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                                                                   EXHIBIT 10.21

                          FIRST AMENDMENT TO AGREEMENT

      THIS FIRST AMENDMENT TO AGREEMENT (the "Amendment") is entered into as of
November 4, 2004 (the "Amendment Effective Date"), between Takeda Pharmaceutical
Company Limited (formerly known as Takeda Chemical industries, Ltd.), with its
head office at 1-1, Doshomachi 4-chome, Chuo-ku, Osaka 540-8645, Japan
(hereinafter called "TAKEDA"), and Peninsula Pharmaceuticals, Inc., with its
head office at 1751 Harbor Bay Parkway, Alameda, CA 94502, USA (hereinafter
called "PENINSULA").

                                    RECITALS

      WHEREAS, PENINSULA and TAKEDA entered into a certain agreement dated
September 30, 2003 relating to a 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 (as defined in the Agreement) in the
Territory (as defined in the Agreement); and

      WHEREAS, the parties desire to amend the Agreement to clarify TAKEDA's
rights under Section 17.2(c) of the Agreement in the event that fifty percent or
more of the voting shares of PENINSULA come to be owned or controlled directly
or indirectly by a person or entity who was not a controlling shareholder of
PENINSULA on September 30, 2003;

      NOW, THEREFORE, PENINSULA and TAKEDA hereby agree that the Agreement is
amended, effective as of the Amendment Effective Date, as provided below:

      1. All capitalized terms used but not otherwise defined herein shall have
the meanings ascribed to such terms in the Agreement.

      2. Section 10.3 of the Agreement is hereby amended to read in its entity
as follows:

            "The introduction, advertisement and sales promotion of the Product
shall be made at PENINSULA's own expense and PENINSULA shall use commercially
reasonable diligent efforts to maximize the sales of the Product, which efforts
shall be at least consistent with those exercised for PENNSULA's other products
of similar scientific and commercial potential. Upon the reasonable request of
TAKEDA and to the extent permitted by applicable laws and regulations, PENINSULA
shall inform TAKEDA of its plans of its promotional and sales activities for the
Product, including its estimated timeline and budget (which may be revised from
time to time to reflect market conditions and regulatory approval status), and
any other related information reasonably requested by TAKEDA."

      3.    Section 17.2(c) of the Agreement is hereby amended to read in its
            entirety as follows :


            "(c) in addition to Sections 17.2 (a) and (b), TAKEDA may terminate
            this Agreement by a registered letter to PENINSULA effective upon
            PENINSULA's receipt of such notice if a substantial change occurs in
            the shareholding of

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            PENINSULA which results in fifty percent (50%) or more of the voting
            shares of PENINSULA becoming owned or controlled directly or
            indirectly by a person or entity (hereinafter called the "Parent
            Company") who was not a controlling shareholder of PENINSULA on the
            Effective Date (hereinafter called the "Change of Control"),
            provided, however, that TAKEDA shall not be able to terminate this
            Agreement pursuant to this Section 17.2 (c) if TAKEDA previously
            consented to such Change of Control, which consent shall not be
            unreasonably withheld."

      4. The address of the head office of PENINSULA has changed to 1751 Harbor
 Bay Parkway, Alameda, CA 94502, USA. All notices required to given by TAKEDA
 under the Agreement shall be sent to PENINSULA's new address in accordance with
 the provisions of Section 18.5 of the Agreement.

      5. Except as amended hereby, all provisions of the Agreement shall remain
in full force and effect.

      6. 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.

      IN WITNESS WHEREOF, the parties have caused this Amendment to be executed:

TAKEDA PHARMACEUTICAL COMPANY LIMITED       PENINSULA PHARMACEUTICALS, INC.

/s/  Saburo Hamanaka                        /s/ Dennis Podlesak


------------------------------------        ------------------------------------
                                            Name:    Dennis Podlesak
Name:  Saburo Hamanaka                      Title:   President & CEO
Title: Corporate Officer
       General Manager
       Division of Americas

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