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EXHIBIT 10.20(b)
ADDENDUM NO. 1
TO COLLABORATION AGREEMENT (p53 PRODUCTS)
This Addendum No. 1 ("Addendum") is made by and between Introgen
Therapeutics, Inc. ("Introgen") and Xxxxx-Xxxxxxx Xxxxx Pharmaceuticals Inc.
("RPRP") as of January 23, 1996 ("Effective Date"), to that certain
Collaboration Agreement (p53 Products) dated as of October 7, 1994 between
Introgen and RPRP (the "Collaboration Agreement").
B A C K G R O U N D
A. Section 5.2 of the Collaboration Agreement provides, among other
things, that RPRP and Introgen shall each have the right to develop the
Collaboration Products within the Field in the Co-Exclusive Territory, which
includes Japan (among other countries).
B. Section 7.2 of the Collaboration Agreement provides that RPRP and
Introgen shall each have the co-exclusive right to market, sell and distribute
Collaboration Products in the Co-Exclusive Territory.
C. To expedite commercialization of the initial Collaboration Products,
RPRP and Introgen desire to initiate "first-in-human" clinical trials in Japan
for two (2) initial Collaboration Products on a cooperative basis, on the terms
and conditions set forth below.
A G R E E M E N T
NOW, THEREFORE, in consideration of the mutual covenants and premises
herein contained, the parties hereto, intending to be legally bound, agree as
follows:
1. Except as otherwise expressly defined herein, capitalized terms
shall have the meaning defined in the Collaboration Agreement.
2. RPRP and Introgen agree to conduct in accordance with this Addendum
a "first-in-human" clinical trial in Japan for the adenoviral P53 Collaboration
Product that is currently the subject of clinical trials in the United States
(the "P53/AV Product"). In addition, the parties agree to conduct an additional
"first-in-human" clinical trial in Japan for [*] Collaboration Product [*], by
the Development Committee under the Collaboration Agreement [*]. It is
understood that RPRP may propose to the Development Committee [*], and
Introgen's representatives on the Development Committee will not unreasonably
withhold their consent to such proposal. If the [*] substantially identical to
this Addendum. Together, the [*] to be conducted hereunder are referred to below
as the "Initial Japanese Clinical Development." [*]
[*] Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been
requested with respect to the omitted portions.
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[*]
3. Promptly following the Effective Date, RPRP and Introgen shall form
a development committee (the "Japanese Development Committee"), which will
consist of three (3) representatives from each of RPRP and Introgen. Introgen
and RPRP may each replace its Japanese Development Committee representatives at
any time, with written notice to the other party. The Japanese Development
Committee shall oversee, review and coordinate the Initial Japanese Clinical
Development. All decisions of the Japanese Development Committee shall be by
absolute majority vote. RPRP's lead representative shall chair all meetings of
the Japanese Development Committee.
(a) The Japanese Development Committee shall meet every four
(4) months, or more often as agreed by the parties, in Tokyo, Japan, or
such other location as the parties agree. The parties agree that at
least one meeting of the Japanese Development Committee per full
calendar year will be held at Introgen's facilities in Houston. At its
meetings, the Japanese Development Committee will [*].
(b) RPRP shall be responsible for preparing reasonably
detailed plans and budgets under which the Initial Japanese Clinical
Development will be carried out. Upon approval of the Japanese
Development Committee, and subject to such approval, such plans and
budgets shall be the "Japanese Development Plan and Budget" for all
purposes of this Addendum.
(c) Promptly following the Effective Date, RPRP shall prepare
and provide to the Japanese Development Committee a proposed Japanese
Development Plan and Budget for the P53/AV Product for which the
Initial Japanese Clinical Development will be conducted. [*] The
Japanese Development Committee shall review such proposal as soon as
possible and shall establish and approve no later than October 31 of
such year the final Program Plan and Budget for the next succeeding
year. The Japanese Development Committee shall review the Japanese
Development Plan and Budget
[*] Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been
requested with respect to the omitted portions.
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on an ongoing basis and may make changes to the Japanese Development
Plan and Budget then in effect; provided, however, the Japanese
Development Plan and Budget in effect at any time shall not be modified
except as approved by the Japanese Development Committee.
4. RPRP shall conduct the Initial Japanese Clinical Development in
accordance with the Japanese Development Plan and Budget and shall use its
reasonable diligent efforts to meet the time schedules contemplated therein. It
is understood that, subject to the Japanese Development Plan and Budget and the
control of the Japanese Development Committee, RPRP will be responsible for the
clinical management and supervision of the clinical trials conducted under this
Addendum.
(a) RPRP agrees to keep Introgen fully informed of the
progress of the Initial Japanese Clinical Development conducted
hereunder. [*] RPRP agrees to provide Introgen English translations of
information generated in connection with the Initial Japanese Clinical
Development. To the extent permitted by law or regulation, all
regulatory approvals and filings with respect to the Initial Japanese
Clinical Development will be made jointly in the names of RPRP and
Introgen, or in such other manner as the parties agree, and as
requested by Introgen, RPRP shall use reasonable diligent efforts to
take such actions as may be necessary or appropriate to enable Introgen
to transfer or extend to third parties co-equal benefits in such
approvals and filings.
(b) [*] All trial protocols and regulatory submissions with
respect to the Initial Japanese Clinical Development, and all
agreements entered into by RPRP with respect to the conduct of the
Initial Japanese Clinical Development, shall be subject to the review
and approval of the Japanese Development Committee.
(c) Without limiting the foregoing, RPRP shall periodically,
and not less often than semi-annually during the term of this Addendum,
provide the Japanese Development Committee with a written report
summarizing the progress of the Initial Japanese Clinical Development
with respect to each Initial Japanese Product during the preceding two
calendar quarters.
5. Subject to the remainder of this Section 5, RPRP will advance the
costs associated with the Initial Japanese Clinical Development. Introgen will
reimburse [*] of RPRP's out-of-pocket costs approved by the Japanese Development
Committee that are paid to third parties to conduct clinical trials under the
Initial Japanese Clinical Development, and [*], supplied under paragraph 6 below
for use in such Initial Japanese Clinical Development ("Reimbursable Costs"),
regardless of the trial outcome. [*], no later than the date that is [*] after
completion of all clinical trials conducted hereunder (the "Due Date"). At
Introgen's option, however, Introgen may [*].
[*] Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been
requested with respect to the omitted portions.
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In the event of such election, Introgen shall issue RPRP, as soon as practicable
after the Due Date, the number of shares of Introgen Series B Convertible
Preferred Stock as shall be equal to the quotient of (i) the Credit Amount, and
(ii) the price per share then applicable under the Series B Preferred Stock
Purchase Agreement, dated October 7, 1994, between RPRP and Introgen (the "Stock
Purchase Agreement") for the next to occur Closing(s)(as such term is defined in
the Stock Purchase Agreement) as adjusted pursuant to Section 19.1 of the Stock
Purchase Agreement. For the avoidance of doubt, following such issuance, to
purchase, under the Stock Purchase Agreement, Introgen equity in such Closing(s)
shall be reduced by an amount equal to such Credit Amount. In the event no
Closings remain under the Stock Purchase Agreement on the Due Date or if all
outstanding shares of Series B Preferred Stock have ten been converted
automatically into shares of Introgen Common Stock under Section 4(b) of
Introgen's Restated Certificate of Incorporation, then so long as a class of
Introgen Common Stock is then traded on any national securities exchange or The
Nasdaq Stock Market, Introgen may elect to satisfy its obligation to pay the
Credit Amount by issuing to RPRP shares of such class of Introgen Common Stock.
Such shares shall be entitled to registration rights on Form S-3 which are
equivalent to those set forth in Section 20 (except for Section 20.2) of the
Company's Series B Preferred Stock Purchase Agreement; provided, however, that
no such registration shall become effective prior to the earlier of December 31,
1998 or sic months following a registration effected pursuant to Section 20.2 of
the Series B Preferred Stock Purchase Agreement. The number of shares of
Introgen Common Stock to be issued to RPRP shall be equal to the quotient of (x)
the Credit Amount, and (y) the average closing price of the Introgen Common
Stock on any national securities exchange on which such stock is traded or on
The Nasdaq Stock Market, as applicable, for the thirty (30) trading days
immediately preceding the Due Date. Notwithstanding anything contained in this
Addendum to the contrary, in no event may Introgen issue, without the written
consent of RPRP, any equity in satisfaction of its obligation to pay any Credit
Amount, to the extent such issuance would cause RPRP to won, when aggregated
with the other shares of Introgen equity then owned by RPRP, in excess of 19.9%
of the outstanding stock of Introgen (calculated on an as-converted to Common
Stock basis). To the extent that Introgen is unable to apply any of the Credit
Amount to the issuance of RPRP of shares of Introgen Series B Preferred Stock or
Common Stock in accordance with the foregoing, and in the event that Introgen
has not yet entered into a Partnering Arrangement (as defined below) the
remainder of such Credit Amount shall be made in eight (8) equal quarterly
installments, with the last installment amount adjusted to reflect changes in
the prime rate occurring during the installment amount adjusted to reflect
changes in the prime rate occurring during the installment payment period, each
of which installment is due within ten (10) days after the end of the eight (8)
calendar quarters following the Due Date. The foregoing amounts to be reimbursed
to RPRP by Introgen shall bear interest at the prime rate of interest, as
published from time to time by Bank of America NT&SA in San Francisco,
California, from the date the amounts are paid by RPRP until the date such
amounts are reimbursed by Introgen. It is understood that [*]. Notwithstanding
anything contained in this Addendum to the contrary, in the event that [*], and
(ii) Introgen and/or the third party shall thereafter be required to pay on an
ongoing basis [*] of the Reimbursable Costs associated with the Initial Japanese
Clinical
[*] Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been
requested with respect to the omitted portions.
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Development for such Initial Japanese Product and (iii) Introgen and/or the
third party shall reimburse RPRP, on the Due Date in accordance with the
foregoing provisions of this Section 5, any Reimbursable Costs (together with
accrued interest thereon) accrued prior to the date of such Partnering
Arrangement.
6. Introgen shall supply [*] quantities of the P53/AV Product to be
used in the Initial Japanese Clinical Development, on the same terms [*].
7. Section 2.5 of the Collaboration Agreement shall be deemed to apply
to all publications of results of the Initial Japanese Clinical Development
(except that all references to the Development Committee shall be deemed to
refer to the Japanese Development Committee), but neither of the last two
sentences of Section 5.4.2, nor any of Section 5.4.3 of the Collaboration
Agreement, shall apply to preclinical data, clinical data or regulatory filings
generated or made in connection with the Initial Japanese Clinical Development
conducted hereunder.
8. RPRP agrees to use its reasonable diligent efforts to conduct and
complete as expeditiously as possible the Initial Japanese Clinical Development.
9. [*]
10. The term of this Addendum shall continue until completion of each
first-in-human clinical trial within the Initial Japanese Clinical Development
conducted hereunder; provided that this Addendum may be extended by the parties
for such longer period as the parties may mutually agree in writing.
11. This Addendum shall be deemed a part of the Collaboration
Agreement. Except as otherwise expressly provided in this Addendum, all rights
and obligations with respect to Collaboration Products in Japan will be as set
forth in the Collaboration Agreement. Following the expiration or termination of
this Addendum, all obligations of the parties under this Addendum, except those
under Paragraphs 4(a), 5 and 7 above, shall terminate and be of no further force
or effect. It is understood that nothing in this Addendum shall be deemed to
[*].
XXXXX-XXXXXXX XXXXX
INTROGEN THERAPEUTICS, INC. PHARMACEUTICALS INC.
By: /s/ Xxxxx X. Xxxxx By: X. X. Xxxx
--------------------------------- --------------------------------
XXXXX XXXXX Vice President &
President General Counsel
Date: 01-23-1996 Date: 01-19-1996
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[*] Certain information on this page has been omitted and filed
separately with the Commission. Confidential treatment has been
requested with respect to the omitted portions.
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