CONFIDENTIAL TREATMENT

                       CLINICAL SERVICES MASTER AGREEMENT


          THIS CLINICAL SERVICES MASTER AGREEMENT (this "MASTER AGREEMENT") is
entered into as of this 1st day of December, 1999 by and between CUBIST
PHARMACEUTICALS, INC. ("SPONSOR"), and IBAH, INC. ("IBAH"), a Delaware
corporation.

          WHEREAS, Sponsor requires various clinical research services from time
to time in support of various projects (individually, a "Project," and
collectively, the "Projects"), which shall be set forth in Exhibits to this
Master Agreement: and

          WHEREAS, IBAH is engaged in the business of providing such services;

          NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO
BE LEGALLY BOUND, Sponsor and IBAH hereby agree as follows:

1.       SCOPE OF MASTER AGREEMENT; OBLIGATIONS

         1.1.     The specific responsibilities and obligations to be performed
                  by IBAH with respect to a Project (the "SERVICES"), as set
                  forth in the applicable Protocol(s), are expressly set forth
                  in Exhibit(s) attached to this Master Agreement, which,
                  together with the Schedule(s) attached hereto, are
                  incorporated by reference herein. The responsibility for the
                  Services is being transferred to IBAH in accordance with 21
                  C.F.R. Section 312.52. Those responsibilities and obligations
                  not specifically transferred to and assumed by IBAH in this
                  Master Agreement or the Exhibit(s) as constituting part of the
                  Services shall be and remain the sole responsibility of
                  Sponsor.

         1.2.     IBAH agrees to provide the Services in accordance with (a) all
                  applicable federal laws and regulations, including standards
                  of Good Clinical Practices; and (b) the standards and
                  practices that are generally accepted in the industry and
                  exercised by other persons engaged in performing similar
                  services.

*Confidential treatment requested: Material has been omitted and filed with
the Commission.

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2.       PAYMENT

         2.1.     In consideration of the Services, Sponsor shall pay to IBAH:
                  (a) the Service Fees (as defined in SECTION 2.2); and (b) the
                  Pass-Through Costs (as defined in SECTION 2.3).

         2.2.     As used in this Master Agreement, the term "SERVICE FEES"
                  means all amounts due for the Services, exclusive of the
                  Pass-Through Costs. The estimated Service Fees and the payment
                  schedule therefor are set forth in the Schedule(s) and the
                  Exhibit(s), and shall be increased to include: (a) the costs
                  of any additional Services required as a result of Project
                  changes by Sponsor; and (b) where a Project requires more time
                  than allotted in the Exhibit(s), and the parties agree to
                  continue such Project beyond the expected conclusion date, any
                  additional costs that may be incurred in order to complete
                  such Project, at the contractual rates set forth in the
                  applicable Exhibit(s).

         2.3.     As used in this Master Agreement, the term "PASS-THROUGH
                  COSTS" means all investigator, Institutional Review Board or
                  other applicable pass-through costs actually incurred by IBAH
                  under this Master Agreement or the Exhibit(s) in order to
                  expedite successful completion of a Project, which costs are
                  normal and routine to studies similar to such Project (e.g.,
                  advancing an investigator's Institutional Review Board fee or
                  reimbursing reasonable additional, unbudgeted patient
                  expenses). In order to enable IBAH to maintain a balance to be
                  applied towards all Pass-Through Costs, IBAH shall invoice
                  Sponsor for all reasonably anticipated Pass-Through Costs (the
                  "ESTIMATED PASS-THROUGH COSTS") in advance of the expected
                  payment date therefor.

         2.4.     Notwithstanding anything contained herein to the contrary, the
                  estimated Service Fees set forth in the Exhibit(s) shall
                  remain in effect for [ ]*. Thereafter, IBAH reserves the right
                  [ ]*.

3.       CONFIDENTIALITY

         3.1.     That certain Confidentiality Agreement by and between IBAH and
                  Sponsor dated October 18, 1999 (the "CONFIDENTIALITY
                  AGREEMENT") is hereby terminated and of no further force or
                  effect.

*Confidential treatment requested: Material has been omitted and filed with
the Commission.

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         3.2.     In connection with the performance of the Services, Sponsor
                  shall provide to IBAH, and IBAH shall have access to,
                  Sponsor's Confidential Information. As used in this Master
                  Agreement, "SPONSOR'S CONFIDENTIAL INFORMATION" means any (a)
                  information provided by, or developed for, Sponsor within the
                  framework of this Master Agreement, the Schedule(s), the
                  Exhibit(s) or the Confidentiality Agreement; or (b) data
                  collected during a Project.

         3.3.     In connection with this Master Agreement, Sponsor will have
                  access to, or become acquainted with, IBAH's Confidential
                  Information. As used in this Master Agreement, "IBAH'S
                  CONFIDENTIAL INFORMATION" means any (a) information generated
                  or obtained in connection with IBAH's pricing, proposals or
                  contracts (including the provisions of this Master Agreement,
                  the Schedule(s) and the Exhibit(s)); (b) of IBAH's procedures,
                  programs, guidelines or policies (including, without
                  limitation, its Standard Operating Procedures); or (c)
                  information designated in writing as "confidential."

         3.4.     Neither Sponsor's Confidential Information nor IBAH's
                  Confidential Information (collectively, "CONFIDENTIAL
                  INFORMATION") shall include any information that:

                  (a)      was known by the receiving party at the time of
                           disclosure to it by the disclosing party, or that is
                           independently developed or discovered by the
                           receiving party, after disclosure by the disclosing
                           party, without the aid, application or use of any
                           item of the disclosing party's Confidential
                           Information, as evidenced by written records;

                  (b)      is now or subsequently becomes, through no act or
                           failure to act on the part of the receiving party,
                           generally known or available;

                  (c)      is disclosed to the receiving party by a third party
                           authorized to disclose it; or

                  (d)      is required by law or by court or administrative
                           order to be disclosed; provided, that the receiving
                           party shall have first given prompt notice to the
                           other party of such required disclosure.

*Confidential treatment requested: Material has been omitted and filed with
the Commission.

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         3.5.     Each party shall exercise due care to prevent the unauthorized
                  use or disclosure of the other party's Confidential
                  Information, and shall not, without the other party's prior
                  written consent, (a) use the other party's Confidential
                  Information for any purpose other than performing its
                  obligations under this Master Agreement and the Exhibit(s); or
                  (b) disclose or otherwise make available, directly or
                  indirectly, any item of the other party's Confidential
                  Information to any person or entity other than those
                  employees, independent contractors, agents or investigators of
                  such party and/or its affiliated entities (collectively,
                  "REPRESENTATIVES") who reasonably need to know the same in the
                  performance of such party's obligations under this Master
                  Agreement (including the Schedule(s) and the Exhibit(s)), or
                  in order to make decisions or render advice in connection
                  therewith. For the convenience of the parties, each party
                  acknowledges that unless precluded in writing by the other
                  party, Confidential Information may be transmitted to a party
                  and/or its Representatives via the Internet. Each party shall
                  advise its Representatives who have access to the other
                  party's Confidential Information of the confidential nature
                  thereof, and agrees that such Representatives will be bound by
                  terms of confidentiality and restrictions on use with respect
                  thereto that are at least as restrictive as the terms of this
                  SECTION 3.

         3.6.     The provisions of this SECTION 3 shall survive for a period of
                  five (5) years from the date of any expiration or termination
                  of this Master Agreement, however caused.

4.       PROPERTY OF SPONSOR

         4.1.     All (a) of Sponsor's Confidential Information (including,
                  without limitation, all original Project records and reports),
                  (b) unused clinical supplies provided by Sponsor, and (c)
                  complete and incomplete Case Report Forms, which in any case
                  are in IBAH's possession, shall be and remain Sponsor's
                  property; PROVIDED, HOWEVER, that IBAH-may retain one copy of
                  Sponsor's Confidential Information in its files for archival
                  purposes, as a means of determining any continuing obligations
                  under this Master Agreement (including the Schedule(s) and the
                  Exhibit(s)).

         4.2.     All inventions, improvements in know-how, new uses, processes
                  and compounds involving the study drug(s) and/or product(s)

*Confidential treatment requested: Material has been omitted and filed with
the Commission.

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                  covered by this Master Agreement and/or the Exhibit(s) that
                  are conceived or reduced to practice as a direct result of the
                  Project(s) ("INVENTIONS") shall be and remain the sole
                  property of Sponsor. IBAH shall cooperate fully with Sponsor
                  in obtaining, at Sponsor's sole cost and expense, any patent
                  protection as may be available for the Inventions, and shall
                  execute all documents reasonably deemed necessary by Sponsor
                  for purposes of procuring such patent protection. IBAH agrees
                  that it shall endeavor to ensure contractually the prompt
                  disclosure to Sponsor by any investigator, employee or other
                  individual retained by IBAH for a Project of any Inventions,
                  as well as the cooperation of such persons in securing patent
                  protection as set forth herein.

         4.3.     Notwithstanding the foregoing, Sponsor acknowledges that IBAH
                  and its professional staff currently possess certain
                  inventions, processes, know-how, trade' secrets, methods,
                  approaches, analyses, improvements, other intellectual
                  properties and other assets including, but not limited to,
                  clinical trial management analyses, analytical methods,
                  procedures and techniques, computer technical expertise and
                  proprietary software, and technical and conceptual expertise
                  in the area of conducting clinical trials, all of which have
                  been developed independently by IBAH without the benefit of
                  any information provided by Sponsor (collectively, "IBAH
                  PROPERTY"). Sponsor agrees that any IBAH Property which is
                  used, improved, modified or developed by IBAH under or during
                  the term of this Master Agreement shall be and remain the sole
                  and exclusive property of IBAH.

5.       RESTRICTIONS ON ANNOUNCEMENTS

IBAH shall not make any announcement, oral presentation or publication relating
to any Project without Sponsor's prior written consent (which consent shall not
be unreasonably withheld), except as required by law or by court or
administrative order. Neither party shall employ or use the name of the other
party in any publication or promotional material or in any form for public
distribution, without the prior written consent of the other party, except as
required by law or by court or administrative order.

6.       FDA INSPECTION

In the event that IBAH receives a Notice of Inspection (a "NOTICE") from the
Food and Drug Administration ("FDA") which relates to any Project, IBAH

*Confidential treatment requested: Material has been omitted and filed with
the Commission.

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shall: (a) notify Sponsor promptly of such Notice; (b) keep Sponsor informed of
the progress of the inspection; and (c) provide to Sponsor a copy of any
documents produced to the FDA pursuant to such Notice. Sponsor acknowledges that
it is IBAH's obligation to respond to a Notice directed to IBAH.

7.       ACCESS TO FACILITIES

Sponsor's authorized representatives may visit IBAH's site and facilities at
reasonable times and with reasonable frequency during normal business hours and
upon reasonable advance written notice, to observe the progress of any Services.
All such visits shall be subject to IBAH's restrictions and procedures relating
to safety, security and protection of Confidential Information, and in
connection therewith, Sponsor's authorized representatives may be required to
sign a confidentiality agreement, or an access agreement for special
access-controlled areas.

8.       INDEMNIFICATION

         8.1      Sponsor shall defend, indemnify and hold harmless IBAH, its
                  affiliated entities, and their respective trustees, officers,
                  agents and employees from any and all losses, costs, expenses,
                  liabilities, claims, actions and damages, directly related to
                  the conduct of the clinical trial and/or IBAH's performance of
                  the services provided under this Agreement, subject to the
                  restrictions set forth in Sections 8.2 and 8.3 below.

         8.2      The above obligation of Sponsor shall not apply nor shall
                  Sponsor be liable for any indemnification or expenses, and in
                  fact, IBAH shall defend, indemnify, and hold harmless Sponsor,
                  for actions or claims in any way arising from or caused by the
                  willful, reckless, or negligent acts or omissions, of IBAH or
                  any of their agents or employees, or arising from or caused by
                  any of their failures to comply strictly with the Protocol,
                  with good clinical practices, with Sponsor's written
                  recommendations and instructions relative to the conduct of
                  the applicable clinical trial, or with any applicable FDA or
                  other governmental requirements or law.

         8.3      The obligation of the indemnifying party hereunder shall apply
                  only if the other party provides prompt written notification
                  upon receipt of notice of any claim or suit, (provided,
                  however, that neither party shall be released from its
                  obligations under this Section 8 if the failure to promptly
                  notify the other party does

*Confidential treatment requested: Material has been omitted and filed with
the Commission.

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                  not materially prejudice the defense of any claim), permits
                  the indemnifying party and its attorneys and personnel to
                  handle and control the defense of such claims or suits,
                  including pretrial, trial or settlement, and the indemnified
                  party fully cooperates and assists in such defense. The
                  indemnified party further agrees that it will not settle or
                  compromise any such claim or suit without the prior written
                  consent of the indemnifying party.

         8.4      The indemnifying parties shall secure and maintain in full
                  force and effect through the performance of the applicable
                  Study (and following termination of the applicable Study to
                  cover any claims arising from the applicable Study) insurance
                  coverage in amounts appropriate to the conduct of the parties
                  business activities and the services contemplated by the
                  applicable Study, and shall provide evidence of insurance
                  coverage in an acceptable form upon request.

9.       TERMINATION

         9.1.     Either party may terminate this Master Agreement and/or any
                  Exhibit at any time and for any reason upon a minimum of [ ']*
                  prior notice. Upon any such early termination, Sponsor shall
                  pay to IBAH all Service Fees and Pass-Through Costs due and
                  owing based upon Services completed and costs incurred through
                  the effective date of termination, including costs for
                  materials and/or services previously acquired or contracted
                  for which will not be used for the Services as a result of
                  such termination.

         9.2.     Any funds held by IBAH which by contract definition or
                  amendment are deemed unearned (including, without limitation,
                  any Estimated Pass-Through Costs not used to satisfy
                  Pass-Through Costs) shall be returned to Sponsor within [ ]*
                  after conclusion of the Project(s) set forth in the applicable
                  Exhibit(s).

         9.3.     Following completion or termination of any Project, IBAH shall
                  forward all original Project records and reports to Sponsor
                  (or to a repository designated by Sponsor in writing) at
                  Sponsor's sole cost and expense. Thereafter, IBAH shall retain
                  any documentation related to such Project in compliance with
                  IBAH's corporate policy on retention and destruction of
                  records.

*Confidential treatment requested: Material has been omitted and filed with
the Commission.

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10.      FORCE MAJEURE

If either party's performance of this Master Agreement or any Exhibit is
prevented, restricted or delayed (either totally or in part) by reason of any
cause beyond the reasonable control of the parties, such as acts of God,
explosion, disease, weather, war, insurrection, civil strike, riot or power
failure, the party so affected shall, upon giving notice thereof to the other
party, be excused from such performance to the extent of such prevention,
restriction or delay; PROVIDED, that the affected party shall use its
commercially reasonable efforts to avoid or remove such causes of
non-performance and shall continue performance with the utmost dispatch whenever
such causes are removed; and PROVIDED FURTHER, that nothing herein shall relieve
either party from the obligation to pay promptly in full all payments that may
be due to the other party under this Master Agreement or the Exhibit(s).

11.      NO CONFLICT

Each party represents and warrants that it is authorized to enter into this
Master Agreement and that the terms hereof are not inconsistent with or a
violation of any contractual or other legal obligation to which it is subject.

12.      LIMITATIONS

         12.1.    Sponsor acknowledges that the results of the Project(s) are
                  inherently uncertain and that, accordingly, there can be no
                  assurance, representation or warranty by IBAH that the study
                  drug(s) and/or product(s) covered by this Master Agreement
                  and/or the Exhibit(s) can, either during the term of this
                  Master Agreement or thereafter, be developed successfully or,
                  if so developed, will receive the required approval(s) from
                  the FDA or other regulatory agency or authority.

         12.2.    Both parties acknowledge that the Services constitute research
                  and development. Accordingly, Sponsor's sole remedy for any
                  breach or default hereof by IBAH shall be termination of this
                  Master Agreement or the applicable Exhibit as herein provided
                  or a return of any Service Fees and unexpended Pass Through
                  costs paid to IBAH for Services improperly performed or not
                  performed. In no event shall IBAH be liable for any special,
                  indirect, incidental or consequential damages (whether in
                  contract or tort).

*Confidential treatment requested: Material has been omitted and filed with
the Commission.

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13.      NON-DEBARMENT

         13.1.    IBAH represents and warrants that IBAH has never been and is
                  not currently:

                  (a)      an individual who has been debarred by the FDA
                           pursuant to 21 U.S.C. Section 335a (a) or (b)
                           (a "DEBARRED INDIVIDUAL") from providing services in
                           any capacity to a person that has an approved or
                           pending drug product application, or an employer,
                           employee or partner of a Debarred Individual; or

                  (b)      a corporation, partnership, or association that has
                           been debarred by the FDA pursuant to 21 U.S.C.
                           Section 335a (a) or (b) (a "DEBARRED ENTITY") from
                           submitting or assisting in the submission of an
                           abbreviated new drug application, or an employee,
                           partner, shareholder, member, subsidiary or affiliate
                           of a Debarred Entity.

         13.2.    IBAH further represents and warrants that IBAH has no
                  knowledge of any circumstances which may affect the accuracy
                  of the representations and warranties set forth in SECTION
                  13.1 including, but not limited to, FDA investigations of, or
                  debarment proceedings against, IBAH or any person or entity
                  performing, or rendering assistance related to, the Services.
                  IBAH will notify Sponsor promptly upon becoming aware of any
                  such circumstances during the term of this Master Agreement.

14.      INDEPENDENT CONTRACTOR

The status of the parties under this Master Agreement is that of independent
contractors, and, except as specifically set forth herein, or in the Schedule(s)
or the Exhibit(s), neither party has any authority to bind or act on behalf of
the other party without its express written consent.

15.      NOTICES

Any notices, requests or other communications given under this Master Agreement
shall be in writing and shall be given by personal delivery, or sent by (a)
facsimile transmission (with message confirmed during normal business hours);
(b) first class mail, postage prepaid; or (c) Federal Express (or equivalent
nationally recognized overnight delivery service), delivery charges prepaid. All
notices shall be given to a party at its respective address set forth below, or
at such other address as such party from time to time may

*Confidential treatment requested: Material has been omitted and filed with
the Commission.

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specify by notice in accordance with this SECTION 15. A notice shall be deemed
given when actually received; PROVIDED, that if any facsimile notice is received
after 5:00 P.M. local time at the place of receipt, it shall be deemed to have
been given as of the next following business day.

         If to IBAH:                   IBAH, Inc.
                                       Four Valley Square
                                       512 Township Line Road
                                       Blue Bell, PA 19422
                                       Attention: Controller, U.S. CRO

         If to Sponsor:                Cubist Pharmaceuticals, Inc.
                                       24 Emily Street
                                       Cambridge, MA 02139
                                       Attention: David P. Graham

16.      ENTIRE AGREEMENT

This Master Agreement, together with all corresponding Schedules, Exhibits,
Amendments or Change Orders, constitutes the entire agreement between Sponsor
and IBAH with respect to the subject matter hereof, and replaces and supersedes
any and all prior and contemporaneous agreements and/or understandings, whether
oral or written, between Sponsor and IBAH with respect to the subject matter
hereof. This Master Agreement (including the Schedule(s) and the Exhibit(s)) may
be amended or modified only by a written instrument executed by a duly
authorized officer of each party.

17.      CONSTRUCTION OF AGREEMENT

The descriptive headings of the Sections of this Master Agreement are for
convenience only and shall not affect the meaning or construction of any of the
provisions of this Master Agreement. The failure of either party to enforce any
provision of this Master Agreement (including the Schedule(s) and/or the
Exhibit(s)) shall not be construed as a waiver or limitation of that party's
subsequent rights to enforce and compel strict compliance with every provision
of this Master Agreement. To the extent any provision of this Master Agreement
or the application thereof is found by a proper authority to be invalid or
unenforceable, it shall be considered deleted herefrom, and the remainder of
this Master Agreement shall continue in full force and effect.

This Master Agreement shall be governed by and construed in accordance with the
laws of the Commonwealth of Pennsylvania, without regard to provisions of
conflicts of law. Any lawsuit arising from or related to this Master Agreement
shall be brought exclusively before the United States

*Confidential treatment requested: Material has been omitted and filed with
the Commission.

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District Court for the Eastern District of Pennsylvania or any Commonwealth
court sitting in Montgomery County, Pennsylvania, and each party hereby consents
to the jurisdiction of any such court.

18.      ASSIGNMENT

Neither Sponsor nor IBAH may assign this Master Agreement or any rights
hereunder or delegate the performance of any duties hereunder without the prior
written approval of the other party, which approval shall not be unreasonably
delayed or withheld; PROVIDED, HOWEVER, that without such consent, either party
may assign this Master Agreement in connection with the transfer or sale of all
or substantially all of its assets, stock or business, or its merger,
consolidation or combination with or into another entity. Subject to the
foregoing, this Master Agreement shall be binding upon, inure to the benefit of
and be enforceable by the parties and their respective successors and permitted
assigns.

19.      SURVIVAL

Any terms of this Master Agreement which by their nature extend beyond its
performance, expiration or termination (including, without limitation, SECTIONS
2 through 5, 8 through 10, 12 and this SECTION 19) shall remain in effect
indefinitely until fulfilled in accordance with their terms.

20.      SIGNATORIES

This Master Agreement may be executed in counterparts, each of which, when
executed and delivered, shall be deemed to be an original, and all of which,
when joined, shall together constitute one and the same agreement. Any photocopy
or facsimile of this Master Agreement, or of any counterpart, shall be deemed
the equivalent of an original.

*Confidential treatment requested: Material has been omitted and filed with
the Commission.


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         IN WITNESS WHEREOF, the parties have executed this Master Agreement by
their duly authorized officers as of the date first above written.

CUBIST PHARMACEUTICALS, INC.                       IBAH, INC.

By: /s/ FRANCIS P. TALLY, M.D.                     By: /s/ LEONARD F. STIGLIANO
   -----------------------------                      -------------------------

Name:  Francis P. Tally, M.D.                      Name:  Leonard F. Stigliano

Title:  Ex. VP Scientific Affairs                  Title:  President, US. CRO

*Confidential treatment requested: Material has been omitted and filed with
the Commission.


CONFIDENTIAL TREATMENT EXHIBIT A TO THE CLINICAL SERVICES MASTER AGREEMENT BETWEEN CUBIST PHARMACEUTICALS, INC. AND IBAH, INC., DATED DECEMBER 21, 1999. THIS EXHIBIT A is entered into this 21st day of December, 1999, by and between Cubist Pharmaceuticals, Inc. (hereinafter "Cubist") and IBAH, Inc. (hereinafter "IBAH"). WHEREAS, Cubist and IBAH entered into a Clinical Services Master Agreement, dated December 1, 1999 (hereinafter the "Master Agreement"), wherein IBAH agreed to provide clinical services and; WHEREAS, Cubist and IBAH agree that IBAH shall provide the services set forth in this Exhibit A, subject to the terms and conditions set forth in the Master Agreement; NOW, THEREFORE, for good and valuable consideration, and INTENDING TO BE LEGALLY BOUND, Cubist and IBAH agree as follows: Based on the Project Specifications, IBAH has provided a description of services to be performed for the Daptomycin Program (hereinafter "the Project") and associated costs. Changes made in the Project scope, at any time during the Project, will result in a corresponding adjustment to the Project costs. I. PROGRAM PLAN A. PROGRAM STATUS TABLE [ ]* *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> II. PROJECT ROLES AND RESPONSIBILITIES ------------------------------------------------------------------------------------------------------------------------ TASK CUBIST IBAH ------------------------------------------------------------------------------------------------------------------------ ------------------------------------------------------------------------------------------------------------------------ A. STUDY MANAGEMENT ------------------------------------------------------------------------------------------------------------------------ 1. Facilitate Project Management X o [ ]* o International Project Manager [ ]* ------------------------------------------------------------------------------------------------------------------------ 2. Manage [ ]* Clindev sites in South Africa X ------------------------------------------------------------------------------------------------------------------------ 3. Coordinate and conduct team meetings X X ------------------------------------------------------------------------------------------------------------------------ 4. Standard Operating Procedures (SOPS) X ------------------------------------------------------------------------------------------------------------------------ 5. Performance tracking X X ------------------------------------------------------------------------------------------------------------------------ 6. Monitor Project payment schedule X X ------------------------------------------------------------------------------------------------------------------------ 7. Project problem solving X X ------------------------------------------------------------------------------------------------------------------------ 8. Clerical and administrative support X ------------------------------------------------------------------------------------------------------------------------ B. CLINICAL TRIAL INITIATION ------------------------------------------------------------------------------------------------------------------------ 1. Drug development and study design X ------------------------------------------------------------------------------------------------------------------------ 2. Patient plan X o CSSTI-[ ]* patients enrolled each U.S./International ([ ]* patients total) o RRC (Companion) [ ]* patients U.S./ [ ]* International ([ ]* patients total) o Bacteremia [ ]* patient U.S. ------------------------------------------------------------------------------------------------------------------------ 3. Site plan X o Up to [ ]* additional Sites U.S. o [ ]* ------------------------------------------------------------------------------------------------------------------------ 4. CRF design X o CSSTI -[ ]* estimated pages o RRC -[ ]* estimated pages o Bacteremia -[ ]* estimated pages ------------------------------------------------------------------------------------------------------------------------ 5. CRF logistics (print, bind, and distribute) X o Material, printing and assembly expenses will be passed through at cost ------------------------------------------------------------------------------------------------------------------------ 6. Investigator identification, recruitment and qualification X ------------------------------------------------------------------------------------------------------------------------ 7. Investigator regulatory document management X o Protocol Amendments and IRB submissions billed per site o Informed Consent Forms development ------------------------------------------------------------------------------------------------------------------------ 8. Certification of Investigator Financial Disclosure X ------------------------------------------------------------------------------------------------------------------------ 9. Investigator agreement negotiation X ------------------------------------------------------------------------------------------------------------------------ 10. Coordination of investigators meeting X o One meeting US; three meetings International ------------------------------------------------------------------------------------------------------------------------ 11. Project team training X X ------------------------------------------------------------------------------------------------------------------------ *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -2- ------------------------------------------------------------------------------------------------------------------------ TASK CUBIST IBAH ------------------------------------------------------------------------------------------------------------------------ ------------------------------------------------------------------------------------------------------------------------ C. CLINICAL TRIAL MANAGEMENT ------------------------------------------------------------------------------------------------------------------------ 1. Clinical monitoring X o IBAH estimates use [ ]* pre-qualified sites (U.S.) [ ]* o (U.S.) and 25 (International) one-day qualification visits o IBAH estimates performance of [ ]* U.S. and [ ]* International initiation visits ([ ]* visits total) o IBAH estimates performance of [ ]* U.S. and [ ]* International interim visits ([ ]* visits total) o IBAH estimates performance of [ ]* U.S. and [ ]* International drug accountability visits ([ ]* visits total) o IBAH estimates [ ]* U.S. and [ ]* International close-out visits [ ]* visits total ------------------------------------------------------------------------------------------------------------------------ 2. Clinical grant payment administration X ------------------------------------------------------------------------------------------------------------------------ 3. CRF tracking, filing and archiving X o CSSTI- [ ]* each US/International CRF pages ([ ]* pages total) o RRC- [ ]* US/[ ]* International CRF pages ([ ]* pages total) o Bacteremia- [ ]* CRF Pages ------------------------------------------------------------------------------------------------------------------------ 4. Medical monitoring X o [ ]* ------------------------------------------------------------------------------------------------------------------------ 5. Safety review of CRFs X o Based on [ ]* cases reviewed ------------------------------------------------------------------------------------------------------------------------ 6. SAE Reporting X o CSSTI U.S. [ ]* o RRC U.S. [ ]* o Bacteremia [ ]* ------------------------------------------------------------------------------------------------------------------------ D. CLINICAL DATA MANAGEMENT ------------------------------------------------------------------------------------------------------------------------ 1. Project database creation and data entry X Fee based on o CSSTI- [ ]* CRF pages each US/International [ ]* o RRC- [ ]* CRF pages US/[1950]* International [ ]* o Bacteremia -[ ]* CRF pages ------------------------------------------------------------------------------------------------------------------------ 2. Case report form review and query resolution X Fee based on: o CSSTI- [ ]* CRF pages each US/International [ ]* o RRC- [ ]* CRF pages US/[ ]* International [ ]* o Bacteremia -[ ]* CRF pages ------------------------------------------------------------------------------------------------------------------------ *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -3- ------------------------------------------------------------------------------------------------------------------------ TASK CUBIST IBAH ------------------------------------------------------------------------------------------------------------------------ ------------------------------------------------------------------------------------------------------------------------ 3. Dictionary processing X ------------------------------------------------------------------------------------------------------------------------ 4. Laboratory data processing (central) X IBAH will use Covance as central lab ------------------------------------------------------------------------------------------------------------------------ 5. Data transfer (standard) X ------------------------------------------------------------------------------------------------------------------------ 6. Data security procedures X ------------------------------------------------------------------------------------------------------------------------ 7. GCP audit of final database X ------------------------------------------------------------------------------------------------------------------------ E. BIOMETRIC ANALYSIS ------------------------------------------------------------------------------------------------------------------------ 1. Statistical analysis plan-one major one minor revision for each X o CSSTI- U.S. o CSSTI-International o RRC-U. S. o RRC-International o Bacteremia-U.S. ------------------------------------------------------------------------------------------------------------------------ 2. Randomization X o 3rd Party IVRS ------------------------------------------------------------------------------------------------------------------------ 3. Project data setup and programming of displays X o CSSTI- [ ]* primary tables and listings and [ ]* secondary tables and listing U.S. and [ ]* secondary tables and listings International o RRC- [ ]* primary tables and listings and [ ]* secondary tables and listing U.S. and [ ]* secondary tables and listings International o Bacteremia [ ]* primary tables and listings and [ ]* secondary tables and listing ------------------------------------------------------------------------------------------------------------------------ 4. Quality control procedures for displays X ------------------------------------------------------------------------------------------------------------------------ 5. Patient evaluability and outcome assessment X ------------------------------------------------------------------------------------------------------------------------ 6. Interim transfer of listings X ------------------------------------------------------------------------------------------------------------------------ 7. Final statistical analysis X ------------------------------------------------------------------------------------------------------------------------ 8. Statistical support for table preparation X ------------------------------------------------------------------------------------------------------------------------ 9. Data loading and review X ------------------------------------------------------------------------------------------------------------------------ 10. Statistical report X ------------------------------------------------------------------------------------------------------------------------ 11. GCP compliance audit of final tables and listings X ------------------------------------------------------------------------------------------------------------------------ *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -4- ------------------------------------------------------------------------------------------------------------------------ TASK CUBIST IBAH ------------------------------------------------------------------------------------------------------------------------ ------------------------------------------------------------------------------------------------------------------------ F. CLINICAL WRITING ------------------------------------------------------------------------------------------------------------------------ ------------------------------------------------------------------------------------------------------------------------ 1. Phase II clinical Study report-Bacteremia, RRC(NA), RRC(Companion) X o One major [ ]* and one minor [ ]* revision and up to [ ]* brief patient narratives o Fee does not include collation or compilation of appendices Phase III clinical study report-CSSTI(NA), CSSTI (International), o One major [ ]* and one minor [ ]* revision and up to [ ]* brief patient narratives o Fee does not include collation or compilation of appendices ------------------------------------------------------------------------------------------------------------------------ 2. GCP audit of final clinical study report X ------------------------------------------------------------------------------------------------------------------------ *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -5- III. PROJECT TIMELINE This Project is estimated to start on or about [ ]*. The projected timeline for this Project is as follows: [ ]* *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -6- IV. IBAH SERVICES A. STUDY MANAGEMENT 1. GLOBAL PROGRAM DIRECTOR/INTERNATIONAL PROJECT MANAGER IBAH's Global Program Director will coordinate the services being provided by all of the disciplines within IBAH and will act as a single point of contact for Cubist until the completion of the Project. The International Project Manager, working in conjunction with the Global Program Director, will manage the international segment of the Project. Key responsibilities of these individuals will include the following: o Prepare detailed Project timelines and ensuring that the major milestones are met o Provide Project status updates at a frequency directed by Cubist o Identify and resolve critical Project issues o Ensure adequate resource allocation across all functions o Oversee Project team meetings o Manage Project financial issues 2. COUNTRY TRIAL MANAGERS IBAH's Country Trial Managers will be dedicated to managing the day-to-day clinical trial activity. They will oversee all site and CRA activities within this Project. Primary responsibilities of these individuals will include the following: o Develop case report forms and monitoring guidelines o Oversee regulatory document management from each of the investigational sites o Review and track CRA activities including scheduling of site visits, site visit reports, monitoring logs, follow-up correspondence, hours worked, routine expense records, and any other pertinent study-related documents o Maintain routine contact with all CRAs to ensure the consistency of program communication and work performed o Provide ongoing quality control of the CRAB performance throughout the Project o Provide Global Program Director and International Project Manager with periodic status reports including progress of site initiations, *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -7- status of ongoing site visits, patient enrollment updates, site visit reports, data query rates, and other study-related reports 3. ASSOCIATED MANAGEMENT SUPPORT IBAH will dedicate clerical/administrative support to the Project. The clerical/administrative fee will cover costs associated with IBAH's services, as well as management and administration associated with this Project. All travel expenses, Federal Express and/or overnight courier services, and telephone conference costs will be passed through at cost to Cubist. B. CLINICAL TRIAL INITIATION 1. PROJECT TEAM TRAINING IBAH will rely on internal and external experts to provide specific therapeutic area training and orientation to the protocol and the CRF prior to study initiation and on an ongoing basis. This training will be designed to ensure that all team members are familiar with the Project requirements and their role within the team. Items discussed at these meetings will include, but will not be limited to: o Therapeutic area and clinical development background o Protocol and CRF o Discussion of therapeutic implications for this study o Monitoring guidelines 2. IBAH S.T.A.R.T In order to facilitate rapid study site initiations, IBAH has established IBAH S.T.A.R.T (Study Trial Acceleration Resource Teams) in North America. The study start-up functional areas that are included in this group are Investigator Recruitment, Investigator Document Management, Investigator Agreement Negotiation, and Investigator Meeting Coordination. A Coordinator will head each S.T.A.R.T. team and will work with the Managers to devise and implement a working strategy to promote an expeditious action plan. The goal is to provide sites with a streamlined communication channel for all S.T.A.R.T activities. The International Project Manager and the Country Trial Managers, for the international portion of this Project, will perform these study start-up activities. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -8- 3. INVESTIGATOR IDENTIFICATION, RECRUITMENT AND QUALIFICATION IBAH will collaborate with Cubist to recruit [ ]* U.S. and [ ]* International additional investigators capable of conducting the Cubist studies. A preliminary telephone interview will be conducted to evaluate a prospective site's interest and potential to meet both patient enrollment and data quality goals for this Project. IBAH anticipates that [ ]* of the proposed sites in the U.S. will not need actual qualification visits because sites qualified, within the past year and experienced in anti-infective protocols, will be given the opportunity to participate in this Project. After obtaining a signed confidentiality agreement from the prospective investigative sites, IBAH will issue a survey form, customized to the protocol. Additional Project information will be distributed to appropriate investigators who are willing to commit to study participation. The outcome of all evaluations, with a final list of proposed investigators, will be forwarded to Cubist for approval prior to final recruitment. If it is necessary to assess the site's ability to achieve study enrollment and data quality goals then a comprehensive pre-study evaluation visit will be scheduled with the selected investigator. Once identified as a qualified study site, an investigator regulatory document package will be sent. 4. INVESTIGATOR REGULATORY DOCUMENT MANAGEMENT In coordination with Cubist, IBAH will develop a template of an informed consent form for the Project, ensuring compliance with all local, state, and federal and international regulatory requirements. Regulatory document packages, with letters of instruction, will be mailed to qualified investigative sites. A dedicated tracking process for regulatory document collection will be utilized. Document collection will cover all criteria required under the principles of Good Clinical Practices (GCP) and International Committee for Harmonization (ICH) guidelines, as well as IBAH Standard Operating Procedures (SOPS). In addition, IBAH S.T.A.R.T., will also collect certification / disclosure information from all investigators and provide this information to Cubist on an ongoing basis. IBAH will track the retrieval of documents on an ongoing basis and provide updates to Cubist as requested. IBAH will prepare copies of all appropriate documents, assemble documents and issue an investigator regulatory binder to all sites, including but not limited to: *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -9- o Investigator's Brochure o Final Protocol and Sample Copy of the CRF o Institutional Review Board (IRB) Approvals of Protocol and Informed Consent Form(s) o Laboratory Certification and Normal Ranges o Completed FDA Form 1572 o Investigator Curriculum Vitae o Financial Disclosure Certification and/or completed Financial Disclosure Form The binders will be maintained at the sites and reviewed for appropriate updates by CRAB responsible for site management over the course of the study. Certification of Investigator Financial Disclosure will be collected and maintained as agreed upon by IBAH and Cubist. The fee for regulatory document collection, processing, and tracking is based upon the number of sites required for the study. File maintenance and updating will be billed at the rate of $[ ]* per site per year after year one. Protocol amendments, which require informed consent revisions and/or IRB re-submission, will be billed at an additional processing fee of $[ ]* for each site. 5. INVESTIGATOR REGULATORY DOCUMENT COLLECTION (INTERNATIONAL) STUDY MASTER FILES In accordance with GCP, IBAH International Regulatory staff will: o Develop Study Master File according to IBAH SOPS under supervision of the Study Manager o Obtain all relevant critical documents for the Project; design an appropriate Critical Document Receipt List as a supporting instrument for the CRAs; review all incoming investigators' documents; approve/reject these documents according to GCP and internal guidelines o Maintain file, i.e. proper filing of all incoming papers (investigator documents, site visit reports); file audits to assure the completeness of the documents and to identify missing documents o Ship investigator documents to Cubist as required o Arrange for archiving of the Study Master File at the end of the Project *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -10- PRE-STUDY APPROVALS IBAH International Regulatory staff will prepare the necessary pre-study filings with local regulatory authorities for permission to proceed with the clinical trial, as well as follow-up with these local authorities to expedite the review and approval process. IBAH Regulatory staff will prepare the dossier (document compilation and submission) and necessary study updates. Fees are based on IBAH's staff time to prepare the dossier(s) and interact with the regulatory agencies and IRBs. IBAH would also be responsible for translation of documents into the different local languages. In addition, any direct charges (dossier filing fees, travel to meetings at agencies, etc.) will be passed through to Cubist at cost. 6. INVESTIGATOR AGREEMENT NEGOTIATION IBAH will be responsible for the following activities related to negotiating the clinical site contracts: o Create an investigator agreement and patient budget o Negotiate investigator agreements that satisfy Cubist requirements o Handle investigator agreements, approval by Cubist and signature by, investigators o Incorporate changes and securing re-approval by Cubist o Communicate with IBAH Grants Administration Department when necessary o Handle investigator agreement amendments and/or addenda o Collect excess grants from sites at study end Protocol and study amendments, which require investigator agreement revisions, amendments and/or re-negotiation, will be billed at an additional processing fee of [ ]* for each site. 7. COORDINATOR'S AND INVESTIGATOR'S MEETING COORDINATION AND ATTENDANCE A Meetings Coordinator will be assigned to manage all logistics of the U.S. and International meetings and will schedule necessary travel and hotel arrangements. Specific responsibilities will include the following: o Identify appropriate location(s) for the meetings o Define meeting requirements and outline a meeting agenda *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -11- o Negotiate, organize, and make all hotel arrangements o Secure discounted travel arrangements and issue tickets to investigators and study coordinators o Prepare necessary meeting materials (e.g., annotated CRFs, presentation materials, etc.) o Coordinate presentations o Manage administrative aspects associated with the meeting IBAH's Project management and clinical trial management staff will be available to conduct or participate in the meetings and will arrive at the location prior to each meeting to assist attendees with any last minute details that may arise. 8. ELECTRONIC MAIL EXCHANGE PRIVATE Upon the mutual written agreement of the parties, IBAH will develop a connection for the exchange of electronic mail between IBAH and Cubist. Upon the mutual agreement of the parties, provisions can be made to allow IBAH staff to access systems on Cubist's network and to allow printing from those systems to be routed and printed on IBAH's printers. PREREQUISITES In order to provide these services, a communications link will need to be established between Cubist and IBAH. Cubist will extend their WAN to IBAH rather than IBAH extending its WAN to Cubist's location because it provides Cubist with a greater degree of security and control. The WAN extension is terminated at the IBAH site with a router that is owned and operated remotely by Cubist. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -12- SERVICES Once the communications link has been established, connections will be extended to a NT Server that would act as the electronic mail-relay that forwards mail between the two companies. (See drawing below). CLIENT CONNECTIONS TO THE IBAH NETWORK [GRAPHIC OF CLIENT CONNECTIONS TO THE IBAH NETWORK] IBAH suggests using a VLAN to provide the interconnection between the two networks because it provides the capability to isolate traffic. Because of the switch's filtering capabilities. Cubist will only see the information on the IBAH network that IBAH feels is appropriate, and IBAH will have access to Cubist's information and systems that is provided over the WAN only from the IBAH equipment directly attached to the VLAN switch. Currently, IBAH is using Micro Exchange Server 5.5 as our electronic mail server and Microsoft Outlook for our electronic mail. The electronic mail between Cubist and IBAH will use the Simple Mail Transport Protocol (SMTP) to provide the mail transport. The mail sent from IBAH would be routed over the IBAH network to an NT server running Internet Information Server 4.0 (IIS) which would provide the SMTP-relay function to forward the mail to Cubist. Likewise, electronic mail from Cubist will arrive at IBAH via Cubist WAN and router. It will be routed to the VLAN switch where it will be delivered to the NT Server running IIS. IIS will then forward it to the IBAH Exchange Server for delivery. Remote access to the Cubist systems is similar. IBAH staff will log onto dedicated PCs attached to the VLAN switch and then open a session on the Cubist's server to perform whatever function is required (data entry, document submission, data analysis, etc.). Again, because of the filtering capabilities of the switch, that traffic will only be accessible on the LAN segment containing the dedicated PCs and printer and the LAN segment to which the Cubist WAN is attached. Because there are no other devices on those segments, the communications remain private. To print a document or export information from the Cubist system to a device here at IBAH, the traffic is sent over the Cubist WAN, through the VLAN switch, and onto the printer or server - again with the privacy of the information maintained because of the switch's filtering capabilities. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -13- CUBIST RESPONSIBILITIES o Provide IBAH with a list of addresses to be included in the IBAH global address list o Provide technical contact for initial configuration, testing and problem resolution o Order communications link between IBAH and Cubist locations o Assume financial and operational responsibility for the communications link o Purchase, configure and operate router and CSU to be deployed at IBAH location IBAH RESPONSIBILITIES o Establish global address list entry for Cubist organization o Enter e-mail addresses for the individual staff members from that Cubist organization in the global address list. o Initial testing & configuration o Routine monitoring o Global address list maintenance - moves, adds & changes o Mail delivery problem resolution INTERNET-BASED IBAH will use the Internet to communicate with Cubist. The costs are much lower with this option. However, because information is transiting the Internet, there will be severe restrictions on the content of the information that may be sent. Deploying encryption software on each PC that will be communicating with IBAH could solve some of the issues associated with this option. C. CLINICAL TRIAL MANAGEMENT 1. CLINICAL MONITORING IBAH will assign a global team of experienced CRAB to perform pre-study qualification, initiation, interim and closeout site visits. Deployment of CRAB, in terms of number and frequency of visits, will be managed based on Cubist input, geographic location and site-specific enrollment data. IBAH's site management and monitoring procedures will be performed in accordance with GCP to ensure each investigative site's compliance with regulations and protocol requirements and to enhance expeditious enrollment of appropriate patients into the clinical study. Regulatory documents will be reviewed by the CRA on an ongoing basis during the study conduct phase, including verification of signed informed consent forms and investigator IRB notifications. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -14- Once all regulatory documents and approvals are received, a site initiation visit will be scheduled. During this visit, the CRA will review the study goals, protocol (with particular attention to inclusion/exclusion criteria, enrollment plan/goal, adverse events, primary efficacy variables and GCP compliance), CRF completion, and clinical supply dispensation/ accountability will be performed with the investigator and his/her staff. CRAs will perform 100% source document verification of CRF data for accuracy and completeness, and will also review source data for appropriate identification, documentation, and reporting of both serious and non-serious adverse events. Drug accountability visits will be performed, as well as reconciliation and removal of clinical supplies at study closeout per Cubist's requirements. In general, the CRAB' efforts will be focused on source document verification and expedient data retrieval. 2. CLINICAL GRANTS ADMINISTRATION As a follow-up to the Investigator Agreement negotiation process, an extension of the IBAH contracts group will administer the clinical grant payments to the site. Included in their responsibilities are the following: o Process financial records for all of the patients in the study o Issue initial and interim payments for each investigator o Reconcile all payments to each of the investigators prior to the final payments o Track account administration with IBAH's finance group o Maintain W9 forms and all relevant and related government reports (U.S. only) Investigator grants, within parameters defined by Cubist, will be passed through at cost to Cubist. A grant administration fee will be applied, based on the number of sites and payments to be managed throughout the duration of the study. 3. CRF TRACKING, FILING AND ARCHIVING Completed CRFs received from investigative sites, ancillary CRF pages, adverse event documentation, and patient-specific correspondence for each study will be logged in and tracked at IBAH. Of these items, CRFs and answered data queries will be entered page-by-page into a computerized tracking system. Fees reflect logging, copying, filing, and ongoing CRF tracking time. A final, complete page listing and original CRFs will be provided to Cubist upon Project completion. Cubist will be billed for the actual number of pages logged/tracked. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -15- 4. MEDICAL MONITORING (DURING BUSINESS HOURS) An IBAH U.S. and International Medical Monitor will oversee the medical aspects of Cubist's clinical program. In addition to acting as medical advisors to the Project Team, the Medical Monitors will be responsible for the following: o Project planning o Review of clinical documentation (protocol, CRF, sample informed consent form) o Project-specific medical training o Evaluate patient eligibility (in conjunction with the Medical Director of Cubist) o Participate in team meetings o Review study reports, regulatory submissions and study manuscripts 5. SAFETY REVIEW OF CRFS Prior to data entry, a U.S. and International Safety Officer will review all pages of each case, ancillary laboratory pages and all data clarification requests. Cubist will be notified immediately of serious adverse events (SAEs) that have not been previously reported by the sites. Notification will occur by telephone, as well as by forwarding to Cubist an SAE form. The SAE form will include details of the SAE obtained from the investigative site and will be sent via facsimile to the designated recipient at Cubist. As follow-up information is obtained by IBAH, the SAE form will be updated and forwarded to Cubist. 6. SAE REPORTING Within one IBAH business day of receipt, IBAH will forward to Cubist all SAE information received from site personnel or IBAH CRAs. Notification to Cubist will occur via telephone, as well as by forwarding a comprehensive SAE form via facsimile. Cubist will be responsible for reporting SAES to the FDA. IBAH's International staff will report SAEs to non-U.S. agencies. The fee for SAE reporting includes costs for IBAH to provide all follow-up information and to update SAE forms as necessary. Cubist will be billed for the actual number of SAE reports. 7. SAFETY PHONE COVER (INTERNATIONAL) During business hours, IBAH has a direct number to IBAH's Safety Surveillance Department for receipt of SAE information. During evening *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -16- hours, weekends and holidays, a designated member of the Safety Surveillance Department will be on call via beeper. All return calls to the sites will be made immediately to obtain the necessary SAE information and to determine the necessity of an SAE report. D. CLINICAL DATA MANAGEMENT 1. DATA MANAGEMENT PLAN IBAH's Clinical Data Manager will develop a Global Data Management Plan. This plan will include the entry and review guidelines, automated edits checks of the data, dictionary coding procedures, and central laboratory loading procedures. Any other data management tasks requested for this Project will also be outlined in this plan. 2. PROJECT DATABASE CREATION Data screens will be developed by IBAH's programming group on an Open VMS System (Alpha 4100) using Domain/CLINTRIAL(R) software. IBAH's Programmers will develop data-entry screens (i.e., CRF data module designs) that mimic the flow of the CRF, thereby improving the ease and integrity of the data-entry process. 3. DATA ENTRY, CASE REPORT FORM REVIEW AND QUERY RESOLUTION IBAH's data-entry specialists will enter all CRF data utilizing a double-entry method. On-line edit checks will be included to provide additional controls against categorically incorrect data. The dual data-entry strategy will utilize numeric and/or text fields that are entered by one member of the data-entry staff and re-entered on-line by a second member of the staff. Cubist will be billed for the actual number of pages entered. IBAH will generate protocol-specific guidelines that are reviewed and approved by Cubist. Using these guidelines, IBAH will conduct a detailed quality control (QC) review of the entire CRF through a combination of manual review and electronic edit checks that will identify conflicting, unclear or incomplete data. IBAH's Clinical Data Analysts (CDAs) will perform this review. IBAH's CQA will oversee these activities and may, in its discretion, perform audits to ensure quality as part of this data service deliverable. If data are unclear, conflicting or incomplete, then queries will be generated and transmitted to the investigative site and IBAH's Client Services Department. All queries (issued and resolved) will be logged into the IBAH tracking system. IBAH's query database will be maintained *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -17- throughout the Project and can provide Cubist with an up-to-date report on the status of queries on an as-needed basis. Cubist will be billed for the actual number of pages reviewed. In addition, each case will be printed as a data listing with 100% verification of critical data fields and text fields against the hard-copy CRF. Also, [ ]*% of the patients will be verified for 100% of the data fields prior to the closing of the database. Standard and protocol-specific edit checks will be created and results of the edit checks will be reviewed by the CDA during the review process and prior to database closure for the generation of queries. All verification will be documented. 4. DICTIONARY PROCESSING IBAH will use MedDRA for coding adverse events and WHO-DRUG for coding medications. A Cubist-modified dictionary can be accommodated at an additional fee to cover loading and validation of Cubist's dictionaries, as well as development of a mapping code. MedDRA for presenting conditions and diagnoses can be provided at an additional fee. IBAH will use standard coding conventions for the mapping procedure unless otherwise instructed at the Project start. An additional cost will be incurred for changes to coding conventions after Project start. An automated process will be used to map literal text to the corresponding term in the dictionary. Unmapped terms will be researched, coded, and reviewed by a dedicated team. Dictionary reports will be inclusive of automated and manually coded terms and will be reviewed by IBAH's Medical Monitors prior to database closure. 5. LABORATORY DATA PROCESSING (CENTRAL) TRANSFER AND VERIFICATION OF CENTRAL LABORATORY DATA IBAH will develop the programs needed for conversion and integration of central laboratory data. Central lab data sets will be loaded into the clinical database. Accession numbers from the laboratory hard copy received with the case will be entered into the database. Verification will compare the header data received electronically against the case data including the patient number, lab date, date of birth, gender, patient initials, and lab accession numbers. Discrepancies will be communicated to the central lab and/or Cubist. Full lab panel validation will be performed on [ ]*% of the patients to verify accuracy of the load. IBAH assumes that all laboratory results will be forwarded with the appropriate normal range and flag attached at the record level. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -18- 6. DATA TRANSFER At the conclusion of the study, IBAH will transfer the Project database to Cubist in standard IBAH SAS data sets using IBAH standard naming conventions and format. Customized data transfers, or interim database closes and transfers, can be accommodated on request at an additional fee. 7. SECURITY PROCEDURES All files, including data and programming, will be backed-up daily and a complete tape will be sent to secure storage off-site on a weekly basis for disaster recovery. All personnel maintain their own log-on IDs and all passwords will be changed monthly. Only authorized personnel will have access to databases, which have additional unique access codes. Data access codes will be changed upon database review and closure to allow only authorized personnel access to the database. As part of routine documentation, a controlled procedure will be used to archive two sets of tapes containing all pertinent system files employed in the Project, (i.e., Domain/CLINTRIAL(R) software, data sets, screen modules, SAS programming, and listing files). 8. MACHINE PROCESSING AND STORAGE IBAH's Database Administrator will maintain the integrity of Cubist's clinical database for the duration of the Project estimated at [ ]*. E. BIOMETRICS ANALYSIS AND TABLE GENERATION 1. STATISTICAL ANALYSIS PLAN/DESIGN OF TABLE SHELLS A statistical analysis plan, including operational definition of endpoints to be analyzed, definition of patient subsets (evaluable and intent-to-treat), visit windows, rules for data handling, and a detailed description of statistical methodology, will be prepared for each study. The statistical plan will include a set of formatted shells for all data displays (data listings, summary tables and graphics) planned for the study, which will be prepared with input from the Clinical Writing Department. If formatted data displays are not required, a detailed table of contents of SAS generated data displays will be included. This plan will be submitted to Cubist for review and approval prior to closing the database for analysis. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -19- 2. PROJECT DATA SETUP AND PROGRAMMING OF DATA DISPLAYS Prior to programming actual data displays (data listings, summary tables and graphics), IBAH will develop data display headers and create the status data set and efficacy data set, if needed, which will be used for the data analysis. After approval of the prototype data display formats by Cubist and the IBAH Project Team, IBAH's programming staff will develop the programs required to generate each data display. Programming will be performed using SAS system software, and will incorporate procedure output and customized report writing features. Any changes to data display formats after approval and programming initiation could result in additional charges. 3. QUALITY CONTROL PROCEDURES FOR DATA DISPLAYS IBAH's Biometrics staff will use a combination of independent programming, hand tabulations from supporting listings, and programming verification to ensure the accuracy and completeness of tables, listings, and statistical results. All report data displays will be verified for accuracy and internal consistency among data displays. A quality control binder, including the quality control strategy for each data display and audit trail, will be included in the Project file. 4. PATIENT EVALUABILITY AND OUTCOME ASSESSMENT Patient evaluability, outcome assessment criteria and relevant algorithms will be developed for the Project by IBAH and presented to Cubist for review and approval. These algorithms will be programmed using SAS to identify evaluable patients and outcome assessments. Biostatisticians will verify the accuracy of the output with independent programming and review of individual patient data. Final decisions regarding patient evaluability and outcome assessment will require approval by Cubist; these are performed once for each patient. Data listings for each patient's evaluability status and outcome assessment will be prepared and submitted to Cubist for classification prior to breaking the blind. Data classification meetings may be held either in person or via teleconference. 5. STATISTICAL ANALYSIS Statistical analysis, in accordance with the approved statistical analysis plan, will be performed by IBAH staff biostatisticians. The analysis includes verification of assumptions needed for statistical inference, determination of investigator-by-treatment interaction, and examination of outlying data points. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -20- Statistical findings which may not be appropriate for the body of a clinical report (e.g., tests for interaction, data distribution issues, etc.), deviations from the planned analyses, and additional exploratory analyses will be included in a statistical appendix to the clinical report. Fees include one major revision and one minor revision. The Project statistician will also review the clinical reports to ensure appropriate representation of statistical methodology and inference. 6. DATA LISTING AUDIT A percentage of quality-controlled data listings may, at IBAH's discretion, be chosen for an audit. From this, a percentage of patients will be chosen within each selected listing for audit. The data listing information will be verified against the selected patient(s) cases. The audit will take place once the listings are determined to be final by IBAH's Biometrics Department. IBAH's CQA will oversee these activities to ensure quality as part of this service deliverable. 7. SUMMARY TABLES AUDIT Following the generation of tables and listings by Biometrics, IBAH may, at its discretion, review a proportion of the summary tables, focusing on critical data elements, against the supporting data listings to independently verify the accuracy of the data and consistency of format. IBAH's CQA will oversee these activities to ensure quality as part of this service deliverable. F. CLINICAL WRITING 1. PHASE II / III CLINICAL STUDY REPORTS Integrated clinical and statistical summaries will be prepared in accordance with ICH guidelines. Draft clinical reports will be generated within [ ]* after receipt of final summary tables and patient listings. IBAH will prepare a phase II/III clinical report for each of the following studies: o Complicated SSTI U.S. study o Complicated SSTI International study o RRC Companion U.S. study o RRC Companion International study o Bacteremia study *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -21- The fee for the phase III reports includes up to [ ]* brief patient narratives and [ ]*. One major revision of the draft reports is considered not to take more than [ ]* after receipt of all requests for changes, and a minor revision will consist of changes that can be completed in up to [ ]*. This fee does not include collation and assembly of appendices. IBAH assumes that the methods for the U.S. studies will be completed and reviewed prior to drafting the methods for the International studies. IBAH also assumes that the protocols for the U.S. and International studies are similar and that all reports will be completed according to the same format and presentation. All phase II/ III clinical reports will receive two independent levels of quality control review before they are released. There will be a QC review by IBAH's Clinical Writer for accuracy and consistency, and a review by the writing manager for accuracy, client format consistency, and appropriate regulatory and clinical perspective. Writing fee estimates are based on receipt of final data. If any changes should occur after work on the reports has begun, IBAH assumes that these changes will not impact the production of the report. If database changes occur which require a substantial amount of time [ ]* for rework or repeat quality control, additional fees will be agreed upon with Cubist before proceeding with the reports. 2. CLINICAL AUDIT IBAH may, at its discretion, perform an audit of the clinical study report. The clinical study report audit will examine the consistency between text and figures quoted in the version of the report agreed upon with Cubist, with those appearing in the statistical tables and listings which accompany the report. This audit will include a review of all sections for format consistency and table of contents cross-reference. In addition, text and figures will be verified against the verified tables/listings and any typographical and grammatical errors that are noted. This audit is performed on the final version, following incorporation of Cubist's comments. IBAH's CAQ will oversee these activities to ensure quality as part of this service deliverable. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -22- V. FINANCIAL CONSIDERATIONS A. GLOBAL PROJECT BUDGET SUMMARY [ ]* DETAILED BUDGETS 1. U.S. Clinical Monitoring Budget for Complicated SSTI and Companion RRC Study [ ]* 2. International Clinical Monitoring Budget for Complicated SSTI and Companion RRC Study [ ]* 3. Global Clinical Budget for Complicated SSTI [ ]* 4. Global Clinical Budget for Companion RRC Study [ ]* 5. Clinical Budget for Gram Positive Bacteremia Study [ ]* C. PAYMENT SCHEDULES 1. INVOICING PROCESS FOR SERVICE FEES IBAH maintains a project accounting system, whereby all direct project costs (service or passthrough expenses) are coded by project. An initial payment of [ ]*, representing approximately [ ]* of Project costs, is due and payable upon execution of this Exhibit A. Subsequent payments shall be made monthly, based on Services performed and upon submission of an invoice to Cubist by IBAH. The subsequent invoices shall be reduced by a prorated portion from the initial payment such that the initial payment is applied evenly over the term of the Project. All payments shall be processed within [ ]*. If any payment of service fees or pass through expenses is late by more than [ ]*, such payment shall be subject to a penalty fee of [ ]* per month of the outstanding balance. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -23- 2. PASS THROUGH EXPENSE INVOICING Grant Payments - IBAH will invoice [ ]* in advance of grant payments due investigators based on estimates. IBAH requires payment from Cubist at least [ ]* in advance of the actual payment to investigators. Payments to investigators will not be released until payments are received by IBAH from Cubist. Upon Cubist's request, IBAH agrees to deposit payments from Cubist into a non-interest bearing bank account. IBAH shall draw upon such account to make the investigator payments. Any remaining funds in the account will be returned to Cubist after the termination of the study, as soon as all contracted obligations to the investigators have been satisfied. In the event payments from Cubist are insufficient to cover the payments to investigators, Cubist will promptly advance funds to IBAH for the amount of grant payments required. IBAH's project accounting system is able to capture and categorize in summary the following key pass-through expenses related to a project: o Travel o Delivery fees o CRF and other printing costs o All other project related expenses that are not related to service fees and any additional detail to support pass-through costs will be provided on a fee basis. 3. ANNUAL PRICE INCREASE Notwithstanding anything contained herein to the contrary, the estimated Service Fees set forth in this Exhibit A shall remain in effect through [ ]*. Thereafter, IBAH reserves the right to increase the price of the remaining Services under this Exhibit A; such increases shall not exceed [ ]*. VI. SIGNATORY AUTHORITY The parties acknowledge and agree that Cubist has authorized IBAH to execute all Clinical Study Agreements with investigators in the Project on behalf of Cubist. Cubist understands and acknowledges that it will be bound by the terms of the investigator agreements. ACCEPTANCE The terms and conditions of the Master Agreement govern this Exhibit A and such document is incorporated herein by reference as if fully set forth herein. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -24- BY AND BETWEEN: CUBIST PHARMACEUTICALS, INC. IBAH, INC. BY: /s/ FRANCIS P. TALLY By: /s/ LEONARD F. STIGLIANO ---------------------------------- ---------------------------- Name: Francis P. Tally Name: Leonard F. Stigliano Title: Ex. VP Scientific Affairs Title: President, U.S. CRO Dated: 12/21/99 Dated: 12/20/99 *Confidential treatment requested: Material has been omitted and filed with the Commission.
CONFIDENTIAL TREATMENT EXHIBIT B TO THE CLINICAL SERVICES MASTER AGREEMENT BETWEEN CUBIST PHARMACEUTICALS, INC. AND IBAH, INC., DATED DECEMBER 1, 1999. THIS EXHIBIT B is entered into this 12th day of April, 2000, by and between Cubist Pharmaceuticals, Inc. (hereinafter "Cubist") an IBAH, Inc. (hereinafter "IBAH"). WHEREAS, Cubist and IBAH entered into a Clinical Services Master Agreement, dated December 1, 1999 (hereinafter the "Master Agreement"), wherein IBAH agreed to provide clinical services and; WHEREAS, Cubist and IBAH agree that IBAH shall provide the services set forth in this Exhibit B, subject to the terms and conditions set forth in the Master Agreement; NOW, THEREFORE, for good and valuable consideration, and INTENDING TO BE LEGALLY BOUND, Cubist and IBAH agree as follows: I. PROJECT PLAN Based on the Project Specifications, IBAH has provided a description of services to be performed for Cubist's complicated urinary tract infection (CUTI) Daptomycin Program, Protocol Number DAP00-03 (hereinafter "the Project") and associated costs. Changes made in the Project scope, at any time during the Project, will result in a corresponding adjustment to the Project costs. A. PROJECT STATUS TABLE [ ]* *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -2- II. PROJECT ROLES AND RESPONSIBILITIES ----------------------------------------------------------------------------------------------------------- TASK CUBIST IBAH ----------------------------------------------------------------------------------------------------------- A. STUDY MANAGEMENT ----------------------------------------------------------------------------------------------------------- 1. Facilitate Project Management X o Program Director [ ]* o International Project Manager [ ]* o CTM [ ]* ----------------------------------------------------------------------------------------------------------- 2. Coordinate and conduct team meetings X X ----------------------------------------------------------------------------------------------------------- 3. Standard Operating Procedures (SOPs) X ----------------------------------------------------------------------------------------------------------- 4. Performance tracking X ----------------------------------------------------------------------------------------------------------- 5. Monitor Project payment schedule X X ----------------------------------------------------------------------------------------------------------- 6. Project problem solving X X ----------------------------------------------------------------------------------------------------------- 7. Clerical and administrative support X (US - [ ]*) International - [ ]* ----------------------------------------------------------------------------------------------------------- B. CLINICAL TRIAL INITIATION ----------------------------------------------------------------------------------------------------------- 1. Drug development and study design X ----------------------------------------------------------------------------------------------------------- 2. Protocol Development X ----------------------------------------------------------------------------------------------------------- 3. Patient plan X o CUTI-[ ]* patients enrolled in U.S./[ ]* patients enrolled in International [ ]* patients total ----------------------------------------------------------------------------------------------------------- 4. Site plan X o Up to [ ]* Sites U.S. o [ ]* sites Internationally - Australia, Belgium, Czech Republic, German Greece Hungary, Poland Russia ----------------------------------------------------------------------------------------------------------- 5. CRF design X o CUTI -[ ]* estimated pages ----------------------------------------------------------------------------------------------------------- 6. CRF logistics (print, bind, and distribute) X o Material, printing and assembly expenses will be passed through at cost ----------------------------------------------------------------------------------------------------------- 7. Investigator identification, recruitment and qualification X ----------------------------------------------------------------------------------------------------------- 8. Investigator regulatory document management X o Protocol Amendments and IRB submissions billed per site o Informed Consent Forms development ----------------------------------------------------------------------------------------------------------- 9. Certification of Investigator Financial Disclosure X ----------------------------------------------------------------------------------------------------------- 10. Investigator agreement negotiation X ----------------------------------------------------------------------------------------------------------- 11. Coordination of investigators meeting X o One meeting US; Two meetings International ----------------------------------------------------------------------------------------------------------- 12. Project team training X X ----------------------------------------------------------------------------------------------------------- *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -3- ----------------------------------------------------------------------------------------------------------- TASK CUBIST IBAH ----------------------------------------------------------------------------------------------------------- C. CLINICAL TRIAL MANAGEMENT ----------------------------------------------------------------------------------------------------------- 1. Clinical monitoring X o IBAH estimates [ ]* U.S. qualification visits and [ ]* International one-day qualification visits ([ ]* visits total) o IBAH estimates performance of [ ]* U.S. and [ ]* International initiation visits [ ]* visits total o BAH estimates performance of [ ]* U.S. and [ ]* International interim visits ([ ]* visits total) o IBAH estimates [ ]* U.S. and [ ]* International close-out visits [ ]* visits total ----------------------------------------------------------------------------------------------------------- 2. Clinical grant payment administration (Assumes 4 payments per site) X ----------------------------------------------------------------------------------------------------------- 3. CRF tracking, filing and archiving X o [ ]* -US [ ]* - International CRF pages [ ]* pages total) ----------------------------------------------------------------------------------------------------------- 4. Medical monitoring X o [ ]* in US o [ ]* in International ----------------------------------------------------------------------------------------------------------- 5. Safety review of CRFs X o Based on [ ]* cases reviewed ----------------------------------------------------------------------------------------------------------- 6. SAE Reporting with Patient Summaries X o CUTI U.S. [ ]*/International [ ]* [ ]* total) ----------------------------------------------------------------------------------------------------------- D. CLINICAL DATA MANAGEMENT ----------------------------------------------------------------------------------------------------------- 1. Project database creation and data entry X Fee based on: o CUT1- [8,250] CRF from US & [ ]* CRF pages from International ([ ]* total) ----------------------------------------------------------------------------------------------------------- 2. Case report form review and query resolution X Fee based on: o CUTI- [ ]* CRF from US & [ ]* CRF pages from International ([ ]* total) ----------------------------------------------------------------------------------------------------------- 3. Dictionary processing of CRFs X o [ ]* CRFs ----------------------------------------------------------------------------------------------------------- 4. Laboratory data processing (central) X X o Covance ----------------------------------------------------------------------------------------------------------- 5. Reconciliation of Safety/Clinical Databases X ----------------------------------------------------------------------------------------------------------- 6. Data transfer (standard) X ----------------------------------------------------------------------------------------------------------- 7. Data security procedures X ----------------------------------------------------------------------------------------------------------- E. BIOMETRIC ANALYSIS ----------------------------------------------------------------------------------------------------------- 1. o Statistical analysis X o plan-includes one major one minor revision ----------------------------------------------------------------------------------------------------------- 2. Randomization X ----------------------------------------------------------------------------------------------------------- 3. Project data setup and programming of displays X o CUTI [ ]* primary tables and listings and [ ]* secondary tables and listing ----------------------------------------------------------------------------------------------------------- 4. Quality control procedures for displays X ----------------------------------------------------------------------------------------------------------- 5. Patient evaluability and outcome assessment X ----------------------------------------------------------------------------------------------------------- 6. Interim transfer of listings X ----------------------------------------------------------------------------------------------------------- *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -4- ----------------------------------------------------------------------------------------------------------- TASK CUBIST IBAH ----------------------------------------------------------------------------------------------------------- 7. Final statistical analysis X ----------------------------------------------------------------------------------------------------------- 8. Statistical support for table preparation X ----------------------------------------------------------------------------------------------------------- 9. Data loading and review X ----------------------------------------------------------------------------------------------------------- 10. Statistical report ----------------------------------------------------------------------------------------------------------- F. CLINICAL WRITING ----------------------------------------------------------------------------------------------------------- 1. Phase III clinical study report-CUTI o [ ]* revision and up to [ ]* brief patient narratives o Fee does not include collation or compilation of appendices ----------------------------------------------------------------------------------------------------------- III. PROJECT TIMELINE The parties acknowledge that IBAH commenced performance of the Service on or about December 20, 1999. The projected timeline for this Project is as follows: [ ]* (Rest of page intentionally left blank) *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -5- IV. IBAH SERVICES A. STUDY MANAGEMENT 1. PROGRAM DIRECTOR/INTERNATIONAL PROJECT MANAGER IBAH's Program Director will coordinate the services being provided by all of the disciplines within IBAH and will act as a single point of contact for Cubist until completion of the Project. The International Project Manager, working in conjunction with the Program Director, will manage the international segment of the Project. Key responsibilities of these individuals will include the following: o Prepare detailed Project timelines and ensuring that the major milestones are met o Provide Project status updates o Identify and resolve critical Project issues o Ensure adequate resource allocation across all functions o Oversee Project team meetings o Manage Project financial issues 2. COUNTRY TRIAL MANAGERS/CLINICAL TRIAL MANAGERS IBAH's Country Trial Managers will be dedicated to managing the day-to-day clinical trial activity. They will oversee all site and CRA activities within this Project. Primary responsibilities of these individuals will include the following: o Develop case report forms and monitoring guidelines o Oversee regulatory document management from each of the investigational sites o Review and track CRA activities including scheduling of site visits, site visit reports, monitoring logs, follow-up correspondence, hours worked, routine expense records, and any other pertinent study-related documents o Maintain routine contact with all CRAB to ensure the consistency of program communication and work performed o Provide ongoing quality control of the CRAs performance throughout the Project Provide Program Director and International Project Manager with periodic status reports including progress of site initiations, status of ongoing site visits, patient enrollment updates, site visit reports, data query rates, and other study-related reports *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -6- 3. ASSOCIATED MANAGEMENT SUPPORT IBAH will dedicate clerical/administrative support to the Project. The clerical/administrative fee will cover costs associated with IBAH's services, as well as management and administration associated with this Project. All travel expenses, Federal Express and/or overnight courier services, and telephone costs will be passed through at cost to Cubist. B. CLINICAL TRIAL INITIATION 1. PROJECT TEAM TRAINING IBAH will rely on internal and external experts to provide specific therapeutic area training and orientation to the protocol and the CRF prior to study initiation and on an ongoing basis. This training will be designed to ensure that all team members are familiar with the Project requirements and their role within the team. Items discussed at these meetings will include, but will not be limited to: o Therapeutic area and clinical development background o Protocol and CRF o Discussion of therapeutic implications for this study Monitoring guidelines 2. CRF DESIGN AND PRINTING IBAH will work in conjunction with Cubist to design a case report form (CRF) for recording pertinent Study data. Data Management, Biometrics, and the CTM will review the CRF and provide input to ensure all relevant data is captured. A review meeting with Cubist will be held to resolve any design questions or other concerns which may arise. IBAH will provide Cubist with bids from independent printing vendors. CRFs will be sent for printing on 3-part NCR after all issues are resolved and final approval from IBAH and Cubist is received. Estimated fees for CRF materials and printing are based on a per case basis. CRFs will be collated into binders with spines and covers, and a protective NCR foldover will be provided with each CRF binder. Actual materials, printing, assembly, and distribution fees will be passed through to Cubist. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -7- 3. IBAH S.T.A.R.T In order to facilitate rapid study site initiations, IBAH has established IBAH S.T.A.R.T (Study Trial Acceleration Resource Teams) in North America. The study start-up functional areas that are included in this group are Investigator Recruitment, Investigator Document Management, Investigator Agreement Negotiation, and Investigator Meeting Coordination. A Coordinator will head each S.T.A.R.T. team and will work with the Managers to devise and implement a working strategy to promote an expeditious action plan. The goal is to provide sites with a streamlined communication channel for all S.T.A.R.T activities. The International Project Manager and the Country Trial Managers will perform these study start-up activities for the international portion of this Project. 4. INVESTIGATOR IDENTIFICATION, RECRUITMENT AND QUALIFICATION IBAH will collaborate with Cubist to recruit [ ]* U.S. and [ ]* International investigators capable of conducting the Cubist CUTI study. A preliminary telephone interview will be conducted to evaluate a prospective site's interest and potential to meet both patient enrollment and data quality goals for this Project. After obtaining a signed confidentiality agreement from the prospective investigative sites, IBAH will issue a survey form, customized to the protocol. Additional Project information will be distributed to appropriate investigators who are willing to commit to study participation. The outcome of all evaluations, with a final list of proposed investigators, will be forwarded to Cubist for approval prior to final recruitment. If it is necessary to assess the site's ability to achieve study enrollment and data quality goals then a comprehensive pre-study evaluation visit will be scheduled with the selected investigator. Once identified as a qualified study site, an investigator regulatory document package will be sent. 5. INVESTIGATOR REGULATORY DOCUMENT MANAGEMENT In coordination with Cubist, IBAH will develop a template of an informed consent form for the Project, ensuring compliance with all local, state, and federal and international regulatory requirements. Regulatory document packages, with letters of instruction, will be mailed to qualified investigative sites. A dedicated tracking process for regulatory document collection will be utilized. Document collection will cover all criteria required under the principles of Good Clinical Practices (GCP) and International Committee for Harmonization (ICH) guidelines, as well as IBAH Standard Operating Procedures (SOPs). In addition, IBAH S.T.A.R.T., will also collect certification / disclosure information from all investigators and provide this information to Cubist on an ongoing basis. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -8- IBAH will track the retrieval of documents on an ongoing basis and provide updates to Cubist as requested. IBAH will prepare copies of all appropriate documents, assemble documents and issue an investigator regulatory binder to all sites, including but not limited to: o Investigator's Brochure o Final Protocol and Sample Copy of the CRF o Institutional Review Board (IRB) Approvals of Protocol and Informed Consent Form(s) o Laboratory Certification and Normal Ranges o Completed FDA Form 1572 o Investigator Curriculum Vitae o Financial Disclosure Certification and/or completed Financial Disclosure Form The binders will be maintained at the sites and reviewed for appropriate updates by CRAs responsible for site management over the course of the study. Certification of Investigator Financial Disclosure will be collected and maintained as agreed upon by IBAH and Cubist. The fee for regulatory document collection, processing, and tracking is based upon the number of sites required for the study. File maintenance and updating will be billed at the rate of [ ]* per site per year after year one. Protocol amendments, which require informed consent revisions and/or IRB re-submission, will be billed at an additional processing fee of [ ]* for each site. 6. INVESTIGATOR REGULATORY DOCUMENT COLLECTION (INTERNATIONAL) STUDY MASTER FILES In accordance with GCP, IBAH's International staff will: o Develop Study Master File according to IBAH SOPS under supervision of the Study Manager o Obtain all relevant critical documents for the Project; design an appropriate Critical Document Receipt List as a supporting instrument for the CRAB; review all incoming investigators' documents; approve/reject these documents according to GCP and internal guidelines o Maintain file, i.e. proper filing of all incoming papers (investigator documents, site visit reports); file audits to assure the completeness of the documents and to identify missing documents o Ship investigator documents to Cubist as required o Arrange for archiving of the Study Master File at the end of the Project *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -9- PRE-STUDY APPROVALS IBAH's Regulatory staff will prepare the necessary pre-study filings with local regulatory authorities for permission to proceed with the clinical trial, as well as follow-up with these local authorities to expedite the review and approval process. IBAH's Regulatory staff will prepare the dossier (document compilation and submission) and necessary study updates. Fees are based on IBAH's staff time to prepare the dossier(s) and interact with the regulatory agencies and IRBs. IBAH will also be responsible for translation of documents into the different local languages. In addition, any direct charges (dossier filing fees, travel to meetings at agencies, etc.) will be passed through to Cubist at cost. 7. INVESTIGATOR AGREEMENT NEGOTIATION IBAH will be responsible for the following activities related to negotiating the clinical site contracts: o Create an investigator agreement and patient budget o Negotiate investigator agreements that satisfy Cubist requirements o Handle investigator agreements, approval by Cubist and signature by investigators o Incorporate changes and securing re-approval by Cubist o Communicate with IBAH Grants Administration Department when necessary o Handle investigator agreement amendments and/or addenda o Collect excess grants from sites at study end Protocol and study amendments, which require investigator agreement revisions, amendments and/or re-negotiation, will be billed at an additional processing fee of [ ]* for each site. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -10- 8. COORDINATOR'S AND INVESTIGATOR'S MEETING COORDINATION AND ATTENDANCE A Meeting Coordinator will be assigned by IBAH to manage all logistics of the U.S. and International meetings and will schedule necessary travel and hotel arrangements. Specific responsibilities will include the following: o Identify appropriate location(s) for the meetings o Define meeting requirements and outline a meeting agenda o Negotiate, organize, and make all hotel arrangements o Secure discounted travel arrangements and issue tickets to investigators and study coordinators o Prepare necessary meeting materials (e.g., annotated CRFs, presentation materials, etc.) o Coordinate presentations o Manage administrative aspects associated with the meeting IBAH's Project Management and Clinical Trial Management staff will be available to conduct or participate in the meetings and will arrive at the location prior to each meeting to assist attendees with any last minute details that may arise. C. CLINICAL TRIAL MANAGEMENT . 1. CLINICAL MONITORING IBAH will assign a global team of experienced CRAs to perform pre-study qualification, initiation, interim and closeout site visits. Deployment of CRAB, in terms of number and frequency of visits, will be managed based on Cubist input, geographic location and site-specific enrollment data. IBAH's site management and monitoring procedures will be performed in accordance with GCP to ensure each investigative site's compliance with regulations and protocol requirements and to enhance expeditious enrollment of appropriate patients into the clinical study. Regulatory documents will be reviewed by the CRA on an ongoing basis during the study conduct phase, including verification of signed informed consent forms and investigator IRB notifications. Once all regulatory documents and approvals are received, a site initiation visit will be scheduled. During this visit, the CRA will review the study goals, protocol (with particular attention to inclusion/exclusion criteria, enrollment plan/goal, adverse events, primary efficacy variables and GCP compliance), CRF completion, and clinical supply dispensation/accountability will be performed with the investigator and his/her staff. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -11- The Clinical Monitoring Plan will provide Project specific guidance for source data verification requirements at the project level. This document will be prepared by the Clinical Trial Manager will be signed off by Cubist. Drug accountability visits will be performed, as well as reconciliation and removal of clinical supplies at study closeout per Cubist's requirements. In general, the CRAs' efforts will be focused on source document verification and expedient data retrieval. 2. CLINICAL GRANTS ADMINISTRATION As a follow-up to the Investigator Agreement negotiation process, an extension of the IBAH contracts group will administer the clinical grant payments to the site. Included in their responsibilities are the following: o Process financial records for all of the patients in the study o Issue initial and interim payments for each investigator o Reconcile all payments to each of the investigators prior to the final payments o Track account administration with IBAH's finance group o Maintain W9 forms and all relevant and related government reports (U.S. only) Investigator grants, within parameters defined by Cubist, will be passed through at cost to Cubist. A grant administration fee will be applied, based on the number of sites and payments to be managed throughout the duration of the study. 3. CRF TRACKING, FILING AND ARCHIVING Completed CRFs received from investigative sites, ancillary CRF pages, adverse event documentation, and patient-specific correspondence for each study will be logged in and tracked at IBAH. Of these items, CRFs and answered data queries will be entered page-by-page into a computerized tracking system. Fees reflect logging, copying, filing; and ongoing CRF tracking time. A final, complete page listing and original CRFs will be provided to Cubist upon Project completion. Cubist will be billed for the actual number of pages logged/tracked. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -12- 4. MEDICAL MONITORING (DURING BUSINESS HOURS) IBAH's U.S. and International Medical Monitor will oversee the medical aspects of Cubist's clinical program. In addition to acting as medical advisors to the Project Team, the Medical Monitors will be responsible for the following: o Project planning o Review of clinical documentation (protocol, CRF, sample informed consent form) o Project-specific medical training o Evaluate patient eligibility (in conjunction with the Medical Director of Cubist) o Participate in team meetings o Review study reports, regulatory submissions and study manuscripts 5. SAFETY REVIEW OF CRFS Prior to data entry, a U.S. and International Safety Officer will review all pages of each case, ancillary laboratory pages and all data clarification requests. Cubist will be notified immediately of serious adverse events (SAES) that have not been previously reported by the sites. Notification will occur by telephone, as well as by forwarding to Cubist an SAE form. The SAE form will include details of the SAE obtained from the investigative site and will be sent via facsimile to the designated recipient at Cubist. As follow-up information is obtained by IBAH, the SAE form will be updated and forwarded to Cubist. 6. SAE REPORTING WITH INITIAL DESCRIPTIVE SUMMARIES Within one IBAH business day of receipt, IBAH will forward to Cubist all SAE information received from site personnel or IBAH CRAB. Notification to Cubist will occur via telephone, as well as by forwarding a comprehensive SAE form via facsimile. Cubist will be responsible for reporting SAEs to the FDA. IBAH's International staff will report SAEs to non-U.S. agencies. The fee for SAE reporting includes costs for IBAH to provide all follow-up information and to update SAE forms as necessary. At the time of receipt of the CRF in house SAE reports will be reconciled with the CRF. Cubist will be billed for the actual number of SAE reports. IBAH will provide initial descriptive patient summaries for all identified serious adverse events. The descriptive narratives will be written from information provided by the investigator on the SAE report forwarded to IBAH at the time of the event. If significant follow-up information becomes available, the narrative will be updated accordingly. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -13- 7. SAFETY PHONE COVER (INTERNATIONAL) During business hours, IBAH has a direct number to IBAH's Safety Surveillance Department for receipt of SAE information. During evening hours, weekends and holidays, a designated member of the Safety Surveillance Department are on call via beeper. All return calls to the sites will be made immediately to obtain the necessary SAE information and to determine the necessity of an SAE report. D. CLINICAL DATA MANAGEMENT 1. DATA MANAGEMENT PLAN IBAH's Clinical Data Manager will develop a Global Data Management Plan. This plan will include the entry and review guidelines, automated edits checks of the data, dictionary coding procedures, and central laboratory loading procedures. Any other data management tasks requested for this Project will also be outlined in this plan. 2. PROJECT DATABASE CREATION Data screens will be developed by IBAH's programming group on an Open VMS System (Alpha 4100) using Domain/CLINTRIAL(R) software. IBAH's Programmers will develop data-entry screens (i.e., CRF data module designs) that mimic the flow of the CRF, thereby improving the ease and integrity of the data-entry process. 3. DATA ENTRY, CASE REPORT FORM REVIEW AND QUERY RESOLUTION IBAH's data-entry specialists will enter all CRF data utilizing a double-entry method. On-line edit checks will be included to provide additional controls against categorically incorrect data. The dual data-entry strategy will utilize numeric and/or text fields that are entered by one member of the data-entry staff and re-entered on-line by a second member of the staff. Cubist will be billed for the actual number of pages entered. IBAH will generate protocol-specific guidelines that are reviewed and approved by Cubist. Using these guidelines, IBAH will conduct a detailed quality control (QC) review of the entire CRF through a combination of manual review and electronic edit checks that will identify conflicting, unclear or incomplete data. IBAH's Clinical Data Analysts (CDAs) will perform this review. IBAH's CQA will oversee these activities and may, in its discretion, perform audits to ensure quality as part of this data service deliverable. If data are unclear, conflicting or incomplete, then queries will be generated and transmitted to the investigative site and IBAH"s Client Services Department. All queries (issued and resolved) will be logged into the IBAH tracking system. IBAH's query database will be maintained throughout the Project and can provide Cubist with an up-to-date report on the status of queries on an as-needed basis. Cubist will be billed for the actual number of pages reviewed. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -14- In addition, each case will be printed as a data listing with 100% verification of critical data fields and text fields against the hard-copy CRF. Also, [ ]*% of the patients will be verified for 100% of the data fields prior to the closing of the database. Standard and protocol-specific edit checks will be created and results of the edit checks will be reviewed by the CDA during the review process and prior to database closure for the generation of queries. All verification will be documented. 4. DICTIONARY PROCESSING IBAH will use MedDRA for coding adverse events and WHO-DRUG for coding medications. A Cubist-modified dictionary can be accommodated at an additional fee to cover loading and validation of Cubist's dictionaries, as well as development of a mapping code. Upon the mutual agreement of the parties, ICD-9 for presenting conditions and diagnoses will be provided at an additional fee. IBAH will use standard coding conventions for the mapping procedure unless otherwise instructed at the Project start. An additional cost will be incurred by Cubist for changes to coding conventions after Project start. An automated process will be used to map literal text to the corresponding term in the dictionary. Unmapped terms will be researched, coded, and reviewed by a dedicated team. Dictionary reports will be inclusive of automated and manually coded terms and will be reviewed by IBAH's Medical Monitors prior to database closure. 5. LABORATORY DATA PROCESSING (CENTRAL) TRANSFER AND VERIFICATION OF CENTRAL LABORATORY DATA IBAH will develop the programs needed for conversion and integration of central laboratory data. Central lab data sets will be loaded into the clinical database. Accession numbers from the laboratory hard copy received with the case will be entered into the database. Verification will compare the header data received electronically against the case data including the patient number, lab date, date of birth, gender, patient initials, and lab accession numbers. Discrepancies will be communicated to the central lab and/or Cubist. Full lab panel validation will be performed on [ ]*% of the patients to verify accuracy of the load. IBAH assumes that all laboratory results will be forwarded with the appropriate normal range and flag attached at the record level. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -15- 6. RECONCILIATION OF THE SAFETY AND CLINICAL DATABASES IBAH will maintain a safety database for Cubist. The safety database will be reconciled with IBAH's clinical database for the Project prior to database closure. Discrepancies will be queried to the safety surveillance department and to the investigator sites as needed. 7. SECURITY PROCEDURES All files, including data and programming, will be backed-up daily and a complete tape will be sent to secure storage off-site on a weekly basis for disaster recovery. All personnel maintain their own log-on IDs and all passwords are changed monthly. Only authorized personnel have access to databases, which have additional unique access codes. Data access codes are changed upon database review and closure to allow only authorized personnel access to the database. As part of routine documentation, a controlled procedure will be used to archive two sets of tapes containing all pertinent system files employed in the Project; (i.e., Domain/CLINTRIAL(R) software, data sets, screen modules, SAS programming, and listing files). 8. MACHINE PROCESSING AND STORAGE IBAH's Database Administrator will maintain the integrity of Cubist's clinical database for the duration of the Project estimated at [ ]* months. E. BIOMETRICS ANALYSIS AND TABLE GENERATION 1. STATISTICAL ANALYSIS PLAN/DESIGN OF TABLE SHELLS A statistical analysis plan, including operational definition of endpoints to be analyzed, definition of patient subsets (evaluable and intent-to-treat), visit windows, rules for data handling, and a detailed description of statistical methodology, will be prepared for the study. The statistical plan will include a set of formatted shells for all data displays (data listings, summary tables and graphics) planned for the study, which will be prepared with input from the Clinical Writing Department. If formatted data displays are not required, a detailed table of contents of SAS generated data displays will be included. This (analysis) plan will be submitted to Cubist for review and approval sixty days prior to closing the database for analysis. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -16- 2. RANDOMIZATION IBAH's Project statistician will generate a randomization schedule according to the study design specified in the protocol. Electronic copies of the randomization will be created for loading into the clinical database at the time of database closure. Electronic and paper copies of the randomization are stored in a secured location in accordance with IBAH SOPs. Fees include verification and review by a senior biostatistician. A randomization list will be distributed to the sites. 3. PROJECT DATA SETUP AND PROGRAMMING OF DATA DISPLAYS Prior to programming actual data displays (data listings, summary tables and graphics), IBAH will develop data display headers and create the status data set and efficacy data set, if needed, which will be used for the data analysis. After approval of the prototype data display formats by Cubist and the IBAH Project Team, IBAH's programming staff will develop the programs required to generate each data display. Programming will be performed using SAS system software, and will incorporate procedure output and customized report writing features. Any changes to data display formats after approval and programming initiation could result in additional charges. 4. QUALITY CONTROL PROCEDURES FOR DATA DISPLAYS IBAH's Biometrics staff will use a combination of independent programming, hand tabulations from supporting listings, and programming verification to ensure the accuracy and completeness of tables, listings, and statistical results. All report data displays will be verified for accuracy and internal consistency among data displays. A quality control binder, including the quality control strategy for each data display and audit trail, will be included in the Project file. 5. PATIENT EVALUABILITY AND OUTCOME ASSESSMENT Patient evaluability, outcome assessment criteria and relevant algorithms will be developed for the Project by IBAH and presented to Cubist for review and approval. These algorithms will be programmed using SAS to identify evaluable patients and outcome assessments. IBAH's Biostatisticians will verify the accuracy of the output with independent programming and review of individual patient data. Final decisions regarding patient evaluability and outcome assessment will require approval by Cubist; these are performed once for each patient. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -17- Data listings for each patient's evaluability status and outcome assessment will be prepared and submitted to Cubist for classification prior to breaking the blind. Data classification meetings may be held either in person or via teleconference. 6. STATISTICAL ANALYSIS Statistical analysis, in accordance with the approved statistical analysis plan, will be performed by IBAH staff biostatisticians. The analysis includes verification of assumptions needed for statistical inference, determination of investigator-by-treatment interaction, and examination of outlying data points. Statistical findings which may not be appropriate for the body of a clinical report (e.g., tests for interaction, data distribution issues, etc.), deviations from the planned analyses, and additional exploratory analyses will be included in a statistical appendix to the clinical report. Fees include one major revision and one minor revision. The Project statistician will also review the clinical reports to ensure appropriate representation of statistical methodology and inference. 7. DATA LISTING AUDIT A percentage of quality-controlled data listings may, at IBAH's discretion, be chosen for an audit. From this, a percentage of patients will be chosen within each selected listing for audit. The data listing information will be verified against the selected patient(s) cases. The audit will take place once the listings are determined to be final by IBAH's Biometrics Department. IBAH's CQA will oversee these activities to ensure quality as part of this service deliverable. 8. SUMMARY TABLES AUDIT Following the generation of tables and listings by IBAH's Biometrics staff, IBAH may, at its discretion, review a proportion of the summary tables, focusing on critical data elements, against the supporting data listings to independently verify the accuracy of the data and consistency of format. IBAH's CQA will oversee these activities to ensure quality as part of this service deliverable. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -18- 9. DATA TRANSFER At the conclusion of the study, IBAH will transfer the Project database to Cubist in standard IBAH SAS data sets using IBAH standard naming conventions and format. All variables within these data sets as well as variables in analytical or summary data sets will be clearly labeled, so that SAS CONTENTS will carry clear labels enabling variables to be traced back to CRFs. IBAH will include any and all FORMAT LIBRARIES, SAS MACROS, or MACRO CATALOGS (if applicable) which were used in the analyses. All SAS programs, which generate data displays, listings, tables, graphics, and statistical analyses, will be included in the transfer. Upon the mutual agreement of the parties, customized data transfers, or interim database closes and transfers, will be accommodated on request at an additional fee. 10. ITEM 11 PREPARATION FOR FDA A MAP detailing the origin of each table or data display expressed in terms of both data sets and programs will be included in the transfer, so that each table or display can be traced to the SAS program and SAS data sets from which it was produced. A written definition for computed variables, which may appear in IBAH-created analytical files, or summary files will be included in the transfer. An annotated CRF, which maps to the SAS data sets on a variable by variable level, will be included in the transfer. F. CLINICAL WRITING 1. PHASE III CLINICAL STUDY REPORTS Integrated clinical and statistical summaries will be prepared in accordance with ICH guidelines. Draft clinical reports will be generated within [ ]* after receipt of final summary tables and patient listings. The fee for this report includes up to [ ]* brief patient narratives and one major and one minor revision. [ ]* of the draft report is considered not to take more than [ ]* days after receipt of all requests for changes, and a minor revision will consist of changes that can be completed in [ ]*. This fee does not include collation and assembly of appendices. Writing fee estimates are based on receipt of final data. If any changes should occur after work on the reports has begun, IBAH assumes that these changes will not impact the production of the report. If database changes occur which require a substantial amount of time [ ]* for rework or repeat quality control, additional fees will be agreed upon with Cubist before proceeding with the reports. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -19- 2. CLINICAL AUDIT IBAH may, at its discretion, perform an audit of the clinical study report. The clinical study report audit will examine the consistency between text and figures quoted in the version of the report agreed upon with Cubist, with those appearing in the statistical tables and listings which accompany the report. This audit will include a review of all sections for format consistency and table of contents cross-reference. In addition, text and figures will be verified against the verified tables/listings and any typographical and grammatical errors that are noted. This audit is performed on the final version, following incorporation of Cubist's comments. IBAH's CQA will oversee these activities to ensure quality as part of this service deliverable. (Rest of page intentionally left blank) *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -20- V. FINANCIAL CONSIDERATIONS A. UNITED STATES BUDGET [ ]* B. INTERNATIONAL BUDGET [ ]* C. PAYMENT SCHEDULES 1. INVOICING PROCESS FOR SERVICE FEES IBAH maintains a project accounting system, whereby all direct project costs (service or passthrough expenses) are coded by project. An initial payment of [ ]* representing approximately [ ]* of Project costs, is due and payable upon execution of this Exhibit B. Subsequent payments shall be made monthly, based on Project progress and upon submission of an invoice to Cubist by IBAH. The subsequent invoices shall be reduced by a prorated portion from the initial payment such that the initial payment is applied evenly over the term of the Project. All payments shall be processed within [ ]*. If any payment of service fees or pass through expenses is late by more than [ ]*, such payment shall be subject to a penalty fee of [ ]* per month of the outstanding balance. 2. PASS THROUGH EXPENSE INVOICING Grant Payments - IBAH will invoice [ ]* days in advance of grant payments due investigators based on estimates. IBAH requires payment from Cubist at least [ ]* days in advance of the actual payment to investigators. Payments to investigators will not be released until payments are received by IBAH from Cubist. Upon Cubist's request, IBAH agrees to deposit payments from Cubist into a non-interest bearing bank account. IBAH shall draw upon such account to make the investigator payments. Any remaining funds in the account will be returned to Cubist after the termination of the study, as soon as all contracted obligations to the investigators have been satisfied. In the event payments from Cubist are insufficient to cover the payments to investigators, Cubist will promptly advance funds to IBAH for the amount of grant payments required. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -21- IBAH's project accounting system is able to capture and categorize in summary the following key pass-through expenses related to a project: o Travel o Delivery fees o CRF and other printing costs o All other project related expenses that are not related to service fees and any additional detail to support pass-through costs will be provided on a fee basis. 3. ANNUAL PRICE INCREASE Notwithstanding anything contained herein to the contrary, the estimated Service Fees set forth in this Exhibit B shall remain in effect for the longer of (a) [ ]* from the date hereof, or (b) [ ]* following the date hereof. Thereafter, IBAH reserves the right to increase the price of the remaining Services under this Exhibit B as of each January l; such increases shall not exceed [ ]*. VI. SIGNATORY AUTHORITY The parties acknowledge and agree that Cubist has authorized IBAH to execute all Clinical Study Agreements with investigators in the Project on behalf of Cubist. Cubist understands and acknowledges that it will be bound by the terms of the investigator agreements. ACCEPTANCE The terms and conditions of the Master Agreement govern this Exhibit B and such document is incorporated herein by reference as if fully set forth herein. BY AND BETWEEN: CUBIST PHARMACEUTICALS, INC. IBAH, INC. By: /S/ MICHAEL DEBRUIN By: /S/ LEONARD F. STIGLIANO ------------------- ------------------------ Name: Michael DeBruin Name: Leonard F. Stigliano Title: Vice President-Clinical Research Title: President, U.S. CRO Dated: April 2, 2000 Dated: April 12, 2000 *Confidential treatment requested: Material has been omitted and filed with the Commission.
CONFIDENTIAL TREATMENT EXHIBIT C TO THE CLINICAL SERVICES MASTER AGREEMENT BETWEEN CUBIST PHARMACEUTICALS, INC. AND IBAH, INC., DATED DECEMBER 1, 1999. This Exhibit C is entered into this 18th day of April, 2000, by and between Cubist Pharmaceuticals, Inc. (hereinafter "Cubist" and IBAH, Inc. (hereinafter "IBAH"). WHEREAS, Cubist and IBAH entered into a Clinical Services Master Agreement, dated December 1, 1999 (hereinafter the "Master Agreement"), wherein IBAH agreed to provide clinical services and; WHEREAS, Cubist and IBAH agree that IBAH shall provide the services set forth in this Exhibit C, subject to the terms and conditions set forth in the Master Agreement; NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Cubist and IBAH agree as follows: I. PROJECT PLAN Based on the Project Specifications, IBAH has provided a description of services to be performed for Cubist's Evaluation of Daptomycin in subjects with Renal Insufficiency Program, Protocol Number DAP-00-01 (hereinafter the "Project") and associated costs. Changes made in the Project scope, at any time during the Project, will result in a.. corresponding adjustment to the Project costs. II. PROJECT RESPONSIBILITIES -------------------------------------------------------------------------------------------------------------- ACTIVITY CUBIST IBAH -------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------- A. STUDY INITIATION -------------------------------------------------------------------------------------------------------------- Protocol Development X -------------------------------------------------------------------------------------------------------------- Protocol Review X -------------------------------------------------------------------------------------------------------------- CRF Design X X -------------------------------------------------------------------------------------------------------------- Printing, Assembly, and Distribution of CRFs X -------------------------------------------------------------------------------------------------------------- Preparation of Randomization Codes X -------------------------------------------------------------------------------------------------------------- Identification and Qualification of Sites (assumes 1 site) X -------------------------------------------------------------------------------------------------------------- Investigator Document Retrieval X -------------------------------------------------------------------------------------------------------------- Negotiation of Phase I Unit Grant X -------------------------------------------------------------------------------------------------------------- Training Site Personnel X X -------------------------------------------------------------------------------------------------------------- Training Project Team X X -------------------------------------------------------------------------------------------------------------- Analytical Laboratory Identification and Coordination X -------------------------------------------------------------------------------------------------------------- *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -2- -------------------------------------------------------------------------------------------------------------- ACTIVITY CUBIST IBAH -------------------------------------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------- B. STUDY CONDUCT -------------------------------------------------------------------------------------------------------------- Project Management X X -------------------------------------------------------------------------------------------------------------- Conduction of Qualification, Initiation, Interim, and Closeout Visits X X -------------------------------------------------------------------------------------------------------------- Verification of CRFs at Phase I Unit X -------------------------------------------------------------------------------------------------------------- Document Corrections to CRFs X -------------------------------------------------------------------------------------------------------------- Site Visit Report Preparation X -------------------------------------------------------------------------------------------------------------- Collection and Tracking CRFs X -------------------------------------------------------------------------------------------------------------- Administration of Grant Payment(s) X -------------------------------------------------------------------------------------------------------------- Reporting SAES to Regulatory Agency X -------------------------------------------------------------------------------------------------------------- Reporting SAES to Cubist X -------------------------------------------------------------------------------------------------------------- Assuring Disposal of Unused Supplies X -------------------------------------------------------------------------------------------------------------- C. CLINICAL DATA MANAGEMENT, BIOMETRICS, AND CLINICAL WRITING -------------------------------------------------------------------------------------------------------------- Custom Database Design X -------------------------------------------------------------------------------------------------------------- CRFs Entry Into Database X -------------------------------------------------------------------------------------------------------------- Generation and Resolution of Data Queries X -------------------------------------------------------------------------------------------------------------- Coding of Data Using IBAH Dictionaries X -------------------------------------------------------------------------------------------------------------- Verification/QC Database X -------------------------------------------------------------------------------------------------------------- Loading & Verification of Laboratory Data X -------------------------------------------------------------------------------------------------------------- Database Closure X -------------------------------------------------------------------------------------------------------------- Statistical Plan and Tables Design X -------------------------------------------------------------------------------------------------------------- Sample Size Calculation X -------------------------------------------------------------------------------------------------------------- Generation of Tables/Listings X -------------------------------------------------------------------------------------------------------------- Statistical Analysis X X -------------------------------------------------------------------------------------------------------------- Database Transfer X -------------------------------------------------------------------------------------------------------------- Integrated Clinical Report X -------------------------------------------------------------------------------------------------------------- III. CLINICAL PROGRAM DESIGN A. STUDY SYNOPSIS TITLE: Evaluation of the Elimination and Safety Profile of Daptomycin in Subjects with Graded Renal Insufficiency, End-Stage Renal Disease, and Healthy Volunteers SPONSOR: Cubist Pharmaceuticals, Inc. CLINICAL PHASE: Phase I NUMBER OF STUDY CENTERS: One (1) OBJECTIVES: Primary: o To determine the elimination profile of single-dose daptomycin in healthy volunteers and in subjects with various stages of renal insufficiency *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -3- Secondary: o To compare the safety profile of single-dose daptomycin in healthy volunteers and in subjects with graded renal failure and end-stage renal disease o To measure the effects that hemodialysis and peritoneal dialysis have on the renal clearance of daptomycin under both dialysis and non-dialysis conditions o To assess the effects that probenecid has on the renal tubular secretion of daptomycin SUBJECT NUMBER: A minimum of [ ]* patients with varying degrees of renal impairment, including a normal renal function group. STUDY DRUG(S): Daptomycm STUDY ENDPOINTS: PRICE: The elimination profile will be obtained from analysis of plasma, serum, urine, and dialysate samples, from subjects with graded renal insufficiency and healthy volunteers. SECONDARY: The daptomycin safety profile data will be obtained through the monitoring of adverse events, chemistry (including serum CPK), hematology, and urinalysis data. B. MONITORING VISIT INFORMATION [ ]* *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -4- C. CLINICAL DATA INFORMATION The estimated number of CRF pages is based on a [ ]*-page CRF for [ ]* patients. CRF pages for patients who fail screening will not be reviewed by IBAH for safety or data-entered unless requested by Cubist. ------------------------------------------------------------------------------- DESCRIPTION NUMBER ------------------------------------------------------------------------------- Estimated Number of CRF pages [ ]* ------------------------------------------------------------------------------- Estimated Number of Tables/Listings: Primary [ ]* Subset [ ]* ------------------------------------------------------------------------------- IV. DESCRIPTION OF SERVICES A description of services to be performed by IBAH's is described below. Changes made by Cubist and agreed to by IBAH in the Project scope, at any time during the program, will result in a corresponding adjustment to the Project costs. A. STUDY MANAGEMENT 1. PROJECT MANAGEMENT IBAH will assign a Project Manager who will act as a single point of contact for Cubist throughout the life of the Project. The Project Manager will work with one of IBAH's staff physicians who will be assigned to the Project as the Medical Monitor. The Project Manager's responsibilities may include, but not be limited to, the following: o Act as primary contact for Cubist and for the investigative site o Prepare and tracking detailed timelines o Ensure milestones are met o Ensure effective communication among all members of the Project team o IBAH Project team training o Identify and resolve critical issues o Manage financial issues IBAH will provide clerical and administrative support for the Project to assist with various tasks. Such tasks may include, but not be limited to, communication (phone, facsimile, mailings), machine processing and storage, coordination of teleconferences and meetings, and preparation of administrative reports. Printing, assembly, shipping and distribution of CRFs, Federal Express and/or overnight carrier and study-related travel, will be passed through at cost to Cubist. 2. CRF DESIGN AND PRINTING Upon approval of a final protocol by Cubist, IBAH will design a CRF to record pertinent data. IBAH's Data Management staff, Biometrics staff, and the Clinical Trial Manager *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -5- (CTM) will review the CRF and provide input to ensure all relevant data are captured. Cubist will be provided with ready-to-use multicopy carbonless forms. IBAH will ship CRFs to site. Such shipping costs will be passed through to Cubist. B. STUDY CONDUCT 1. CLINICAL MONITORING IBAH's CRA will perform initiation, interim and a closeout visit at the investigational site. IBAH's site management and monitoring procedures will be performed in accordance with Good Clinical Practices to ensure investigative site compliance with regulations and protocol requirements. IBAH's CRA will ensure protocol procedure compliance, and will be available at the time of first dosing if required by Cubist and agreed upon by IBAH. IBAH's CRA will review source data and CRF data for appropriate identification, documentation and reporting of both serious and non-serious adverse events. Drug accountability will be performed by IBAH's CRA at each interim visit and at the closeout visit. The completed CRFs will be retrieved and reviewed at each visit. All IBAH travel expenses related to this study will be passed through to Cubist. 2. SAE REPORTING WITH INITIAL DESCRIPTIVE SUMMARIES All serious adverse events (SAES) will be forwarded to Cubist within one IBAH business day of receipt. Notification to Cubist will occur via telephone, as well as by receipt of a comprehensive SAE form. In the event that follow-up information is required for an event (hospital discharge summary, etc.), IBAH's Safety Surveillance Department will periodically contact the site until information is obtained and the SAE form is updated as necessary. IBAH will provide initial descriptive patient summaries for all identified serious adverse events. The descriptive narratives will be written from information provided by the investigator on the SAE report forwarded to IBAH at the time of the event. If significant follow-up information becomes available, the narrative will be updated accordingly. 3. CRF TRACKING, FILING, AND ARCHIVING Completed case report forms, ancillary CRF pages, adverse event documentation, and patient and site-specific correspondence for the study will be logged in and tracked at IBAH. CRFs and answered data queries will be submitted to the IBAH document management group for a page-by-page entry into a computerized tracking system. A photocopy will be made within the same business day the CRF arrives and the original CRF will be filed in a central document unit at IBAH. The copy will be circulated throughout the various departments at IBAH as a working copy. Fees reflect an additional 20% of the estimated CRF pages to cover logging, copying, filing, and ongoing CRF tracking time for all pages. A final, complete page listing and the original CRFs will be provided to Cubist upon Project completion. The fee charged will reflect the actual number of pages tracked. Pages for screened volunteers will be tracked and filed. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -6- C. CLINICAL DATA MANAGEMENT 1. PROJECT DATABASE CREATION AND DATA ENTRY Data screens will be developed by IBAH's programming group on an Open VMS System (Alpha 4100) using Domain/CLINTRIAL(R) software. IBAH's Programmers will develop data-entry screens (i.e., CRF data module designs) that mimic the flow of the CRF, thereby improving the ease and integrity of the data-entry process. All screen programs will undergo testing at IBAH prior to initiation of the full-scale data entry effort. IBAH's Data Entry Specialists will enter all CRF data by utilizing a double-entry method. On-line edit checks will be included to provide additional controls against categorically incorrect data. The double data entry strategy will utilize numeric and/or text fields that are entered by one member of the data entry staff 'and re-entered on-line by a second member of the staff. All data will be double-entered at IBAH, with the exception of comment fields, which will be quality controlled on-line. In addition to the double-entry strategy, each case will be printed as a data listing with 100% verification of critical data fields and text fields against the hard copy CRF by one of IBAH's Clinical Data Analysts (CDA). Also, [ ]*% of the volunteers will be verified for 100% of the data fields prior to the closing of the database. Standard and protocol-specific edit checks will be created and results of the edit checks will be reviewed by the CDA during the review process and prior to database closure for the generation of queries. All verification will be documented. The estimated fee for data entry of CRFs is based on CRF pages entered. Actual pages will be invoiced. This page estimate is based on randomized volunteers only and does not include entry of any screen failure volunteers. Any ancillary pages (e.g., Labs, EKGs, etc.) that are not included in the CRF estimate will be viewed as additional pages and an additional fee will be charged. 2. CASE REPORT FORM REVIEW AND QUERY RESOLUTION IBAH will generate protocol-specific guidelines, which will be reviewed and approved by Cubist. Using these guidelines, IBAH will conduct a detailed quality control (QC) audit of the entire CRF through a combination of manual review and electronic edit checks that will identify conflicting, unclear, or incomplete data. This review will be performed by CDAs who are independent of the Medical Monitor involved with the Project. If data are unclear, conflicting or incomplete, then data clarification requests (DCRs) will be generated and transmitted to the investigative site(s) and the Medical Monitor. All DCRs (issued and resolved) will be logged into the IBAH tracking system. IBAH's DCR database will be maintained throughout the project and can provide Cubist with an *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -7- up-to-date report on the status of DCRs on an as needed basis. The fee for generation and resolution of data queries is included in the data entry estimate. 3. DICTIONARY PROCESSING IBAH will use MedDRA for coding adverse events and WHO-DRUG for coding medications. IBAH will use standard coding conventions for the mapping procedure unless otherwise instructed at the study start. An additional cost will be incurred for changes to coding conventions after study start. An automated process will be used to map literal text to the corresponding term in the dictionary. Unmapped terms will be researched, coded, and reviewed by a dedicated team. Dictionary reports will be inclusive of automated and manually coded terms and will be reviewed by Cubist. 4. LABORATORY DATA PROCESSING (CENTRAL) TRANSFER AND VERIFICATION OF CENTRAL LABORATORY DATA IBAH will develop the programs needed for conversion and integration of central laboratory data. Central lab data sets will be loaded into the clinical database. Accession numbers from the laboratory hard copy received with the case will be entered into the database. Verification will compare the header data received electronically against the case data including the patient number, lab date, date of birth, gender, patient initials, and lab accession numbers. Discrepancies will be communicated to the central lab and/or Cubist. Full lab panel validation will be performed on [ ]* of the patients to verify accuracy of the load. IBAH assumes that all laboratory results will be forwarded with the appropriate normal range and flag attached at the record level. 5. DATA TRANSFER At the conclusion of the study, IBAH will transfer the Project database to Cubist in standard IBAH SAS data sets, using IBAH's standard naming conventions and format. Upon the mutual written agreement by the parties, customized data transfers, or interim database closes and transfers, will be provided for an additional fee. 6. SECURITY PROCEDURES All files, including data and programming, will be backed-up daily and a complete tape will be sent to a secure storage off-site on a weekly basis for disaster recovery. All personnel maintain their own log-on Ids and all passwords will be changed monthly. Only authorized personnel will have access to databases, which have additional unique access codes. Data access codes will be changed upon database review and closure to allow only authorized personnel access to the database. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -8- As part of routine documentation, a controlled procedure will be used to archive two sets of tapes containing all pertinent system files employed in the project (i.e., Domain/CLINTRIAL(R) software, data sets, screen modules, SAS programming, and listing files). 7. MACHINE PROCESSING AND STORAGE IBAH's Database Administrator will maintain the integrity of Cubist's clinical database for the duration of the Project. D. BIOMETRICS 1. PROJECT DATA SETUP AND PROGRAMMING OF DATA DISPLAYS Prior to programming actual data displays (data listings, summary tables and graphics), IBAH will develop data display headers and create the status data set and efficacy data set, if needed, which will be used for the data analysis. After approval of the prototype data display formats by Cubist and the IBAH Project Team, IBAH's programming staff will develop the programs required to generate each data display. Programming will be performed using SAS system software, and will incorporate procedure output and customized report writing features. Any changes to approved data display formats will result in additional charges. IBAH assumes that Cubist will be responsible for providing the table design and statistical plan for the study. Fees are based on an estimate of the total number of primary and secondary data displays. However, the cost will be based on the actual number of data displays generated. Primary data displays are considered new code development. Secondary data displays are defined as those data displays utilizing much of the programming code developed to produce the primary output. The fee for data displays generation includes minor changes, following review by Cubist, to take no more than [ ]* days. All additional changes to tables will result in additional charges. 2. QUALITY CONTROL PROCEDURES FOR DATA DISPLAYS IBAH's Biometrics staff will use a combination of independent programming, hand tabulation from supporting listings, and programming verification to ensure the accuracy and completeness of tables, listings, and statistical results. All report data displays will be verified for accuracy and internal consistency among data displays. A quality control binder, including the quality control strategy for each data display and audit trail, will be included in the Project file. 3. STATISTICAL ANALYSIS IBAH's biostatisticians will perform statistical analysis in accordance with the approved statistical analysis plan. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -9- 4. DATA TRANSFER Cubist will provide IBAH's statistician with a complete list of the data tables to be transferred to Cubist in an Excel spreadsheet following database close. E. CLINICAL WRITING 1. CLINICAL REPORT IBAH will prepare an integrated clinical and statistical summary in accordance with ICH guidelines. A Draft Clinical Report will be generated within three (3) weeks after receipt of final summary tables and patient data listings. All clinical reports will receive two independent levels of quality control reviews before they are released. There will be a QC review by IBAH's Clinical Writer for accuracy and consistency and a review by IBAH's Writing Manager for accuracy, client format consistency and appropriate clinical and regulatory prospective. The fee for this report includes one major and one minor revision and up to [ ]* brief patient narratives. [ ]* of the draft report is considered to be up to [ ]* of requested changes, and a minor revision will consist of up to one-half (1/2) day of requested changes. A final pharmacokinetic report will be provided by Cubist. IBAH will accept the PK report as 100% accurate. IBAH will extract the appropriate information from the PK report for inclusion in the clinical report. The fee for this report does not include collation and assembly of the report appendices. The writing fee estimates are based on receipt of final data and, if minor changes to the database occur after work on the document has begun, they will not impact the production of the document. If database changes occur which require a substantial amount of time [ ]* for rework or repeat quality control, additional fees will be agreed upon in writing with Cubist before proceeding. (Rest of page intentionally left blank) *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -10- V. ESTIMATED CLINICAL BUDGET [ ]* VI. PROJECT TIMELINE SUMMARY The parties acknowledge that IBAH estimates that the Project will begin on or about [ ]*. The Project timeline is as follows: [ ]* VII. PAYMENT SCHEDULES 1. INVOICING PROCESS FOR SERVICE FEES IBAH maintains a project accounting system, whereby all direct project costs (service or passthrough expenses) are coded by project. An initial payment of [ ]*, representing approximately [ ]* of Total Estimated Service Fees, shall be due and payable upon execution of this Exhibit C. Subsequent payments shall be made monthly, based on Project progress and upon submission of an invoice to Cubist by IBAH. The subsequent invoices shall be reduced by a prorated portion from the initial payment such that the initial payment is applied evenly over the term of the Project. All payments of service fees and pass through expenses shall be made by Cubist within [ ]* of receipt of invoice. If any payment of service fees or pass through expenses is late by more than [ ]*, such payment shall be subject to a penalty fee of [ ]* per month of the outstanding balance. 2. PASS-THROUGH EXPENSE INVOICING IBAH's project accounting system is able to capture and categorize in summary the following key pass-through expenses related to a project: o Travel o Delivery fees o CRF and other printing costs o All other Project related expenses that are not related to service fees Any additional detail to support pass-through costs will be provided on a fee basis. 3. ANNUAL PRICE INCREASE Notwithstanding anything contained herein to the contrary, the estimated service fees set forth in this Exhibit C shall remain in effect for the longer of (a) [ ]* from the date hereof, or (b) [ ]* of the first calendar year following the date hereof. Thereafter, IBAH reserves the right to increase the price of the remaining Services under this Exhibit C as of each January 1; such increases shall not exceed the [ ]*. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -11- ACCEPTANCE The terms and conditions of the Master Agreement govern this Exhibit C and such document is incorporated herein by reference as if fully set forth herein. CUBIST PHARMACEUTICALS, INC. IBAH, INC. By: /s/ MICHAEL DEBRUIN By: /s/ LEONARD F. STIGLIANO ------------------- ------------------------ Name: Michael DeBruin, M.D. Name: Leonard F. Stigliano Title: Vice President, Clinical Research Title: President, U.S. CRO Date: April 11, 2000 Date: April 18, 2000 *Confidential treatment requested: Material has been omitted and filed with the Commission.
CONFIDENTIAL TREATMENT EXHIBIT D TO THE CLINICAL SERVICES MASTER AGREEMENT BETWEEN CUBIST PHARMACEUTICALS, INC. AND IBAH, INC., DATED DECEMBER 1, 1999. THIS EXHIBIT D is entered into this 10th day of May, 2000, by and between Cubist Pharmaceuticals, Inc. (hereinafter "Cubist") and IBAH, Inc. (hereinafter "IBAH"). WHEREAS, Cubist and IBAH entered into a Clinical Services Master Agreement, dated December 1, 1999 (hereinafter the "Master Agreement"), wherein BAH agreed to provide clinical services and; WHEREAS, Cubist and IBAH agree that IBAH shall provide the services set forth in this Exhibit D, subject to the terms and conditions set forth in the Clinical Services Master Agreement; NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Cubist and IBAH agree as follows: I. PROJECT OVERVIEW IBAH will provide pre-NDA services in connection with the Daptomycin Program (hereinafter "the Projects"). Changes made in the Projects scope, at any time during the Projects, will result in a corresponding adjustment to the Project Costs. II. PROJECT ROLES AND RESPONSIBILITIES IBAH will perform pre-NDA services for the Projects as specified and requested on an as needed basis by Cubist and agreed upon by IBAH. III. PROJECT TIME-LINE IBAH commence performance of the services on or about [ ]*. Unless otherwise agreed to in writing by the parties, the terms of this Exhibit D shall be for [ ]*. IV. BUDGET A. PER DIEM RATES [ ]* The fees for services provided under this Exhibit D shall not exceed [ ]* unless expressly requested by Cubist in writing, and agreed to in writing by the parties. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> -2- B. PAYMENT SCHEDULES 1. INVOICING PROCESS FOR PER DIEM RATES IBAH maintains a project accounting system, whereby all direct project costs (estimated per diem rates or pass-through expenses) are coded by project. All payments shall be processed within [ ]* days upon receipt of an invoice from IBAH. If any payment is late by more than [ ]* days, such payment shall be subject to a penalty fee of [ ]* per month of the outstanding balance. 2. PASS-THROUGH EXPENSE INVOICING IBAH's project accounting system is able to capture and categorize in summary the following key pass-through expenses related to a project: o Travel o Delivery fees o All other project related expenses that are not related to per diem rates Any additional detail to support pass-through costs will be provided on a fee basis. 3. ANNUAL PRICE INCREASE Notwithstanding anything contained herein to the contrary, the per diem rates set forth in this Exhibit D shall remain in effect for the longer of (a) [ ]* from the date hereof, or (b) [ ]*. Thereafter, IBAH reserves the right to increase the price of the per diem rates under this Exhibit D as of each January 1; such increases shall not exceed the percentage change of [ ]*. 4. TERMS AND CONDITIONS The terms and conditions of the Master Agreement govern this Exhibit D and such document is incorporated herein by reference as if fully set forth herein. IN WITNESS WHEREOF, the parties have executed this Exhibit D by their duly authorized officers. CUBIST PHARMACEUTICALS, INC. IBAH, INC. By: /s/ MICHAEL DEBRUIN By: /s/ LEONARD F. STIGLIANO ------------------- ------------------------ Name: Michael DeBruin, M.D. Name: Leonard F. Stigliano Title: Vice President - Clinical Research Title: President, U.S. CRO Dated: April 24, 2000 Dated: May 10, 2000 *Confidential treatment requested: Material has been omitted and filed with the Commission.
CONFIDENTIAL TREATMENT EXHIBIT E TO THE CLINICAL SERVICES MASTER AGREEMENT BETWEEN CUBIST PHARMACEUTICALS, INC. AND OMNICARE CLINICAL RESEARCH. INC. (F/K/A IBAH, INC.), DATED DECEMBER 1, 1999. THIS EXHIBIT E is entered into this 17TH day of OCTOBER, 2000, by and between Cubist Pharmaceuticals, Inc. (hereinafter "Cubist") and Omnicare Clinical Research, Inc. (F/K/A IBAH, Inc.) (hereinafter "Omnicare Clinical Research"). WHEREAS, Cubist and Omnicare Clinical Research entered into a Clinical Services Master Agreement, dated December 1, 1999 (hereinafter the "Master Agreement"), wherein Omnicare Clinical Research agreed to provide clinical services and; WHEREAS, Cubist and Omnicare Clinical Research agree that Omnicare Clinical Research shall provide the services set forth in this Exhibit E, subject to the terms and conditions set forth in the Master Agreement; NOW, THEREFORE, for good and valuable consideration, AND INTENDING TO BE LEGALLY BOUND, Cubist and Omnicare Clinical Research agree as follows: I. PROJECT PLAN Based on the Project specifications, Omnicare Clinical Research has provided a description of services to be performed for Cubist's Phase III study of Cidecin(TM) (daptomycin) in the treatment of moderate to severe community-acquired acute bacterial pneumonia due to S. PNEUMONIAE, Protocol Number DAP-00-05 (hereinafter "the Project") and associated costs. Changes made in the Project scope, at any time during the Project, will result in a corresponding adjustment to the Project costs. A. PROJECT STATUS TABLE [ ]* *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> II. PROJECT ROLES AND RESPONSIBILITIES --------------------------------------------------------------------------------------------------------------- TASK CUBIST OMNICARE CLINICAL RESEARCH --------------------------------------------------------------------------------------------------------------- A. STUDY MANAGEMENT --------------------------------------------------------------------------------------------------------------- 1. Facilitate Project Management X o Global Program Director - [ ]* days total o International Project Manager (EU) - average [ ]* days total o Clinical Trial Managers (North America) - [ ]* days total o Count Trial Managers (EU) - [ ]* days total --------------------------------------------------------------------------------------------------------------- 2. Coordinate and conduct team meetings X X o Omnicare Clinical Research anticipates [ ]* face-to-face meetings will occur during the course of this Project o Fee assumes [ ]* meetings to occur at Omnicare Clinical Research and at Cubist ---------------------------------------------------------------------------------------------------------------- 3. Standard Operating Procedures (SOPs) X ---------------------------------------------------------------------------------------------------------------- 4. Performance tracking submitted to Cubist in a written report X --------------------------------------------------------------------------------------------------------------- 5. Monitor Project payment schedule X X --------------------------------------------------------------------------------------------------------------- 6. Project problem solving X X --------------------------------------------------------------------------------------------------------------- 7. Clerical and administrative support X o North America - [ ]* days total o EU- [ ]* days total --------------------------------------------------------------------------------------------------------------- B. CLINICAL TRIAL INITIATION --------------------------------------------------------------------------------------------------------------- 1. Drug development and study design X --------------------------------------------------------------------------------------------------------------- 2. Protocol Development X o Fee includes [ ]* major [ ]* and [ ]* minor [ ]* revision --------------------------------------------------------------------------------------------------------------- 3. Patient plan X o [ ]* patients enrolled in North America o [ ]* patients enrolled in International o [ ]* patients total --------------------------------------------------------------------------------------------------------------- 4. Site plan X o North America: [ ]* sites o International: [ ]* sites Countries include: Australia, Benelux/Netherlands, Croatia, Czech Republic, Finland, France, Germany, Greece, Hungary, Iceland, New Zealand, Norway, Russia, Slovak Republic, Spain, Sweden, Switzerland, UK --------------------------------------------------------------------------------------------------------------- 5. CRF design X o [ ]* estimated pages per patient, plus [ ]* ancillary pages --------------------------------------------------------------------------------------------------------------- 6. CRF logistics (print, bind, and distribute) X o Material, printing and assembly expenses will be passed through at cost *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> --------------------------------------------------------------------------------------------------------------- 7. Investigator identification, recruitment and qualification X o [ ]* sites will be identified to obtain [ ]* qualified North American sites o [ ]* sites will be identified to obtain [ ]* qualified EU sites --------------------------------------------------------------------------------------------------------------- 8. Investigator regulatory document management X o Protocol Amendments and IRB submissions billed per site o Informed Consent Forms development --------------------------------------------------------------------------------------------------------------- 9. Certification of Investigator Financial Disclosure X --------------------------------------------------------------------------------------------------------------- 10. Investigator agreement negotiation X --------------------------------------------------------------------------------------------------------------- 11. Coordination of investigators' meetings X o One meeting North America o Three meetings International --------------------------------------------------------------------------------------------------------------- 12. Project team training X X --------------------------------------------------------------------------------------------------------------- *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> --------------------------------------------------------------------------------------------------------------- TASK CUBIST OMNICARE CLINICAL RESEARCH --------------------------------------------------------------------------------------------------------------- B. CLINICAL TRIAL INITIATION CONT. --------------------------------------------------------------------------------------------------------------- 13. IVRS System for Randomization X o Fee is based on the following assumptions - French, Spanish, Russian, Slovak, Czech, Hungarian, German, Finnish, Croatian, Flemish, Swedish, Greek, and English - Patients are randomized to one of two treatment arms - Detailed specifications can take one to four weeks to develop and approve, based on sponsor availability - Validated IVRS delivered [ ]* weeks after receiving Cubist's written approval of detailed specifications - Cubist-requested changes to the approved specifications will result in delivery delays - Omnicare Clinical Research will provide training and documentation for the investigators' meetings with related travel costs passed through to Cubist - Omnicare Clinical Research Help Desk support provided 24 hours a day, 7 days a week, once the system is delivered; Help Desk support is Multilingual via AT&T's Language Line(R) o Functionality includes: 2 treatment groups, 1 randomization call per patient, editing of all non-stratification-related patient data, system- and role-based security via protocol code and caller identification with passwords, comprehensive standard system fax-back reporting on demand o If randomization is required prior to system completion and validation, Cubist will a for a manual randomization service at an additional price --------------------------------------------------------------------------------------------------------------- C. CLINICAL TRIAL MANAGEMENT --------------------------------------------------------------------------------------------------------------- 1. Clinical, monitoring X o Onmicare Clinical Research estimates [ ]* North America qualification visits and [ ]* International one-day qualification visits ([ ]* visits total) o Omnicare Clinical Research estimates performance of [ ]* North America and [ ]* International initiation visits ([ ]* visits total) o Omnicare Clinical Research estimates performance of [ ]* North America and [ ]* International interim visits ([ ]* visits total) o Omnicare Clinical Research estimates [ ]* North America and [ ]* International close-out visits ([ ]* visits total) --------------------------------------------------------------------------------------------------------------- 2. Clinical grant payment administration X o [ ]* payments per site in North America o [ ]* payments per site in International --------------------------------------------------------------------------------------------------------------- *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> --------------------------------------------------------------------------------------------------------------- TASK CUBIST OMNICARE CLINICAL RESEARCH --------------------------------------------------------------------------------------------------------------- 3. CRF tracking, filing and archiving X o [ ]* pages - North America; [ ]* pages - International; [ ]* pages - received from CROs designated by Cubist* o [ ]* pages total * Omnicare Clinical Research shall not be responsible for any delays or interruption in performance of the services due, in any way, to the provision of data or other information to be supplied by such other CRO designated by Cubist. --------------------------------------------------------------------------------------------------------------- 4. Medical monitoring X o [ ]* months in North America o [ ]* months in International o 24 hour coverage North America/International --------------------------------------------------------------------------------------------------------------- 5. Safety review of CRFs X o Based on [ ]* cases reviewed --------------------------------------------------------------------------------------------------------------- *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> --------------------------------------------------------------------------------------------------------------- TASK CUBIST OMNICARE CLINICAL RESEARCH --------------------------------------------------------------------------------------------------------------- 6. SAE Reporting with Initial Descriptive Summaries v o [ ]* total ([ ]* X in North America/[ ]* in International) o IND Safety Report distribution in countries in which CTX/CTA is held by Omnicare Clinical Research o Cubist to be billed for actual SAEs reported --------------------------------------------------------------------------------------------------------------- D. CLINICAL DATA MANAGEMENT --------------------------------------------------------------------------------------------------------------- 1. Project database creation and data entry. Fee based on: X o [ ]* CRF pages from North America o [ ]* CRF pages from International o [ ]* CRF pages received from other CROs designated by Cubist o [ ]* total CRF pages * Omnicare Clinical Research shall not be responsible for any delays or interruption in performance of the services due, in any way, to the provision of data or other information to be supplied by such other CRO designated by Cubist --------------------------------------------------------------------------------------------------------------- 2. Case report from review and query resolution. Fee based on: X o [ ]* CRF pages from North America o [ ]* CRF pages from International o [ ]* CRF pages received from other CROs designated by Cubist o [ ]* total CRF pages * Omnicare Clinical Research shall not be responsible for any delays or interruption in performance of the services due, in any way, to the provision of data or other information to be supplied by such other CRO designated by Cubist --------------------------------------------------------------------------------------------------------------- 3. Dictionary processing of CRFs X o MedDRA for adverse events, and concurrent surgical procedures o WHO-DRUG for medications --------------------------------------------------------------------------------------------------------------- 4. Laboratory data processing (fee assumes previously used central lab) X X --------------------------------------------------------------------------------------------------------------- 5. Reconciliation of Safety/Clinical Databases X --------------------------------------------------------------------------------------------------------------- 6. Data transfers (standard) X o 3 interim transfers --------------------------------------------------------------------------------------------------------------- 7. Data security procedures X --------------------------------------------------------------------------------------------------------------- 8. DCR Status Reports by site --------------------------------------------------------------------------------------------------------------- E. BIOMETRIC ANALYSIS --------------------------------------------------------------------------------------------------------------- 1. Statistical analysis plan X o Includes one major one minor revision --------------------------------------------------------------------------------------------------------------- 2. Project data setup and programming of displays X o [ ]* tables, listings, and figures ([ ]* unique and [ ]* repeat) o Due to efficiencies, Cubist to be billed for [ ]* unique and [ ]* repeat tables, listings, and figures o Additional tables, listings, and figures will be billed at the per task cost, as outlined in the budget --------------------------------------------------------------------------------------------------------------- *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> --------------------------------------------------------------------------------------------------------------- TASK CUBIST OMNICARE CLINICAL RESEARCH --------------------------------------------------------------------------------------------------------------- 3. Quality control procedures for displays X --------------------------------------------------------------------------------------------------------------- 4. Patient evaluability and outcome assessment X --------------------------------------------------------------------------------------------------------------- 5. Final statistical analysis X --------------------------------------------------------------------------------------------------------------- 6. Statistical support for Item 11 preparation X --------------------------------------------------------------------------------------------------------------- 7. Final data transfer X --------------------------------------------------------------------------------------------------------------- F. CLINICAL WRITING --------------------------------------------------------------------------------------------------------------- 1. Phase III clinical study report X o One major (up to [ ]*) and one minor (up to [ ]*) revision and up to [ ]* brief patient narratives o Fee does not include collation or compilation of appendices --------------------------------------------------------------------------------------------------------------- *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> III. PROJECT TIMELINE The parties acknowledge that Omnicare Clinical Research commenced performance of the services on or about [ ]*. The projected timeline for this Project is as follows: [ ]* (REST OF PAGE INTENTIONALLY LEFT BLANK) *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> IV. OMNICARE CLINICAL RESEARCH SERVICES A. STUDY MANAGEMENT 1. GLOBAL PROGRAM DIRECTOR/INTERNATIONAL PROJECT MANAGER Omnicare Clinical Research's Global Program Director will coordinate the services being provided by all of the disciplines within Omnicare Clinical Research and will act as a single point of contact for Cubist until completion of the Project. The International Project Manager, working in conjunction with the Global Program Director, will manage the international segment of the Project. Key responsibilities of these individuals will include the following: o Prepare detailed Project timelines and ensure that major milestones are met, copies of all documents will be forwarded to Cubist o Provide Global Project status updates weekly in written report o Bi-weekly Internal teleconferences to include the Program Director, Project Director, Project Managers and Clinical Trial Managers, outstanding issues, action plans and follow up items from this teleconference will be forwarded to Cubist in a written format o Identify and resolve critical Project issues, written reports of issues identified and resolution strategy will be forwarded to Cubist for discussion o Ensure adequate resource allocation across all functions o Oversee Project team meetings o Manage Project financial issues 2. COUNTRY TRIAL MANAGERS/CLINICAL TRIAL MANAGERS Omnicare Clinical Research's Country/Clinical Trial Managers will be dedicated to managing the day-to-day clinical trial activity. They will oversee all site and CRA activities within this Project. Primary responsibilities of these individuals will include the following: o Develop case report forms and monitoring guidelines o Oversee regulatory document management from each of the investigational sites o Review and track CRA activities including scheduling of site visits, site visit reports, monitoring logs, follow-up correspondence, hours worked, routine expense records, and any other pertinent study-related documents o Maintain routine contact with all CRAs to ensure the consistency of program communication and work performed *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> o Provide ongoing quality control of the CRAs performance throughout the Project o Provide Cubist with written Project status tracking report that provides an overview of information regarding: Site start-up activity, regulatory document collection, enrollment activity, number of SAE's, and number of outstanding queries o Provide Global Program Director and International Project Manager with periodic status reports including progress of site initiations, status of ongoing site visits, patient enrollment updates, site visit reports, data query rates, and other study related reports 3. ASSOCIATED MANAGEMENT SUPPORT Omnicare Clinical Research will dedicate clerical/administrative support to the Project. The clerical/administrative fee will cover costs associated with Omnicare Clinical Research's services, as well as management and administration associated with this Project. All travel expenses, Federal Express and/or overnight courier services, and telephone costs will be passed through at cost to Cubist. B. CLINICAL TRIAL INITIATION 1. Protocol Design Omnicare Clinical Research's Clinical Writing Department will work with a multidisciplinary team composed of Medical and Client Services, Regulatory, Data Management, Clinical Quality Assurance and Biometrics personnel to gather input and expertise in the design of the Project protocol to Cubist's specifications. An Omnicare Clinical Research Statistician will provide the statistical section of the protocol, including a description of the study design, definition of the efficacy and safety endpoints, and proposed methodology for the statistical analysis. Sample size calculations will also be performed, if necessary. The fee for this protocol includes one major and one minor revision. One major revision of the draft protocol is to be up to [ ]* of requested changes, and a minor revision will consist of up to [ ]* day of requested changes. If additional revisions are requested by Cubist, these revisions will be incorporated based on the following per diem rates: Director: [ ]* Senior Writer: [ ]* Clinical Writer: [ ]* *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> 2. PROJECT TEAM TRAINING Omnicare Clinical Research will rely on internal and external experts to provide specific therapeutic area training and orientation to the protocol and the CRF prior to study initiation and on an ongoing basis. This training will be designed to ensure that all team members are familiar with the Project requirements and their role within the team. Items discussed at these meetings will include, but will not be limited to: o Therapeutic area and clinical development background o Protocol and CRF o Discussion of therapeutic implications for this study o Monitoring guidelines 3. CRF DESIGN AND PRINTING Omnicare Clinical Research will work in conjunction with Cubist to design a case report form (CRF) for recording pertinent study data. Omnicare Clinical Research's Data Management and Biometrics Departments, and the CTMs will review the CRF and provide input to ensure all relevant data is captured. A review meeting with Cubist will be held to resolve any design questions or other concerns which may arise. Onmicare Clinical Research will provide Cubist with bids from independent printing vendors. CRFs will be sent for printing on 3-part NCR after all issues are resolved and final approval from Omnicare Clinical Research and Cubist is received. Estimated fees for CRF materials and printing are based on a per case basis. CRFs will be collated into binders with spines and covers, and a protective NCR fold-over will be provided with each CRF binder. Actual materials, printing, assembly, and distribution fees will be passed through to Cubist. 4. INVESTIGATOR IDENTIFICATION, RECRUITMENT AND QUALIFICATION Omnicare Clinical Research will collaborate with Cubist to recruit [ ]* North America and [ ]* International investigators capable of conducting the Cubist CAP study. A preliminary telephone interview will be conducted to evaluate a prospective site's interest and potential to meet both patient enrollment and data quality goals for this Project. After obtaining a signed confidentiality agreement from the prospective investigative sites, Omnicare Clinical Research will issue a survey form, customized to the protocol. Additional Project information will be distributed *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> to appropriate investigators who are willing to commit to study participation. The outcome of all evaluations, with a final list of proposed investigators, will be forwarded to Cubist for approval prior to final recruitment. If it is necessary to assess the site's ability to achieve study enrollment and data quality goals then a comprehensive pre-study evaluation visit will be scheduled with the selected investigator. Once identified as a qualified study site, an investigator regulatory document package will be sent. All pre-study visit reports will be forwarded to Cubist for review. Cubist will have final approval on all Investigator sites that are proposed to participate in the Project. 5. INVESTIGATOR REGULATORY DOCUMENT MANAGEMENT In coordination with Cubist, Omnicare Clinical Research will develop a template of an informed consent form for the Project, ensuring compliance with all local, state, and federal and international regulatory requirements. Regulatory document packages, with letters of instruction, will be mailed to qualified investigative sites. A dedicated tracking process for regulatory document collection will be utilized. Document collection will cover all criteria required under the principles of Good Clinical Practices (GCP) and International Committee for Harmonization (ICH) guidelines, as well as Omnicare Clinical Research Standard Operating Procedures (SOPs). In addition, Omnicare Clinical Research will collect certification/disclosure information from all investigators and provide this information to Cubist on an ongoing basis. Omnicare Clinical Research will track the retrieval of documents on an ongoing basis and provide written updates to Cubist as requested. Omnicare Clinical Research will prepare copies of all appropriate documents, assemble documents and issue an investigator regulatory binder to all sites, including but not limited to: o Investigator's Brochure o Final Protocol and Sample Copy of the CRF o Institutional Review Board (ERB) Approvals of Protocol and Informed Consent Form(s) o Laboratory Certification and Normal Ranges o Completed FDA Form 1572 o Investigator Curriculum Vitae o Financial Disclosure Certification and/or completed Financial Disclosure Form *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> The binders will be maintained at the sites and reviewed for appropriate updates by CRAs responsible for site management over the course of the study. Certification of Investigator Financial Disclosure will be collected and maintained as agreed upon by Omnicare Clinical Research and Cubist. The fee for regulatory document collection, processing, and tracking is based upon the number of sites required for the study. File maintenance and updating will be billed at the rate of [ ]* per site per year after year one. Protocol amendments which require informed consent revisions and/or IRB re-submission will be billed at an additional processing fee of [ ]* for each site. 6. INVESTIGATOR REGULATORY DOCUMENT COLLECTION STUDY MASTER FILES In accordance with GCP, Omnicare Clinical Research's staff will: o Develop Study Master File according to Omnicare Clinical Research SOPS under the supervision of the International Project Manager and the Global Project Director. o Obtain all relevant critical documents for the Project; design an appropriate Critical Document Receipt List as a supporting instrument for the CRAs; review all incoming investigators' documents; approve/reject these documents according to GCP and internal guidelines o Maintain files, i.e. proper filing of all incoming papers (investigator documents, site visit reports); audit files to assure the completeness of the documents and to identify missing documents o Ship investigator documents to Cubist as requested o Arrange for archiving of the Study Master File at the end of the Project PRE-STUDY APPROVALS Omnicare Clinical Research's Regulatory staff will prepare the necessary pre-study filings with local regulatory authorities for permission to proceed with the clinical trial, as well as follow-up with these local authorities to expedite the review and approval process. Omnicare Clinical Research's Regulatory staff will prepare the dossier (document compilation and submission) and necessary study updates. Fees are based on Omnicare Clinical Research's staff time to prepare the dossier(s) and interact with the regulatory agencies and IRBs. Omnicare Clinical Research will also be responsible for translation of documents into the different local languages. In addition, any direct charges (dossier filing fees, travel to meetings at agencies, etc.) will be passed through to Cubist at cost. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> 7. INVESTIGATOR AGREEMENT NEGOTIATION Omnicare Clinical Research will be responsible for the following activities related to negotiating the clinical site contracts: o Create an investigator agreement and patient budget o Negotiate investigator agreements that satisfy Cubist requirements Handle investigator agreements, approval by Cubist and signature by investigators o Incorporate changes and secure re-approval by Cubist Communicate with Omnicare Clinical Research's Grants Administration Department when necessary Handle investigator agreement amendments and/or addenda Collect excess grants from sites at study end Protocol and study amendments which require investigator agreement revisions, amendments and/or re-negotiation will be billed at an additional processing fee of [ ]* for each site. 8. COORDINATORS' AND INVESTIGATORS' MEETING COORDINATION AND ATTENDANCE A Meeting Coordinator will be assigned by Omnicare Clinical Research to manage all logistics of the North America and International meetings and will schedule necessary travel and hotel arrangements. Specific responsibilities will include the following: o Identify appropriate locations for the meetings o Define meeting requirements and outline a meeting agenda o Negotiate, organize, and make all hotel arrangements o Secure discounted travel arrangements and issue tickets to investigators and study coordinators o Prepare necessary meeting materials (e.g., annotated CRFs, presentation materials, etc.) o Coordinate presentations o Manage administrative aspects associated with the meeting Omnicare Clinical Research's Project Management and Clinical Trial Management staff will be available to conduct or participate in the meetings and will arrive at the location prior to each meeting to assist attendees with any last minute details that may arise. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> 9. INTERACTIVE VOICE RESPONSE SYSTEM (IVRS) Omnicare Clinical Research, through its designated agent or such other party as may be agreed upon by the parties, will design, develop, validate, and maintain a telephone-based computerized central response system. The IVRS System will be available 24 hours a day, seven days a week and will be accessible by a touch tone telephone-based central computerized system. All randomization activities related to 1VRS will entail input and review by an Omnicare Clinical Research Statistician for methodology and execution. Costs for these services are included. All systems undergo a separate validation process, and full user/sponsor documentation will be produced. The IVRS developed for Cubist will include patient randomization to determine the treatment type to be given to the patient. A 24-hour Help Line (Multilingual) that is staffed by an IVRS Specialist trained in working with site staff for all IVRS systems will be established. Omnicare Clinical Research will provide documented procedures for the ongoing operation of the system, and will train qualified staff accordingly to perform ongoing system maintenance and help desk service. C. CLINICAL TRIAL MANAGEMENT 1. CLINICAL MONITORING Omnicare Clinical Research will assign a global team of experienced CRAs to perform pre-study qualification, initiation, interim and closeout site visits. Omnicare Clinical Research will provide CV's to Cubist for all CRA's and Cubist will have final approval on the CRA's assigned to the project. Deployment of CRAs, in terms of number and frequency of visits, will be managed based on Cubist input, geographic location and site-specific enrollment data. Omnicare Clinical Research's site management and monitoring procedures will be performed in accordance with GCP to ensure each investigative site's compliance with regulations and protocol requirements and to enhance expeditious enrollment of appropriate patients into the clinical study. Regulatory documents will be reviewed by the CRA on an ongoing basis during the study conduct phase, including verification of signed informed consent forms and investigator IRB notifications. Once all regulatory documents and approvals are received, a site initiation visit will be scheduled. During this visit, the CRA will review the study goals and protocol (with particular attention to inclusion/exclusion criteria, *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> enrollment plan/goal, adverse events, primary efficacy variables and GCP compliance). In addition, CRF completion and clinical supply dispensation/ accountability will be performed with the investigator and his/her staff. The Clinical Monitoring Plan will provide Project specific guidance for source data verification requirements at the Project level, monitoring report expectations and site management expectations. This document will be prepared by the Clinical Trial Manager and will be signed off by Cubist. Drug accountability will be performed at each visit, as well as reconciliation and removal of clinical supplies at study closeout per Cubist's requirements. In general, the CRAs' efforts will be focused on source document verification and expedient data retrieval. 2. CLINICAL GRANTS ADMINISTRATION As a follow-up to the Investigator Agreement negotiation process, Omnicare Clinical Research will administer the clinical grant payments to the site. Included in their responsibilities are the following: o Process financial records for all of the patients in the study o Issue initial and interim payments for each investigator o Reconcile all payments to each of the investigators prior to the final payments o Track account administration with Omnicare Clinical Research's finance group o Maintain W9 forms and all relevant and related government reports (North America only) Investigator grants, within parameters defined by Cubist, will be passed through at cost to Cubist. A grant administration fee will be applied, based on the number of sites and payments to be managed throughout the duration of the study. 3. CRF TRACKING, FILING AND ARCHIVING Completed CRFs received from investigative sites, ancillary CRF pages, adverse event documentation, and patient-specific correspondence for each study will be logged in and tracked at Omnicare Clinical Research. Of these items, CRFs and answered data queries will be entered page-by-page into a computerized tracking system. Fees reflect logging, copying, filing, and ongoing CRF tracking time. A final, complete page listing and original CRFs will be provided to Cubist upon Project completion. Cubist will be billed for the actual number of pages logged/tracked. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> 4. MEDICAL MONITORING Omnicare Clinical Research's North America and International Medical Monitors will oversee the medical aspects of Cubist's clinical program. In addition to acting as medical advisors to the Project Team, the Medical Monitors will be responsible for the following: o Project planning o Review of clinical documentation (protocol, CRF, sample informed consent form) o Project-specific medical training o Evaluate patient eligibility (in conjunction with the Medical Director of Cubist) o Resource for Investigator to discuss patient specific issues o Participate in team meetings o Review study reports, regulatory submissions and study manuscripts The Medical Monitor will also be available via beeper during non-business hours to address medical issues for the Project. 5. SAFETY REVIEW OF CRFS Prior to data entry, a North America and International Safety Officer will review all pages of each case, ancillary laboratory pages and all data clarification requests. Cubist will be notified immediately of serious adverse events (SAEs) that have not been previously reported by the sites. Notification will occur by telephone, as well as by forwarding to Cubist an SAE form. The SAE form will include details of the SAE obtained from the investigative site and will be sent via facsimile to the designated recipient at Cubist. As follow-up information is obtained by Omnicare Clinical Research, the SAE form will be updated and forwarded to Cubist. 6. SAE REPORTING WITH INITIAL DESCRIPTIVE PATIENT SUMMARIES Within one Omnicare Clinical Research business day of receipt, Omnicare Clinical Research will forward to Cubist all SAE information received from site personnel or Omnicare Clinical Research CRAB. Notification to Cubist will occur via telephone, as well as by forwarding a comprehensive SAE form via facsimile. Cubist will be responsible for reporting SAES to the FDA. Omnicare Clinical Research's International staff will report SAES to non-U.S. agencies. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> The fee for SAE reporting includes costs for Omnicare Clinical Research to provide all follow-up information and to update SAE forms as necessary. Omnicare Clinical Research will provide initial descriptive patient summaries for all identified serious adverse events. The descriptive narratives will be written from information provided by the investigator on the SAE report forwarded to Omnicare Clinical Research at the time of the event. If significant follow-up information becomes available, the narrative will be updated accordingly. Omnicare Clinical Research will review the Project SAE tracking report against the overall program SAE tracking report on a monthly basis. This review will be performed by the Medical Monitor. At the time of receipt of the CRF in-house, SAE reports will be reconciled with the CRF. Cubist will be billed for the actual number of SAE reports. 7. SAFETY PHONE COVER (INTERNATIONAL) During business hours, Omnicare Clinical Research has a direct number to Omnicare Clinical Research's Safety Surveillance Department for receipt of SAE information. During evening hours, weekends and holidays, a designated member of the Safety Surveillance Department is on call via beeper. All return calls to the sites will be made immediately to obtain the necessary SAE information and to determine the necessity of an SAE report. D. CLINICAL DATA MANAGEMENT 1. DATA MANAGEMENT PLAN Omnicare Clinical Research's Clinical Data Manager will develop a Global Data Management Plan, the specific contents of which will be mutually agreed upon by the parties. The parties currently anticipate that the Global Data Management Plan will include the information set forth in Attachment 1, attached hereto and incorporated herein by reference. This plan will include the entry and review guidelines, automated edit checks of the data, dictionary coding procedures, reporting requirements, and central laboratory loading procedures. Any other data management tasks requested for this Project will also be outlined in this plan. This plan will be submitted to Cubist for review and approval. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> 2. PROJECT DATABASE CREATION Data screens will be developed by Omnicare Clinical Research's programming group on an Open VMS System (Alpha 4100) using Domain/CLINTRIAL(R) software. Omnicare Clinics Research's Programmers will develop data-entry screens (i.e., CRF data module designs) that mimic the flow of the CRF, thereby improving the ease and integrity of the data-entry process. 3. DATA ENTRY, CASE REPORT FORM REVIEW AND QUERY RESOLUTION Omnicare Clinical Research's data-entry specialists will enter all CRF data utilizing a double entry method. On-line edit checks will be included to provide additional controls again; categorically incorrect data. The dual data-entry strategy will utilize numeric and/or text fields that are entered by one member of the data-entry staff and re-entered on-line by a second member of the staff. Cubist will be billed for the actual number of pages entered. Omnicare Clinical Research will generate protocol-specific guidelines that are reviewed and approved by Cubist. Using these guidelines, Omnicare Clinical Research will conduct a detailed quality control (QC) review of the entire CRF through a combination of manual review and electronic edit checks that will identify conflicting, unclear or incomplete data. Omnicare Clinical Research's Clinical Data Analysts (CDAs) will perform this review. Omnicare Clinical Research's CQA will oversee these activities and may, in its discretion, perform audits to ensure quality as part of this data service deliverable. If data are unclear, conflicting or incomplete, then queries will be generated and transmitted to the investigative site and Omnicare Clinical Research's Client Services Department. All queries (issued and resolved) will be logged into the Omnicare Clinical Research tracking system. Omnicare Clinical Research's query database will be maintained throughout the Project and will provide Cubist with DCR reports by site on a weekly basis. Cubist will be billed for the actual number of pages reviewed. In addition, each case will be printed as a data listing with 100% verification of critical data fields and text fields against the hard-copy CRF. Also, [ ]*% of the patients will be verified for 100% of the data fields prior to the closing of the database. Standard and protocol-specific edit checks will be created and results of the edit checks will be reviewed by the CDA during the review process and prior to database closure for the generation of queries. All verification will be documented. 4. DICTIONARY PROCESSING Omnicare Clinical Research will use MedDRA for coding adverse events, concurrent surgical procedures and WHO-DRUG for coding medications. A *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> Cubist-modified dictionary can be accommodated at an additional fee to cover loading and validation of Cubist's dictionaries, as well as development of a mapping code. Upon the mutual agreement of the parties, ICD-9 for presenting conditions and diagnoses will be provided at an additional fee. Omnicare Clinical Research will use standard coding conventions for the mapping procedure unless otherwise instructed at the Project start. An additional cost will be incurred by Cubist for changes to coding conventions after Project start. An automated process will be used to map literal text to the corresponding term in the dictionary. Unmapped terms will be researched, coded, and reviewed by a dedicated team. Dictionary reports will be inclusive of automated and manually coded terms and will be reviewed by Omnicare Clinical Research's Medical Monitors prior to database closure. 5. CENTRAL LABORATORY DATA TRANSFER AND VERIFICATION Omnicare Clinical Research will develop the programs needed for conversion and integration of central laboratory data. Central lab data sets will be loaded into the clinical database. Accession numbers from the laboratory hard copy received with the case will be entered into the database. Verification will compare the header data received electronically against the case data including the patient number, lab date, date of birth, gender, patient initials, and lab accession numbers. Discrepancies will be communicated to the central lab and/or Cubist. Full lab panel validation will be performed on [ ]*% of the patients to verify accuracy of the load. Omnicare Clinical Research assumes that all laboratory results will be forwarded with the appropriate normal range and flag attached at the record level. 6. RECONCILIATION OF THE SAFETY AND CLINICAL DATABASES Omnicare Clinical Research will maintain a safety database for Cubist. The safety database will be reconciled with Omnicare Clinical Research's clinical database for the Project prior to database closure. Discrepancies will be queried to the Safety Surveillance Department and to the investigator sites as needed. 7. INTERIM DATA TRANSFERS Omnicare Clinical Research will transfer the Project database to Cubist in standard SAS data sets using Omnicare Clinical Research standard naming conventions and format at three (3) predetermined time points during the study as specified in the Data Management Plan. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> 8. SECURITY PROCEDURES All files, including data and programming, will be backed-up daily and a complete tape will be sent to secure storage off-site on a weekly basis for disaster recovery. All personnel maintain their own log-on IDs and all passwords are changed monthly. Only authorized personnel have access to databases, which have additional unique access codes. Data access codes are changed upon database review and closure to allow only authorized personnel access to the database. As part of routine documentation, a controlled procedure will be used to archive two sets of tapes containing all pertinent system files employed in the Project, (i.e., Domain/CLINTRIAL(R) software, data sets, screen modules, SAS programming, and listing files). 9. MACHINE PROCESSING AND STORAGE Omnicare Clinical Research's Database Administrator will maintain the integrity of Cubist's clinical database for the duration of the Project estimated at [ ]* months. E. BIOMETRICS ANALYSIS AND TABLE GENERATION 1. STATISTICAL ANALYSIS PLAN/DESIGN OF TABLE SHELLS A Statistical Analysis Plan, including operational definition of endpoints to be analyzed, definition of patient subsets (evaluable and intent-to-treat), visit windows, rules for data handling, and a detailed description of statistical methodology will be prepared for the study. The statistical plan will include a set of formatted shells for all data displays (data listings, summary tables and graphics) planned for the study, which will be prepared with input from the Clinical Writing Department. If formatted data displays are not required, a detailed table of contents of SAS generated data displays will be included. This analysis plan will be submitted to Cubist for review and approval sixty days prior to closing the database for analysis. 2. PROJECT DATA SETUP AND PROGRAMMING OF DATA DISPLAYS Prior to programming actual data displays (data listings, summary tables and graphics), Omnicare Clinical Research will develop data display headers and create the status data set and efficacy data set, if needed, which will be used for the data analysis. After approval of the prototype data display formats by Cubist and the Omnicare Clinical Research Project Team, Omnicare Clinical Research's programming staff will develop the programs required to generate each data display. Programming will be performed using SAS system *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> software, and will incorporate procedure output and customized report writing features. Any changes to data display formats after approval and programming initiation could result in additional charges. 3. QUALITY CONTROL PROCEDURES FOR DATA DISPLAYS Omnicare Clinical Research's Biometrics staff will use a combination of independent programming, hand tabulations from supporting listings, and programming verification to ensure the accuracy and completeness of tables, listings, and statistical results. All report data displays will be verified for accuracy and internal consistency among data displays. A quality control binder, including the quality control strategy for each data display and audit trail, will be included in the Project file. 4. PATIENT EVALUABILITY AND OUTCOME ASSESSMENT Patient evaluability, outcome assessment criteria and relevant algorithms will be developed for the Project by Omnicare Clinical Research and presented to Cubist for review and approval. These algorithms will be programmed using SAS to identify evaluable patients and outcome assessments. Omnicare Clinical Research's Biostatisticians will verify the accuracy of the output with independent programming and review of individual patient data. Final decisions regarding patient evaluability and outcome assessment will require approval by Cubist; these are performed once for each patient. Data listings for each patient's evaluability status and outcome assessment will be prepared and submitted to Cubist for classification prior to breaking the blind. Data classification meetings may be held either in person or via teleconference. 5. STATISTICAL ANALYSIS Statistical analysis, in accordance with the approved Statistical Analysis Plan, will be performed by Omnicare Clinical Research staff biostatisticians. The analysis includes verification of assumptions needed for statistical inference, determination of investigator-by-treatment interaction, and examination of outlying data points. Statistical findings which may not be appropriate for the body of a clinical report (e.g., tests for interaction, data distribution issues, etc.), deviations from the planned analyses, and additional exploratory analyses will be included in a statistical appendix to the clinical report. Fees include one major revision and one minor revision. *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> The Project statistician will also review the clinical report to ensure appropriate representation of statistical methodology and inference. 6. DATA LISTING AUDIT A percentage of quality-controlled data listings may, at Omnicare Clinical Research's option and discretion, be chosen for an audit. From this, a percentage of patients will be chosen within each selected listing for audit. The data listing information will be verified against the selected patients' cases. The audit will take place once the listings are determined to be final by Omnicare Clinical Research's Biometrics Department. Omnicare Clinical Research's CQA Department will oversee these activities to ensure quality as part of this service deliverable. 7. SUMMARY TABLES AUDIT Following the generation of tables and listings by Omnicare Clinical Research's Biometrics staff, Omnicare Clinical Research may, at its discretion, review a proportion of the summary tables, focusing on critical data elements, against the supporting data listings to independently verify the accuracy of the data and consistency of format. Omnicare Clinical Research's CQA Department will oversee these activities to ensure quality as part of this service deliverable. 8. ITEM 11 PREPARATION FOR FDA A MAP detailing the origin of each table or data display expressed in terms of both data sets and programs will be included in the transfer, so that each table or display can be traced to the SAS program and SAS data sets from which it was produced. A written definition for computed variables, which may appear in Omnicare Clinical Research-created analytical files or summary files, will be included in the transfer. An annotated CRF, which maps to the SAS data sets on a variable by variable level, will be included in the transfer. 9. DATA TRANSFER At the conclusion of the study, Omnicare Clinical Research will transfer the Project database to Cubist in standard Omnicare Clinical Research SAS data sets using Omnicare Clinical Research standard naming conventions and format. All variables within these data sets, as well as variables in analytical or summary data sets, will be clearly labeled, so that SAS CONTENTS will carry clear labels enabling variables to be traced back to CRFs. Omnicare Clinical Research will include any and all FORMAT LIBRARIES, SAS *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> MACROS, or MACRO CATALOGS (if applicable) which were used in the analyses. All SAS programs, which generate data displays, listings, tables, graphics, and statistical analyses, will be included in the transfer. Upon the mutual agreement of the parties, customized data transfers, or interim database closes and transfers, will be accommodated on request at an additional fee. F. CLINICAL WRITING 1. PHASE III CLINICAL STUDY REPORT An integrated clinical and statistical summary will be prepared in accordance with ICH guidelines. A draft clinical report will be generated within three (3) weeks after receipt of final summary tables and patient listings. All clinical documents will receive two levels of quality control reviews before they are released. There will be a QC review by the clinical writer for accuracy and consistency,, and a review by the writing manager for accuracy, client format consistency, and appropriate regulatory and clinical perspective. The fee for this report includes one major and one minor revision and up to [ ]* brief patient narratives. One major revision of the draft report is to be up to [ ]* of requested changes, and a minor revision will consist of up to [ ]* of requested changes. The fee for this report does not include collation or assembly of the report appendices. Writing fee estimates are based on receipt of final data. If database changes occur which require a substantial amount of time [ ]* for rework or repeat quality control, additional fees will be agreed upon with Cubist before proceeding with the reports. Attendance at Cubist requested meetings (on-site teleconferences/video conferences or client review/planning meetings at Cubist/Omnicare Clinical Research) will be billed to Cubist according to the following per diem rates: Director: [ ]* Senior Writer: [ ]* Clinical Writer: [ ]* 2. CLINICAL AUDIT Omnicare Clinical Research may, at its option and discretion, perform an audit of the clinical study report. The clinical study report audit will examine the consistency between text and figures quoted in the version of the report *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> agreed upon with Cubist, with those appearing in the statistical tables and listings which accompany the report. This audit will include a review of all sections for format consistency and table of contents cross-reference. In addition, text and figures will be verified against the verified tables/listings and any typographical and grammatical errors that are noted. This audit is performed on the final version, following incorporation of Cubist's comments. Omnicare Clinical Research's CQA Department will oversee these activities to ensure quality as part of this service deliverable. (REST OF PAGE INTENTIONALLY LEFT BLANK) *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> o FINANCIAL CONSIDERATIONS o ESTIMATED NORTH AMERICAN BUDGET [ ]* *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> o ESTIMATED INTERNATIONAL BUDGET [ ]* (REST OF PAGE INTENTIONALLY LEFT BLANK) *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> C. PAYMENT SCHEDULES 1. INVOICING PROCESS FOR SERVICE FEES Omnicare Clinical Research maintains a project accounting system, whereby all direct project costs (service or pass-through expenses) are coded by project. An initial payment of [ ]* representing approximately [ ]* of the estimated service fees, is due and payable upon execution of this Exhibit E. Subsequent payments shall be made monthly, based on Project progress and upon submission of an invoice to Cubist by Omnicare Clinical Research. The subsequent invoices shall be reduced by a prorated portion from the initial payment such that the initial payment is applied evenly over the term of the Project. All payments shall be processed within [ ]* days. If any payment of service fees or pass through expenses is late by more than [ ]* days, such payment shall be subject to a penalty fee of [ ]* per month of the outstanding balance. 2. PASS THROUGH EXPENSE INVOICING Grant Payments - Omnicare Clinical Research will invoice [ ]* days in advance of grant payments due investigators based on estimates. Omnicare Clinical Research requires payment from Cubist at least [ ]* days in advance of the actual payment to investigators. Payments to investigators will not be released until payments are received by Omnicare Clinical Research from Cubist. Upon Cubist's request, Omnicare Clinical Research agrees to deposit payments from Cubist into a non-interest bearing bank account. Omnicare Clinical Research shall draw upon such account to make the investigator payments. Any remaining funds in the account will be returned to Cubist after the termination of the study, as soon as all contracted obligations to the investigators have been satisfied. In the event payments from Cubist are insufficient to cover the payments to investigators, Cubist will promptly advance funds to Omnicare Clinical Research for the amount of grant payments required. Omnicare Clinical Research's project accounting system is able to capture and categorize in summary the following key pass-through expenses related to Cubist's Project: o Travel o Delivery fees o CRF and other printing costs *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> All other Project related expenses that are not related to service fees and any additional detail to support pass-through costs will be provided on a fee basis. 3. ANNUAL PRICE INCREASE Notwithstanding anything contained herein to the contrary, the estimated Service Fees set forth in this Exhibit E shall remain in effect for the longer of (a) [ ]* from the date hereof, or (b) [ ]* following the date hereof. Thereafter, Omnicare Clinical Research reserves the right to increase the price of the remaining Services under this Exhibit E as of each January 1; such increases shall not exceed the [ ]*. (REST OF THE PAGE INTENTIONALLY LEFT BLANK) *Confidential treatment requested: Material has been omitted and filed with the Commission. <PAGE> VI. SIGNATORY AUTHORITY The "parties acknowledge and agree that Cubist has authorized Omnicare Clinical Research to execute all Clinical Study Agreements with investigators in the Project on behalf of Cubist. Cubist understands and acknowledges that it will be bound by the terms of the investigator agreements. ACCEPTANCE The terms and conditions of the Master Agreement govern this Exhibit E and such document is incorporated herein by reference as if fully set forth herein. BY AND BETWEEN: Cubist Pharmaceuticals, Inc. Omnicare Clinical Research, Inc. BY: /s/ MICHAEL DEBRUIN, M.D. BY: /s/ DALE B. EVANS -------------------------- ----------------- Name: Michael DeBruin Name: Dale B. Evans Title: VP Clinical Research Title: President Dated: October 12, 2000 Date: October 17, 2000

Source: OneCLE Business Contracts.