PORTIONS DENOTED WITH [***]
HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
CLINICAL DEVELOPMENT MASTER
SERVICE AGREEMENT
This Agreement
is between Miravant Pharmaceuticals, Inc., a wholly owned
subsidiary of Miravant Medical Technologies, a Delaware
corporation, with offices at 336 Bollay Drive, Santa Barbara,
California 93117 (hereinafter “Sponsor”) and Kendle
International Inc., having its principal place of business at 1200
Carew Tower, 441 Vine Street, Cincinnati, Ohio 45202 (hereinafter
“CRO”) and is effective as of the 27 th day
of April, 2005.
WITNESSETH
:
WHEREAS,
Sponsor is in the business of discovering, developing and marketing
photodynamic therapy pharmaceutical products; and,
WHEREAS, CRO is
engaged in the business of providing clinical trials management and
related clinical development services to the pharmaceutical
industry; and,
WHEREAS, both
Sponsor and CRO desire to enter into a Clinical Development Master
Service Agreement for the purpose of delineating in advance the
terms and conditions which will govern the relationship between the
parties and define the conditions under which Sponsor would award
to CRO and CRO would accept from and perform for Sponsor, certain
services.
NOW, THEREFORE,
the parties hereto agree as follows:
I.
DEFINITIONS
1.1
“Act" shall mean the Food and
Drug and Cosmetic Act.
1.2
“Agreement” shall mean
this Clinical Development Master Service Agreement as agreed
between the parties.
1.3
“EMEA” means the
European Medicines Evaluation Agency.
1.4
“FDA” means the United
States Food and Drug Administration or any successor entity
thereto.
1.5
“Investigator” means a
licensed physician engaged by Sponsor to conduct the
Study.
1.6
“IRB” means the
Institutional Review Board(s) organized in accordance with the US
Food, Drug and Cosmetic Act.
1.7
“Proposal” shall mean
written descriptions of services (and costs) offered by CRO in
response to a Request for Proposal from Sponsor.
1.8
“Protocol” shall refer
to the particular Protocol prepared for the study and under which
the Services described in the Task Order are to be
performed.
1.9
“Regulatory Authority”
shall mean: (a) any and all national, multi-national (as used in
this Agreement including without limitation the European Union), or
other governmental or industry agency or body with authority over
the manner in which a Study is conducted in a country; and/or (b)
any and all national or multi-national authority responsible for
granting regulatory approval in a particular country or
multi-national group or union of countries.
1.10
“Services” shall mean
the particular tasks to be performed by CRO as set out in any Task
Order or document attached thereto including, but not limited to,
the Proposal.
1.11
“Site” means the
physical location at which a particular Investigator conducts the
Study.
1.12
“Study” shall mean the
clinical trial of the pharmaceutical identified in the Task Order
(by study drug name or protocol number).
1.13
“Task Order” shall mean
the written agreement between Sponsor and CRO which sets out with
specificity the Services to be performed, the obligations
transferred pursuant to any federal or local law, the timeline for
the performance of the Services, the costs associated with the
Services, the schedule of payments for the performance of the
Services and specifically incorporates by reference the terms and
conditions of this Agreement. No Task Order shall be effective
until it is accepted in writing by both Sponsor and CRO. The terms
and conditions of this Agreement shall be made a part of and
incorporated by reference into each Task Order. The template Task
Order to be used by the parties is attached hereto as Exhibit
A.
|
|
|
The existence
of this Agreement shall not preclude or limit the ability of the
parties to enter into independent contracts outside of this
Agreement when the nature of the work and particular program
requirements make the entry of an independent and free standing
contract both necessary and reasonable. The existence of any
contractual relationship outside of this Agreement shall have no
effect on the validity of this Agreement or any Task Order entered
in accordance with its terms.
|
|
2.1
|
There shall be
no limit to the number of Task Orders that may be entered into and
regulated by the terms and conditions of this Agreement. Each Task
Order shall constitute a unique agreement and shall stand alone
with respect to any other Task Order entered under this Agreement.
The performance of obligations under any one Task Order shall not
effect, and shall at all times be unrelated to, the performance of
any other Task Order entered under this Agreement.
|
|
2.2
|
CRO will
perform the Services and all of its other obligations set forth
herein in strict accordance with:
|
(a)
all applicable statutes, rules and
regulations including, without limitation, the Act, the Declaration
of Helsinki, the EMEA and any proposed FDA regulations provided by
Sponsor;
(c)
the mandates of the IRB approving
the Study;
(d)
the CRO’s standard operating
procedures; and
(e)
any other written instructions from
Sponsor.
|
|
Further, CRO
will perform the Services in a competent and professional manner,
consistent with the current state of clinical research and good
clinical practices acceptable to the FDA and applicable Regulatory
Authority.
|
2.3
In the event there is any material
change totaling more than $100,000 in the scope of Services set
forth in a Task Order, the parties will agree in writing to such
change and shall cooperate with each other in reaching agreement
with respect to any corresponding increase or decrease in the Task
Order budget. Any changes in scope less than $100,000 will not
require an Amendment. Miravant agrees to pay for these additional
services.
|
2.4
|
If the
assumptions under which the parties create a Task Order budget and
timeline prove to be materially inaccurate, in whole or in part,
then the parties will review both the Task Order budget and the
timeline and make all reasonable revisions to ensure that the Study
is sufficiently funded and to promote the best interests of the
Study.
|
|
2.5
|
Unless
otherwise stated and agreed to by the parties, in the event of a
conflict between the terms of this Agreement, a Task Order, or the
Proposal, the terms of this Agreement shall govern first followed
by the individual Task Order and, lastly, the Proposal.
|
|
3.1
|
The term of
this Agreement shall commence on the date set forth above and shall
remain in effect until terminated by either party as provided
herein.
|
|
3.2
|
During times in
which there are no Task Orders in effect, this Agreement may be
terminated by either party immediately upon written notice. Sponsor
or CRO may terminate any individual Task Order immediately upon
written notice in the event of medical risk to Study participants
or upon regulatory action by the FDA or any other Regulatory
Authority in the country in which the Services are performed. Both
parties agree that termination of a Task Order shall not constitute
termination of this Agreement.
|
|
3.3
|
Either party
may terminate this Agreement or any individual Task Order as
follows:
|
|
(a)
|
on written
notice effective immediately if the other party commits a material
breach of this Agreement or a Task Order which is not cured within
thirty (30) days of receipt of written notice from the other party;
or
|
|
(b)
|
on written
notice effective immediately if the other party becomes insolvent,
is dissolved or liquidated, makes a general assignment for the
benefit of its creditors, files or has filed against it, a petition
in bankruptcy, or has a receiver appointed for a substantial part
of its assets; or
|
|
(c)
|
on sixty (60)
days prior written notice.
|
|
3.4
|
Upon early
termination of any Task Order, Sponsor shall pay to CRO (i) a
pro-rata portion of the fees owing to CRO based on the degree of
completion of the Services as of the time of termination (ii) all
pass through expenses incurred or accrued at the time of
termination; and (iii) all non-cancelable expenses;. Upon notice of
termination, the parties shall negotiate in good faith the tasks to
be undertaken and the costs associated with the winding down and
closing out of the Study or applicable Task Order.
|
|
3.5
|
In the event a
study is delayed, the parties agree to adjust the time and costs
estimates in the form of a change order. If the delay extends for
greater than one (1) month, or if the parties are unable to agree
to a change order, then either party may terminate this Agreement.
In the event this Agreement is terminated pursuant to the
foregoing, then Sponsor shall pay CRO an amount equal to (i) a
pro-rata portion of the compensation as provided under Article 9
based on the degree of completion of the services of the date of
termination; (ii) all pass-through expenses incurred up to and
including the date of termination; and (iii) all non-cancelable
expenses.
|
|
3.6
|
This Agreement
may survive its termination but only as necessary to allow
completion of any particular Task Order and for the limited purpose
of regulating the obligations and duties of the parties with
respect to particular Task Order obligations that extend beyond
contract termination.
|
IV.
REGULATORY
|
4.1
|
Both parties
shall promptly notify the other party of any regulatory inspections
of investigator sites of which it becomes aware. Where appropriate
and permitted by the Regulatory Authority, Sponsor will have the
right to be present at any such inspections and will have primary
responsibility for preparing any responses which may be required.
In the event CRO’s participation in any regulatory review is
material in terms of personnel time and expense, the parties shall
review costs associated with participation and shall agree to a
reasonable rate of compensation in advance of the performance of
any regulatory services. CRO shall reasonably act to secure the
cooperation of investigators with respect to regulatory
review.
|
|
4.2
|
As set forth in
the individual Task Orders, CRO’s personnel will make
periodic site visits to the Study sites. CRO will provide Sponsor
with visit schedules and it is agreed that Sponsor personnel may,
upon reasonable notice and in its discretion, accompany CRO’s
personnel on such site visits.
|
|
4.3
|
Designated
representatives of Sponsor shall, upon reasonable notice to CRO,
have access to and shall be permitted to review all documents,
information, data and materials in the possession of CRO directly
relating to the work performed hereunder with the exception of any
such documents, information, data and/or materials that contain
information deemed, in good faith by CRO, to be confidential,
privileged, proprietary, or not directly related to the performance
of this Agreement or any Task Order. Sponsor, its agents and its
consultants shall keep strictly confidential any documents,
information, data or materials belonging to CRO that are
confidential to CRO.
|
|
4.4
|
The transfer of
obligations from Sponsor to CRO pursuant to 21 CFR 312.52 or any
other federal or local law will be agreed to and set forth in each
individual Task Order.
|
V. OWNERSHIP OF
DATA
|
5.1
|
Except as
otherwise provided herein, all data, documents and information
provided by Sponsor to CRO together with all data or reports
generated or prepared by CRO in connection with the Study shall be
the sole and exclusive property of Sponsor. Sponsor will pay all
costs associated with the shipping and storage of documents and
records and will provide CRO with written instructions regarding
the shipping, storage and/or disposal of all such
documents.
|
|
5.2
|
Notwithstanding
the foregoing, CRO data, documents, and all information of a
privileged and/or proprietary nature, including without limitation
all CRO-developed computer software, processes, procedures and
related manuals, are the sole and exclusive property of
CRO.
|
|
5.3
|
At the
completion of the Services by CRO, all Sponsor property and
Confidential Information, regardless of the method of storage or
retrieval, shall be delivered to Sponsor in such form as is then
currently in the possession of CRO. Alternatively, at
Sponsor’s written request, such Sponsor property and
Confidential Information may be retained by CRO for Sponsor for a
period of two (2) years, or disposed of pursuant to the written
directions of Sponsor. Sponsor shall pay the costs associated with
any of the above options. CRO, however, reserves the right to
retain, at its own cost and subject to the confidentiality
provisions herein, one copy of all Sponsor property and
Confidential Information provided to Sponsor as the result of the
Services to be used to satisfy regulatory requirements or to
resolve disputes regarding the Services. Nothing in this Master
Agreement shall be construed to transfer from Sponsor to CRO any
FDA or regulatory record-keeping requirements unless such transfer
is specifically provided for in the applicable Transfer of
Obligations.
|
|
5.4
|
Sponsor may, at
its own discretion, file and prosecute in its own name and at its
own expense, applications for foreign and United States letters
patent or any patentable information derived from the Services in
accordance with this Article V. Upon the request and at the sole
expense of Sponsor, CRO shall assist in prosecuting such
applications and shall execute and deliver any and all instruments
necessary to make, file, and prosecute all such applications,
divisions, continuations, continuations-in-part, or reissue
thereof. CRO will be reimbursed for reasonable expenses and
personnel charges incurred in complying with Sponsor’s
request.
|
VI.
CONFIDENTIALITY
|
6.1
|
During the term
of this Agreement and for a period of two (2) years thereafter, CRO
and its employees, agents and contractors will keep strictly
confidential and will not use for any purpose other than as
described herein all information transmitted to it by Sponsor,
developed by CRO or generated by investigators hereunder. For
purposes hereof, confidential information shall not include, and
the obligations of confidentiality and use shall not apply to,
information that:
|
|
(a)
|
is or becomes
publicly available through no fault of CRO;
|
|
(b)
|
is received
from a third party which CRO believes in good faith has a right to
disclose it;
|
|
(c)
|
is already
known to CRO as shown by its prior written records; or
|
|
(d)
|
is required by
law, rule or regulation to be disclosed.
|
|
6.2
|
Notwithstanding
the foregoing, CRO may disclose the confidential information to
employees, consultants and/or subcontractors who have a need to
know such confidential information for purposes of performing
CRO’s obligations under this Agreement or any individual Task
Order. CRO will use its best efforts to require any third party to
whom it discloses such information to maintain its confidentiality
to the same extent as CRO.
|
|
6.3
|
It may become
necessary for CRO to disclose to Sponsor information which CRO
considers proprietary, privileged and confidential. If disclosure
occurs, then Sponsor agrees to protect the information as
confidential with same degree of care as Sponsor would protect its
own confidential information and will not use such information for
any purpose other than in connection with the performance of
obligations hereunder.
|
|
6.4
|
The parties are
subject to a Confidentiality and Non-Disclosure Agreement dated
October 19, 2004 which shall remain in full force and effect
according to its terms.
|
VII. OBLIGATIONS IN THE
EVENT OF POSSIBLITY OF FRAUD; DEBARRED PERSONS
|
7.1
|
If, during the
course of conducting the Services, CRO becomes aware of information
which indicates possible fraud at an investigator site, and after a
reasonable investigation determines that the possibility of fraud
is real, CRO will promptly inform Sponsor of its findings and it
will be the Sponsor’s responsibility to conduct a full
investigation. If this investigation confirms fraud then it will be
the responsibility of the Sponsor to notify the FDA or any other
Regulatory Authority. After completion of its investigation, the
Sponsor will provide evidence to CRO either (i) that fraud was not
committed or, (ii) if fraud was committed, that confirms the proper
reporting of the fraud or misrepresentation to the FDA. If the
Sponsor does not investigate the possible fraud within a reasonable
time, or if fraud is confirmed by investigation and the Sponsor
does not fulfill its obligations to report the fraud within a
reasonable time, then CRO will report its suspicions of possible
fraud to the appropriate governmental agency and notify the Sponsor
of this action in writing.
|
|
7.2
|
CRO represents
and warrants that CRO has not been nor is currently:
|
|
(a)
|
an individual
who has been debarred by the FDA pursuant to 21 U.S.C. §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. §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 entity of a Debarred Entity.
|
|
(c)
|
CRO further
represents and warrants that CRO has no knowledge of any
circumstances which may affect the accuracy of the representations
and warranties set forth in Section 7.2 including, but not
limited to, FDA investigations of, or debarment proceedings
against, CRO or any person or entity performing, or rendering
assistance related to, the Services. CRO will notify Sponsor
promptly upon becoming aware of any such circumstances during the
term of this Master Agreement.
|
VIII.
INDEMNIFICATION
|
8.1
|
Sponsor will
indemnify, defend and hold harmless CRO and its employees,
officers, directors, parent and affiliated companies, agents,
subcontractors, authorized independent contractors (including but
not limited to participating clinical investigators and the
providers of laboratory services) successors and assigns
(hereinafter “Indemnitee”) from all losses, costs,
expenses, liabilities and damages of every kind and nature,
including without limitation interest, penalties, reasonable
attorney’s fees and arbitration and/or litigation costs,
arising out of claims brought against CRO in connection with the
Study or CRO’s performance of this Agreement or any Task
Order (collectively the “Claims”) except to the extent
that any such Claim is caused solely by the Indemnitee’s own
negligence or intentional misconduct in the performance of its
obligations and responsibilities under this Agreement or any Task
Order.
|
|
8.2
|
Indemnitee may
tender to Sponsor the defense of any claim by giving Sponsor timely
written notice after such claim was served upon Indemnitee. Sponsor
shall defend Indemnitee from any claim so tendered to Sponsor at
Sponsor’s sole cost and expense and Sponsor shall keep
Indemnitee informed as to the progress of its defense of any such
claim. Sponsor shall have the right to control the defense and
disposition (including, without limitation, settlement, litigation
or appeal) of any such claim. The parties agree, however, that no
such settlement shall serve to establish liability on the part of
CRO, its parent, employees or agents without the express written
consent of CRO. Sponsor shall be obligated to fully indemnify the
Indemnitee as described in this Article VIII.
|
|
8.3
|
CRO agrees to
indemnify, defend and hold harmless Sponsor against any and all
losses, costs, expenses, liabilities and damage, including without
limitation interest, penalties and reasonable attorney’s fees
to the extent such losses result from CRO’s negligent
performance of the obligations required herein.
|
|
8.4
|
Upon their
written request, Sponsor will indemnify each clinical investigator
and the clinical investigator’s institution, directors,
officers, employees and agents pursuant to the terms
hereof.
|
|
8.5
|
Neither party,
nor its affiliates, nor any of their respective directors,
officers, employees or agents shall have any liability of any type
(including, but not limited to, contract, negligence, and tort
liability), for any special, incidental, indirect or consequential
damages , including, but not limited to the loss of opportunity,
loss of use, or loss of revenue or profit, in connection with or
arising out of this Agreement, any Task Order, or the Services
contemplated hereunder, even if such damages may have been
foreseeable to such party. In addition, in no event shall the
collective, aggregate liability (including, but not limited to,
contract, negligence and tort liability) of CRO and its affiliates
and its and their respective directors, officers, employees and
agents under this Agreement or any Task Order hereunder exceed the
amount of the Budget for a particular Task Order from which such
liability arose. Notwithstanding the foregoing, nothing in this
Section 8.5 is intended to limit or restrict the indemnification
rights or obligations of any party under this Article 8.
|
IX. PAYMENT AND
BUDGET
|
9.1
|
Each Task Order
will include a budget and payment schedule which will set forth
CRO’s fee for performance of the Services and the estimated
costs and expenses associated therewith.
|
|
9.2
|
In the event
Sponsor makes any material changes totaling over $100,000 to the
Study or the Services to be performed in the Task Order, the
parties will agree in writing as to any increase or decrease in the
fees and expenses in accordance with Section 2.3 of this
Agreement.
|
|
9.3
|
When
appropriate, a Task Order shall include appropriate currency
exchange rate fluctuation language to protect both parties from
losses due to such fluctuations.
|
|
9.4
|
Payments will
be made in accordance with the payment plan agreed to for each
individual Task Order. Except as provided above, Sponsor will pay
CRO within thirty (30) days of date of invoices. Checks will be
made payable to Kendle International Inc., and mailed to the
address first set forth above, “Attention:
Controller”.
|
|
9.5
|
Within sixty
seventy five (75) after the conclusion of the Services for each
Task Order, CRO will submit to Sponsor a final invoice which will
include an accounting reconciling all activities actually performed
and associated fees and costs, all payments made by Sponsor and all
amounts invoiced by CRO. Any overpayment by Sponsor shall be
credited or refunded to Sponsor by CRO at the time of submission of
such final invoice. Any underpayment by Sponsor shall be paid to
CRO within thirty (30) days after receipt by Sponsor of such final
invoice.
|
|
9.6
|
CRO shall keep
and maintain complete and accurate books and records in sufficient
detail to determine amounts owed to CRO hereunder. Such books and
records shall be maintained for at lease one (1) year following
termination of a Task Order and shall be made available for
inspection, copying and audit by Sponsor, upon reasonable notice by
Sponsor, for the sole purpose of determining the accuracy of
amounts invoiced thereunder.
|
|
9.7
|
The parties
agree that, because each Task Order shall constitute a unique
agreement, payments due under other Task Orders shall not be set
off or applied to sums due as a result of the performance of other
Task Orders.
|
|
10.1
|
Neither party
will solicit or hire employees of the other party while such
employees are providing these Services or for a period of six
months after the termination thereof without the other
party’s prior written consent. Notwithstanding the foregoing,
should either party hire any of the employees of the other party
with whom that party comes into contact as a result of the Study,
the hiring party shall pay the other 100% of such employee’s
annual compensation as a recruitment fee.
|
XI. LIMITATION OF
LIABILITY
|
11.1
|
CRO’s
entire liability or damages arising out of or related to this
Agreement, regardless of the form of action, whether in contract,
equity, negligence, intended conduct, tort or otherwise, will be
limited to and will not exceed, in the aggregate for all claims,
actions and causes of action of every kind and nature the lesser
of, i) the amount paid to CRO under this Agreement for the specific
item that caused the damage or that is the subject matter of, or is
directly related to, the cause of action, or ii) the amount paid by
Sponsor in the 12 month period proceeding such claim. In no event
will the measure of damages payable by CRO include, nor will CRO be
liable for, any amounts for loss of income, profit or savings or
indirect, incidental, consequential, exemplary, punitive or special
damages of any party, including third parties, even if CRO has been
advised of the possibility of such damages in advance, and all such
damages are expressly disclaimed. No cause of action which arose
out of an event or events which occurred more than one year prior
to the filing of a suit alleging a claim or cause of action may be
asserted by Sponsor.
|
12.1 This
Agreement may not be assigned by either party without the
other’s prior written consent which shall not be unreasonably
withheld.
|
12.2
|
The
relationship between the parties is that of an independent
contractor and neither party shall have the authority to bind or
act on behalf of the other party without its prior written consent.
This Agreement shall not constitute, create, or in any way be
interpreted as a joint venture, partnership or business
organization of any kind.
|
|
12.3
|
This Agreement
shall constitute the entire understanding of the parties and shall
not be changed or modified except in writing and signed by
authorized representatives of the parties. All prior Agreements,
whether written or oral between the parties relating to the subject
matter hereof are superseded by this Agreement and are of no
further force or effect. Notwithstanding the foregoing, the
following agreements, in existence on the date hereof, will remain
in full force and effect and are considered to be independent and
separate from this Agreement: ( Insert details of other
agreements here ).
|
|
12.4
|
The convenants
and conditions contained herein will apply to and bind the
successors, representatives and assigns of all parties
hereto.
|
|
12.5
|
If any
provision of this Agreement shall be deemed void in whole or in
part for any reason whatsoever, the remaining provisions shall
remain in full force and effect.
|
12.6 This
Agreement shall be governed by and interpreted in accordance with
the laws of the State of Ohio.
|
12.7
|
Waiver by
either party or the failure by either party to claim a breach of
any provision of this Agreement shall not be deemed to constitute a
waiver or estoppel with respect to any subsequent breach of any
provision hereof.
|
|
12.8
|
Each party, on
behalf of itself, its agents, employees, subcontractors and
representatives agree not to use the name of the other party or its
agents, employees, subcontractors and representatives in any
publication, promotional material or other writing or oral
statement for public distribution, relative to the subject matter
or existence of this Agreement, except as otherwise required by law
or SEC regulations or previously consented to in writing by the
other party. Notwithstanding the foregoing, Sponsor consents to CRO
advising prospective clients that CRO has performed clinical
research services for Sponsor.
|
|
12.9
|
Either
party’s failure to perform its obligations hereunder shall be
excused to the extent and for a period of time such nonperformance
is caused by an event of force majeure , including but not
limited to, the occurrence of war, invasion, acts of terrorism,
fire, explosion, flood, riot, strikes, acts of God, acts of
government or governmental agencies or instrumentalities or
contingencies or causes beyond such party’s reasonable
control.
|
|
12.10
|
Any notices
which either party may require or shall desire to give hereunder
will be deemed to be duly given when delivered personally or
received by the addressee through mail (electronic or postage
prepaid), telefax or telex at the address first provided above,
“Attention: General Counsel”, or to other address(es)
of which such party shall have given written notice. Notices given
other than through postage prepaid mail shall be confirmed by
postage prepaid mail.
|
|
12.11
|
This Agreement
is designed, where appropriate and where required under any
individual Task Order, to accommodate the provision of services on
a global basis. Under such circumstances, Sponsor acknowledges that
all or part of the Services may be performed by CRO, its
subsidiaries or affiliates and that such performance will
constitute performance by the CRO for purposes of this Agreement
and the individual Task Order.
|
|
12.12
|
Articles, 5, 6,
8, 11.1, 12.5, 12.6, 12.7, 12.8, 12.10 and this Section 12.12 shall
survive termination of this Agreement and shall be binding to the
respective successors, assigns, subsidiaries or
affiliates.
|
|
12.13
|
CRO
shall maintain adequate levels and types of
insurance coverage appropriate to its business, including without
limitation workers’ compensation, comprehensive general
liability, and errors and omissions coverage.
|
|
12.14
|
No printed
standard terms appearing on any purchase order, invoice or despatch
order relating to the Services will be effective in adding or
changing the terms of this Agreement (or any Task
Order).
|
AS TO SPONSOR:
AS TO CRO:
By:
/s/ Glenn A. Wilson
By: /s/ Karl Brenkert
Name:
Glenn A. Wilson
Name: Karl Brenkert
Title:
Sr. Vice President Pharmaceuticals Title: Sr.
Vice President & CFO
Date:
May 2, 2005
Date: April 28,
2005
Title: Chief
Financial Officer
Miravant
Pharmaceuticals, Inc. (“Sponsor”) and Kendle
International Inc. (“Kendle”) have entered into a
Clinical Development Master Services Agreement dated
_______________(“Master Agreement”) which provides that
a Task Order be entered into to set out with specificity the
details of a particular Study. The terms contained herein are
pursuant to and governed by such Master Agreement.
The Master
Agreement effective as of __________ is hereby incorporated by
reference.
This Task Order
is effective as of the _____ day of February, 2005 and shall
terminate at the conclusion of the work to be performed by
Kendle.
A.
Description of Services
|
3.
|
Responsibilities Overview
|
B.
Timeline for Performance of Services [Kendle and
Sponsor shall cooperate to meet the timelines set forth
below.]
C
Description of Transferred Obligations
D.
Budget which shall include the following
information:
|
1.
|
Total amount of
Work Order;
|
|
2.
|
Identification
of pass-through expenses, if any, as fixed or pass-throughs;
and
|
|
3.
|
Amount of
expenses allocated to travel, investigator payments, and
other.
|
E.
Schedule of Payment which shall include the
following information:
|
1.
|
Sponsor billing
address and billing contact person information;
|
|
2.
|
Third party
Federal Express billing number, if appropriate;
|
|
3.
|
Type of
invoice, i.e. time and materials, milestone, unit or otherwise;
and
|
|
4.
|
Currency
exchange rate fluctuation language as follows (IF
APPLICABLE):
|
1. Since
pricing and subsequent invoicing are denominated in [U.S. dollars]
while at least a portion of expenditure on the services provided
will arise in (one or more different currencies), and the contract
pricing totals do not include a margin to cover currency exchange
rate fluctuations (“CERF”), the parties agree to review
CERF’s every three months throughout the term of this Task
Order in accordance with this Section ___.
2. The contract
pricing is based on the following exchange rates : 1 US dollar =
_________ Pounds Sterling = _______ Euro (etc.). Provided no
currency in which expenditure occurs increases or decreases by more
than 3% with respect to the (original pricing currency, same as in
1 above), the review will conclude that no adjustment to the
original pricing is required in relation to the services provided
to that date.
3. Where a CERF
between the [U.S. dollar] and any other currency of expenditure
exceeds 3%, one party will have the potential for gain and the
other will have the potential for unacceptable and unintentional
loss. Both parties agree that where this occurs it will be
necessary to adjust the pricing of the services to eliminate any
loss which would otherwise be incurred by the CRO or Sponsor
through no fault of either party.
4. Sponsor
agrees that if a CERF produces an unscheduled loss not specifically
included in the contract price, Sponsor will agree to a positive
price adjustment (i.e. a payment to the CRO) in relation to the
services affected, with the effect of offsetting this loss in its
entirety.
|
5.
|
The CRO agrees
that if a CERF produces an unscheduled gain not included in the
contract price, the CRO will agree to a negative price adjustment
(i.e. a reduction in price) in relation to the services affected,
with the effect of offsetting this gain in its entirety. In the
calculation of the adjustments referred to above, the % CERF will
be multiplied by the proportion of service pricing that is
denominated in the currencies that have been subject to the CERF,
and these services will then be invoiced at the adjusted prices
until reviewed by the parties.
|
AGREED TO AND
ACCEPTED BY
KENDLE
INTERNATIONAL INC.
MIRAVANT PHARMACEUTICALS,
INC.
_______________________________
____________________________
Name:
Name: Glenn A. Wilson
Title:
Title: Sr. VP, Pharmaceuticals
Date:
Date:
____________________ _______
Name:
John M. Philpott
Title: Chief
Financial Officer
Date:
PORTIONS DENOTED WITH [***]
HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND
EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR CONFIDENTIAL
TREATMENT
TASK
ORDER
For Study
31293
Miravant
Pharmaceuticals, Inc. and Kendle International Inc. have entered
into a Clinical Development Master Services Agreement dated April
27, 2005 (“Master Agreement”) which provides that a
Task Order be entered into to set out with specificity the details
of a particular Study. The terms contained herein are pursuant to
and governed by such Master Agreement.
The Master
Agreement effective as of April 27, 2005 is hereby incorporated by
reference.
This Task Order
is effective as of the 14th day of June, 2005 and shall terminate
as of the 1st day of July, 2008.
A.
Protocol : “MRVT-920101-OPH005, A
Phase III Randomized multicentre, multinational, double-masked
placebo controlled study of Photrex™ (Rostaporfin)
Photodynamic Therapy in the treatment of classic and occult
subfoveal choroidal neovascularization associated with age-related
macular degeneration.”
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR
CONFIDENTIAL TREATMENT
The table below
and the endnotes which follow summarize the assumptions used for
the key cost drivers for Miravant’s project. Certain
assumption changes may result in a revision in costs. If this
situation appears likely, it will be discussed fully with
Miravant.
|
Service
|
Category
|
Description
|
Assumption
|
|
General
Study Parameters
|
|
|
|
Site
and Patient Information
|
|
|
|
|
Number of
sites
|
[***]
|
|
|
|
Number of
participating countries
|
[***]
|
|
|
|
Participating
countries and number of sites per country
|
[***]
|
|
|
|
Participating
countries and number of enrolled patients per country
|
[***]
|
|
|
|
Number of
screened patients
|
[***]
|
|
|
|
Number of
enrolled patients
|
[***]
|
|
|
|
Number of
completed patients
|
[***]
|
|
|
|
Screen failure
rate
|
15 %
|
|
|
|
Drop out
rate
|
10.9 %
|
|
|
|
SAE
rate
|
2.3 %
|
|
|
|
Number of
SAEs
|
[***]
|
|
|
Project
Period
|
|
|
|
|
Implementation
|
[***]
|
|
|
|
Enrollment
duration
|
[***]
|
|
|
|
Treatment
duration
|
[***]
|
|
|
|
Study close out
(treatment end through submission of final clinical study report to
sponsor)
|
[***]
|
|
|
|
Total project
duration
|
[***]
|
|
|
CRF
Pages
|
|
|
|
|
e-CRF pages per
completed patient (Miravant Assumption)
|
82
|
|
|
|
Unique e-CRF
pages (Miravant Assumption)
|
14
|
|
|
|
Total number of
CRF pages
|
60,762
|
|
|
Miscellaneous
|
|
|
|
|
Number of
Central Labs
|
1
|
|
|
|
Number of
Associate CROs
|
2
|
|
Study
Documents
|
|
|
|
CRFs
|
|
|
|
|
Develop
CRF
|
Included in EDC set up
Costs
|
|
|
|
Review
CRF
|
Yes
|
PORTIONS
DENOTED WITH [***] HAVE BEEN OMITTED AND FILED SEPARATELY WITH THE
SECURITIES AND EXCHANGE COMMISSION PURSUANT TO A REQUEST FOR
CONFIDENTIAL TREATMENT
|
|
|
Ship
CRFs
|
No
|
|
|
|
Print
CRFs
|
N/A EDC
|
|
|
Protocol and Informed
Consent
|
|
|
|
|
Develop and
write Informed Consent (does not include revisions)
|
Yes
|
|
|
|
Use sponsor
provided template to write consent
|
Yes
|
|
|
Miscellaneous
|
|
|
|
|
Translate study
documents
|
Yes
|
|
|
|
Ship final
study documents to sponsor
|
Yes
|
|
Drug
and Clinical Trial Materials Management
|
|
|
|
Drug
Management
|
|
|
|
|
Drug Management
provided by 3rd party vendor
|
Yes (fees included in pass through
costs)
|
|
|
|
Ship
drug
|
Yes
|
|
|
|
Number of drug
shipments per site
|
7
|
|
Site
Identification / Essential Document Collection
|
|
|
|
Site
Identification
|
|
|
|
|
Conduct
feasibility analysis
|
No - Already Paid for Under Separate
Contract
|
|
|
|
Identify
sites
|
Yes
|
|
|
|
Kendle
responsible for confidentiality agreements
|
Yes
|
|
|
|
Number of sites
identified by Kendle
|
[***]
|
|
|
|
Number of sites
contacted by Kendle to identify requested number of
sites
|
[***]
|
|
|
Essential Document
Collection
|
|
|
|
|
Collect
essential documents
|
Yes
|
|
|
|
Number of sites
requiring document collection
|
[***]
|
|
IRB and
Ethics Committee Submissions
|
|
|
|
IRB /
Ethics Committee Submissions
|
|
|
|
|
Obtain
IRB/Ethics Committee approvals
|
Yes
|
|
|
|
Number of local
Ethics Committee submissions (Note: some countries require one
submission per site)
|
[***]
|
|
Clinical Regulatory
|
|
|
|
General
|
|
|
|
|
Submit Clinical
Trial Application to Regulatory Authorities (includes preparation
of IMPD in Europe)
|
Yes
(Costs reflected in fee estimate are
based on detailed assumptions outlined in proposal text)
|
|
|
|
Number of
countries submitting to Regulatory Authorities (Note: some
countr
|
|
