Document:

<PAGE>

                                                                   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

                                      1.
<PAGE>
            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

                                      2.<PAGE>
                                                                   Exhibit 10.22

[ * ] = 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 406 OF THE SECURITIES ACT OF 1933, AS AMENDED.

November 2, 2004

Hiroyuki Mitsudera, Ph.D.
Coordinator
Pharmaceutical Production Division
Takeda Pharmaceutical Company Limited
17-85, Jusohonmachi 2-chome,
Yodogawa-ku, Osaka  532-8686, Japan

Re:   FIRM ORDER FOR [*] KG OF API OF TAK-599

Dear Mr. Mitsudera:

Please consider this letter a binding commitment by Peninsula to place with
Takeda a firm order for [*] kg of API to support our Phase 3 clinical programs
on the date on which we receive from Takeda the executed First Amendment to the
Agreement between the parties as of 30 September, 2003 ("Agreement") in the form
attached to this letter.

The estimated price for the [*] kg of API shall be US$[*], and shall be payable
in installments in accordance with the following payment schedule:

<TABLE>
<CAPTION>
                           Date                                  Payment Amount
                           ----                                  --------------
<S>                                                              <C>
Within 30 days after the date of the firm order                    US$200,000

January 1, 2005                                                    US$200,000

July 1, 2005                                                         US$[*]

October 1, 2005                                                      US$[*]

Within 30 days after acceptance of the delivered API, but            US$[*]
in no event sooner than January 1, 2006
</TABLE>

Peninsula shall have the ability to cancel the firm order at any time by
providing written notice to Takeda. In such event, Peninsula will be responsible
for the actual out-of-pocket expenses incurred by Takeda to manufacture the API
up through the date of cancellation, plus all non-cancelable expenses incurred
by Takeda in connection with the manufacture of the API for Peninsula
(collectively, the "Cancellation Expenses"). In no event shall the Cancellation
Expenses exceed $[*]. If the total amount of the installment payments made by
Peninsula for the API (the "Installment Payments") is less than the amount of
the Cancellation Expenses, Peninsula shall pay Takeda the difference between the
Installment Payments and the Cancellation Expenses. If the amount of the
Installment Payments is greater than the amount of the Cancellation Expenses,
Takeda shall pay Peninsula the difference between the Installment Payments and
the Cancellation Expenses. Any such payments required to be made shall be made
within 30 days after the date of cancellation of the firm order.

[ * ] = 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 406 OF THE SECURITIES ACT OF 1933, AS AMENDED.
<PAGE>
Except as expressly set forth in this letter, all other terms set forth in the
Agreement between Takeda and Peninsula shall govern the supply by Takeda of the
[*] kg of API to Peninsula.

Please have Takeda countersign below indicating its agreement with the above
terms. Should you have any questions, please feel free to contact me.

With best regards,

/s/ Debra Odink
-----------------------
Debra Odink
VP, Pharmaceutical Chemistry & Product Development

AGREED:

Takeda Pharmaceutical Company Limited

/s/ H. Mitsudera
-------------------------------
Hiroyuki Mitsudera
Coordinator
Pharmaceutical Production Division

[ * ] = 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 406 OF THE SECURITIES ACT OF 1933, AS AMENDED.
<PAGE>
                                  ATTACHMENT A

ATTACHMENT A IS FILED AS EXHIBIT 10.21 TO THE REGISTRATION STATEMENT ON FORM
S-1, AS AMENDED, FILE NO. 333-111193, AS FILED BY PENINSULA PHARMACEUTICALS,
INC.

[ * ] = 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 406 OF THE SECURITIES ACT OF 1933, AS AMENDED.<PAGE>
                                                                   Exhibit 10.23

                              AMENDED WORK ORDER #1

         This Amended Work Order #1 (the "Work Order") shall, as of September 1,
2004, supersede in its entirety Work Order #1.

1. SERVICES. Consultant shall provide the Services described in this Work Order
and in the Master Consulting Services Agreement effective September 1, 2003
between the parties (the "Master Agreement"). Unless otherwise defined herein,
all initially capitalized terms used herein shall have the meaning set forth in
the Master Agreement. The Services covered under this Work Order consist of
project management of Peninsula's intravenous doripenem and PPI-0903 programs,
including project management of Peninsula's intravenous doripenem Phase 3
clinical trials and PPI-0903 Phase I clinical trials.

2. RATE. The following individuals will perform the Services requested by
Peninsula at the following rates:

<TABLE>
<CAPTION>
                                                                          RATE PER
JOB TITLE/ROLE:                              CONSULTANT:                  CONSULTANT:
---------------                              -----------                  -----------
<S>                                          <C>                          <C>
                                             1)       Taylor Kilfoil
Dedicated Project Managers (3x)              2)       Marc Perry          $22,500.00 / Month
                                             3)       George Faurot

Clinical/Regulatory Document                 Gary Eiger                   $85.00 / hour
Administrator

Senior Clinical Research                     Michele Sayre                $95.00 / hour
Associate(s)                                 TBD*

Project Management Services                  TBD*                         $110.00 / hour
</TABLE>

* The parties shall agree in advance on the identity of those individuals who
will be performing Senior Clinical Research Associate and Project Management
services on behalf of Consultant hereunder.

Dedicated Project Manager services performed by Taylor Kilfoil, George Faurot
and Marc Perry shall each be billed at the monthly rate specified above until
the later of the date on which (a) all intravenous doripenem Phase 3 clinical
trials have been completed, and (b) PPI-0903 Phase I clinical trials have been
completed.

The rate of $22,500.00 per month ($270,000.00 per year) per Dedicated Project
Manager for project management services set forth under this Section 2 is based
upon such Dedicated Project Manager performing 40 hours of Services per work
week, with an annual total of 1936 hours worked. This allows for each Dedicated
Project Manager to have 10 unpaid vacation days and 8

                                       1
<PAGE>
unpaid public holidays during the course of each calendar year in which Services
are performed. On a quarterly basis, the parties shall review the actual number
of hours worked by each Dedicated Project Manager to determine if both parties
are adhering to the terms of this Agreement and whether the monthly rate for
Services performed by such Dedicated Project Manager should be adjusted going
forward to reflect the actual number of hours of Services performed by such
Dedicated Project Manager.

3. TERM OF WORK ORDER. This Work Order shall be effective as of September 1,
2004 and, unless earlier terminated as permitted herein, shall expire on the
later of the date on which (a) all intravenous doripenem Phase 3 clinical trials
have been completed, and (b) PPI-0903 Phase I clinical trials have been
completed

4. TERMINATION OF WORK ORDER BY PENINSULA. This Section 4, rather than Section
9.2 of the Master Agreement, shall govern the terms on which Peninsula may
terminate this Work Order. Prior to the completion of the intravenous doripenem
Phase III clinical trials, Peninsula may terminate this Work Order for any
reason upon ninety (90) days' written notice to Consultant. However, Peninsula
may terminate this Work Order effective upon Consultant's receipt of written
notice if there are significant or unexpected delays in the intravenous
doripenem Phase III clinical trials and/or if Peninsula's intravenous doripenem
program is terminated in its entirety. At any time after the completion of the
intravenous doripenem Phase III clinical trials, Peninsula may terminate this
Work Order effective upon Consultant's receipt of written notice. At any time
during the term of this Work Order, Peninsula shall have a right to terminate
this Work Order for an uncured material breach in accordance with the provisions
of Section 9.3 of the Master Agreement.

5. TERMINATION OF WORK ORDER BY CONSULTANT. This Section 5, rather than Section
9.4 of the Master Agreement, shall govern the terms on which Consultant may
terminate this Work Order. Consultant shall have a right to terminate this Work
Order for an uncured material breach in accordance with the provisions of
Section 9.3 of the Master Agreement. In addition, prior to the completion of the
intravenous doripenem Phase III clinical trials, Consultant may terminate this
Work Order for any reason upon one hundred twenty (120) days' written notice to
Consultant.

6. PAYMENT. Payments shall be sent to Consultant at:

            InClin, Inc.
            5150 El Camino Real, Suite A33
            Los Altos, CA  94022
            FEIN No.: 94-3302268

REMAINDER OF PAGE INTENTIONALLY LEFT BLANK.

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