Document:

Exhibit 10.59

 

CONFIDENTIAL TREATMENT

 

FIRST ADDENDUM TO LICENSE AGREEMENT

BETWEEN INTERNATIONAL
HEALTH MANAGEMENT ASSOCIATES, INC.

AND CUBIST
PHARMACEUTICALS, INC., DATED NOVEMBER 22, 2000

 

This Addendum
sets forth certain clarifications and amendments to the License Agreement
between International Health Management Associates, Inc., (“IHMA”) and CUBIST
Pharmaceuticals, Inc. (“CUBIST”) dated November 22, 2000, and is effective the
27th day of September, 2002 (“the License Agreement”).  By this Addendum, the parties hereto
memorialize their [*] which, inter alia, resulted in CUBIST licensing
rights under U.S. Patent No. 6,248,360 (“the ‘360 Patent”) from the University
of Utah Research Foundation (“UNIVERSITY”), [*] to IHMA, and the parties
executing an Escrow Agreement dated September 27, 2002 (“the ESCROW
AGREEMENT”).  This Addendum is entered
into pursuant to Article 8.11 of the License Agreement between the
parties.  Except to the extent this
Addendum clarifies or amends certain terms and conditions in the License
Agreement, all other terms and conditions of the License Agreement that are not
addressed in this Addendum shall remain in full force and effect, and this
Addendum shall itself be construed and applied so as to be consistent with the
terms and conditions of the License Agreement. 
This Amendment shall not be construed to modify or amend any provision
of the ESCROW AGREEMENT.

 

WHEREAS,
IHMA and CUBIST desire [*] concerning the License Agreement; and

 

WHEREAS,
IHMA and CUBIST have agreed to the terms herein as the basis [*]; and

 

WHEREAS,
IHMA and CUBIST agree that in the resolution of [*] as memorialized in this
Addendum, each has given and received from the other

 

1

 

consideration that is in addition
to the consideration given or received in their Licensing Agreement.

 

NOW THEREFORE, in
consideration of the mutual covenants herein stated, IHMA and CUBIST agree to
clarify or amend particular terms of their License Agreement as follows:

 

1.                                      REDUCTION
IN LICENSING FEES AND ROYALTIES FOR PAYMENTS TO THE UNIVERSITY

 

In fulfillment
of any and all duties under Article 5 of the License Agreement for IHMA to
defend and indemnify and hold CUBIST harmless from and against any claim, suit,
demand or loss as a result of the rights asserted by the UNIVERSITY in the ‘360
Patent, from whom CUBIST has obtained an exclusive license in exchange for
certain payments, IHMA and CUBIST agree that, subject to the provisions of the
ESCROW AGREEMENT, any payments by CUBIST due to IHMA under Article 3.1 and 3.2
of the License Agreement shall be reduced by the amounts which CUBIST actually
pays to the UNIVERSITY under its license.

 

In addition,
since notice of allowance of IHMA’s original patent application was received
before the patent application could be refiled (the original “milestone”
payment), IHMA and CUBIST agree to amend the language of Section 3.1(b) to
provide for payment of this milestone upon filing with the U.S. Patent and
Trademark Office application no. 09/888,114 (“the CIP Application”), a
continuation-in-part of 09/829,405, which is a continuation of 09/598,089, now
U.S. Patent No. 6,248,360.  IHMA and
CUBIST further agree to amend the language of Section 3.1(c) to reduce by [*]
the milestone for selection of the first single formulation of oral ceftriaxone
for clinical trials, to compensate CUBIST for the milestone it must pay to the
UNIVERSITY for issuance of the CIP.  The
parties believe that the CIP will issue within a brief time period before or
after selection of the first single formulation of oral

 

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ceftriaxone for clinical trials. 
However, provisions for payment of the [*] to IHMA are made in Section
3.1(c) if the CIP application is finally rejected and the CIP
Application is abandoned.

 

Articles 3.1
and 3.2 of the License Agreement are therefore amended to offset the amounts
which CUBIST is obligated to pay in licensing fees, milestone payments, and
royalty payments to the UNIVERSITY. 
CUBIST shall be entitled to deduct the appropriate amount of the fee,
milestone, or royalty payment made to the UNIVERSITY from any payment due to
IHMA, according to the following provisions which shall be deemed to supercede
Articles 3.1(a)-3.1(h) and Article 3.2(a):

 

3.1 Licensing Fees.     The licensing fees which shall be paid by
CUBIST to IHMA, are as follows:

 

(a)                        CUBIST
shall pay to IHMA the sum of one million dollars ($1,000,000), of which five
hundred thousand dollars ($500,000) shall be paid within five (5) business days
of the Effective Date, and five hundred thousand dollars ($500,000) paid within
sixty (60) days of the Effective Date. 
This payment, due IHMA under this Article 3.1(a) and previously made by
CUBIST, shall be reduced by the amount of [*] to offset the licensing fee paid
by CUBIST to the UNIVERSITY.  And,

 

(b)                       CUBIST
will pay to IHMA the sum of two hundred and fifty thousand dollars ($250,000)
upon filing with the U.S. Patent and Trademark Office application no.
09/888,114, a continuation in part (“CIP”) application to the ‘360 Patent (“CIP
application”);  And,

 

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(c)                        CUBIST
will pay to IHMA the sum of two hundred and twenty thousand dollars ($220,000)
within thirty (30) days of CUBIST selecting the first single oral formulation
of oral ceftriaxone for clinical trials. 
CUBIST will pay IHMA an additional thirty thousand dollars ($30,000) if
the CIP application is finally rejected and the CIP application is abandoned.  And,

 

(d)                       CUBIST
will pay IHMA the sum of nine hundred thousand dollars ($900,000) within thirty
(30) days following the date on which CUBIST completes its initial
first-into-man study.  Initial
first-into-man study means, for purposes of this milestone payment, a single
dose pharmacokinetic study (including a study that may be conducted outside the
U.S. before any Investigational New Drug Application (IND) is filed, or in the
U.S. after an IND is approved), completion of which means preparation of the
final report on the data in the study. 
And,

 

(e)                        CUBIST
will pay IHMA the sum of four hundred and seventy thousand dollars ($470,000)
within thirty (30) days following the date on which the United States Patent
and Trademark Office issues IHMA a patent covering the oral formulation of
ceftriaxone chosen for clinical development. 
And,

 

(f)                          CUBIST
will pay IHMA the sum of one million eight hundred thousand dollars
($1,800,000) within thirty (30) days following the date on which CUBIST
successfully completes its first pivotal Phase III clinical drug trials
relating to any Licensed Products. 
“Completion,” for purposes of this milestone payment, means the final
report on the data in the first pivotal Phase III clinical drug trial.  And,

 

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(g)                       CUBIST
will pay IHMA the sum of one million seven hundred and fifty thousand dollars
($1,750,000) within thirty (30) days following the date on which CUBIST files a
New Drug Application (NDA) with the FDA covering any Licensed Products.  And,

 

(h)                       CUBIST
will pay IHMA the sum of four million two hundred and fifty thousand dollars
($4,250,000) within thirty (30) days following the date on which the FDA
approves a NDA of CUBIST covering any Licensed Products.  And,

 

Article 3.1(i)
and 3.1(j) as stated in the License Agreement remain in full force and effect.

 

3.2
Royalties

 

(a)        Commencing with the initial sale of Licensed Products in any
jurisdiction, CUBIST shall pay to IHMA royalties equal to:  (i) 
[*] of CUBIST’s (and/or its Affiliate’s and/or sublicensees) Net Sales
of Licensed Products in the Territory up to [*]; plus  (ii) [*] of CUBIST’s (and/or its Affiliate’s and/or
sublicensees’) Net Sales of Licensed Products in the Territory above [*] up to
[*]; plus  (iii) [*] of CUBIST’s (and/or
its Affiliate’s and/or sublicensees’) Net Sales of Licensed Products in the
Territory above [*].

 

5

 

Article
3.2(b), 3.2(c), 3.2(d), and 3.2(e) in the License Agreement remain in full
force and effect.

 

In the event
any fee, milestone payment, or royalty payment due to the UNIVERSITY is not
paid by CUBIST in accordance with the terms of that certain License Agreement
dated December 27, 2001 between CUBIST and the UNIVERSITY, then CUBIST shall
pay to IHMA the amount of that milestone payment due but not paid to the
UNIVERSITY.  In the event CUBIST has not
paid to the UNIVERSITY, in accordance with the terms of that certain License
Agreement dated December 27, 2001 between CUBIST and the UNIVERSITY, any amount
due under its license for licensing fees and royalties which correspond to the
licensing fees or royalties set out in Article 3.1 of the License Agreement
prior to CUBIST’s payment to IHMA, then CUBIST shall pay to IHMA that amount
due under the License Agreement prior to this amendment.  If CUBIST thereafter pays the UNIVERSITY a
licensing fee or a royalty for which CUBIST has previously paid IHMA a
licensing fee or royalty which did not include the appropriate deduction as
provided herein, then the amount of the licensing fee or royalty paid to the
UNIVERSITY may be deducted from the next licensing fee or royalty due IHMA
under the amended Article 3.1.

 

In the event
that any royalty payment by CUBIST to the UNIVERSITY exceeds, in any quarter,
[*] by reason of a defined “minimum royalty due,” then the sum due IHMA shall
be reduced by that same difference.  The
effect of this provision shall be that the royalties due IHMA will be adjusted
only to reflect royalty payments which CUBIST has actually made to the
UNIVERSITY.  Insofar as any payment to
the UNIVERSITY under a minimum royalty due results in a reduction in the
royalty paid during a different quarter, then the royalty to be paid to IHMA
shall be increased, with the effect of paying IHMA the full royalty specified
in the

 

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License Agreement before this Addendum, less only CUBIST’s actual
payments to the UNIVERSITY.

 

In the event
that CUBIST pays a milestone payment to the UNIVERSITY for a subsequent
INDIVIDUAL LICENSED PRODUCT (as that term is used in the License Agreement
between CUBIST and the UNIVERSITY) containing ceftriaxone (such as a pediatric
extension for an oral formulation of ceftriaxone), then CUBIST shall be
entitled to deduct the amount of that milestone payment that CUBIST pays to the
UNIVERSITY for a subsequent INDIVIDUAL LICENSED PRODUCT.  Other than as expressly provided in this
Addendum, no licensing fee or royalty, nor other obligation by CUBIST to IHMA,
may be reduced nor is affected by additional licensing fees and/or royalties
CUBIST may have to pay to the UNIVERSITY as a result of licensing any rights
under the ‘360 Patent from the UNIVERSITY.

 

2.                                      CUBIST
HAS PAID IHMA THE MILESTONE PAYMENTS WITHHELD, LESS THE SUMS PAID BY CUBIST TO
THE UNIVERSITY FOR ITS LICENSE

 

Pursuant to
the ESROW AGREEMENT, CUBIST paid to IHMA the sum of [*] in complete
satisfaction of its obligation for the licensing fees required under Article
3.1(b), (d), and (e) as amended herein (which includes a credit of [*]
reflecting the amount Cubist paid the UNVERSITY for its license), together with
an agreed upon amount of [*], in full satisfaction of any accrued interest
payments.  The Escrow Agreement is made
an exhibit to this Addendum and, as to the obligations between CUBIST and IHMA
in it, it is made a part hereof.

 

This Addendum
and the ESCROW AGREEMENT [*] payment of licensing fees due, and [*] regarding
the [*] to and including the date of this Addendum.

 

3.                                      RIGHTS
OF IHMA AND CUBIST EACH TO ENTER INTO LICENSES FOR THE ‘360 PATENT AND TECHNOLOGY

 

A.                                   Upon
execution of the Sublicense, CUBIST grants an exclusive sublicense of the
rights granted to CUBIST by the UNIVERSITY, to use the ‘360 Patent and
technology in developing and practicing oral delivery of cefipime and
cefditoren only, as set forth completely in that Sublicense.  The

 

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Sublicense between IHMA and
CUBIST by which IHMA has the exclusive right to practice the ‘360 Patent in
connection with cefipime and cefditoren is made a part hereof.

 

B.                                     The
parties acknowledge that CUBIST declined [*] the “ROFO” (“Right of First
Opportunity”) [*] defined in Article 3.6 of the License [*].  Therefore, all Right of First Opportunity to
License IHMA Technology Applicable to Other Products set out in Article 2.9 of
the License Agreement has no further effect.

 

C.                                     The
parties further acknowledge that in the License Agreement IHMA reserved to
itself all of its rights to use and apply the ‘360 Patent and related
technology in pharmaceuticals other than ceftriaxone.  The parties further acknowledge that since the License Agreement,
in December 2001 CUBIST obtained an exclusive license of the rights of the
UNIVERSITY in the ‘360 Patent (which the UNIVERSITY obtained through its
employee, Dr. Jeong Soo Lee, the co-inventor with Dr. Choi).  Finally, the parties acknowledge that
pursuant to the License Agreement, CUBIST has fully compensated Dr. Choi for
his work for CUBIST, pursuant to both Article 2.8 and that certain Sponsored
Research Agreement dated February 1, 2002 between CUBIST and IHMA (“the SRA”),
in conducting further research which concerns application of the ‘360 Patent to
develop oral delivery of ceftriaxone.

 

D.                                    The
parties acknowledge that the license between IHMA and CUBIST, and the license
between the UNIVERSITY and CUBIST and the sublicense between CUBIST and IHMA,
when such sublicense has been executed, entitle CUBIST and IHMA to grant
licenses or sublicenses of rights under the ‘360 Patent as follows:

 

1.                                       IHMA
may solicit, negotiate and enter into exclusive license(s) with any other
person(s), which grant it/them the right to make,
have made, import, use, offer to
sell and sell any product or method that, but for the existence of a license,
would constitute infringement of the ‘360 Patent with respect to oral
formulations, or methods related to oral formulations, of cefditoren and
cefepime, or either of those pharmaceuticals.

 

8

 

2.                                       IHMA
may solicit, negotiate and enter into non-exclusive license(s) with any other
person(s), which grant it/them the right to research, develop, make, have made, import, use, lease and sell any product or method that, but
for the existence of a license, would constitute infringement of the
‘360 Patent with respect to oral formulations, or methods related to oral
formulations, of any pharmaceutical products except ceftriaxone.

 

3.                                       CUBIST
may solicit, negotiate and enter into non-exclusive license(s) with any other
person(s) which grant it/them the right to
make, have made, import, use, offer
to sell and sell any product or method that, but for the existence of a
license, would constitute infringement of the ‘360 Patent with respect
to oral formulations, or methods related to oral formulations, of any
pharmaceutical products.

 

4.                                       CUBIST
may solicit, negotiate and enter into exclusive or non-exclusive license(s)
with any other person(s) which grant it/them the right to research, develop, make, have made, import, use, lease and sell any product or method that, but
for the existence of a license, would constitute infringement of the
‘360 Patent with respect to oral formulations, or methods related to oral
formulations, of ceftriaxone.

 

E.                                      Insofar
as IHMA or CUBIST, or both of them, desires to secure the right to enter
into an exclusive license with any other person(s) which grant it/them the
right to use the ‘360 Patent and related technology in developing and
practicing oral delivery of any pharmaceutical besides ceftriaxone, cefipime
and cefditoren, then IHMA and CUBIST will negotiate between them for the
purpose of defining the licensing fees and royalties which shall be paid by
such person, the manner in which those licensing fees and royalties shall be
shared between IHMA and CUBIST, and the particular pharmaceutical to which such
exclusive license shall be limited.  It
is understood that the rights of the UNIVERSITY to receive licensing fees and
royalties arise under its license to CUBIST, and CUBIST shall have sole
responsibility

 

9

 

to pay such licensing fees and
royalties out of such portion of the licensing fees and royalties as IHMA and
CUBIST agree shall be received by CUBIST.

 

4.                                      PATENT
PROSECUTION AND MAINTENANCE

 

The following
provisions shall be deemed to supercede Article 2.4 of the License Agreement:

 

IHMA, using
mutually acceptable patent counsel, shall prosecute and maintain patents and
patent applications on IHMA Technology in the United States and up to
twenty-five (25) foreign countries selected by CUBIST.  IHMA shall furnish or have furnished to
CUBIST copies of documents relevant to patent applications, and maintenance of
patent applications, and IHMA shall confer with CUBIST regarding any patent
application applicable to IHMA Technology licensed to CUBIST in the License
Agreement, so that each such patent application may be satisfactory to IHMA and
to CUBIST.  Any differences between IHMA
and CUBIST with respect to filing, prosecution and maintenance of patents
covered by the License Agreement will be discussed and resolved to their mutual
satisfaction.

 

IHMA shall be
responsible for all expenses associated with the filing, prosecution, issuance
and maintenance of patents applying IHMA Technology licensed to CUBIST in the
License Agreement in the United States and up to twenty-five (25) foreign
countries selected by CUBIST in the Territory. 
At the request of CUBIST, IHMA shall provide written evidence that it
has performed this obligation.  CUBIST
shall be responsible for all expenses associated with the preparation, filing
and maintenance of patents for IHMA Technology licensed to CUBIST in the
License Agreement in such additional countries as CUBIST may direct, and shall
reimburse IHMA for all such expenses. 
IHMA shall provide CUBIST with detailed invoices for all reimbursable
patent expenses for additional countries, which CUBIST shall pay directly or
reimburse to IHMA, within thirty (30) days following receipt of invoices,

 

IN WITNESS WHEREOF,
the parties hereto have caused this Addendum to be executed by their respective
officers, who are each authorized to sign on behalf of his respective
corporation, and have duly

 

10

 

delivered and executed this
Addendum to be effective on September 27, 2002, intending it to be an
instrument under seal.

 

11

 

INTERNATIONAL HEALTH MANAGEMENT ASSOCIATES,
INC.

 

	
  By:

  	
  /s/ Steven
  W. Bluth

  	
   

  
	
   

  
	
  Name:

  	
  Steven W.
  Bluth

  
	
   

  	
   

  
	
  Title:

  	
  Vice
  President

  
	
   

  	
   

  
	
  Date:

  	
  27 FEB -3

  	
   

  
				

 

 

CUBIST PHARMACEUTICALS, INC.

 

	
  By:

  	
  /s/ Oliver
  S. Fetzer

  	
   

  
	
   

  
	
  Name:

  	
  Oliver S.
  Fetzer

  
	
   

  	
   

  
	
  Title:

  	
  Senior Vice
  President

  
	
   

  	
   

  
	
  Date:

  	
  2/28/03

  	
   

  
				

 

12Exhibit
10.67

 

CONFIDENTIAL
TREATMENT

 

AMENDMENT
NO. 2

to the

MANUFACTURING AND SUPPLY AGREEMENT

entered into as of
September 30, 2001

by and between

ACS Dobfar, SpA and
Cubist Pharmaceuticals, Inc.

 

This AMENDMENT NO. 2 (“Amendment  No.
2”), to that certain Manufacturing and Supply Agreement (the “Agreement”)
entered into as of September 30, 2001, is made this 12th day of
February, 2003, by and between ACS Dobfar, SpA, an Italian corporation (“ACSD”)
and Cubist Pharmaceuticals, Inc., a Delaware corporation (“Cubist”).
Unless otherwise defined herein, capitalized terms used but not defined herein
shall have the meaning set forth in the Agreement, and the Agreement shall be
amended to incorporate any additional definitions provided for in this
Amendment No. 1, including definitions in the preamble and recitals hereto.

 

WHEREAS, Cubist and ACSD desire to amend
the Agreement as set forth in this Amendment No. 1;

 

NOW, THEREFORE, in consideration of the
foregoing and the mutual promises made herein, and for other good and valuable
consideration, the receipt and sufficiency of which are hereby acknowledged,
the parties hereto agree to amend the Agreement as follows:

 

1.                                       Amendment
of Section 2.1.  The
Agreement is hereby amended by deleting Section 2.1 thereof in its entirety and
replacing it with the following Section 2.1:

 

2.1                               Facility
Construction and Timetable

 

(a) By [*] (the Facility
Completion Target Date), ACSD will construct, equip, test and
qualify (IQ/OQ/PQ) and make operational the Facility in accordance with current
Good Manufacturing Practices. ACSD’s obligations hereunder include, but are not
limited to:

 

(i)                                     construction
of building(s) necessary to perform the Process in a dedicated Facility;

 

(ii)                                  provision
of [*] for production of commercial batches of Product;

 

(iii)                               the
[*] of all required [*] for the manufacturing and warehousing of Product and
validation of Process: and

 

(iv)                              [*]
to manufacture Product.

 

Subject to adjustment in accordance with Section 2.2,
ACSD will complete all activities and to meet all dates set forth in this
Agreement. ACSD agrees that the following events (the “Targets”) shall occur by
[*]: (i)  ACSD shall produce [*] full
commercial consistency batches for FDA registration of the Facility;  (ii) all data and reports related thereto
shall be completed and ready for submission to the FDA; (iii) ACSD shall
commence validation processes; and (iv) ACSD will be prepared in all respects
for a site inspection by the FDA.  The
target date for FDA approval of the NDA Manufacturing Supplement for the ACSD
facility (the Facility Approval Target Date) is [*]. In addition, ACSD
shall (i) complete IQ/OQ/PQ and validation of the fermentation process by [*];
and (ii) complete

 

* CONFIDENTIAL TREATMENT REQUESTED: MATERIAL HAS BEEN OMITTED AND FILED
WITH THE COMMISSION 

 

 

theconsistency batches, the IQ/OQ/PQ, and the [*]
validation batches for the purification process by [*].   ACSD agrees that time is of the essence in
completing the tasks set forth in this Section 2.1 in order to comply with
ACSD’s obligation to supply Product in [*]. 
In connection with ACSD completing all activities required to meet the
aforementioned dates, Cubist shall remit to ACSD [*]of [*] on each of (i) the
date of execution by both parties of this Amendment No. 2 (the “February
Payment”);  (ii)May 1, 2003 (the “May
Payment”); and (iii) August 1, 2003 (the “August Payment”).

 

(b) By March 1, 2003,
ACSD and Cubist shall mutually agree upon a schedule for all tasks required to
meet the Targets set forth in section 2.1(a) above (the “Schedule”). In the
event that, in Cubist’s sole discretion, Cubist determines that the Schedule
will not enable [*], the May and August Payments shall not be payable to ACSD
and ACSD shall promptly refund to Cubist the February Payment.

 

2.                                       Amendment
of Section 3.2.  The
Agreement is hereby amended by deleting Section 3.2 thereof in its entirety and
replacing it with the following Section 3.2:

 

3.2                               Process
Validation

 

ACSD will develop and complete a validation process at
the Facility in accordance with Exhibit D herein, and at ACSD
expense. [*] and limits for the process must span the [*]and limits developed
and documented during the manufacture of consistency batches at [*]. No Process
changes will be made during the period beginning on [*] and ending on the [*].
All post-validation process changes must be approved by Cubist in writing.
Cubist will provide [*] and [*]as such reports become available. ACSD will
provide Cubist with a [*]for the Facility and Process.

 

3.                                       Amendment
of Section 3.3.  The
Agreement is hereby amended by deleting Section 3.3 thereof in its entirety and
replacing it with the following Section 3.3:

 

3.3                               Process
Improvements

 

Following the [*] of the date of the Facility
Approval, ACSD may continue operating [*] Process improvements with the prior
written approval of Cubist. No Process improvements will be made during the
period beginning on [*] and ending on the [*]. 
[*]for the purpose of improving ACSD’s margins will be entirely at
ACSD’s expense. ACSD will reimburse Cubist for any additional Cubist expenses
[*]. All [*] related to the [*] will be implemented only after [*]. The
authorization will be obtained in writing following a successful and complete
cGMP change control process outlined in the approved standard operating
procedures (SOPs) of both ACSD and Cubist.

 

4.                                       Amendment
of Section 3. The Agreement is hereby amended by adding the
following Section 3.5 immediately following the end of Section 3.4 of the
Agreement

 

* CONFIDENTIAL TREATMENT REQUESTED: MATERIAL HAS BEEN OMITTED AND FILED
WITH THE COMMISSION 

 

2

 

3.5                               Q.A.
Director

 

In order to ensure and maintain consistent quality
assurance with respect to the Product and the process, on or before April 1,
2003  ACSD
shall have hired, with the approval of Cubist (which approval shall not be
unreasonably withheld), a full-time Quality Assurance Director and shall engage
an independent validation consultant, each with significant experience in the
process of manufacturing and supply of pharmaceutical products.

 

5.                                       Amendment
of Section 5.1.  The
Agreement is hereby amended by deleting Section 5.1 thereof in its entirety and
replacing it with the following Section 5.1:

 

5.1                               Purchase
Commitment

 

Contingent upon the receipt of the necessary Product
and Facility Approvals, Cubist will purchase a [*] kilograms of Product during
the term of this Agreement, [*] and further subject to the [*]. In the event
that the [*], or the [*], Cubist shall not be required to purchase [*] kg of
Product [*] or in any other year during the term of the Agreement.
Notwithstanding anything to the contrary herein, ACSD will [*] to be delivered
in the year [*] and, if longer, the [*], in accordance with the commercial
Process specified in the Exhibits B-1, C-1 and D herein which may be modified
in writing by Cubist from time to time. To the extent that there is any
conflict between the specifications set forth in Exhibit C-1 and those set
forth in Exhibit B-1, the specifications set forth in Exhibit C-1 shall
supersede in all respects. During the period prior to the receipt of Product
Approvals, Cubist [*] in accordance with Exhibits B-1, C-1,
and D herein. Any such Product purchases shall count toward the [*]
kilograms of Product that Cubist is required to purchase. Subject to the
conditions of this Agreement, Cubist agrees to make the following yearly
purchases:

 

	
  Year

  	
   

  	
  Purchase Minimum(kg)

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  2004

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  2005

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  2006

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  2007

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  2008

  	
   

  	
  [*]*

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  2009

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
  2010

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
  [*]

  	
   

  

 

The above schedule will be extended for any delays
caused by ACSD.

 

6.                                       Amendment
of Section 5.6.  The
Agreement is hereby amended by deleting Section 5.6(a) in its entirety and
replacing it with the following Section 5.6(a)

 

* CONFIDENTIAL TREATMENT REQUESTED: MATERIAL HAS BEEN OMITTED AND FILED
WITH THE COMMISSION 

 

3

 

5.6                               Obligation
to Supply

 

(a)          ACSD shall accept and
fill each order for Product submitted by Cubist [*], provided that such request
is delivered to ACSD at least [*] days prior to the beginning of the
corresponding quarter. ACSD shall not be in breach of this Section 5.6 if
[*].  Delivery dates will be set
independently from Product release and invoice dates as described in Section
5.7;

 

7.                                       Amendment
of Section 6.1.  The
Agreement is hereby amended by deleting Section 6.1 thereof in its entirety and
replacing it with the following Section 6.1:

 

6.1                               Product
Price

 

(a)                                  Subject
to the provisions of Sections 5, 6 and 7, Cubist will [*], including the
additional [*] kg required to be purchased by Cubist in [*], at a price of [*]
per kilogram (USD [*]/kg);

 

8.                                       Amendment
of Section 6.2.  The
Agreement is hereby amended by deleting Section 6.2 thereof in its entirety and
replacing it with the following Section 6.2:

 

6.2                               Product
Price [*]

 

Cubist will pay ACSD [*] per kilogram (USD [*]) on the
[*] purchased over the life of the contract other than the [*] kgs of Product
[*] in [*] until cumulative [*] payments equal [*] (USD [*]). Once the
cumulative [*] payments have accrued to [*] (USD [*]), Cubist will immediately
stop paying the [*] and will pay [*] per kilogram (USD [*]/kg) of Product, as
provided in Section 6.1 herein.

 

	
  Year

  	
   

  	
  Purchase

  Minimum

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2005

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2006

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2007

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2008

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2009

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
  2010

  	
   

  	
  [*]

  	
   

  	
  [*]

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
   

  	
   

  
	
   

  	
   

  	
   

  	
   

  	
  [*]

  	
   

  

 

* CONFIDENTIAL TREATMENT REQUESTED: MATERIAL HAS BEEN OMITTED AND FILED
WITH THE COMMISSION 

 

4

 

The above schedule will be extended for any delays
caused by ACSD. In the event that Cubist [*] as provided in Section 5.1, Cubist
will pay [*] corresponding to the original minimum purchase commitment in the
year specified in this Section 6.2. Any delays [*] (including, but not limited,
to [*]) will extend [*].

 

9.                                       Amendment
of Section 7.  The
Agreement is hereby amended by deleting Section 7 thereof in its entirety and
replacing it with the following Section 7:

 

7.                                      Exclusivity

 

ACSD covenants that it will not promote, sell, deliver
or provide any Product or Daptomycin to any third party without the prior
written consent of Cubist, or produce any product, bulk drug substance or
active pharmaceutical ingredient in the Facility other than the Product.
Notwithstanding the foregoing, ACSD shall be permitted to produce vancomycin
(the “Competing Product”) in the Facility for Eli Lilly & Company, provided
that the following conditions have been and continue to be met at all times:

 

(i)                                     ACSD
has met all of the Targets and as well as the Facility Approval Target Date;

 

(ii)                                  ACSD
fills all Product orders in accordance with the schedules set forth in Cubist’s
Purchase Orders;

 

(iii)                               ACSD,
at its cost, completes all cleaning validation processes in accordance with FDA
requirements; and

 

(iv)                              At
Cubist’s request, ACSD Promptly purchases separate, dedicated additional
columns that will be used solely for the production of the Product.

 

In the event that any of conditions (i) through (iv)
are not met, ACSD shall lose its right to produce the Competing Product and
shall cease production thereof upon receipt of written notice from Cubist.

 

10.                                 Amendment
of Section 12.1.  The
Agreement is hereby amended by deleting Section 12.1 thereof in its entirety
and replacing it with the following Section 12.1:

 

12.1                        Term

 

This Agreement shall take effect as of the Effective
Date and shall remain in effect until the seventh anniversary of Facility
Approval or until ACSD has received all payments due under Section 6.2 unless
sooner terminated in accordance with Section 12.2 or extended in accordance
with this Section 12.1. Thereafter, this Agreement shall automatically renew
for additional two-year terms. Not later than the sixth (6h)
anniversary of the Effective Date, Cubist shall notify ACSD in writing whether
Cubist desires to extend the Agreement for an additional two years. All 

 

* CONFIDENTIAL TREATMENT REQUESTED: MATERIAL HAS BEEN OMITTED AND FILED
WITH THE COMMISSION 

 

5

 

applicable terms and conditions of this Agreement
shall remain in effect during such extension term, unless expressly amended in
writing by the parties. Cubist may renew this Agreement for additional two-year
extension terms by providing written renewal notice to ACSD not later than
twelve (12) months prior to the expiration of the then current extension term.

 

11.                               Amendment
of Section 12.2.  The
Agreement is hereby amended by adding the following Section 12.2(c) immediately
following Section 12.2(b) of the Agreement:

 

(c)                                In
the event that any current Cubist supplier of Product purchases substantially
all of the stock or assets relating to that portion of ACSD’s business that is
related to the subject of this Agreement, all payments hereunder shall be
promptly returned to Cubist and Cubist shall have the right to modify any
Purchase Requirements set forth herein. Cubist shall also have the right to
pursue an alternative source of supply for the Product.

 

12.                                 Amendment to
Exhibits B and C and Addition of New Exhibit F.  The
Agreement is hereby amended by replacing Exhibits B (In-Process Testing
Procedures and Specifications) and C (Product Release Test Methods and
Specifications) with Exhibits B-1 (CMC section of the Cubist U.S. NDA filing)
and C-1 (Master Product Specifications) attached hereto. To the extent that
there is any conflict between the specifications set forth in Exhibit C-1 and
those set forth in Exhibit B-1, the specifications set forth in Exhibit C-1
shall supersede in all respects.

 

13.                                 No Other
Amendments.  Except to the extent amended hereby,
all of the definitions, terms, provisions and conditions set forth in the
Agreement are hereby ratified and confirmed and shall remain in full force and
effect.  The terms and conditions herein
and subject matter hereof shall at all times be considered Confidential
Information of Cubist, as defined in the Agreement. The Agreement and this
Amendment No. 2 shall be read and construed together as a single agreement
and the term “Agreement” shall be deemed a reference to the Agreement as
amended by this Amendment No. 2.  This
Amendment No. 2 may be signed in any number of counterparts, each of which
shall be deemed to be an original and all of which together shall constitute but
one and the same instrument.  In making
proof of this Amendment No. 2 it shall not be necessary to produce or account
for more than one such counterpart.

 

6

 

IN
WITNESS WHEREOF, this Amendment No. 2 has been executed under
seal by the parties hereto as of the day and year first above written.

	
   

  	
  ACS DOBFAR SpA

  	
   

  
	
   

  	
   

  	
   

  	
   

  
	
   

  	
  By:

  	
    /s/ Marco
  Feliciani

  	
   

  
	
   

  
	
   

  	
  Title: 
  President

  
	
   

  
	
   

  	
  Date: 02/20/03

  

 

 

	
   

  	
  CUBIST PHARMACEUTICALS,
  INC.

  
	
   

  
	
   

  	
  By:

  	
    /s/ Michael W. Bonney

  	
   

  
	
   

  	
   

  
	
   

  	
  Title: 
  President/COO

  
	
   

  	
   

  
	
   

  	
  Date: 2/13/03

  

 

7

Exhibit B-1

 

CMC Section of US
NDA Filing

 

[*]

 

                CONFIDENTIAL
TREATMENT REQUESTED: MATERIAL HAS BEEN OMITTED AND FILED WITH THE COMMISSION

 

8

 

Exhibit C-1

 

Specifications

 

[*]

 

                CONFIDENTIAL
TREATMENT REQUESTED: MATERIAL HAS BEEN OMITTED AND FILED WITH THE COMMISSION

 

9

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