CLINICAL RESEARCH SERVICES AGREEMENT
BETWEEN
YM BIOSCIENCES, INC.
AND
PHARM-OLAM INTERNATIONAL LTD.
PAGE 1 OF 19
CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
TABLE OF CONTENTS
RECITALS 1
1. DEFINITIONS 1
2. INTERPRETATION 7
3 APPOINTMENT & RELATIONSHIP OF PARTIES 7
4. REPRESENTATIONS & WARRANTIES 8
5. POI's OBLIGATIONS 8
6. YM's OBLIGATIONS 10
7. LIMITATION OF LIABILITY 10
8. CRO COMPENSATION 10
9. AUDIT 11
10. CLINICAL STUDY AGREEMENT NEGOTIATION 12
11. INSURANCE 12
12. CONFIDENTIALITY 12
13. INTELLECTUAL PROPERTY 13
14. ARBITRATION 13
15. NON-SOLICITATION OF STAFF 14
16. TERM & TERMINATION 14
17 CONSEQUENCES OF TERMINATION 16
18. REPETITION OF THE STUDY 17
19. DELAYS 17
20. GENERAL PROVISIONS 17
21. APPLICABLE LAW 19
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CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
SCHEDULE 1 CONSIDERATION & COST CALCULATION (POI Budget Proposal)
SCHEDULE 2 PAYMENT SCHEDULE
SCHEDULE 3 CLINICAL STUDY AGREEMENT TEMPLATE
SCHEDULE 4 ADVERSE EVENT REPORTING
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CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
This Clinical Research Services Agreement (this Agreement) is made and entered
into effective as of 16 December 2003 (the "Effective Date"), by and between YM
BIOSCIENCES, INC. (hereafter "YM"), a Canadian corporation, with its principal
office at 5045 Orbitor Drive, Building 11, Suite 400, Mississauga, Ontario L4W
4Y4, Canada, and PHARM-OLAM INTERNATIONAL Ltd. (hereafter "POI"), a Texas
limited partnership, with its principal office at 000 Xxxxxxxxx, Xxxxx 000,
Xxxxxxx, XX 00000, Xxxxxx Xxxxxx.
RECITALS
WHEREAS, YM develops, manufactures, and sells pharmaceutical products;
and
WHEREAS, POI is a contract research organization that plans, implements,
and manages clinical trials; and
WHEREAS, YM desires to engage POI to assist YM in planning, implementing,
and managing a clinical trial on the Investigational Product, as hereafter
defined; and
WHEREAS, POI is willing to accept such engagement on the terms and
conditions set forth herein;
NOW, THEREFORE, in consideration of the premises and the mutual covenants
and obligations set forth herein, and for other good and valuable consideration,
the receipt and sufficiency of which are acknowledged, the parties agree as
follows:
1. DEFINITIONS
For purposes of this Agreement and the Protocol, each capitalized term
shall have the meaning ascribed to it in this Agreement. Each capitalized term
not defined in this Agreement shall have the meaning ascribed to that term in
the Protocol. In the event of a discrepancy in the meaning ascribed to a term in
the body of this Agreement and the meaning ascribed to that term in the
Protocol, the definition utilized in the body of this Agreement shall control.
1.1 "Case Report Form" or "CRF" means the record of pertinent
information collected on each subject who participates in the Study;
1.2 "Clinical Laboratory Agreement" means the Agreement between POI
and the clinical laboratory or laboratories that will provide clinical
laboratory services for the Study.
1.3 "Clinical Research Associate" or "CRA" means the person assigned
by POI to monitor one or more Study sites.
1.4 "Clinical Trial Agreement" means the agreement between POI and
an Investigator that details the respective rights and obligations of both
parties in relation to the Study;
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CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
1.5 "Clinical Trial Materials" means the Investigational Product,
competitor substances, the Protocol, the investigational drug brochure, informed
consent form, guidelines for use of the Investigational Product, and all other
materials provided by YM to conduct the Study.
1.6 "Closeout Services" means those services described in Section 17
to be performed by POI upon termination of this Agreement.
1.7 "Confidential Information" means any information, whether
written or oral, including all notes, studies, customer lists, forms, business
or management methods, marketing data, fee schedules, or trade secrets of any
member of the POI Group or of YM, as appropriate, disclosed or otherwise made
available to one party by the other party pursuant to this Agreement.
Confidential Information shall also include the terms and provisions of this
Agreement and any transaction or documents executed by the parties pursuant to
this Agreement. In addition, Confidential Information shall include any data,
including clinical study data, or information developed or generated in the
course of performance of this Agreement. Publication of the fact that YM and POI
have entered into a clinical research service agreement, without disclosing the
terms and provisions of this Agreement, shall not be construed as unauthorized
disclosure of Confidential Information.
Confidential Information does not include any information that (i)
is or becomes generally available to and known by the public, other than as a
result of an unauthorized disclosure directly or indirectly by the receiving
party or its affiliates, advisors, or representatives; (ii) is or becomes
available to the receiving party on a non-confidential basis from a source other
than the furnishing party or its affiliates, advisors, or representatives,
provided that such source is not and was not bound by a confidentiality
agreement with or other obligation of secrecy to the furnishing party of which
the receiving party has knowledge at the time of such disclosure; or (iii) has
already been or is hereafter independently developed by the receiving party by
persons not having access to the Confidential Information of the furnishing
party.
1.8 "Data Safety Monitoring Board" means the group of individuals
appointed to monitor safety issues relating to the Study.
1.9 "CRO Compensation" means the compensation to be paid by YM to
POI as set out in Schedules 1 and 2.
1.10 "Effective Date" means the effective date of this Agreement as
set forth in the initial paragraph of this Agreement.
1.11 "Food and Drug Administration" or "FDA" means the United States
government agency responsible for ensuring compliance with the Food, Drug, and
Cosmetics Act of 1938.
1.12 "Force Majeure Event" means an event beyond the reasonable
control of the relevant party including, but not limited to, acts of God, a
public enemy, or a civil or military authority; fires or other catastrophes;
strikes, lockouts, or other industrial action taken by the employees of any
party or any third party; delays in transportation; riots; or invasions, wars,
or threats of war.
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CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
1.13 "Good Clinical Practice" means the clinical standards
established by the FDA and counterpart agencies of each country in which the
Study will take place, designed to regulate the activities of YM's
investigators, monitors, and Institutional Review Boards involved in clinical
drug testing.
1.14 "Institutional Review Board/Ethics Committe" or "IRB/EC" means
the independent group of professionals designated to ensure that the Study is
safe and effective for human participation and that the Study adheres to the
regulations issued by the FDA and any other applicable country-specific laws,
regulations or guidelines.
1.15 "Investigational New Drug Application" or "IND" means the
petition filed by YM with the FDA requesting the FDA to allow human testing on
the Investigational Product.
1.16 "Investigational Product" means the product (drug, device, or
biologic) described in the Protocol that will be evaluated in this Study.
1.17 "Investigator" means an individual who actually conducts a
clinical investigation, i.e., under whose immediate direction the
Investigational Product is administered or dispensed to, or used involving a
subject, or, in the event of an investigation conducted by a team of
individuals, is the responsible leader of that team.
1.18 "POI Group" means the following persons and entities, as
constituted at the date of this Agreement or subsequently: (i) POI; and (ii) any
person or entity that directly, or indirectly through one or more
intermediaries, controls, is controlled by, or is under common control with POI.
1.19 "POI's Obligations" means the obligations of POI under this
Agreement.
1.20 "Project Manager" means the manager assigned by POI to be the
primary contact person between POI and YM during the Study.
1.21 "Protocol" means the plan that describes the objectives, study
design, and methodology of the Study entitled, "A Phase III study of DPPE
(tesmilifene) combined with Epirubicin and Cyclophosphamide versus Epirubicin
and Cyclophosphamide alone as first line Treatment in Metastatic/Recurrent
Breast Cancer," and any approved amendments thereto, which is herein
incorporated by reference.
1.22 "Regulatory Requirements" means those laws, regulations, and
professional and ethical standards and guidelines then in effect in the
countries in which the Study is conducted that apply to the Investigational
Product or clinical trials in general.
1.23 "Related Products" means any product (drug, device, or
biologic), other than the Investigational Product, administered or utilized as
part of this Study.
1.24 "Serious Adverse Event" shall take the meaning given this term
in the Protocol.
1.25 "Services" means the services to be furnished by POI in
connection with the Study as set out in this Agreement including the schedules.
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CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
1.26 "Standard Operating Procedures" or "SOP's" means internal
procedures for the management of a clinical trial designed to ensure that the
trial is carried out in a consistent, controlled, and effective manner.
1.27 "Study" means the clinical trial of the Investigational
Product, the details of which are set out in the Protocol.
1.28 "Study Documents" means the documents produced by POI in
connection with the Study that are necessary for the production of the final
study report.
1.29 "Term" means the duration of this Agreement as set out in
Section 16.
1.30 "YM's Obligations" means the obligations of YM under this
Agreement.
2. INTERPRETATION
2.1 Words of any gender used in this Agreement shall be held and
construed to include any other gender, and words in the singular number shall be
held to include the plural, and the plural to include the singular, unless the
context requires otherwise.
2.2 The headings of the sections of this Agreement are inserted for
convenience only and in no way define, limit, or prescribe the intent of this
Agreement.
2.3 Unless otherwise specified, references in this Agreement to
Sections and Schedules are to the sections of, and schedules to, this Agreement.
All Schedules are deemed to be incorporated into, and form part of, this
Agreement, and the term "Agreement" shall be construed accordingly.
2.4 Unless otherwise specified, any reference to a statute, rule, or
regulation shall be to that statute, rule, or regulation as amended from time to
time.
2.5 If the terms of this Agreement, including the Schedules, and the
Protocol should conflict, the terms of this Agreement shall control.
3 APPOINTMENT AND RELATIONSHIP OF PARTIES
3.1 YM hereby engages the services of POI, and POI accepts such
engagement, under the terms and conditions contained in this Agreement.
3.2 During the Term, POI shall at all times be the independent
contractor of YM, and nothing in this Agreement is intended, nor shall be
construed, to create between YM and POI the relationship of principal and agent,
employer and employee, partnership, or joint venture, and the parties shall not
represent themselves otherwise.
3.3 YM shall be liable for its own debts, obligations, acts or
omissions, including but not limited to the payment of all required
compensation, withholding, social security and other taxes or benefits for YM's
employees. Likewise, POI shall be liable for its own debts, obligations, acts or
omissions, including but not limited to the payment of all required
compensation, withholding, social security and other taxes or benefits for the
Investigators and POI's employees.
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CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
3.4 If the Internal Revenue Service or any other government
authority shall, at any time, question or challenge the independent contractor
status of POI, upon receipt by either party of notice from the Internal Revenue
Service or any other governmental authority, the receiving party shall promptly
notify the other party and afford the other party the opportunity to participate
in any discussion or negotiation with the Internal Revenue Service or other
government authority, regardless as to who initiates such discussions or
negotiations.
4. REPRESENTATIONS AND WARRANTIES
4.1 POI warrants to YM that (i) it has the authority to enter into
this Agreement; and (ii) all consents and approvals required for the Study, have
been, or will be obtained prior to initiation of the Study, with the exception
of regulatory approval by Health Canada and the United States Food and Drug
Administration, which will be obtained by YM.
4.2 POI warrants and represents that it has not been and is not
currently an individual, corporation, partnership, association or entity that
has been debarred by the FDA pursuant to United States regulation 21 U.S.C.
ss.335a (a) or (b) ("Debarred Person"). POI further warrants and represents that
no Debarred Person has performed or rendered, or will perform or render, any
services or assistance relating to activities taken pursuant to this Agreement.
POI further warrants and represents that it has not been excluded from
participation in any Federal health care program as defined in United States
Regulation 42 U.S.C 1320a-7b(f) ("Excluded Person"). POI further warrants and
represents that no Excluded Person has performed or rendered, or will perform or
render, any services or assistance relating to activities taken pursuant to this
Agreement.
4.3 YM warrants to POI that it has the authority to enter into this
Agreement.
5. POI'S OBLIGATIONS
In addition to POI's Obligations set forth in the Schedules, the
Protocol and elsewhere in this Agreement, POI shall have the following
obligations:
5.1 Before commencement of the Study, POI shall assign to the Study
a Project Manager and sufficient personnel, including CRAs, with suitable
experience and training to fulfill POI's obligations under this Agreement. Any
change in the Project Manager thereafter must be reasonably acceptable to YM. YM
may request that POI remove any personnel, including the Project Manager whom XX
xxxxx, in its sole discretion, to be unfit or otherwise unsatisfactory. POI
shall promptly replace any such personnel with personnel of similar skills and
experience.
5.2 POI shall apply to the Study systems of quality control designed
to ensure that the generation of data, and the recording and reporting of data
is in compliance with the Regulatory Requirements, Good Clinical Practice, the
Protocol, and this Agreement, in that order.
5.3 POI shall use its best efforts to perform the Services within
the time frames specified in the Schedules.
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5.4 POI shall be responsible for all the legal and regulatory
requirements, including applicable guidelines, in all countries in which the
Study will be conducted, with the exception of (i) regulatory approval by Health
Canada and the United States Food and Drug Administration to conduct the Study,
which will be obtained by YM, and (ii) adverse event reporting to Health Canada
and the United States Food and Drug Administration which will be done by YM.
Such responsibilities of POI shall include, but are not limited to, the
procurement and maintenance of all consents, approvals, licenses, and operating
certificates required to conduct the Study in the applicable country, including
translations, and the approval of the Protocol and the informed consent forms by
an IRB/EC. POI shall also develop, comply with, and require its agents,
employees and contractors to comply with, policies and procedures designed to
assure, at all times, that such consents, approvals, licenses, and operating
certificates remain in effect throughout the Term. POI shall ensure that any
institutions and investigational teams retained to participate in the Study have
the necessary staff and other resources to carry out the Study in accordance
with the timelines required by YM. POI further agrees to ensure that any
institutions and investigational teams retained to participate in the Study have
the expertise and experience, and the necessary licences, required to perform
the Study efficiently and that such Study shall be performed with care and skill
and to the best of their ability commensurate with such skill and experience and
adhering at all times to applicable laws.
5.5 POI shall retain all material Study Documents and CRFs until
this Agreement has terminated and all Closeout Services have been performed. All
Study Documents and CRFs will be forwarded to YM after the Study is completed or
upon termination of this Agreement. YM shall be permitted full access to such
Study Documents and CRFs at any time upon written request to POI.
5.6 YM shall have the right to visit and co-monitor a Study site or
inspect and audit any of the Study Documents and CRFs maintained by POI. All
such visits and inspections must be conducted during normal working hours on
regular business days, unless otherwise agreed. POI shall arrange access to the
Study site as soon as reasonably practicable following notification by YM.
5.7 POI will provide YM with written status reports in accordance
with POI's SOPs.
5.8 POI shall notify YM after becoming aware of a Serious Adverse
Event in accordance with the procedure set out in Schedule 4.
5.9 POI shall indemnify and save harmless YM, its officers, agents,
and employees from all third party suits, actions, losses, damages, claims, or
liability of any character, types, or description, including without limiting
the generality of the foregoing, all expenses of litigation, court costs, and
reasonable attorney's fees arising from (i) injury or death to any person, or
injury to property, received or sustained by any person or persons or property,
arising out of, or occasioned by POI (or its agents or employees), in connection
with its execution or performance of services under this Agreement; (ii) any
negligent wrongful act or omission, reckless conduct or willful misconduct of
POI, its employees, agents, directors and officers; or (iii) any deviation by
POI from the terms of the Protocol or this Agreement or requirements or
restrictions imposed by an IRB/EC. The Investigators are not and shall not be
deemed the agents of POI for purposes of this Section 5.9. YM will notify POI of
any claim or suit which may be subject to the provisions of this Section 5.9 as
soon as reasonably practicable after receiving notice of the claim. POI shall
have the sole right to control and settle any such claim or suits, and YM shall
make all reasonable efforts to cooperate (at POI's expense) as requested by POI
in handling any such claim or suit.
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CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
6. YM'S OBLIGATIONS
In addition to YM's Obligations set forth in the Schedules and
elsewhere in this Agreement, YM shall have the following obligations:
6.1 YM shall provide POI, at no expense to POI (i) with all
information and documentation reasonably necessary for POI to perform its duties
hereunder, including but not limited to, all Clinical Trial Materials; and (ii)
with all advice, guidance, and assistance reasonably requested by POI to fulfill
it duties under this Agreement, including the schedules, and the Protocol.
6.2 YM shall be responsible for (i) obtaining regulatory approval
from Health Canada and from the United States Food and Drug Administration to
conduct the Study in Canada and in the United States; and (ii) reporting adverse
events to Health Canada and to the United States Food and Drug Administration in
conformance with the legal and regulatory requirements.
6.3 YM shall indemnify and save harmless POI, its officers, agents,
and employees from all third party suits, actions, losses, damages, claims, or
liability of any character, types, or description, including without limiting
the generality of the foregoing, all expenses of litigation, court costs, and
attorneys' fees for injury or death to any person, or injury to property
(collectively, "Claims"), received or sustained by any person or persons or
property, arising out of, or occasioned by the Investigational Product or the
acts or omissions of YM (or its agents or employees), in connection with the
Study or their execution or performance of this Agreement except to the extent
that such Claims arise from or are caused (i) by POI's (its agents or employees)
execution or performance of services under this Agreement; (ii) any negligent
wrongful act or omission, reckless conduct or willful misconduct of POI, its
employees, agents, directors and officers; or (iii) any deviation by POI from
the terms of the Protocol or this Agreement or requirements or restrictions
imposed by an IRB/EC. POI will notify YM of any claim or suit which may be
subject to the provisions of this Section 6.2 as soon as reasonably practicable
after receiving notice of the claim. YM shall have the sole right to control and
settle any such claims or suits, and POI shall make all reasonable efforts to
cooperate (at YM's expense) as requested by YM in handling any such claim or
suit.
7. LIMITATION OF LIABILITY
NOTWITHSTANDING THE ABOVE, NEITHER PARTY, NOR THEIR AFFILIATES, NOR
ANY OF THEIR RESPECTIVE DIRECTORS, OFFICERS, EMPLOYEES, OR AGENTS SHALL HAVE ANY
LIABILITY FOR ANY SPECIAL, INCIDENTAL, INDIRECT, OR CONSEQUENTIAL DAMAGES,
INCLUDING BUT NOT LIMITED TO THE LOSS OF OPPORTUNITY, OR LOSS OF REVENUE OR
PROFIT.
8. CRO COMPENSATION
8.1 YM shall pay POI the amounts set forth in Schedules 1 and 2 for
all services provided and expenses incurred by POI pursuant to this Agreement,
according to the payment schedule set forth in Schedule 2.
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CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
8.2 POI shall submit invoices to YM upon the completion of each
payment milestone event set forth in Schedule 2. YM shall make full payment of
such sums by cheque or in cleared funds to such bank account in the United
States as POI may reasonably specify from time to time, upon receipt of invoice
("Due Date"), without any deduction, set off or withholding except any tax,
duties or governmental charges which YM is required by law to deduct or
withhold. Any amounts which remain unpaid for ninety (90) days or more after the
Due Date shall bear interest at the rate equal to 10% per annum. Interest shall
be computed on the basis of a 365 or 366-day year, as the case may be. If any
amounts remain unpaid for ninety (90) days or more after the Due Date, POI shall
have the right to discontinue all work and services under this Agreement until
such amounts are paid in full.
8.3 If YM is required by law to make any tax deduction or
withholding, YM shall provide reasonable assistance as requested by POI to
assist POI to claim exemption from, or if that is not possible a credit for, the
deduction or withholding under any applicable double taxation or similar
agreement. YM shall also supply POI from time to time with proper evidence as to
the deduction or withholding and payment over of the tax deducted or withheld.
8.4 YM shall reimburse POI for all reasonable airfare, hotel, and
other travel expenses incurred by POI in its performance of the Services,
including but not limited to, expenses incurred by POI in connection with
initiation visits, monitoring visits, and closeout visits and in connection with
attendance at Project Meetings and Investigators' Meetings. YM shall also
reimburse POI for all photocopying, courier, and other similar expenses incurred
by POI in its performance of its duties under this Agreement. Notwithstanding
the foregoing, YM shall not be responsible for any costs described in this
Section 8.4 that exceed the amounts budgeted for such expenses in Schedule 1,
without prior written approval being obtained from YM. Any amounts approved by
YM in excess of those specified in Schedule 1, shall be separately invoiced to
YM and YM shall pay these invoices according to the terms of Paragraph 8.2.
9. AUDIT
9.1 POI shall maintain and shall cause to be maintained, complete
and accurate books of account containing all particulars that may be necessary
for the purpose of calculating any fees, expenses or other costs (collectively,
the "Service Costs") relating to the Services and any deliverables as set out in
Schedule 1. Such books of record shall be kept at its principal place of
business.
9.2 Upon the written request of YM, POI shall permit YM or its third
party independent auditors to have access during normal business hours, upon ten
(10) days' notice to POI, to such records, including working papers and
supporting documents, of POI, its independent contractors and agents as may be
reasonably necessary to verify the accuracy of the Service Costs.
9.3 If any audit reveals any overpayment of Service Costs, POI shall
forthwith pay the amount of the overpayment to YM; provided however, that, in
the event that POI shall not be in agreement with the amount of the overpayment,
such matter shall be resolved pursuant to the provisions of Section 14 herein.
9.4 If any audit reveals any underpayment of Service Costs, YM shall
forthwith pay the amount of the underpayment to POI, provided however, that, in
the event that YM shall not be in agreement with the amount of the overpayment,
such matter shall be resolved pursuant to the provisions of Section 14 herein.
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CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
9.5 Both parties shall treat all financial information subject to
review under this Section 9 in accordance with the confidentiality provisions of
this Agreement.
9.6 The costs of conducting any audit hereunder shall be borne by YM
unless the audit reveals an overpayment of Services Costs of greater than 5% in
which case, costs shall be borne by POI up to a maximum of THIRTY THOUSAND
DOLLARS (USD $30,000.00).
10. CLINICAL STUDY AGREEMENT NEGOTIATION
Where possible, POI will endeavour to use the Clinical Study Agreement
template attached at Schedule 3 to this Agreement when entering into agreements
with any investigational teams or sites engaged for the purpose of conducting a
clinical trial on the Investigational Product in the United States and Canada.
POI shall not make any modification to the Clinical Study Agreement template
attached at Schedule 3 or enter into any clinical study agreement using such
modified form of agreement without YM's prior written approval. In any case, POI
shall not enter into any agreement with any investigational teams or sites
engaged for the purpose of conducting a clinical trial on the Investigational
Product, without YM's approval of the form and content of the agreement.
11. INSURANCE
11.1 YM and POI shall each maintain, at its sole cost and expense,
insurance coverage with a reputable insurer (which shall be either occurrence
based or claims made coverage) in an amount usual and customary for companies
engaged in activities as contemplated by this Agreement. All such insurance
shall be in place before the first patient is enrolled in the Study. Each shall
designate the other party as an additional named insured on all such policies,
and an endorsement shall be made on each such policy prohibiting the insurer
from canceling the policy for any reason or substantially modifying its terms
without first giving the other party at least twenty- eight (28) days written
notice of its intention to do so.
If either party maintains a claims-made policy and this Agreement
expires or terminates for any reason, then that party shall either continue to
maintain the same or higher coverage with the same insurance carrier for a
period of four (4) years thereafter; or shall purchase "Tail Coverage" effective
until the fourth (4th) anniversary date of the expiration or termination of this
Agreement or obtain and maintain "Prior Acts" coverage equivalent in time and
coverage as the "Tail Coverage" described herein.
11.2 Upon request by either party, the other party shall provide
evidence of that party's compliance with this Section.
12. CONFIDENTIALITY
12.1 Except as specified in the following Section 12.2, each of the
parties agrees (i) that it shall not disclose any Confidential Information of
the other party to other persons without the express written authorization of
the other party; (ii) that such Confidential Information shall not be used in
any way detrimental to the other party or for any purpose not related to the
performance of the Services or the Study; and (iii) that the parties will keep
such Confidential Information confidential and will ensure that its affiliates
and advisors who have access to such Confidential lnformation comply with these
non-disclosure obligations.
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CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
12.2 Notwithstanding the foregoing, the parties may disclose
Confidential Information to (i) those of its representatives, including, but not
limited to the other party's legal, financial and accounting advisors, who need
to know Confidential Information for the purpose of conducting this Study, it
being understood and agreed by the parties that such representatives will be
informed of the confidential nature of the Confidential Information, will agree
to be bound by this Section 12, and will be directed by the respective party not
to disclose to any other person any Confidential Information; and (ii) the FDA,
an IRB/EC, or comparable governmental or professional body with jurisdiction
over the Study provided such disclosure is requested by the respective
governmental or professional body or is required in order to satisfy Section
5.4.
12.3 In the event that either party determines that it is required
by law to disclose the other party's Confidential Information, or such
disclosure is in response to a subpoena or a similar legal process, such
disclosure shall be permitted provided that the other party required to make
such disclosure promptly notifies the other party and assists the other party in
obtaining a protective order or other appropriate remedy.
13. INTELLECTUAL PROPERTY
13.1 POI acknowledges and agrees that any and all intellectual
property rights (including, but not limited to, inventions, discoveries,
improvements and know-how, whether patentable or not) that may arise or be
conceived during, or are related to, the Study , including without limitation
all data generated in the course of the Study, completed Case Report Forms and
all Clinical Trial Materials (hereinafter the "Intellectual Property") shall
belong solely to YM. POI shall cooperate with YM, and shall use its best efforts
to ensure that any institutions and investigational teams which participate in
the Study, including their employees and agents, cooperate with YM, in obtaining
assignments or other documents required to transfer to YM all Intellectual
Property. In addition, POI shall use its best efforts to ensure that any
institutions and investigational teams which participate in the Study, including
their employees and agents, cooperate with YM, at YM's sole expense, in
preparing patent applications relating to the Intellectual Property, where
required.
13.2 The Parties agree that POI has no rights to publish or present,
at any time, the data generated in the course of the Study.
13.3 YM acknowledges that, as between POI and YM, any and all
intellectual property rights in works authored by POI before the Effective Date
of this Agreement and works authored by POI independent of the Study shall
belong to POI.
14. ARBITRATION
All disputes, disagreements, controversies, questions or claims arising
out of or relating to this Agreement and all other agreements entered into
pursuant to the terms of this Agreement, including, without limitation, with
respect to their formation, execution, validity, application, interpretation,
performance, breach, termination or enforcement ("Disputes") shall be determined
by arbitration under the International Commercial Arbitration Act (Ontario) (the
"International Act"), provided that:
14.1 any hearing in the course of the arbitration shall be held in
Toronto, Ontario;
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CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
14.2 the number of arbitrators shall be one;
14.3 any award or determination of the arbitrator shall be final and
binding on the parties and there shall be no appeal on any ground, including,
for greater certainty, on the ground of alleged errors of law. For greater
certainty, Article 34 of the International Act shall apply to an arbitration
under this section 14;
14.4 despite Article 26 of the International Act, the arbitrator
shall not, without the written consent of all parties to the arbitration, retain
any expert;
14.5 an arbitrator may apportion the costs of the arbitration,
including the reasonable fees and disbursements of the parties, between or among
the parties in such manner as the arbitrator considers reasonable, provided that
an arbitrator shall not award costs on a distributive basis;
14.6 all awards for the payment of money shall include prejudgment
and postjudgment interest in accordance with sections 127 to 130 of the Courts
of Justice Act (Ontario) with necessary modifications; and
14.7 all matters in relation to the arbitration shall be kept
confidential to the full extent permitted by law, and no individual shall be
appointed as an arbitrator unless he or she agrees in writing to be bound by
this dispute resolution provision.
15. NON-SOLICITATION OF STAFF
During the term of this Agreement and for a period of twelve months
following its termination or expiration, YM shall not directly or indirectly (i)
solicit or entice any employee or contractor of POI with whom it comes into
contact as a result of participation in the Study, to be employed by it or any
other person or entity; or (ii) approach any such employee or contractor for
such purpose or authorize or approve the taking of such action by any other
person.
16. TERM AND TERMINATION
16.1 This Agreement shall commence on the Effective Date and, unless
terminated pursuant to this Section 16, shall continue until such time as the
Services and Closeout Services have been completed. This Agreement does not
cover any services required for long-term patient follow up. The parties shall
endeavour to enter into a separate agreement for such services.
16.2 This Agreement may be terminated upon the mutual, written
consent of both parties. This Agreement may also be terminated by YM without
cause upon thirty (30) days prior written notice to the other party.
16.3 Either party may immediately terminate this Agreement for
cause, upon written notice to the other party stating the date of termination,
pursuant to the following:
16.3.1 Termination by POI. POI may terminate this Agreement for
cause upon the occurrence of any of the following events:
(i) YM fails to maintain the insurance coverage required by
Section 11.1;
PAGE 14 OF 19
CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
(ii) The FDA, IRB/EC, or any regulatory authority with
jurisdiction over the Study suspends or revokes any consent, approval, license,
or operating certificate required to conduct the Study;
(iii) YM breaches any material provision of this Agreement,
other than those specifically referenced in this Section 16.3.1, and fails to
remedy that breach within 30 days after receiving notice of such breach; or
(iv) YM files a petition for the appointment of a receiver in
liquidation or a trustee with respect to itself or any of its property; or any
person other than YM files a petition for the appointment of a receiver in
liquidation or a trustee with respect to YM in bankruptcy, insolvency, or
reorganization, compromise, adjustment or other relief relating to the relief of
debtors, and such involuntary petition is not vacated or set aside or stayed
within 60 days from YM's receiving notice of such petition.
16.3.2 Termination by YM: YM may terminate this Agreement for cause
upon the occurrence of any of the following events:
(i) The FDA, IRB/EC, or any regulatory authority with
jurisdiction over the Study suspends or revokes any consent, approval, license,
or operating certificate required to conduct the Study;
(ii} The occurrence of a Serious Adverse Event which causes
the study to be terminated due to safety concerns by the Data Safety Management
Board;
(iii) If POI enters into a Clinical Trial Agreement with an
Investigator relating to the Study, and the Investigator or any member of the
Investigator's staff fails to possess all qualifications, training, and licenses
necessary to perform the duties and obligations of that individual under that
agreement or fails in any material manner to abide by the provisions of the
Regulatory Requirements or this Agreement; provided, however, that POI may cure
any such deficiency by removing forthwith the affected individual from providing
services under this Agreement;
(iv) POI breaches any material provision of this Agreement,
other than those specifically referred to in this Section 16.3.2, and fails to
remedy that breach within 30 days after receiving notice of such breach;
(v) POI files a petition for the appointment of a receiver in
liquidation or a trustee with respect to itself or any of its property; any
entity POI controls makes a -voluntary assignment for the benefit of creditors
or files a petition in bankruptcy or insolvency or for reorganization,
compromise, adjustment, or other relief; or if any person other than POI files a
petition for the appointment of a receiver in liquidation or a trustee with
respect to POI or any entity it controls in bankruptcy, insolvency, or
reorganization, compromise, adjustment or other relief relating to the relief of
debtors, and such involuntary petition is not vacated or set aside or stayed
within 60 days from POI's receiving notice of the petition; or
(vi) POI is unable to perform its obligations under this
Agreement due to a Force Majeure Event for a period greater than thirty (30)
days.
PAGE 15 OF 19
CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
16.4 In the event of any change or reinterpretation of a Regulatory
Requirement, the adoption of any new law or regulation, or the initiation of an
enforcement action with response to laws, regulations, or guidelines applicable
to this Agreement, any of which shall affect the legality of this Agreement, the
parties agree to negotiate in good faith to amend this Agreement to comply with
the offended law or regulation. If the parties do not agree to such amendment
within 30 days prior to the effective date of the offended law or regulation (or
such earlier time as may be required to comply), then either party may terminate
this Agreement immediately by giving written notice to such effect to the other
party.
17. CONSEQUENCES OF TERMINATION
17.1 Upon termination of this Agreement, POI shall immediately
provide to YM complete and up-to-date written records accounting for the full
amount of Investigational Product dispensed, and the amount of unused
Investigational Product remaining in the possession of POI, or the
investigational teams or sites participating in the Study. POI shall, and shall
ensure that the investigational teams or sites participating in the Study,
return without delay any unused quantities of the investigational Product,
including samples, unless YM requests that such Investigational Product be
destroyed, in which case POI shall arrange for such destruction and provide
appropriate proof to YM that such destruction has occurred.
17.2 The termination of this Agreement for any reason shall not
affect any right or remedy existing hereunder prior to the effective date of
termination.
17.3 Upon early termination of this Agreement pursuant to Sections
16.2, 16.3, or 16.4, YM shall continue to pay POI the amounts set forth in
Schedules 1 and 2 for all services actually provided and expenses actually
incurred by POI prior to the date of termination of this Agreement. Without
limiting the foregoing, upon termination of this Agreement, YM shall, in
addition to all CRO Compensation then due, compensate POI, as specified in
Schedules 1 and 2, for all Closeout Services required to terminate and closeout
the Study, including but not limited to, any activities necessary to satisfy the
requirements of any governmental, regulatory, or professional authority with
jurisdiction over the Study. Further, upon termination of this Agreement by YM
prior to the completion of the Study pursuant to Section 16.2, YM shall pay POI
a termination fee that shall equal 10% of the remaining compensation, if any,
owed to POI pursuant to Section 8.1 and Schedules 1 and 2 as of the date of
termination. This termination fee shall be paid, in part, to compensate POI for
having to reassign its personnel and incur out-of-pocket expenses not covered by
Section 8.1 and Schedules 1 and 2.
17.4 In the event that, at the date of termination of this
Agreement, the amount already paid by YM to POI exceeds the total of: (1) the
cost for services actually provided by POI up to the date of termination, (2)
expenses actually incurred by POI up to the date of termination, (3) the cost
for the Closeout Services; and (4) the termination fee according to Section
17.3, if applicable, then the excess amount shall be immediately refunded to YM.
17.5 In no event shall the amount payable to POI by YM pursuant to
this Agreement exceed the maximum amounts specified in Schedule 1 or 2, without
the prior written agreement of the Parties.
PAGE 16 OF 19
CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
18. REPETITION OF THE STUDY
In the event of a material error by POI as agreed to by POI in the
performance of the Services, POI shall repeat the applicable Services upon YM's
request at no additional expense to YM.
19. DELAYS
19.1 YM may, in its sole discretion, require POI to delay or suspend
Services. If (a) YM requests such a delay due to no fault of POI; and (b) YM
requests that POI staff continue to be assigned to the project during the period
of such delay or suspension; the parties shall negotiate in good faith a monthly
maintenance fee payable by YM during the period that Services are suspended and
staff continue to be assigned. While the monthly maintenance fee is being paid,
payments due as outlined in Schedules 1 and 2 shall not be payable. Such delay
shall last no longer than six (6) months, after which time POI shall have the
right to terminate this Agreement.
20. GENERAL PROVISIONS
20.1 This Agreement sets forth the entire agreement and
understanding among the parties as to the matters contained therein, and merges
and supersedes any prior discussions, agreements, and understanding of every
kind and nature relating thereto.
20.2 Any amendment of or modification to this Agreement shall become
effective only if it is in writing and executed by the parties.
20.3 This Agreement shall be binding upon, and inure to the benefit
of, the parties and their respective legal representatives, trustees, receivers,
successors and permitted assigns.
20.4 Except as otherwise specified in this Agreement or otherwise
agreed to by the parties in writing, all notices, requests, demands, and other
communications provided for in this Agreement shall be in writing in English and
shall be deemed to have been given at the time when personally delivered, or
mailed by registered or certified mail, return receipt requested, to the address
of the other party stated below or to such other address as any such party may
have fixed by notice, provided, however, that any notice of change of address
shall be effective only upon receipt by addressee.
All notices to YM shall be addressed to:
Xxxxx X.X. Xxxxx
President and CEO
YM BioSciences Inc.
0000 Xxxxxxx Xxxxx
Xxxxxxxx 00, Xxxxx 000
Xxxxxxxxxxx, Xxxxxxx X0X0X0 Xxxxxx
PAGE 17 OF 19
CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
If notices or communications by telephone or facsimile are
specifically authorized in this Agreement or otherwise agreed
to by the parties in writing, calls to YM shall be placed and
facsimiles to YM shall be sent to the following numbers:
Phone: (000) 000-0000
Fax: (000) 000-0000
All notices to POI shall be addressed to:
Xxxx Xxxxx
Executive Vice President
Pharm-Olam International Ltd.
000 Xxxxxxxxx,
Xxxxx 000 Xxxxxxx, XX 00000
Xxxxxx Xxxxxx
If notices or communications by telephone or facsimile are
specifically authorized in this Agreement or otherwise agreed
to by the parties in writing, calls to POI shall be placed and
facsimiles to POI shall be sent to the following numbers:
Phone: (000) 000-0000, ext. 121
Fax: (000) 000-0000
The parties shall give notice to each other of any change of their
address or telephone, facsimile, or similar number at the earliest possible
opportunity.
20.5 All agreements of the parties, as well as any rights or
benefits accruing to them, pertaining to a period of time following the
termination or expiration of this Agreement or any of its provisions, including
but not limited to Paragraph 5.9, 6.3, and Sections 7 through 15, and 17, shall
survive such termination or expiration hereof and shall not be merged.
20.6 The waiver by any party of breach or default by any other party
shall not operate as a waiver of a continuing or subsequent breach or default of
the same or a different nature or kind.
20.7 If any provision of this Agreement or the application of any
such provision to any person or circumstance is held invalid, the remainder of
this Agreement and the application of such provision to other persons or
circumstances shall not be affected unless the invalid provision substantially
impairs the benefits of the remaining provisions of this Agreement.
20.8 No party may assign this Agreement or its rights and duties
hereunder, without the prior written consent of the other party, except that YM
may assign this Agreement to a purchaser or acquirer of substantially all of the
business to which this Agreement relates.
20.9 The provisions of this Agreement shall be self-executing and
shall not require further agreement by the parties except as may otherwise be
specifically provided in this Agreement; provided, however, that, at the request
of a party, the other party shall execute such additional instruments and
perform such additional acts as may be reasonably necessary to effectuate this
Agreement.
20.10 This Agreement may be executed in counterpart originals, with
each counterpart to be deemed an original, but all counterparts together shall
constitute a single instrument.
PAGE 18 OF 19
CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
20.11 In the event that performance by a party of any of its
obligations under the terms of this Agreement shall be interrupted or delayed by
a Force Majeure Event, that party shall be excused from such performance for the
same amount of time as such occurrence shall have lasted or such period of time
as is reasonably necessary after such occurrence abates for the effects thereof
to have dissipated.
21. APPLICABLE LAW
This Agreement shall be governed by and be construed under the laws of
Ontario, Canada without giving effect to its choice-of-law rules, and exclusive
venue of any action or other proceeding that may be brought or arise out of, in
connection with, or by reason of this Agreement shall be in Ontario, Canada.
IN WITNESS WHEREOF, this Agreement is executed by the parties hereto and
is effective as of the day and year first above written.
YM BIOSCIENCES, INC.:
By:___________________________
Xxxxx X.X. Xxxxx, its President and CEO
PHARM-OLAM INTERNATIONAL LTD.:
By Pharm-Olam Management, Inc., its General Partner
By:__________________________________
PAGE 19 OF 19
CLINICAL RESEARCH SERVICES AGREEMENT
10 March 2004
Schedule 1 - Clinical Services Cost
Pharm-Olam International
Clinical Services Cost
Study: Breast Cancer - YMB1002-02
Number of Patients: 700 over 70 sites ([*] months recruitment)
Countries: [*]
Date: 18th February 2004
[*]
Schedule 1 - Data Management Cost
Pharm-Olam International
Data Management Cost
Study: Breast Cancer - YMB1002-02
Number of Patients: 700 over 64 sites ([*] months recruitment)
Countries: [*]
Date: 18th February 2004
[*]
Schedule 1 - Pass Through Costs
Pharm-Olam International
Pass Through Costs
Study: Breast Cancer - YMB1002-02
Number of Patients: 700 over 64 sites ([*] months recruitment)
Countries: [*]
Date: 18th February 2004
[*]
SCHEDULE 1 - TRANSLATION TIMES
PHARM-OLAM INTERNATIONAL
TRANSLATION TIMES
STUDY: BREAST CANCER - YMB1002-02
NUMBER OF PATIENTS: 700 OVER 64 SITES ([*] MONTHS RECRUITMENT)
--------------------------------------------------------------------------------
COUNTRIES: [*]
Date: 18th February 2004
Note: This is an assumption and depends on the final number of pages to be
translated
-------------------------------------------------------------------------------------------------------
Document Assumptions Number of Days
Eastern Europe
-------------------------------------------------------------------------------------------------------
Full protocol
(Russia and Mexico only) 5 days each country 10
-------------------------------------------------------------------------------------------------------
Patient information sheet 1 per language (9 languages excl.
US, canada and India) 9
-------------------------------------------------------------------------------------------------------
Consent form 0.5 per language 4.5
-------------------------------------------------------------------------------------------------------
Drug labels 1 per language 9
-------------------------------------------------------------------------------------------------------
Ethics committee approval letters 0.5 per site (47 sites) 23.5
-------------------------------------------------------------------------------------------------------
Import licence and
regulatory approval letters 1 per language 9
-------------------------------------------------------------------------------------------------------
Insurance certificate 1 per language 9
-------------------------------------------------------------------------------------------------------
Investigator contracts 2 per language 18
-------------------------------------------------------------------------------------------------------
SAEs 0.25 per SAE 12.5
(50 to be translated into Russian) (all SAEs to be translated)
-------------------------------------------------------------------------------------------------------
TOTAL 104.5
-------------------------------------------------------------------------------------------------------
--------------------------------------------------------------------------------
N.B. These translation times are an estimate, a more accurate costing can be
provided after a review of the full study documentation. If you require local
language correspondence ( e.g. to/from Regulatory Authorities, EC's and
investigators) to be translated this will be charged at (pound)75 per page.
--------------------------------------------------------------------------------
Pharm-Olam International
YM Biosciences Proposal Confidential
Schedule 2
Payment Schedule
PAYMENT SCHEDULE FOR SERVICES AND DATA MANAGEMENT:
---------------------------------------------------- ------------------- ------------------ ------------------- ----------------
SERVICES (GBP) SERVICES (USD) DATA MANAGEMENT TOTAL
---------------------------------------------------- ------------------- ------------------ ------------------- ----------------
[*]% at Execution of Letter of Intent (pound)[*] $[*] $ [*] $[*]
Amount Received to Date [*] [*] [*] [*]
Balance Due (pound)[*] $[*] $ [*] $ [*]
---------------------------------------------------- ------------------- ------------------ ------------------- ----------------
[*]% at 1st Patient In (pound)[*] $[*] $[*] $[*]
---------------------------------------------------- ------------------- ------------------ ------------------- ----------------
Balance (less [*]% holdback) payable in three (pound)[*] $[*] $[*] $[*]
parts: (pound)[*] per month for [*] months
((pound)[*]);(pound)[*] per patient randomized
((pound)[*]); and(pound)[*] per patient finalized
((pound)[*]) (i.e., completed treatment or
dropped out of study
---------------------------------------------------- ------------------- ------------------ ------------------- ----------------
Final Payments (of the holdback):
|X| After last final close-out visits (pound)[*] $[*] $[*] $[*]
|X| On delivery of final report and CRFs (pound)[*] $[*] $[*] $[*]
---------------------------------------------------- ------------------- ------------------ ------------------- ----------------
TOTAL GRANT (POUND)[*] $[*] $[*] $[*]
---------------------------------------------------- ------------------- ------------------ ------------------- ----------------
Note: Total is based on 700 patients at 64 sites but excluding pass-through
costs. If the number of patients is reduced, the costs and payments will be
reduced pro-rata.
PAYMENT SCHEDULE FOR INVESTIGATOR COSTS:
Billed monthly to YM BioSciences, Inc., as patients are competed and after
validation by YM that patients are evaluable.
PAYMENT SCHEDULE FOR PASS-THROUGHS:
All pass-through costs are estimates and will be invoiced on a monthly basis as
incurred.
FINAL PAYMENT:
The Final Payment represents a [*]% holdback: (pound)[*] is due on completion of
all the final close out visits and (pound)[*] is due on delivery of the final
report and delivery of case report forms to YM. YM and POI will in good faith
endeavor to enter into an agreement for provision of services for the
`follow-up' of patients and it is contemplated that this Final Payment will be
dealt with as part of that agreement.
REFERENCE FOREIGN EXCHANGE RATE FOR SERVICES:
The USD figures are for reference only and the conversion rate used is 1.75 USD
to 1 GBP
PAYMENT RELATED TO CANADIAN-SOURCED SERVICES:
Services budget includes approximately US$[*] per month for Canadian-sourced
services.
--------------------------------------------------------------------------------
Schedule 2 - Payment Schedule Page 1 of 1
CONFIDENTIAL
CLINICAL STUDY AGREEMENT
This Clinical Study Agreement ("Agreement") is made and entered into by and
among PHARM-OLAM INTERNATIONAL LTD. (hereinafter referred to as "POI"), YM
BIOSCIENCES, INC. (hereinafter referred to as "Sponsor"), [INVESTIGATOR NAME]
("Principal Investigator") and [INSTITUTION NAME] ("Institution") for the
conduct of a clinical trial in accordance with the protocol entitled, "A Phase
III study of DPPE (tesmilifene) combined with Epirubicin and Cyclophosphamide
versus Epirubicin and Cyclophosphamide alone as first line Treatment in
Metastatic/Recurrent Breast Cancer.", ("Protocol"), and all current and future
amendments thereto as signed and approved by the Principal Investigator, which
is incorporated into this Agreement by reference.
WHEREAS, POI is a clinical research organization retained by the Sponsor for
this Study (defined below).
WHEREAS, this study will be a multi-site Study with each Principal Investigator
initially completing [NUMBER OF PATIENTS] eligible evaluable patients.
1. TERMS
1.1 "Study" shall mean the conduct of the clinical trial as set forth in
the Protocol. "Eligible Evaluable Patient" shall mean any patient who is
qualified to participate in the Study pursuant to the Protocol and either
completes the Study or is discontinued from the Study due to withdrawal of
consent or adverse event. "Study Drug" shall mean [DESCRIPTION OR NAME OF
DRUG]. Capitalized terms used herein and not defined shall have the
meanings ascribed to them in the Protocol.
2. TERM OF THE AGREEMENT
2.1 The term of this Agreement shall commence on the date that it is fully
executed and continue until six (6) months after the earlier of the
following: (1) the date the Study is completed and final clinical research
data is accepted by POI; or (2) the date the Study is terminated as
provided for herein.
3. SUB-INVESTIGATORS
3.1 The Principal Investigator may have one or more sub-investigators
("Sub-investigator") work on the Study. Such Sub-investigator shall be
subject to all of the terms and conditions of this Agreement, including
all obligations of the Investigator. No Sub-investigator may work on the
study unless he or she is qualified through experience and training to
conduct clinical trials and agrees to be involved through completion of
the Study. The Sub-investigator's name shall appear in the appropriate
space on the FDA Form 1572. In this Agreement "Investigator" will refer to
the Principal Investigator and any Sub-investigator.
4. INVESTIGATOR OBLIGATIONS
4.1 The Investigator shall adhere to any and all laws, regulations and
guidelines, including (a) any applicable Guidelines for Good Clinical
Practice, (b) the laws and customs governing medical practice and ethics
prevailing in the country where the Study takes place, and (c) all
guidelines and instructions supplied by POI and/or the Sponsor. Strict
compliance by the Investigator with the Study Protocol is required (slight
deviations based on medical necessity will not violate this provision).
Any modifications recommended by the Investigator or the Institution's
Institutional Review Board ("IRB") before initiation of the Study or
during the review process must be brought to the attention of POI. The
Protocol may not be altered without the prior written consent of POI
and/or the Sponsor for the Study, and a subsequent review and approval by
the IRB. The Principal Investigator thoroughly understands the Protocol
and, as of the date of signing this Agreement, has no further questions or
concerns about the Study's design or conduct.
Schedule 3 - Clinical Study Agreement Template Page 1 of 12
4.2 The Investigator shall exercise independent medical judgment as to the
compatibility of each patient with the Protocol and obtain written
informed consent before including any patient in the Study. Investigator
shall maintain independent records that corroborate that the informed
consent was executed before the inclusion of the patient in the Study.
4.3 The Investigator shall obtain written IRB approval to conduct the
Study. The IRB shall receive a copy of the Protocol as part of the
original submission to the IRB as well as any Protocol modifications that
are made after IRB approval has been obtained. When required, the patient
informed consent form approved by the IRB shall be modified to reflect
changes in the Protocol. The modified form shall be submitted to the IRB
for approval, and upon IRB approval signed by each patient participating
in the Study.
4.4 The Investigator is expected to be available during normal business
hours for consultation with POI's clinical research associates by
telephone and during periodic site visits to assess Study progress.
4.5 The Investigator shall have a study coordinator to assist the
Investigator with the administration of the Study. The Study coordinator
shall be available during normal business hours for consultation with POI
by telephone and during periodic site visits.
4.6 All Study Drug and other materials provided by POI and/or the Sponsor
shall be used solely for the purposes of conducting the Study and shall
not be provided to any third party without the prior written approval of
POI. In accordance with applicable regulations, the Investigator shall
provide careful custody and accurate dispensing records for the Study
Drug. In addition, the Investigator shall retain shipping invoices for
supplies received from the Sponsor.
5. SAFETY
5.1 The Investigator and/or the Institution will immediately notify POI of
any serious and/or unexpected experiences suffered by patients, whether or
not deemed therapy related. Serious adverse events will be reported to POI
within 24 hours. A follow up written report must be submitted to the POI
and Institution's IRB as soon as possible, but in no event more than three
days after occurrence or identification of the event.
6. STUDY RECORDS
6.1 Case Report Forms will be provided to the Investigator along with
Study supplies. The Investigator shall complete and review all Case Report
Forms for completeness and accuracy, shall submit data in a timely manner
and shall maintain complete records of patient identification, clinical
observations and clinical supplies disposition. The Investigator shall
also maintain independent case histories for each patient, in addition to
the Case Report Forms provided to the Investigator. The Investigator is
required to retain Study documents and maintain the master patient log in
accordance with all applicable regulations.
Schedule 3 - Clinical Study Agreement Template Page 2 of 12
6.2 THE INVESTIGATOR SHALL RECORD ALL ENTRIES ON CASE REPORT FORMS IN A
TIMELY MANNER FOLLOWING EACH PATIENT VISIT.
6.3 The Study will have quality assurance audits that will be performed
several times during the duration of the Study. During the term of this
Agreement, the Institution and Investigator agree to permit
representatives of POI and Sponsor to examine at any reasonable time
during normal business hours (1) the facilities where the Study is being
conducted, (2) raw Study data, and (3) any other relevant information (and
to make copies) necessary for POI or Sponsor to confirm that the Study is
being conducted in conformance with the Protocol and in compliance with
applicable laws, regulations and regulatory guidelines. The applicable
health regulatory authority also may conduct independent inspections of
the Study under its jurisdiction. The Investigator and Institution shall
cooperate fully in such audits and inspections.
7. TERMINATION
7.1 Sponsor reserves the right to discontinue the Study for any reason
upon thirty (30) days advance written notice of Study termination to the
Investigator. The Investigator will stop enrolling patients upon receipt
of notice of Study termination. Upon termination the Investigator shall
deliver to POI, at the expense of POI, all unused Case Report Forms and
Study Drug, and all other material and information provided by POI and/or
Sponsor, or generated during the Study. POI and/or Sponsor reserve the
right to discontinue the Study without advance written notice to the
Investigator if patient safety becomes a concern to POI or Sponsor. POI
and/or Sponsor reserve the right to terminate this Agreement at any time
for cause. In case of termination, the payments due under this Agreement
shall be prorated based on actual work properly performed in accordance
with the Protocol as of the date of the termination.
8. CONFIDENTIALITY
(i) Basic Obligation of Confidentiality
Investigator and Institution hereby acknowledges and agrees that in
the course its involvement with Sponsor, Sponsor and/or POI may
disclose to Investigator and Institution or Investigator and
Institution may otherwise have access or be exposed to Confidential
Information. All information disclosed by POI and/or the Sponsor, or
developed hereunder by the Institution, the Investigator or
associated staff, is deemed Confidential Information. Confidential
Information shall include the Protocol, the terms of this Agreement,
Case Report Forms and all materials and information concerning the
Sponsor and the Study disclosed to the Investigator or Institution
during the Study. Sponsor hereby agrees to provide such access to
Investigator and Institution and Investigator and Institution agrees
to receive and hold all Confidential Information on the terms and
conditions set out in this Agreement. Except as set out in this
Agreement, Investigator and Institution will keep strictly
confidential all Confidential Information and all other information
belonging to Sponsor that Investigator and Institution acquires,
observes or is informed of, directly or indirectly, in connection
with Investigator and Institution's involvement, in any capacity,
with Sponsor and will not, without Sponsor's prior written consent,
disclose any Confidential Information or recollections thereof to
any person.
Schedule 3 - Clinical Study Agreement Template Page 3 of 12
(ii) Non-disclosure
Unless Sponsor first gives Investigator and Institution written
permission to do so, Investigator and Institution will not at any
time, either during or after Investigator and Institution's
involvement in any capacity with Sponsor:
o Use or copy Confidential Information or Investigator and
Institution's recollections thereof; or
o Publish or disclose Confidential Information or
Investigator and Institution's recollections thereof to
any person other than Sponsor or its employees who are
under an obligation of confidentiality with Sponsor; or
o Permit any Confidential Information to be used, copied,
translated or adapted except as otherwise expressly
permitted by this Agreement.
(iii) Taking Precautions
Investigator and Institution will take all reasonable precautions
necessary or prudent to prevent material in Investigator and
Institution's possession or control that contains or refers to
Confidential Information from being discovered, used or copied by
third parties.
(iv) Sponsor's Ownership of Confidential Information
As between Investigator and Institution and Sponsor, all right,
title and interest in and to the Confidential Information is and
shall remain Sponsor's property.
(v) Control of Confidential Information and Return of Information
All physical materials containing Confidential Information, whether
or not produced or prepared by Investigator and Institution,
including, without limitation, memoranda, drawings, plans, samples,
case report forms accounts, reports, financial statements,
estimates, computer files and materials prepared in the course of
Investigator and Institution's responsibilities to or for the
benefit of Sponsor, shall belong to Sponsor. Investigator and
Institution further agrees that, upon written request from Sponsor
at any time, Investigator and Institution shall:
o Return to Sponsor all original copies of the Confidential
Information; and
o Destroy any and all copies or other reproductions or extracts
thereof and all other documents, memoranda, notes and other
writings prepared by or for Investigator and Institution based
on the Confidential Information.
Investigator and Institution is not granted any license or other
rights to any of the Confidential Information except as expressly
set out in this Agreement.
(vi) Purpose of Use
Investigator and Institution will use the Confidential Information
only for the purposes of fulfilling Investigator and Institution's
responsibilities under this Agreement or as authorized or directed
by Sponsor.
Schedule 3 - Clinical Study Agreement Template Page 4 of 12
9. PUBLICATION
9.1 The Parties agree that presentation and publication of clinical
research findings may be made by the Institution or the Investigator;
provided, however, no Confidential Information of the Sponsor is revealed
and no single site data is presented and/or published prior to the
publication of the multi-center data from the Study, or until twelve (12)
months have elapsed following database lock, whichever comes first.
Institution agrees to provide the Sponsor with a copy of any and all
communications, presentations and publications thirty (60) days before it
is released and to discuss any issues of data interpretation or
confidentiality with Sponsor staff. Institution and Investigator shall
cause each of its employees, agents and contractors to comply with the
terms and conditions of this Paragraph 9.
10. OWNERSHIP OF WORK PRODUCT
10.1 The Investigator and Institution agree that all inventions,
improvements in know-how, data, inventions, discoveries, new uses,
processes and compounds, whether patentable or not, copyrightable or
susceptible to any other form of legal protection, made, conceived or
reduced to practice relating to the Study, or made, conceived or reduced
to practice at any time with the use or possession of any Confidential
Information or any analog of the Study drug ("Inventions") shall be and
remain the sole property of Sponsor. The Investigator shall fully
cooperate with Sponsor in obtaining, at Sponsor's sole cost and expense,
the patent and all such intellectual property protection as may be
available with respect to such Inventions, and shall execute all documents
reasonably deemed necessary by Sponsor for purposes of procuring such
patent and intellectual property protection.
11. DEBARMENT
11.1 The Investigator and Institution warrant and represent that neither
the Investigator nor the Institution have been, or are currently, an
individual, corporation, partnership, association or entity that has been
debarred by the U.S. Food and Drug Administration ("FDA") pursuant to 21
U.S.C. ss.335a (a) or (b) ("Debarred Person").
11.2 The Institution further warrants and represents that no Debarred
Person has performed or rendered, or will perform or render, any services
or assistance relating to activities taken pursuant to this Agreement.
11.3 The Institution and Investigator further warrant and represent that
they have no knowledge of any circumstances which may affect the accuracy
of the foregoing warranties and representations, including, but not
limited to, FDA investigations of, or debarment proceedings against, the
Institution or any other person or entity performing services or rendering
assistance relating to activities taken pursuant to this Agreement.
11.4 The Institution and Investigator shall immediately notify POI if they
become aware of any such circumstances at any time.
12. PAYMENT
12.1 Grant payments hereunder will be made by POI, upon receipt of funds
from the Sponsor, to [THE PAYEE] and pursuant to Exhibit A incorporated
herein.
Schedule 3 - Clinical Study Agreement Template Page 5 of 12
13. INDEMNIFICATION
13.1 Sponsor agrees to defend, indemnify and hold harmless Institution,
the Investigators and their respective employees ("INSTITUTION
INDEMNITEES") from any and all third party claims, demands, costs,
expenses (including without limitation reasonable attorneys' fees),
liabilities and/or losses (such third party claims, demands, costs,
expenses, liabilities and/or losses including reasonable attorneys' fees
shall collectively be referred to as the "LOSSES") which may be asserted
against Institution Indemnitees related to the Study drug. Sponsor's
indemnification obligations under this paragraph 13.1 shall not apply to
the extent any such Losses arise from, result from or relate to: (i) a
material breach of this Agreement, or violation of applicable law, rule or
regulation by any of the Institution Indemnitees; (ii) the negligence or
willful misconduct of any of the Institution Indemnitees; or (iii) any
unauthorized deviation or diversion by any of the Institution Indemnitees
from the Protocol (except for any such deviation required as medical
necessity).
13.2 Institution agrees to defend, indemnify and hold harmless Sponsor,
its subsidiaries, affiliates, directors, officers, shareholders,
employees, successors and/or assigns ("SPONSOR INDEMNITEES") from any and
all Losses related to (i) a material breach of this Agreement, or a
violation of applicable law, rule, or regulation by any of the Institution
Indemnitees; (ii) the negligence or willful misconduct of any of the
Institution Indemnitees; or (iii) any unauthorized deviation or diversion
by any of the Institution Indemnitees from the Protocol (except for any
such deviation required as medical necessity). Institution's
indemnification obligations under this Paragraph 13.2 shall not apply to
the extent any such Losses arise from, result from or relate to: (i) a
material breach of this Agreement, or violation of applicable law, rule or
regulation by any of the Sponsor Indemnitees; (ii) the negligence or
willful misconduct of any of the Sponsor Indemnitees; or (iii) any
unauthorized deviation or diversion by any of the Sponsor Indemnitees from
the Protocol (except for any such deviation required as medical
necessity).
13.3 The party against whom a claim that is subject to indemnification
hereunder is brought (in this context, the "INDEMNIFIED PARTY") agrees to
promptly notify the indemnifying party (in this context, the "OTHER
PARTY") in writing, of any claims asserted against the Indemnified Party
to which the Indemnified Party is entitled to indemnification hereunder.
The Indemnified Party shall deliver to the Other Party any appropriate
court document or other document relative to or in relation to such claim.
The Other Party shall control the investigation, trial, defense and
settlement of any such lawsuit or action and any appeal arising therefrom
and shall employ or engage attorneys of its own choice. The Indemnified
Party may, at its own cost, participate in such investigation, trial and
defense of such lawsuit or action and any appeal arising therefrom. The
Indemnified Party shall provide full reasonable cooperation to the Other
Party at all times during the pendency of the claim or lawsuit including,
without limitation, providing the Other Party with all available
information, access to personnel and documents concerning the claim..
13.4 NOTWITHSTANDING THE ABOVE, NEITHER THE SPONSOR NOR THE INSTITUTION,
THEIR RESPECTIVE AFFILIATES, NOR ANY OF THEIR RESPECTIVE DIRECTORS,
OFFICERS, EMPLOYEES, OR AGENTS SHALL HAVE ANY LIABILITY FOR ANY SPECIAL,
INCIDENTAL, INDIRECT, OR CONSEQUENTIAL DAMAGES, INCLUDING BUT NOT LIMITED
TO THE LOSS OF OPPORTUNITY, OR LOSS OF REVENUE OR PROFIT.
Schedule 3 - Clinical Study Agreement Template Page 6 of 12
14. ASSIGNMENT/SPONSOR'S RIGHTS
14.1 This Agreement is for professional services. Neither the Institution
nor Investigator may assign, delegate or otherwise transfer any of its
rights or obligations under this Agreement without the prior written
consent of POI and the Sponsor. The Institution and Investigator
understand and agree that its obligations under this Agreement are for the
benefit of Sponsor and POI and the Sponsor and POI shall have the right to
enforce the terms of this Agreement. Accordingly, it is agreed that POI
shall have the right to assign all of its rights under this Agreement to
Sponsor.
15. SURVIVAL
15.1 The terms of Paragraphs 8, 9, 10, 13, 14 and 15 shall survive the
expiration or termination of this Agreement.
16. FINANCIAL DISCLOSURE
16.1 For purposes of this paragraph, any Investigator performing services
pursuant to this Agreement, and any spouse or dependent child of such
Investigator shall be jointly referred to as "Investigator Personnel". The
Investigator and Institution agree to submit a written disclosure of: (1)
any financial arrangement in which any Investigator who performs services
pursuant to this Agreement, participates, which could affect the outcome
of the Study as defined in 21 CFR 54.2(a); (2) any propriety interest by
any Investigator Personnel in the Study Drug or test product, as defined
in 21 CFR 54.2(c); (3) any significant equity interest owned by any
Investigator Personnel in the Sponsor company, as defined in 21 CFR
54.2(b) and (4) receipt by any Investigator Personnel of any significant
payments of other sorts as defined by 21 CFR 54.2(f). The Investigator and
Institution further agree to assist POI and Sponsor, upon request in
obtaining any information and executing any documents necessary to comply
fully with 21 CFR part 54, or any rules or regulations thereunder.
17. INSURANCE
17.1 Before initiation of the Study, the Institution and the Investigator
shall provide POI with evidence of professional liability coverage in the
amount equivalent to acceptable industry standards of coverage.
18. GOVERNING LAW
18.1 This Agreement shall be governed by and construed in accordance with
the laws of the province of Ontario, Canada.
19. ILLEGALITY
19.1 If any term or provision of this Agreement shall for any reason be
held invalid, illegal, or unenforceable in any respect, such invalidity,
illegality or unenforceability shall not affect any other term or
provision hereof, and this Agreement shall be construed as if such term or
provision, to the extent the same shall have been held invalid, illegal,
unenforceable, had never been contained herein.
20. WAIVER
20.1 No waiver or modification of any of the terms of this Agreement shall
be valid unless in writing and signed by authorized representatives of all
parties hereto. Failure by any party to enforce any rights under this
Agreement shall not be construed as a waiver of such rights nor shall a
waiver by any party in one or more instances be construed as constituting
a continuing waiver in other instances.
Schedule 3 - Clinical Study Agreement Template Page 7 of 12
21. ASSIGNS
21.1 This Agreement shall be binding on and shall inure to the benefit of
the parties hereto and their respective permitted assigns and successors
in interest; provided, however, neither party shall assign this Agreement
or any part thereof without the prior written consent of the other party.
22. INDEPENDENT CONTRACTOR
22.1 In conducting this Study, the Institution, Investigator and approved
personnel will be acting as independent contractors, and not as agents,
partners, or employees of POI or Sponsor. The Investigator and approved
personnel will not have any authority to make agreements with third
parties that are binding on POI or Sponsor.
23. USE OF NAME
23.1 The Institution, Investigator and POI, on behalf of themselves and
their employees, investigators, agents or independent contractors involved
in the Study, agree that they shall not employ or use the name, symbols
and/or marks of the other party, Sponsor, any Institutional Review Board
or any Investigator, in any publication or promotional material or in any
form for public distribution without the prior written consent of the
other party in each instance, except as required by law.
24. REPRESENTATIONS AND WARRANTIES
24.1 The Investigator, Institution, Sponsor and POI warrant and represent
that they are authorized to enter into this Agreement and that the terms
of this Agreement are not inconsistent with or a violation of any
contractual or other legal obligation to which they are subject.
24.2 The Institution and Investigator warrant and represent that: (1) they
have the staff and other resources to carry out the Study in accordance
with the Sponsor's timelines and (2) their employees, agents and other
personnel who will carry out the Study shall have the expertise and
experience necessary to perform the Study efficiently and that such Study
shall be performed with care and skill and to the best of their ability
commensurate with such skill and experience and adhering at all times to
applicable law.
25. CONSTRUCTION
25.1 If the terms of this Agreement and the Protocol should conflict, the
terms of this Agreement shall control.
26. COUNTERPARTS
This Agreement may be signed by facsimile and in counterparts and each of
such counterparts will constitute an original document and such
counterparts, taken together, will constitute one and the same document.
Schedule 3 - Clinical Study Agreement Template Page 8 of 12
IN WITNESS WHEREOF, the parties hereto have caused this Agreement to be
executed by their duly authorized representatives as of the date first
above written.
PRINCIPAL INVESTIGATOR: PHARM-OLAM INTERNATIONAL, INC.:
X___________________________ X______________________________
INVESTIGATOR NAME XXXX XXXXX, EXECUTIVE VICE PRESIDENT
DATE:________________________ DATE:___________________________
INSTITUTION: YM BIOSCIENCES INC.:
X___________________________ X___________________________
(SIGNATURE) [NAME AND TITLE]
NAME:_______________________
TITLE:________________________ DATE:________________________
DATE:________________________
Schedule 3 - Clinical Study Agreement Template Page 9 of 12
EXHIBIT A
PAYMENT SCHEDULE
Payee (______________________________) will be paid a clinical grant of
$__________ (THIS INCLUDES OVERHEAD) for each eligible, evaluable patient who
completes the Study according to the Protocol. Payment for patients who are lost
to follow-up, withdraw consent or do not complete the Study due to adverse event
or death will be prorated as negotiated with POI.
Payment will be made pursuant to the following schedule:
o ____________ upon execution of this Agreement and the Study site
initiation,
o The succeeding payments shall be based on verified patient progress
according to the number of patients and/or procedures completed
prior to each milepost (the first day of every calendar month of
study participation). These successive payments will be paid
approximately 45 days after acceptance of all the closing documents
for each succeeding period.
Investigator represents that he can enroll ____ subjects within the first month
and a minimum of ______ subjects per month thereafter. The
Institution/Investigator will use their best efforts to meet these target
enrollments (which includes completion of relevant case report forms). Failure
to meet these target enrollments can result, at Sponsor's discretion, in
termination of the site.
In the event that payments made to the Payee pursuant to the payment schedule
exceed payment amounts due to the Payee as of the date of termination of the
Study, Payee shall promptly refund all unearned amounts to POI.
Schedule 3 - Clinical Study Agreement Template Page 10 of 12
EXHIBIT B (PAGE 1 OF 2)
CLINICAL STUDY AGREEMENT
GRANT INFORMATION FORM
NAME OF PROTOCOL:
PROTOCOL:
NUMBER OF SUBJECTS:
ANTICIPATED START DATE:
ESTIMATED COMPLETION DATE:
PRINCIPAL INVESTIGATOR:
PRINCIPAL INVESTIGATOR ADDRESS:
GRANT INFORMATION
PERSON RESPONSIBLE FOR GRANT NEGOTIATIONS:
PHONE NUMBER:
SOCIAL SECURITY or TAX ID NUMBER, or Employer ID NUMBER:
GRANT CHEQUES MADE PAYABLE TO:
GRANT CHEQUES TO BE SENT TO (PO BOXES ARE NOT ACCEPTABLE)
TO:
___________________
Schedule 3 - Clinical Study Agreement Template Page 11 of 12
EXHIBIT B (PAGE 2 OF 2)
CONDITIONS OF PAYMENT
Schedule 3 - Clinical Study Agreement Template Page 12 of 12
SCHEDULE 4
ADVERSE EVENT REPORTING
DPPE YMB1002-02
15 DAY MAXIMUM TURNAROUND TIME FOR REPORTING TO REGULATORY BODIES
[FLOW CHART APPEARS HERE]
In the event of Xxxxxxxx or Xxxx being absent from the YM office they will
delegate a member of the YM team to monitor the intake and processing of the
events.
