angiogenesis
Project only, subject furthermore to the provisions of the CG Agreement,”
immediately after the phrase “and subject to the provisions of Section 5.5,” in
the third line of such Section.

 

2.5          Novel Validated Angiogenesis Project Target.  A new Section 6.5
shall be added to the Collaboration Agreement with the following as its text:

 

“Novel Validated Angiogenesis Project Target.  The Parties recognize and
acknowledge that as a part of Rigel’s ongoing relationship with Cell Genesys in
the angiogenesis field, Rigel has certain obligations and has granted certain
rights to Cell Genesys that are each described and defined in the CG Agreement.
Such rights of Cell Genesys may include without limitation (i) the nonexclusive
right to use Novel Validated Angiogenesis Targets to research and develop
Therapeutic Candidates (within the meaning of such term as defined and used in
the CG Agreement); and (ii) pursuant to Section 2.2(b)(i) of the CG Agreement,
the “royalty-free, exclusive, worldwide license, with the right to grant and
authorize sublicenses, under any Information and intellectual property created
by Rigel (solely or jointly with Novartis) under the Novartis Angiogenesis
Collaboration, to make, have made, use, sell, offer for sale and import
Therapeutic Candidates within the CG Program Field”.  The rights with respect to
Novel Validated Angiogenesis Targets and Project Technology granted Novartis
pursuant to the Collaboration Agreement and this Amendment are hereby made
subject to any conflicting rights granted Cell Genesys pursuant to the CG
Agreement solely to the extent of the conflict with such rights of Cell
Genesys.”

 

ARTICLE 3

 

FINANCIAL TERMS

 

3.1          Milestone Payments to Rigel. Novartis will pay Rigel Milestone
Payments in respect of achievements in the Angiogenesis Project in the amounts
and upon the events specified in Section 7.2 of the Collaboration Agreement.

 

3.2          Access Payment.

 

(a)           Section 7.3 of the Collaboration Agreement is hereby amended to
insert the phrase “other than the Angiogenesis Project” immediately after the
phrase “each Joint Project” in the second line of such Section.

 

(b)           Novartis shall pay Rigel a project access fee in relation to the
Angiogenesis Project of four million dollars ($4,000,000) within thirty (30)
days after the receipt of an invoice from Rigel on or after the Amendment Date.

 

3.3          Extension Fee. The Extension Fee payable by Novartis to extend the
Exclusivity Term with respect to any Novel Validated Angiogenesis Project Target
shall be as specified (with respect to any Novel Validated Target) pursuant to
Section 7.5 of the Collaboration Agreement.

 

3.4          Research Support of Angiogenesis Project. The Collaboration
Agreement is hereby amended by replacing Exhibit B thereto with the amended and
restated Exhibit B appended to this Amendment.

 

ARTICLE 4

 

CONFIDENTIALITY

 

4.1          The following Section 10.2.3 shall be added to the Collaboration
Agreement:

 

“Novartis is aware and authorizes that Rigel may disclose to Cell Genesys under
the CG Agreement Confidential Information generated by Rigel solely or jointly
with Novartis under the Angiogenesis Project, such Confidential Information to
be used by Cell Genesys exclusively as provided in the CG Agreement.”

 

ARTICLE 5

 

MISCELLANEOUS

 

5.1          This Amendment shall become effective upon the Amendment Date and
will form an integral part of the Collaboration Agreement.

 

5.2          Except as expressly amended hereby, all clauses of the
Collaboration Agreement shall remain unchanged in full force and effect.

 

5.3          This Amendment may be executed in two (2) or more counterparts,
each of which shall be deemed an original, but all of which together shall
constitute one and the same instrument.

 

In Witness Whereof, the Parties hereto have duly executed this Second Amendment.

 

Rigel Pharmaceuticals, Inc.

Novartis Pharma AG

 

 

 

By:

/s/   Raul R. Rodriguez

 

By:

/s/   J. Heim

 

 

 

Name:

  Raul R. Rodriguez

 

Name:

  J. Heim

 

 

 

Title:

  Vice President, Business Development

 

Title:

  Sr. Scientific Expert MCB

 

 

EXHIBIT A

 

Angiogenesis Project

 

[*]

 

Exhibit B

 

Exhibit B to the Collaboration Agreement shall be deleted and replaced in its
entirety with the following:

 

“EXHIBIT B

 

 

Project

 

Number of Rigel FTEs

 

Commencement Date

 

Type of Project

B-1: T-Cell Project

 

12

 

Effective Date

 

Joint Project

B-2: B-Cell Project

 

12

 

August 24, 1999

 

Joint Project

B-3: Epithelial Cell Project

 

n.a.

 

January 1, 2000

 

At-Novartis Project

B-4: Angiogenesis Project

 

12 in first and second year after Commencement Date

 

 8 in third year after Commencement Date

 

Amendment Date

 

Joint Project

 

EXHIBIT C

 

RIGEL-CELL GENESYS AGREEMENT (Redacted)

 

See Exhibit 10.19 to Rigel Pharmaceuticals, Inc.’s Quarterly Report on Form 10Q
for the quarter ended September 30, 2001

 

 

 

[ * ]

=

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.