AGREEMENT Between BioCancell Therapeutics Ltd. Beck Science Center, 8 Hartom St. Jerusalem 97775, Israel (Hereinafter: “BioCancell”) And between Meir Medical Center Kfar Saba, Israel (Hereinafter: “the Medical Center”)
EXHIBIT
10.6
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AGREEMENT
Between
BioCancell
Therapeutics Ltd.
Xxxx
Science Center, 0 Xxxxxx Xx.
Xxxxxxxxx
00000, Xxxxxx
(Hereinafter:
“BioCancell”)
And
between
Meir
Medical Center
Kfar
Saba, Israel
(Hereinafter:
“the Medical Center”)
BioCancell
and the Medical Center shall be hereinafter collectively referred to in this
Agreement as “Parties”; each
one of which also referred to as “Party”.
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Whereas
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BioCancell
has expressed its interest in carrying out, managing and funding the
clinical trial the subject of which being “Phase 2b, Multicenter Trial of
Intravesical DTA-H19/PEI in Patients with Intermediate-Risk Superficial
Bladder Cancer”, bearing protocol no. BC-07-0l, a copy of which is
attached as Appendix A hereto (hereinafter “the Trial”);
and
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Whereas
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The
Medical Center has declared it holds the proper facilities and staff
required to perform the Trial, and that it is willing to put such
facilities and staff at the disposal of BioCancell, for the purpose of
performing the Trial; and
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Whereas
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The
Parties agree that BioCancell shall maintain any and all management
authorities with regard to the performance of the Trial in all of its
stages; and
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Whereas
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BioCancell
has agreed to pay the Medical Center the consideration, specified in
Appendix C hereto, for the performance of all the undertakings of the
Medical Center under this Agreement, all according to the terms and
conditions of this Agreement
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NOW, THEREFORE, it is
hereby declared and agreed between the parties as follows:
| 1. |
General
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| 1.1. |
The
preface and appendices to this Agreement constitute an integral part
hereof.
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| 1.2. |
Titles
of the sections in this Agreement shall be used for terms of reference
only, and could not be used for the interpretation of this
Agreement.
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| 1.3. |
This
Agreement contains the entire understanding of the Parties and the
Principle Investigator with respect to the subject matter hereof, and
supersedes all prior or pre-existing negotiations, declarations,
presentations, commitments and/or agreements, whether written or oral,
whether explicit or implied, between the Parties and the Principle
Investigator, with respect to such subject
matter.
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| 1.4. |
In
the event of a contradiction between this Agreement and any of the terms
of its appendices, the terms and conditions of this Agreement shall
prevail.
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| 1.5. |
Anything
in this Agreement denoting the singular shall also denote the plural, and
anything denoting the feminine gender shall also denote the masculine
gender, and vice versa, insofar as no other meaning is inferred by the
context.
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| 2. |
Appendices
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The
appendices to the Agreement are:
| 2.1. |
Appendix
A: The Trial Protocol
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| 2.2. |
Appendix
B: The Trial Personnel Clearance
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| 2.3. |
Appendix
C: The Consideration
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| 2.4. |
Appendix
D: Schedule 4 of the Guidelines.
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| 2.5. |
Appendix
E: The Trial Documents and Related
Activities.
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| 3. |
Definitions
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In this
Agreement, the following terms shall have the specific meaning attributed to
them in the table below:
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The
Agreement
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This
agreement and its appendices.
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Serious Adverse
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As
defined in the Trial Protocol and in the Guidelines.
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Event
Monitors
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Any
body or person/s nominated by, or representing BioCancell and/or any
company of the BioCancell Group to monitor the Trial (i.e., conduct
on-site audits for Good Clinical Practices compliance).
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Completed
CRF
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A
CRF having, according to the sole and absolute discretion of BioCancell
and/or any third party appointed by BioCancell, no discrepancies in its
details and no unanswered queries.
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CRF
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Case
Report Forms containing any and all data of the Subjects, which has been
gathered during the Trial. The CRF shall be in hardcopy
format.
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The End of the
Trial
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The
point in time, in which a Completed CRF has been submitted to BioCancell
by the Principal Investigator, as defined herein, for all the Subjects
participating in the Trial, or the date of termination of the Trial
according to the terms and conditions of the Agreement; the earlier of the
two.
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FDA
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The
United States of America Food and Drug Administration.
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The
Guidelines
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Ministry
of Health guidelines entitled “Clinical Trials of Human Subjects” as may
be amended and modified from time to time.
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The Helsinki
Declaration
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The
1964 Declaration of Helsinki regarding the recommendations guiding
physicians in bio-medical research involving human beings, as amended in
Tokyo, 1975.
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ICH-GCP
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Harmonized
Tripartite Guideline for Good Clinical Practice as may be amended and
modified from time to time.
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IND
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Investigational
New Drug Application (US code of Federal Regulations 21 CFR Part
312).
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Inspector/s
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Any
inspecting body legally authorized to perform inspections in clinical
trials, including, inter alia, the MOH, FDA or any other state regulated
medical authority.
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Invention
Rights
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Any
and all intellectual property rights, relating to the Trial Data or to the
BioCancell Data, including, inter alia, the right to register and/or own
any inventions stemming directly or indirectly from the Trial Data and/or
the BioCancell Data. Without derogating from the generality of the above,
the Invention Rights shall include, inter alia, patents, information,
data, know-how, formulas, concepts, tests, drawings, specifications,
applications, designs and trade secrets, methodologies, engineering and
manufacturing processes and research processes, stemming directly or
indirectly from the BioCancell Data and/or the Trial
Data.
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Investigator
Brochure
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A
document, which is submitted along with the Trial Protocol to the relevant
Helsinki Committee and FDA, and the content of which is outlined in the
GCP Guidelines.
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Medical Center Helsinki
Committee Ministry of Health Approval
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A
committee appointed pursuant to the National Health Regulations and whose
role is to approve any and all medical experiments on humans conducted by
the Medical Center Approval from the Director General of the Ministry of
Health, or whomever he/she has delegated the authority to for this
purpose, for the performance of the Trial at the Medical Center, according
to the National Health Regulations and the Guidelines.
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Ministry of
Health/MOH
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The
Israeli Ministry of Health.
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National Health
Regulations
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Israel
National Health Regulations (Clinical Trials on Human Subjects), 5741-1980
as may be amended from time to time.
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Publications
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All
publications, manuscripts, abstracts and papers relating directly
or indirectly to the subject matter of the Trial, and which were initiated
or composed directly or indirectly, in whole or in part, by the Principal
Investigator and/or by the Medical Center and/or by any of the Trial
Personnel.
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The BioCancell
Data
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Any
and all information provided by BioCancell or by the BioCancell Group to
the Medical Center, Principal Investigator or any member of the Trial
Personnel with regard to the Trial, including, without limitation, the
Trial Protocol and the Investigator Brochure which shall be the sole
property of the BioCancell Group.
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The BioCancell Group
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The
group of companies consisting of BioCancell Group Therapeutics, Inc and
BioCancell Therapeutics Ltd.
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The
Guidelines
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Ministry
of Health guidelines entitled “Clinical Trials of Human Subjects” as may
be amended and modified from time to time.
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The
Product(s)
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DTA-H19/PEI
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The
Reports
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Any
and all reports required by BioCancell, by any state regulated medical
authority, or by any applicable laws, rules, regulations or
guidelines.
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The
Subjects
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A
group of persons chosen by the Principal Investigator to participate in
the Trial and who signed a written informed consent for the participation
in the Trial, all according to the criteria established in the Trial
Protocol.
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The Trial
Data
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Any
and all clinical data, technical information, records, files and materials
relating to the Trial, including the Trial Documents, case report forms,
source documents (such as subjects charts and physical notes), as well as
other related data generated during or as a result of the Trial which
shall be the sole property of the BioCancell Group.
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Trial
Documents
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Any
and all documents required by BioCancell, the MOH, the Medical Center or
any applicable laws, rules, regulations or guidelines, for the initiation,
performance and completion of the Trial; without derogating from the
generality of the above, the Trial Documents shall include any and all
documents specified in Appendix E to this Agreement.
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Trial
Personnel
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The
medical and administrative staff involved in the Trial, including those
who shall be employed by the Medical Center and cleared according to the
undertaking attached to this Agreement as Appendix B.
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The Trial
Protocol
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A
document that describes the objective(s), design, methodology, statistical
considerations, and organization of the Trial. The Trial Protocol usually
also gives the background and rationale for the trial, but these could be
provided in other protocol referenced documents. Throughout this Agreement
the term Trial Protocol refers to the protocol and its amendments, which
are attached to this Agreement as Appendix
X.
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| 4. |
Precedent
Condition
|
The
Parties hereby agree and undertake that the Agreement shall not enter into
effect before both of following cumulative approvals have been granted
(hereinafter: “the Approvals”):
| 4.1. |
The
approval of the Trial Protocol by Medical Center Helsinki Committee and
the MOH, if such latter approval is required by the Guidelines;
and
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| 4.2. |
The
approval of the Agreement in general, its budget and Appendix C in
particular, by the MOH and the committee of engagement with commercial
companies in accordance Section 9 of the Guidelines;
and
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| 4.3. |
The
approval of the Trial Protocol, Investigator Brochure and related
documents by the FDA.
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| 5. |
The Principal
investigator
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| 5.1. |
Xx.
Xxxx Xxxxxxxxxx MD, of the Medical Center (hereinafter: “the Principal
Investigator”)
has agreed to serve as the principal investigator of the
Trial.
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| 5.2. |
The
Principal Investigator undertakes to perform the Trial in compliance with
the following: (a) Trial Protocol, (b) the Guidelines, (c) the
instructions and the terms specified in the approval of the Medical Center
Helsinki Committee, (d) the ICH-GCP, (e) the Helsinki Declaration, (f) the
applicable laws, rules and regulations regulating such studies which are
applicable in Israel, (g) written instructions and prescriptions issued by
BioCancell regarding the Trial and/or the Product, all as may be amended
from time to time, and (h) the requirements in accordance with the FDA
Form 1572 “Statement of
Investigator.” Every PI at each site must sign this form for submission to
the FDA.
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| 5.3. |
The
Principal Investigator has declared that he holds the professional ability
and credentials required for performing the Trial in accordance with the
Trial Protocol and any applicable laws, rules, regulations and guidelines,
all as detailed above.
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5.4.
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In
the event that the Principal Investigator, for any reason whatsoever,
shall be unable to conduct the Trial, or shall cease to be available for
the performance of the undertakings set forth in this Agreement, the
Medical Center shall use its best efforts to appoint, within 20 days, a
successor investigator whose identity shall be approved in advance by
BioCancell (the “Successor
Investigator”).
Such Successor Investigator shall undertake all the duties and
responsibilities of the Principal Investigator as detailed in the
Agreement. Should the Medical Center not be able to appoint a Successor
Investigator, or if the appointed Successor Investigator is not acceptable
by BioCancell, either party shall be entitled to terminate this Agreement
forthwith and without further
liability.
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| 5.5. |
In
the event of the replacement of the Principal Investigator, as described
under this Section 5, the Principal Investigator shall have no claim
towards BioCancell and/or the Medical Center and/or any third party acting
on their behalf in direct or indirect connection with such
replacement.
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| 6. |
Medical Center
undertaking
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| 6.1. |
The
Medical Center represents that it has the requisite skills, knowledge,
experience and human resources to undertake and conduct the Trial in
accordance with the provisions of this
Agreement.
|
| 6.2. |
The
Medical Center undertakes to perform the Trial in compliance with the
following: (a) the Trial Protocol, (b) the Guidelines, (c) the
instructions and the terms specified in the approval of the Medical Center
Helsinki Committee, (d) the ICH-GCP, (e) the Helsinki Declaration, (f) the
applicable laws, rules and regulations regulating such studies which are
applicable in Israel, and (g) written instructions and prescriptions
issued by BioCancell regarding the Trial and/or the Product, all as may be
amended from time to time.
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| 6.3. |
The
Medical Center hereby undertakes to furnish BioCancell, the Principal
Investigator and all of the Trial Personnel with the facilities and
personnel necessary for the adequate performance of the Trial according to
the terms and conditions of the Trial Protocol, and to fully collaborate
with the Principal Investigator, BioCancell, and/or any other third party
nominated by BioCancell, with regard to performing its duties
hereunder.
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| 7. |
BioCancell
Undertaking
|
| 7.1. |
BioCancell
hereby undertakes to allow the Principal Investigator to use the
BioCancell Data, exclusively for the purpose of performing the Trial,
during the Term of This Agreement and according to the terms and
conditions of this Agreement.
|
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The
Principal Investigator shall strictly abide by any and all
instructions given to him by BioCancell with regard to the BioCancell
Data, while recognizing that BioCancell or any other company from the
BioCancell Group was and shall remain, during the Term of this Agreement
and thereafter, the sole and exclusive owner of any and all rights in the
BioCancell Data and the Trial Data, and the use
thereof.
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| 7.2. |
BioCancell
shall remunerate the Medical Center, the Principal Investigator and the
Trial Personnel, according to the terms of Appendix C hereto, for all
services rendered.
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| 8. |
Consideration
|
In
consideration for the performance of all of the tasks, duties and undertakings
of the Principal Investigator, the Trial Personnel and the Medical Center under
this Agreement, BioCancell hereby undertakes to pay the Medical Center the
amount specified in Appendix C hereto, according to the installments, timetable
and manner specified therein.
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| 9. |
Product
Supply
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| 9.1. |
BioCancell
will, at its own expense, supply to the Medical Center all necessary
quantities of the drugs to be used in the Trial, and only for the purposes
as described in the Protocol. Any surplus shall be returned to BioCancell
without delay, upon completion of the Trial or termination of this
agreement for any reason whichever is the
earlier.
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| 9.2. |
The
Medical Center will ensure that the Product is managed and stored in
accordance with GCP and with any special instructions issued by
BioCancell. The Medical Center will maintain proper records of receipts,
dispensing and returns of the
Product.
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| 9.3. |
BioCancell
will continue to supply the Product after the termination of the Trial
and/or Agreement to the patients participating in the trial in accordance
with Appendix D.
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| 10. |
Trial Personnel Compliance and
Clearance
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| 10.1. |
The
Medical Center and the Principal Investigator hereby undertake to exercise
their best efforts so that the Trial Personnel shall abide by: (a) the
Trial Protocol, (b) the Guidelines, (c) the instructions and the terms
specified in the approval of the Medical Center Helsinki Committee, (d)
the ICH-GCP, (e) the Helsinki Declaration, (f) the applicable laws, rules
and regulations regulating such studies which are applicable in Israel,
and (g) written instructions and prescriptions issued by BioCancell
regarding the Trial and/or the Product, all as may be amended from time to
time.
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| 10.2. |
The
Trial will also be conducted in accordance with the “Statement of
Investigator” (FDA form no. 1572).
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| 10.3. |
Trial
Personal Clearance:
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10.3.1.
|
The
Medical Center and the Principal Investigator shall deploy all possible
efforts to see to it that none of the Trial Personnel (including the
Principal Investigator and any other investigators) are debarred by the
FDA or by the MOH in any capacity whatsoever, and that (1) none of the
Trial Personnel appear in the FDA debarment list, detailing all firms or
persons debarred pursuant to Section 306 (a) and (b) of the Federal Food,
Drug, and Cosmetic Act (21 U.S.C. 335 (a) and (b)), as published in the
Federal Registrar from time to time; and (2) none of the Trial Personnel
are debarred according to the terms and conditions of the Israeli
Physicians Ordinance [New Version], 1976 or pursuant to any other
applicable law.
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10.3.2.
|
The
Medical Center and the Principal Investigator shall provide BioCancell
with the written confirmation thereof, in a form attached as Appendix B
hereto.
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| 11. |
Compliance with the Trial
Budget and Cooperation with BioCancell
Subcontractors
|
| 11.1. |
The
Medical Center and the Principal Investigator hereby undertake to perform
the Trial in accordance with, the budget of the Trial, as such term is
derived from
Appendix C hereto (hereinafter: “the Trail
Budget”)
and not to deviate therefrom without the prior written approval of
BioCancell in relation
thereto.
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| 11.2. |
The
Medical Center hereby undertakes that any deviation from the Trial Budget
without the prior written consent of BioCancell shall be born by the
Medical Center.
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| 11.3. |
The
Medical Center and the Principal Investigator hereby undertake to fully
cooperate with any and all sub-contractors nominated by BioCancell for the
purpose of the Trial, including, inter alia, clinical research
organizations, logistics companies, laboratories,
etc.
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| 12. |
Trial
Documents
|
| 12.1. |
The
Principal Investigators shall prepare and submit the Trial
Documents.
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| 12.2. |
The
Principal Investigator shall perform all the activities specified in
Appendix E hereto.
|
| 12.3. |
Any
and all amendments to the Trial Protocol shall be performed only after
securing the approval of BioCancell and the competent regulatory
authority.
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| 13. |
Confidentiality
|
| 13.1. |
The
Parties and the Principal Investigator hereby agree and undertake that
they are aware that the BioCancell Data and the Trial Data (hereinafter,
jointly and severally “the Confidential
Information”)
are confidential information, and that BioCancell has disclosed such
Confidential Information to the Medical Center and Principal Investigator
for the sole purpose of conducting the
Trial.
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| 13.2. |
The
Parties and the Principal Investigator hereby agree and undertake that
they are aware that the Confidential Information is the sole and exclusive
property of BioCancell and/or any other company from the BioCancell Group.
Accordingly, The Principal Investigator shall retain the Confidential
Information under the strictest safeguarding and not use, disclose or
divulge the Confidential Information in part or in whole, directly or
indirectly, for a period of seven (7)
years.
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| 13.3. |
The
Medical Center and the Principal Investigator shall maintain the
confidentiality of the Confidential Information using the same degree of
care used by them in relation to their own confidential information, and
shall without limitation, keep the Confidential Information in a safe and
separate place and not make any copies thereof (whether in hardcopy or
electronic file) unless first receiving BioCancell’s written
consent.
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| 13.4. |
The
Medical Center and the Principal Investigator hereby further undertake to
limit access to the Confidential Information to the Trial Personnel and
any third parties on a “need to know basis” only, and such Trial Personnel
and third parties to accept, in writing, the undertaking of the Principal
Investigator in relation to the Confidential Information under this
Agreement, as a condition precedent for receipt of any part of the
Confidential Information.
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| 13.5. |
At
the request of BioCancell, the Medical Center and the Principal
Investigator shall forthwith return to BioCancell the Confidential
Information or any part thereof.
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| 13.6. |
The
Medical Center and the Principal Investigator hereby state that they are
aware of the fact that any unauthorized disclosure or use of the
Confidential Information shall cause immediate and/or irreparable injury
to BioCancell, and that BioCancell cannot be adequately compensated for
such injury in monetary damages. Thus, in order to safeguard BioCancell
from any possible breach of confidentiality, the Principal Investigator
and the Medical Center hereby undertake that BioCancell would be permitted
to obtain, from any Court or Tribunal, any temporary or permanent
injunction relief, necessary to prevent such unauthorized disclosure or
use or peril thereof, and hereby renounce filing and/or submitting any
objection to any request by BioCancell or by any company from the
BioCancell Group, relating to such temporary or permanent
injunction.
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| 13.7. |
For
the avoidance of any doubt, it is hereby clarified that such an
undertaking is supplementary to and will not prejudice any right or
remedy, which is or shall be available to BioCancell under any applicable
law or agreement.
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| 13.8. |
The
Medical Center and the Principal Investigator hereby undertake to exercise
their best efforts to see to it that the Trial Personnel shall abide by
the undertakings set forth in this Section
13.
|
| 13.9. |
In
the event that the Medical Center and the Principal Investigator are
required by law, regulation, rule, act or order of any governmental
authority or agency to disclose Confidential Information, they shall be
entitled to do so provided that it shall reasonably attempt to first
notify BioCancell of any such required disclosure, so that BioCancell may
seek an appropriate protective order, and limit such disclosure as far as
is possible under applicable law. Such disclosure shall, however, not
relieve the Medical Center and the Principal Investigator of their other
obligations contained herein.
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| 14. |
Invention
Rights
|
| 14.1. |
The
Medical Center and the Principal Investigator hereby acknowledge that the
idea and initiative for the Trial were exclusively those of BioCancell,
and that the involvement of the Medical Center and the Principal
Investigator in the Trial is strictly the consequence of their nomination
by BioCancell.
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| 14.2. |
The
Parties and the Principal Investigator hereby irrevocably agree and
undertake that the Confidential Information, except for medical records of
the Subjects, is the exclusive property of BioCancell, may be freely
utilized by BioCancell in any manner it sees fit. Notwithstanding the
above, BioCancell shall have the right to review Subjects’ medical records
to verify entries in the CRF’s. BioCancell hereby undertakes full
responsibility to ensure the safekeeping of patients’ confidentiality and
personal data and shall be fully responsible for taking every measure to
apply this commitment.
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| 14.3. |
The
Parties and the Principal Investigator hereby irrevocably agree and
undertake that the Invention Rights shall be the absolute and exclusive
property of BioCancell and that BioCancell shall have unrestricted free
right to use such Invention Rights.
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| 14.4. |
The
Medical Center and the Principal Investigator hereby undertake to disclose
to BioCancell any and all applicable information relating to Invention
Rights and exercise their best efforts with regards to registration of the
Inventions Rights on the name of BioCancell and/or a name designated in
writing by BioCancell, if and to the extent requested to do so by
BioCancell.
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| 14.5. |
If
by operation of law or for any reason, any Invention Rights to be owned by
BioCancell pursuant to this Section 14 are not automatically deemed
proprietary BioCancell upon their creation, the Medical Center and the
Principal Investigator hereby further undertake to cause the Trial
Personnel to, irrevocably grant and assign all such intellectual property
rights to BioCancell. The Medical Center warrants that it has and will
continue to have agreements with its personnel, including any Trial
Personnel, to effectuate the terms of this section and it shall enforce
such agreements to provide BioCancell with the benefit of this
section.
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| 15. |
Inspections
|
| 15.1. |
The
Medical Center and the Principal Investigator hereby undertake to allow
the Monitors to perform monitoring visits in all sites related to the
Trial, during or after the Trial, and assist the Monitors in their duties.
For the avoidance of doubt, it is hereby clarified that the Monitors shall
be entitled to monitor and/or inspect among others the Trial Documents and
Trial Data as well as to insure compliance with the Trial
Protocol.
|
| 15.2. |
The
Medical Center and the Principal Investigator hereby undertake to allow
the Inspectors to perform inspections of all sites related to the Trial,
during or after the Trial (and each such inspection shall hereinafter be
referred to as “an Inspection”), and to assist the Inspectors in their
duties, if and to the extent requested to do so by the
Inspectors.
|
| 15.3. |
The
Medical Center and the Principal Investigator shall immediately inform
BioCancell in the event of an Inspection and/or upon gaining knowledge of
any intention to perform an Inspection. The Medical Center and the
Principal Investigator shall provide BioCancell with copies of any
inquiries, correspondence or communications to or from any such
Inspectors.
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| 16. |
Publications
|
| 16.1. |
BioCancell
covenants that it will not at any time, without first obtaining the
consent in writing of the Medical Center (which consent may by refused or
granted in its absolute discretion), use the Medical Center’s name or the
name of the Principal Investigator or otherwise disclose the fact of their
involvement in the performance of the Trial in any advertising, publicity
or publication.
|
Meir-final agreement
|
|
0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
However,
BioCancell may use the name of the Medical Center and/or the Principal
Investigator for listing the Trial on xxxxxxxxxxxxxx.xxx.
| 16.2. |
Publications
of the Trial and/or its results, in whole or in part, shall be within the
sole and absolute discretion of BioCancell. The Medical Center, the
Principal Investigator or the Trial Personnel, and any employees and/or
officers and/or representatives of any of the foregoing shall not publish
or refer to the Trial and/or its results, in whole or in part, without
obtaining the prior consent BioCancell in writing. BioCancell reserves the
right to reject any such request, at its sole discretion. For the
avoidance of doubt BioCancell has the right, at all times, to publish any
article or data generated from the services rendered under this
Agreement.
|
| 16.3. |
Without
derogating from this Section 16, BioCancell hereby undertakes to abide by
the rules of publications issued by the MOH and set forth in Section 2 of
Appendix D attached hereto.
|
| 17. |
Reports
|
| 17.1 |
The
Medical Center and the Principal Investigator hereby undertake to submit
the Reports to BioCancell and/or competent authorities, whether Israeli or
foreign.
|
| 17.2. |
The
Medical Center and the Principal Investigator hereby undertake to disclose
in the Reports any and all data provided to them by BioCancell, in
accordance with any applicable laws, rules, regulations and guidelines,
including, inter alia, safety data.
|
| 17.3. |
The
Medical Center will cause the Principal Investigator to provide
BioCancell, within 45 (forty five) days of the end of each period of three
(3) months during the period of the Trial, with a written report on the
progress of the Trial in the said
period.
|
| 17.4. |
45
(forty five) days following the End of the Trial, the Principal
Investigator shall submit to BioCancell a summary report, which shall
include, in a full and detailed manner, a declaration regarding the
activities performed during the Trial and the results obtained
therein.
|
| 18. |
Serious Adverse
Event
|
| 18.1. |
In
the event one or more of the Subjects sustains any Serious Adverse Event
related to the Trial, the Principal Investigator shall inform BioCancell
and the Medical Center Helsinki Committee and/or the Medical Center
management and/or the authorized national health
authorities.
|
| 18.2. |
The
Principal Investigator shall report such Serious Adverse Event in the
timetable and manner prescribed in the Trial Protocol and
Guidelines.
|
| 18.3. |
In
the occurrence of a Serious Adverse Event the Principal Investigator and
the Medical Center Helsinki Committee shall be entitled to immediately
cease the performance of the Trial, pending a prior notice of at least 24
hours to BioCancell regarding such decision and its
execution.
|
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|
|
0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
| 18.4. |
In
the occurrence of a Serious Adverse Event BioCancell will immediately take
all measures at their disposal to evaluate the risk to the other patients
and will instruct the Principal Investigator which measures to take with
regard to that risk.
|
| 18.5. |
BioCancell
has an obligation, as the trial sponsor, to notify each investigator of
any Serious Adverse Events that are reported by any site during the trial
that are submitted to the FDA in a safety report. Each Principal
Investigator is obligated to provide these reports to the appropriate
Helsinki Committee.
|
| 19. |
The
Legal Status of the Medical Center and the Principal
Investigator
|
| 19.1. |
The
Parties and the Principal Investigator hereby agree that the relationship
between BioCancell, on one hand, and the Medical Center and the Principal
Investigator, on the other hand, are that of a client and an independent
contractor, with the Medical Center and the Principal Investigator lacking
any capacity whatsoever to legally bind BioCancell to a relationship of
employer-employee, principal-agent or any other legal relationship
differing from that of a client and an independent
contractor.
|
| 19.2. |
Should
any court of law rule in a manner opposed to Section 19.1 above, the
Medical Center and the Principal Investigator, jointly and severally,
hereby undertake to indemnify BioCancell with regards to the respective
damage caused by each of them separately due to such a
ruling.
|
| 20. |
Term and
Termination
|
| 20.1. |
This
Agreement shall be in full force and effect as of the latter of either:
(a) the date of its execution by the last Party or (b) the date the
Approvals have been granted; and until the End of the Trial (and the
period in which this Agreement shall be in full force and effect shall be
referred to in this Agreement as “the Term of this
Agreement”).
|
| 20.2. |
The
Parties may bring this Agreement to an early end at any time, in writing,
by prior notice of at least 30 (thirty) days, upon the occurrence of one
(or more) of the following events:
|
|
20.2.1.
|
The
MOH has voided its approval granted for the performance of the Trial or
has conditioned the approval by conditions which the Medical Center and/or
the Principal Investigator, as the case may be, have notified BioCancell
that they are unable to comply
with.
|
|
20.2.2.
|
The
FDA has placed the Trial on clinical
hold.
|
|
20.2.3.
|
BioCancell
decides upon its sole and absolute discretion to bring the Trial to an
end. For the sake of good order, the Parties and the Principal
Investigator hereby state and undertake that they are aware, and agree,
that BioCancell is entitled to terminate this Agreement, upon its sole and
absolute discretion, at any moment whatsoever; and in this case no party
hereto shall have any claim whatsoever towards BioCancell and/or any other
company from the BioCancell Group with regard to such early
termination.
|
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|
|
0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
|
20.2.4.
|
A
Party and/or the Principal Investigator is found to be in breach of this
Agreement and does not cure such breach within a period of 30 (thirty)
days following receipt of a notice in writing from any of the other
Parties in relation thereto.
|
|
20.2.5.
|
A
Party and/or the Principal Investigator enter into bankruptcy or
liquidation proceedings or a receiver is appointed over part or all of
their assets, and such proceedings are not ceased within a period of 45
(forty five) days following receipt by such Party of a written notice in
relation thereto from any or all of the other
Parties.
|
| 20.3. |
In
the event of termination of this agreement the Parties and the Principal
Investigator shall bring the Trial to an end as
follows:
|
|
20.3.l.
|
Any
and all Confidential Information and remaining supply of Product shall be
returned to BioCancell.
|
|
20.3.2.
|
The
Parties and the Principal Investigator shall cooperate in swiftly
dispersing the Subjects and Trial Personnel, if the need arises, while
preserving the latest Trial Data and providing as many Completed CRF’s as
possible, and all to the satisfaction of
BioCancell.
|
| 20.4. |
The
obligation of the Parties and the Principal Investigator pursuant to
sections 13, 14, 16, 17, and 21 shall survive termination of this
Agreement.
|
| 21. |
Insurance and
Indemnification
|
| 21.1. |
BioCancell
has agreed to insure, in accordance with the terms and conditions set
forth in Appendix D attached hereto, the Subjects, the Trial Personnel,
the Principal Investigator and the Medical
Center.
|
| 21.2. |
BioCancell
has agreed to indemnify the Trial Personnel the Principal Investigator and
the Medical Center according to the terms of Sub-Section 21.3 below
(hereinafter each of them shall also be referred to as: the “Indemnitee”) for damages arising as a
direct result of their involvement in the performance of the Trial
(hereinafter: the “Damages”), provided
that the damages are not as a result of an expected side effect of the
Products and subject to the conditions detailed
herein:
|
|
21.2.1.
|
The
Damages are not caused as a result of negligence or misconduct of the
Indemnitee;
|
|
21.2.2.
|
The
Indemnitee performed the Trial in accordance with the Trial protocol and
the additional requirements set in this
Agreement;
|
| 21.3. |
Promptly
after receipt by the Indemnitee of a notice of the commencement of any
claim, action, suit, proceeding or investigation in respect of which
indemnity may be sought pursuant to this Section 21 (hereinafter: the
“Claim”), the Indemnitee shall
provide a notice to BioCancell, in writing, describing in reasonable
detail the facts and circumstances upon which the asserted Claim for
indemnification is based, and shall thereafter keep BioCancell reasonably
informed with respect thereto. BioCancell shall have the right to assume
the defense of any Claim, at its sole discretion. In any event, the
Indemnitee shall cooperate with BioCancell in the defense of any Claim for
which BioCancell assumes the defense BioCancell shall not be liable for
the settlement by the Indemnitee of any Claim affected without the consent
of BioCancell. BioCancell shall be entitled to enter into any settlement
of a Claim at its sole discretion. BioCancell may not assume the blame or
liability of the Medical Center, Trial Personnel or the PI without their
prior written consent.
|
Meir-final agreement
|
|
0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
| 22. |
Notices
|
| 22.1. |
Notices
to be given by one Party to another shall be in the English language, and
shall be deemed property given if reduced to writing and transmitted to
the Party’s address appearing on the first page of this Agreement, by air
courier or by certified registered mail - all to be effective 3 (three)
days after their sending date, or by facsimile with confirmation receipt -
to be effective at the first business day following the date of
transmission.
|
| 22.2. |
However,
a notice shall be considered properly given, only in case a copy thereof
was communicated as follows:
|
|
Notice
to BioCancell
|
Notice
to Medical Center
|
|
|
BioCancell
Therapeutics Ltd.
|
/s/
Xxxxxx Xxxxxxxxxx
|
|
|
Xxxx
Science Center, 8 Hartom St.
|
XXXXXX
XXXXXXXXXX M.D.
|
|
|
Jerusalem,
00000 Xxxxxx
|
DEPUTY
DIRECTOR
|
|
|
Attn:
Ran Xxxxxx
|
XXXX
GENERAL HOSPITAL
|
|
|
Director,
Strategic Alliances
|
KFAR
SABA, ISRAEL
|
|
|
Telephone:
x000-0-000-0000
|
Telephone:
|
|
|
Facsimile: x000-0-000-0000
|
Facsimile:
|
| 22.3. |
The
addresses of the Parties, listed in page 1 of this Agreement, shall be
subject to any change of such address notified in writing by one Party to
the other, according to the procedure stipulated in this
Section.
|
| 23. |
Miscellanies
|
| 23.1. |
Expenses
of the Parties, Each Party and the Principal Investigator shall bear all
its own expenses, including the expenses of its attorneys, in connection
with the negotiation, execution and performance of this
Agreement.
|
| 23.2. |
Waiver
and forbearance. No rights of any Party shall be prejudiced or restricted
by any indulgence or forbearance, to any other person or entity, and no
waiver by any Party in respect of any breach shall operate as a waiver in
respect of any subsequent breach.
|
| 23.3. |
Governing
law and jurisdiction. This Agreement shall be exclusively governed by the
Laws of the State of Israel. Any and all disputes arising hereunder shall
be resolved by a competent court having jurisdiction over such matters in
the Tel-Aviv Jaffa District, Israel
|
| 23.4. |
Assignment.
This Agreement shall not be assigned, without the prior written consent of
all of the other Parties, save for an assignment of rights by BioCancell
to any company within the BioCancell
Group.
|
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|
0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
| 23.5. |
Counterparts.
This Agreement and any amendment hereto may be executed in multiple
counterparts, each of which shall be deemed an original agreement and all
of which shall constitute one and the same
agreement.
|
| 23.6. |
Amendments.
Modification or amendment to this Agreement shall only be valid if
performed by a written instrument, signed by all Parties to this
Agreement.
|
| 23.7. |
Severability.
If any provision of this Agreement is determined by a court of competent
jurisdiction to be invalid, illegal, or unenforceable, that determination
shall not affect any other provision of this Agreement, and each such
other provision shall be construed and enforced as if the invalid,
illegal, or unenforceable provision were not contained
herein.
|
[Remainder of page left
intentionally blank. Signature page follows.]
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|
|
0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
IN
WITNESS WHEREOF, the parties hereto have caused this Agreement to be duly
executed and each of the undersigned hereby warrants and represents that he or
she has been and is, on the date of this Agreement, duly authorized by all
necessary and appropriate action to execute this Agreement.
IN
WITNESS WHEREOF, the parties have executed this Agreement as at the date first
above written:
|
BioCancell
Therapeutics Ltd.
|
Meir
Medical Center
|
|
By:
/s/ Xxx
Xxxxx
|
By:
/s/ Xxxxxx
Xxxxxxxxxx M.D.
|
|
Print
Name: Xxx Xxxxx
|
Print
Name: Xxxxxx Xxxxxxxxxx
M.D.
|
|
Title:
CEO
|
Title:
Deputy Director
Meir
General Hospital
Kfar
Saba, Israel
|
|
|
|
|
By:
/s/ Xxxxxxxx
Xxxxx
|
By:_____________________
|
|
Print
Name:_______________
|
|
|
Title:
VP Clinical Development
|
Title:____________________
|
I the
undersigned, Xx. Xxxx Xxxxxxxxxx MD, hereby declare and confirm that I have read
and understood the Agreement. I hereby agree to be appointed as the Principal
Investigator of the Trial on behalf of the Medical Center, and accept and
undertake to comply with all the terms, conditions, provisions, instructions and
stipulations set forth in the Agreement, including without limitation,
provisions referring to the Parties.
| /s/ Xxxx Xxxxxxxxxx M.D. | |||
| The Principal Investigator |
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|
0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
Appendix
A
The Trial
Protocol
See attached
separately
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|
0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
Appendix
B
The Trial Personnel
Clearance
An Undertaking with regard
to a Clinical Trial’s Personnel
We, the
undersigned, hereby warrant and undertake in relation of clinical trial bearing
protocol number BC-07-01, researching “Phase 2b, Multicenter Trial of
Intravesical DTA-H19/PEI in Patients with Intermediate-Risk Superficial Bladder
Cancer”, that we have not, we do not and we will not use nor employ, in any
capacity, the services of any person debarred under Section 306 (a) or (b) of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 335 (a) and (b)), or
debarred under the Israeli Physicians Ordinance [New Version], 1976 or pursuant
to any other applicable law.
| /s/ Xxxx Xxxxxxxxxx | /s/ Xxxxxx Xxxxxxxxxx | ||
|
|
|
||
|
|
8.11.07
|
||
| Date | |||
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|
0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
Appendix C
The
Consideration
1. Terms and
Definitions
In this
Appendix C terms shall have the meaning assigned to them in the Agreement. The
following terms shall have the meanings assigned to them hereunder.
|
Complete
Screening
|
A
Screening of a Subject in which all examinations and/or tests and/or
treatment and/or evaluations included in the Screening process, as
detailed in the Trial Protocol, have been performed and the data collected
and registered in the CRF
|
|
|
Complete Evaluation Visit or
Complete Treatment Visit
|
A
Visit of a Participating Subject in which all examinations and/or tests
and/or treatment and/or evaluations scheduled for the visit have been
performed, as detailed in the Trial Protocol, and the data collected and
registered in the CRF
|
|
|
Evaluation
Visit
|
Any
Visit, as defined below, of visits 7, 11, 15, and 19 as these visits are
numbered and defined in the Trial Protocol.
|
|
|
Participating
Subject
|
A
Subject who that has undergone Screening, as defined below, and was
determined to meet the requirements specified in the Trial protocol and
who is participating in the Trial according to the terms and conditions of
the Trial Protocol
|
|
|
Screening
|
A
series of tests and examinations as defined in table 4 of the Trial
Protocol designed to evaluate a Subject's suitability for participating in
the Trial, as detailed in the Trial Protocol.
|
|
|
Treatment
Visit
|
Any
Visit, as defined below, of visits 1-6, 8-10, 12-14, and 16-18 as these
visits are numbered and defined in the Trial Protocol.
|
|
|
Visits
|
Any
one of the scheduled nineteen (19) visits of a Participating Subject as
detailed in table 4 and 5 of the Trial
Protocol.
|
| 2. |
The
Consideration
|
| 2.1. |
In
consideration for the performance, in good faith, by the Principal
Investigator and the Medical Center, of all of their undertakings under
this Agreement, BioCancell hereby undertakes to pay to the Medical Center
the following amounts:
|
|
Visit
#
|
Procedure
|
Costs
of procedure (NIS)
|
Totals
costs per visit
|
|
Screening
|
Urine
cytology
Video
cystoscopy
Histology
& Pathology
Doctor’s
fee
Study
nurse
Study
coordinator
TUR
|
140
370
180
1,000
250
250
960
|
3,150
|
Meir-final agreement
|
|
0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
|
Visit
# 1
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|
Visit
# 2
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|
Visit
# 3
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|
Visit
# 4
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|
Visit
# 5
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|
Visit
# 6
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|
Visit
# 7
|
Urine
cytology
Video
cystoscopy
Histology
& Pathology
Doctor’s
fee
Study
nurse
Study
coordinator
TUR
|
140
370
180
500
250
250
960
|
2,650
|
|
Total per first treatment
period
|
13,300
|
||
|
Visit
# 8
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|
Visit
# 9
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
Meir-final agreement
|
|
0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
|
Visit
# 10
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|||
|
Visit
# 11
|
Urine
cytology
Video
cystoscopy
Doctor’s
fee
Study
nurse
Study
coordinator
|
140
370
500
250
250
|
1,510
|
|||
|
Visit
# 12
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|||
|
Visit
# 13
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|||
|
Visit
# 14
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|||
|
Visit
# 15
|
Urine
cytology
Video
cystoscopy
Doctor’s
fee
Study
nurse
Study
coordinator
|
140
370
500
250
250
|
1,510
|
|||
|
Visit
# 16
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|||
|
Visit
# 17
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|||
|
Visit
# 18
|
Doctor’s
fee
Study
nurse (Drug administration & blood sampling)
Study
coordinator
|
750
250
250
|
1,250
|
|||
Meir-final agreement
|
|
0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
|
Visit
# 19
|
Urine
cytology
Video
cystoscopy
Doctor’s
fee
Study
nurse
Study
coordinator
|
140
370
500
250
250
|
1,510
|
|||
|
Total
per continued treatment period (if no recurrence)
|
15,780
|
|||||
|
Total
per first treatment period & continued treatment
period
|
13,300
+ 15,780
|
29,080
|
||||
|
General
|
Unscheduled
Histology & Pathology (If applicable)
|
180
|
180
|
|||
|
General
|
Unscheduled
Video cystoscopy
|
370
|
370
|
|||
|
General
|
Unscheduled
TUR
|
960
|
960
|
|||
|
Pharmacy
|
500
US $
|
500
US $
|
* Blood
work and Urine analysis will be perform by an external central Lab (the costs
will be covered by the sponsor).
| 3. |
Limitation of
Payments
|
| 3.1. |
For
the avoidance of doubt, it is hereby declared and agreed that BioCancell
shall not pay any additional payments or any other amounts, which are not
clearly mentioned and specified in section 2
above.
|
| 3.2. |
It
is further clarified that the amounts specified in section 2 above include
payment by BioCancell for all services rendered from the Medical Center
including but not limited to office services, Trial Personal required for
performing the Trial including the Principal Investigator, physicians,
nurses, receptionists and study coordinator, use of the Medical Center's
facilities, and all tests, procedures, examinations and evaluations as
detailed in the Trial
protocol.
|
| 3.3. |
The
considerations do not include cost of analysis of hematology and chemistry
samples which will be performed by BioCancell's
sub-contractor/s.
|
| 4. |
Terms of
Payment
|
| 4.1. |
The
Medical Center shall send an invoice at the end of each calendar quarter
(31/3, 30/6, 30/9, and 31/12) detailing the Complete Screening, Complete
Treatment Visits and Complete Evaluation Visits (together hereinafter:
“Complete
Visits”)
performed as well as on which Subjects or Participating Subjects the
relevant Complete Visit was
performed.
|
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|
|
0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
| 4.2. |
Payments
detailed in section 2 shall be conditioned upon payment for Complete
Visits and shall be included in the first invoice sent by the Medical
Center.
|
| 4.3. |
Payment
shall be maid by BioCancell within 30 (thirty) days of receipt of the
Medical Center’s invoice.
|
| 4.4. |
All
Payments shall he performed in the last day of the calendar year during
which the relevant payment date occurred. (Occurrence of the relevant
payment date shall be at the termination and completion of the stage and
conditions of which entitles the Medical Center for payment according to
this Appendix C).
|
| 4.5. |
Immediately
upon receiving the payment as per the issued invoice the Medical Center
will provide BioCancell with a receipt approving the
payment.
|
| 5. |
Currency of
Payments
|
All of
the payments subject of this Appendix C shall be performed by BioCancell to the
Medical Center in NIS (New Israel Shekel).
| 6. |
General Observations and
Clarifications
|
For the
sake of good order it is hereby clarified that, unless otherwise agreed upon in
writing by BioCancell:
| 6.1. |
No
payment would be performed for any activities performed by the Principal
Investigator and/or by the Medical Center, prior to the commencement of
the Trial.
|
| 6.2. |
Without
derogating from any right of BioCancell, in the event that no Completed
CRF's are provided to BioCancell, regarding a Subject, in relation to
which BioCancell has performed payments to the Medical Center, BioCancell
shall be entitled to perform one of the following three, according to its
absolute discretion:
|
| 6.2.1. |
Write-off
the amount paid by BioCancell in relation to Subject(s) for which no
Completed CRFs have been provided (hereinafter: “the Return
Amount”) from the
amount remaining due to the Medical Center by BioCancell according to this
Agreement (hereinafter: “the Remaining
Amount”).
|
| 6.2.2. |
Order
the Medical Center, in writing, to pay BioCancell the Return Amount within
a period no longer than 45 (forty-five) days from the End of the Trial,
The Medical Center hereby undertakes that it shall pay the Return Amount,
as specified above, and renounces any contentions and/or claims whatsoever
in relation thereto.
|
| 6.2.3. |
In
the event that the Return Amount shall exceed the remaining Amount,
BioCancell shall be entitled to exercise its rights under the above
sub-sections 6.3.1 arid 6.3.2 in concert, to the extent that BioCancell
shall fully collect the Return Amount from the Medical
Center.
|
| 6.3. |
No
advance payments would be performed by BioCancell to the Medical
Center.
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Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
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Appendix
D
Schedule 4 of the
Guidelines
|
Title
of the trial: “Phase 2b, Multicenter Trial of Intravesical DTA-H19/PEI in
Patients with Intermediate-Risk Superficial Bladder
Cancer”
|
|
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The
protocol name and number: BC-07-01
|
|
|
Name
of the investigational product: DTA-H19/PEI
|
|
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Name
of the Principal Investigator:
|
Department:
Urology
|
|
Name
of the medical institution:
|
|
|
The
Sponsor’s name and address: BioCancell Therapeutics Ltd., Xxxx Science
Center, 0 Xxxxxx Xx., Xxxxxxxxx 00000,
Xxxxxx
|
|
| 1. |
Sponsor
undertaking
|
|
The
Sponsor undertakes to act in accordance with the local and international
law for clinical trials, and in particular with regard to the following
issues:
|
| 1.1.1. |
Responsibility
for the safety and good order of the investigational
product;
|
| 1.1.2. |
Supply
of information regarding the trial;
|
| 1.1.3. |
Notice
to the Ministry of Health regarding the performance of a multi-centre
trial in Israel;
|
| 1.1.4. |
Monitoring
the trial process;
|
| 1.1.5. |
Safety
reports;
|
| 1.1.6. |
Accountability
in respect of the investigation
product;
|
| 1.1.7. |
Retention
of documents.
|
| 2. |
The
Sponsor undertakes that if it shall decide to publish the results of the
clinical trial in scientific literature, it shall publish them in full and
without taking matters out of their
context.
|
| 3. |
Insurance:
|
| 3.1. |
The
Sponsor undertakes to insure its legal liability pursuant to the laws of
the State of Israel against claims that may be filed by subjects in the
clinical trial and/or third party claims – all in connection with the
clinical trial, whether in the period of conducting the clinical trial or
thereafter. The insurance shall be extended to include the legal liability
of the medical institution and/or the clinical trial personnel and/or the
Principal Investigator (hereinafter referred to as “the parties conducting the
trial”)
deriving from their Involvement in the conduct of the clinical trial,
subject to an exception of an act committed negligently or an intentional
deviation from the clinical trial
protocol.
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0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
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x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
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| 3.2. |
The
Sponsor shall be given notice of any claim or any potential claim
immediately after such comes to the knowledge of the medical institution
or the Principal Investigator.
|
| 3.3. |
The
Principal Investigator, the medical institution and its employees shall
give the Sponsor, upon its written request, reasonable support in any
event of a claim that may be filed against it as
aforesaid.
|
| 4. |
The
Sponsor undertakes to supply the medical institution with the
investigational product throughout the period of the clinical trail until
the conclusion thereof, free of charge. Furthermore, the Sponsor
undertakes to pay all additional costs deriving from the conduct of the
clinical trail, provided that such costs do not derive from the regular
medical treatment of the sickness.
|
| 5. |
If
after the termination of the clinical trial it is ascertained and
recommended by the Principal Investigator that the welfare of the patient
participating in the clinical trial necessitates continuation of his
treatment with the investigational product and there is no other
appropriate alternative medical treatment, the Sponsor undertakes to also
continue supplying the investigational product, without charge, after the
termination of the clinical trial for a period of three years, except in
one of the following cases:
|
| 5.1. |
The
investigational product was approved for marketing in the State of Israel
after its registration for its requested scope and it can be obtained from
the sick fund with which the patient is
insured.
|
| 5.2. |
The
development of the product was discontinued or the results of the clinical
trials were unsuccessful.
|
| 5.3 |
The
administration of the investigational product for the said protracted
period is likely to harm the patient’s health, since there is insufficient
information regarding the safety of the product administered over the long
term.
|
| 5.4. |
Where
the investigational product is not a medical preparation, such as:
cosmetic products / food / food additive / herbal
remedy.
|
The
decision as to the continuation of administering the investigational product is
given to the medical institution’s Helsinki Committee (“the Helsinki
Committee”), that
is entitled to re-examine its determination from time to time. The Principal
Investigator and the Sponsor have a right of appeal against such decision to the
Ministry of Health’s director-general or such person as empowered by him such
regard.
| 6. |
The
continued administration of the investigational product after termination
of the clinical trial is subject to the following terms and
conditions:
|
| 6.1. |
The
continued treatment shall be given within the context of an orderly
monitoring protocol that shall be written by the Principal Investigator
and approved by the Sponsor and the Helsinki
Committee.
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0
Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
| 6.2. |
The
Principal Investigator is responsible for continuing to routinely monitor
the subject’s medical condition and to report to the Helsinki Committee
any exceptional events that occur during the ongoing treatment, as is the
norm in clinical trials.
|
The
principal investigation shall report to the Helsinki Committee at least once a
year as to the progress of the subject’s treatment.
The
medical institution in which the ongoing treatment shall be given shall attend
to appropriate insurance cover for the liability of the medical institution and
the Principal Investigator vis-a-vis the patient, in respect of the continuation
of administering the investigational product after the termination of the
clinical trial.
| 7. |
This
Appendix constitutes an integral part of the agreement between the company
sponsoring the clinical trial and the medical
institution.
|
|
BioCancell
Therapeutics Ltd.
By: /s/Xxx
Xxxxx
Print
Name: Xxx Xxxxx
Title:
CEO
|
Meir
Medical Center
By:
/s/ Xxxxxx
Xxxxxxxxxx
Print
Name: Xxxxxx Xxxxxxxxxx M.D.
Title:
Deputy Director
Meir
General Hospital
Kfar Saba,
Israel
|
|
By:
/s/ Xxxxxxxx Xxxxx
Print
Name: Xxxxxxxx Xxxxx
Title:
VP Clinical Development
|
By:_____________________
Print
Name:_______________
Title:____________________
|
I the
undersigned, Xx. Xxxx Xxxxxxxxxx MD, hereby declare and confirm that I have read
and understood this Appendix D.
| /s/ Xxxx Xxxxxxxxxx | |||
|
The Principal Investigator |
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Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
Phone:
x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
|
Appendix E
The Trial Documents and Related
Activities
The Trial
Documents shall include, inter alia, all the documents set forth in the
Guidelines, as well as the documents specified hereunder.
Any and
all terms not specifically defined in this Appendix shall have the meaning
attributed to them in the Agreement.
Prior to the initiation of the
Trial:
| 1. |
The
executed signature page of the Trial Protocol;
and
|
| 2. |
Investigator
Brochure; and
|
| 3. |
The
current curriculum vitae of the Principal Investigator;
and
|
| 4. |
The
list of all sub-investigators, all of which necessarily being listed on
either the FDA form no. 1572, or on the Principal Investigator’s Statement
Form; and
|
| 5. |
The
written approval of the Medical Center Helsinki Committee, indicating that
it has reviewed and approved the Trial Protocol;
and
|
| 6. |
The
written approval of the MOH with regards to the content of all publicity
and advertisements, related to the Trial, which are to be performed prior
to the commencement of the Trial;
and
|
| 7. |
A
list of all participants in the Helsinki Committee, convened in relation
to the Trial (hereinafter: “the Helsinki
Committee”);
and
|
| 7.1. |
Should
the Principal Investigator be a member of the Helsinki Committee, the
written Statement of the chairman of the Helsinki Committee confirming
that the Principal Investigator did not participate in the voting,
relating to the Trial, during the hearing of the said Helsinki Committee;
and
|
| 7.2. |
A
financial disclosure form, confirming that the Principal Investigator
holds no financial interests in
BioCancell.
|
While conducting the
Trial:
| 1. |
A
review of all the Trial Documents and verification the accuracy and
completeness thereof in relation to the source documents, on which the
above documents were based; and
|
| 2. |
Report
to the Medical Center Helsinki Committee of any Severe Adverse Events, as
such terms are defined in the Trial Protocol, to the Subject(s), in
accordance with the Guidelines; and
|
| 3. |
Report
to the Medical Center Helsinki Committee of any deviation from the Trial
Protocol; and
|
| 4. |
Maintain
adequate records of Subjects identification, clinical observations, as
well as study drug receipt and dispensation (hereinafter: “the
Records”),
in accordance with any applicable laws, rules, regulations and guidelines,
as amended from time to time. In any event, the Principal Investigator and
BioCancell shall maintain the Records for a period of no less than 15
(fifteen) years following the end of the
Trial.
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Xxxxxx Xx, Xxxxxxxxx Xxxxxx 00000
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x000-0-000-0000 Fax: x000-0-000-0000
xxx.xxxxxxxxxx.xxx
xxxx@xxxxxxxxxx.xxx
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| 5. |
Compare
the data in the CRF with the source documents relating to each subject
participating in the Trial, and confirm the accuracy of the CRF;
and
|
| 6. |
Maintain
a log, documenting the Product(s) provided to each subject during the
Trial; and
|
| 7. |
Report
no later than 7 (seven) days before additional quantities of Product(s)
are required to proceed with the
Trial.
|
| 8. |
Complete
all CRFs
|
| 9. |
Re-validate
the approval of the relevant Helsinki Committee to the Trial, within a
reasonable time prior to its expiration
date.
|
| 10. |
A
written detailed periodic report on the progress of the Trial in the said
period (section 17.3 of the
Agreement).
|
At the end of the
Trial:
| 1. |
All
Completed CRFs;
|
| 2. |
A
summary report, which shall include, in a full and detailed manner, a
declaration regarding the activities performed during the Trial and the
results obtained therein (section 17.4 of the
Agreement).
|
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