EXHIBIT 10.45

[***] = 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.
 
SECOND AMENDMENT TO AGREEMENT
 
This Second Amendment To Agreement (the “Amendment”) is entered into as of
November 19, 2007 (the “Amendment Effective Date”), between Takeda
Pharmaceutical Company Limited, with its head office at 1-1, Doshomachi 4-chome,
Chuo-ku, Osaka 540-8645, Japan (hereinafter called “TAKEDA”), Cerexa, Inc., with
its head office at 1751 Harbor Bay Parkway, Alameda, CA 94502, USA (hereinafter
called “CEREXA”) and Forest Laboratories Holdings Limited, with its head office
at Milner House, 18 Parliament Street, Hamilton, HM11 Bermuda (hereafter “FOREST
HOLDINGS”).
 
RECITALS
 
Whereas, PENINSULA PHARMACEUTICALS, INC. and TAKEDA CHEMICAL INDUSTRIES, LTD
(former name of TAKEDA) entered into a certain agreement dated September 30,
2003, as amended to date, relating to the compound coded by TAKEDA as TAK-599
(the “Agreement”), pursuant to which TAKEDA has granted to PENINSULA exclusive
rights to develop and commercialize the Product in the Territory, which
Agreement and rights were assigned by PENINSULA to CEREXA effective as of June
30, 2005; and
 
Whereas, effective January 11, 2007, CEREXA became a wholly-owned subsidiary of
Forest Laboratories, Inc., a Delaware corporation having its principal offices
at 909 Third Avenue, New York, New York 10022 USA (“FOREST”) and which is the
corporate parent of FOREST HOLDINGS.  FOREST HOLDINGS generally acquires and
manages pharmaceutical intellectual property assets on behalf of FOREST and its
subsidiaries (collectively, the “FOREST GROUP”) and arranges for the supply of
the FOREST GROUP’s requirements of proprietary active pharmaceutical ingredients
and products; and
 
Whereas, the parties desire to amend the Agreement with regard to the clinical
and commercial supply of the Compound.
 
Now, Therefore, CEREXA and TAKEDA and FOREST HOLDINGS hereby agree, effective as
of the Amendment Effective Date, as follows:
 
1. All capitalized terms used but not otherwise defined in this Amendment shall
have the meanings ascribed to such terms in the Agreement. Throughout the
recitals and text of the Agreement, each occurrence of the word “PENINSULA” is
hereby amended and replaced with the word “CEREXA”.
 
2. The Parties acknowledge that, pursuant to Section 7.4 and Section 8.2 of the
Agreement, TAKEDA has notified CEREXA that TAKEDA has elected to cease supply of
the Compound to CEREXA, and CEREXA hereby notifies TAKEDA that (i) CEREXA elects
to continue the Agreement by manufacturing or having a Third Party or a member
of the FOREST GROUP manufacture the Compound on its behalf, and (ii) FOREST
HOLDINGS would like to assume such manufacturing role under direct license from
TAKEDA.
 

 
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3. FOREST HOLDINGS is hereby made a party to the Agreement and the rights and
obligations of CEREXA will apply, mutatis mutandis, to FOREST HOLDINGS, to the
extent of its interest and obligations as hereinafter provided (i.e.,
manufacturing the Compound to be used for the Product to be developed or sold by
CEREXA, its affiliate(s) or its sublicensee(s) pursuant to the Agreement), and
FOREST HOLDINGS agrees to the provisions of this Amendment referring to FOREST
HOLDINGS set forth below, in each case with respect to rights or obligations
accruing from and after the Amendment Effective Date and not intending to
modify, amend, limit or restrict any such rights or obligations to the extent
accrued prior to the Amendment Effective Date.
 
CEREXA and FOREST HOLDINGS hereby agree that (i) TAKEDA’s liabilities and
obligations under the Agreement shall be no greater than would have been the
case if CEREXA by itself, and not FOREST HOLDINGS, had assumed the manufacturing
role under direct license from TAKEDA and FOREST HOLDINGS had not been made a
party to the Agreement, and (ii) CEREXA and FOREST HOLDINGS shall be responsible
for, and indemnify, hold TAKEDA harmless and defend TAKEDA against any and all
third-party claims, suits, losses, damages, costs and fees to the extent such
claims etc. would not have arisen if CEREXA by itself, and not FOREST HOLDINGS,
had assumed the manufacturing role under direct license from TAKEDA and FOREST
HOLDINGS had not been made a party to the Agreement.
 
4. Notwithstanding anything to the contrary in the Agreement, CEREXA, FOREST
HOLDINGS and TAKEDA agree that the Agreement is hereby amended as follows, in
each case with respect to rights or obligations accruing from and after the
Amendment Effective Date and not intending to modify, amend, limit or restrict
any such rights or obligations to the extent accrued prior to the Amendment
Effective Date:
 
(a) Subject to Item 9 of this Amendment, any further obligations of TAKEDA,
including under Articles 7 and 8 and Sections 6.1, 6.6, 6.7, 6.8 and 12.2(a) of
the Agreement related to the manufacturing and supply of the Compound to CEREXA
hereby terminate, and CEREXA and FOREST HOLDINGS shall not have any further
right to compel TAKEDA to manufacture and supply the Compound to CEREXA and/or
FOREST HOLDINGS.
 
(b) Section 6.3 of the Agreement is hereby amended to read in its entirety as
follows:
 

“CEREXA shall have the sole responsibility hereunder to apply for, obtain and
maintain Registrations in the Territory. All the expenses necessary for applying
for, obtaining securing and maintaining Registrations in the Territory shall be
borne by CEREXA. At CEREXA’s request, TAKEDA shall, to the extent reasonable and
as far as available to TAKEDA at that time, cooperate in the preparation and
maintenance of all regulatory filings for Products filed by CEREXA, including,
without limitation, preparing all sections of INDs that are applicable to
preclinical data generated by TAKEDA. CEREXA shall bear all of TAKEDA’s
reasonable out-of-pocket costs incurred in providing such assistance and
cooperation to CEREXA.”
 

 
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For the avoidance of doubt, effective as of the Amendment Effective Date,
TAKEDA’s cooperation in the preparation and maintenance of all regulatory
filings for the Products filed by CEREXA pursuant to Section 6.3 of the
Agreement with respect to the preparation of any sections of INDs that are
applicable to manufacturing activities of the Products (such as Chemistry,
Manufacturing and Controls portions of INDs and NDAs) shall be limited to the
activities specifically set forth in this Amendment, especially those set forth
in Items 6 and 7 hereof.
 
(c) Section 9.1 of the Agreement is hereby amended to read in its entirety as
follows:
 
“CEREXA shall, through FOREST HOLDINGS or its designee, procure its requirements
of the Compound and other materials which are necessary for manufacturing the
Product at its own responsibility and expense.”
 
(d) Section 11.1 of the Agreement is hereby deleted in its entirety, and CEREXA
shall not be entitled to include the company name of TAKEDA as the licensor on
any packaging materials and other printed materials, including promotional
materials, for the Product in the Territory (the “Mark”), except that CEREXA (or
its affiliate or sublicensee, as applicable) shall be entitled to use the Mark
to the extent required by applicable laws and regulations to indicate that
Product is manufactured and distributed by such party under license from TAKEDA.
 
(e) Subsection (b) of Section 13.2 of the Agreement is hereby amended to read
(in relevant part) as follows:
 
“the processing (including the manufacture of the Compound or the Product by
CEREXA, any member of the FOREST GROUP or a third party manufacturer arranged by
CEREXA or any member of the FOREST GROUP), use or sale of the Product by CEREXA
or its distributor or sublicensee;”
 
5. In addition to the license granted to CEREXA pursuant to Section 2.1 of the
Agreement, TAKEDA hereby grants to FOREST HOLDINGS the exclusive license
(subject only to the rights reserved to TAKEDA set forth in this Item 5), with
rights to sublicense, under the Information, Manufacturing Know-How and Patents
to make and have made the Compound and all intermediates thereof anywhere in the
world, to the extent the Compound and all intermediates thereof thus
manufactured are for Product to be sold or distributed in the Territory, without
any additional consideration to TAKEDA other than already set forth in the
Agreement; provided, however, that TAKEDA reserves the right under the
Information, Manufacturing Know-How and Patents to make and have made the
Compound and all intermediates thereof in the Territory to the extent and as far
as the Compound thus manufactured are used for the Product to be sold outside
the Territory.
 

 
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6. Within [***] after the Amendment Effective Date, TAKEDA shall disclose to
FOREST HOLDINGS the Manufacturing Know-How Controlled by TAKEDA as of the
Amendment Effective Date, to the extent items of Which are listed in Schedule 1
attached hereto; and upon written request by FOREST HOLDINGS and within [***]
after the receipt of such request, TAKEDA shall disclose to FOREST HOLDINGS the
Manufacturing Know-How, to the extent items of which are listed in the Schedule
2 attached hereto.
 
Effective as of the Amendment Effective Date, FOREST HOLDINGS may purchase all
of its requirements of the Compound to be used for the Product to be developed
or sold by CEREXA, its Affiliates, or its sublicensee(s) under the Agreement
from any Third Party Manufacturer and/or manufacture by itself the Compound and
may use such Manufacturing Know-How to do so under the license granted by TAKEDA
pursuant to Item 5 of this Amendment.
 
CEREXA and FOREST HOLDINGS acknowledge that (i) the information, data and
know-how identified in Schedule 3 attached hereto relating to the manufacture of
AMPA is Controlled not by TAKEDA, but by [***] (hereinafter “[***]”), and (ii)
TAKEDA has introduced CEREXA and FOREST to [***]. If there is any other
information, data and know-how relating to the manufacture of the Compound
and/or any intermediates thereof that is in the possession of TAKEDA or its
Third Party Manufacturer, but is not Controlled by TAKEDA, if any, then TAKEDA
shall use commercially reasonable efforts to secure access and rights to such
information, data and know-how so that it Controls the same and can disclose
same to FOREST HOLDINGS for its use hereunder. To TAKEDA’s knowledge as of the
Amendment Effective Date, there is no such information, data or know-how
possessed but not Controlled by TAKEDA which is currently used by TAKEDA to the
manufacture of the Compound or its intermediates, except as set forth in
Schedule 3 attached hereto.
 
TAKEDA shall provide, at such times and locations as separately determined by
the parties and at the expense of FOREST HOLDINGS, reasonable, diligent and good
faith cooperation, to the extent reasonable and as far as available to TAKEDA at
that time and necessary for the establishment of manufacturing capacity of the
Product, to enable FOREST HOLDINGS to establish such manufacturing capability,
including, without limitation, assisting in qualifying FOREST HOLDINGS or its
designated third party manufacturer to manufacture Compound and all
intermediates thereof.
 
7. TAKEDA shall assist FOREST HOLDINGS with identifying a third party that will
be able to supply FOREST HOLDINGS or its designee with those intermediates
required for the manufacture of Compound. To the extent requested by FOREST
HOLDINGS and at FOREST HOLDINGS’ expense, TAKEDA shall provide reasonable
assistance to facilitate the assignment to FOREST HOLDINGS of current
agreement(s) between TAKEDA and Third Party Manufacturer(s) with regard to the
manufacture of the Compound or of intermediates, and/or in enabling FOREST
HOLDINGS to enter into its own agreement(s) with such party (or parties);
provided, however, that TAKEDA shall not be obligated to assign such
agreement(s).
 
CEREXA and FOREST HOLDINGS acknowledge that (i) TAKEDA has identified all the
Third Party Manufactures that have been supplying TAKEDA with those
intermediates required for the manufacture of Compound, and (ii) introduced
CEREXA and FOREST to such Third Party Manufactures.
 

 
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8. If TAKEDA desires to purchase the Compound or the Product from FOREST
HOLDINGS for purposes of the sale or distribution of the Product outside of the
Territory, FOREST HOLDINGS, subject to the availability of capacity in light of
FOREST HOLDINGS’ requirements for purposes of the Territory, shall comply with
TAKEDA’s desire at a price equal to [***], and subject to such other
commercially reasonable supply terms and conditions as are separately determined
by the mutual agreement of the parties.
 
9. Notwithstanding the other provisions of this Amendment, TAKEDA shall continue
to be obligated to supply to CEREXA, and CEREXA shall purchase from TAKEDA, the
amount of the Compound covered by that certain order submitted by CEREXA prior
to the Amendment Effective Date and annexed to this Amendment as Schedule 4. For
the avoidance of doubt, any Compound supplied to CEREXA by TAKEDA prior to the
Amendment Effective Date or pursuant to this Item 9 shall be subject to the
terms of the Agreement as in effect immediately prior to the Amendment Effective
Date.
 
10. The above-mentioned cooperations are CEREXA’s and FOREST HOLDINGS’ sole and
exclusive remedy for TAKEDA’s election to cease supplying the Compound
hereunder, and in each case CEREXA and FOREST HOLDINGS shall have no right to
demand from TAKEDA any compensation therefore.
 
11. For the avoidance of doubt, TAKEDA acknowledges that the sublicense of
rights under the Agreement to members of the FOREST GROUP is not subject to the
provisions of Section 2.4 of the Agreement.
 
12. Except as amended by this Amendment, all provisions of the Agreement shall
remain in full force and effect.
 
13. This Amendment may be executed in one or more counterparts, each of which
shall be an original, and all of which shall constitute together the same
document.
 

 
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            In Witness Whereof, the parties have caused this Amendment to be
executed by their duly authorized officers in duplicate.
 

Takeda Pharmaceutical Company Limited
 
By: /s/ Takashi Inkyo                                                         
       Name: Takashi Inkyo
       Title:   General Manager
                   Pharmaceutical Production Division
 
Cerexa, Inc.
 
By: /s/ Rick Orr                                                         
       Name: Rick Orr
       Title:   Senior Vice President, Operations
 
 
 
Forest Laboratories Holdings Limited
 
By: /s/ David Solomon                                             
       Name: David Solomon
       Title:   Director
 
 

 

 
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