CLINICAL RESEARCH SERVICES AGREEMENT BETWEEN ADVAXIS, INC AND APOTHECARIES LIMITED.
BETWEEN
ADVAXIS,
INC
AND
APOTHECARIES
LIMITED.
TABLE
OF CONTENTS
|
RECITALS
|
2 | ||||||||
|
1.
|
DEFINITIONS
|
2
|
|||||||
|
2.
|
INTERPRETATION
|
6
|
|||||||
|
3.
|
APPOINTMENT
& RELATIONSHIP OF PARTIES
|
6
|
|||||||
|
4.
|
REPRESENTATIONS
& WARRANTIES
|
7
|
|||||||
|
5.
|
APOTHECARIES’
OBLIGATIONS
|
7
|
|||||||
|
6.
|
THE
COMPANY’s OBLIGATIONS
|
9
|
|||||||
|
7.
|
CRO
COMPENSATION
|
10
|
|||||||
|
8.
|
INSURANCE
|
11
|
|||||||
|
9.
|
CONFIDENTIALITY
|
11
|
|||||||
|
10.
|
INTELLECTUAL
PROPERTY
|
12
|
|||||||
|
11.
|
ARBITRATION
|
12 | |||||||
|
12.
|
NON-SOLICITATION
OF STAFF
|
13
|
|||||||
|
13.
|
TERM
& XXXXXXXXXXX
|
00
|
|||||||
|
00
|
XXXXXXXXXXXX
XX XXXXXXXXXXX
|
00
|
|||||||
|
00.
|
GENERAL
PROVISIONS
|
16
|
|||||||
|
16.
|
APPLICABLE
LAW
|
18
|
|||||||
|
Attachment
I and IA
|
Payment
Schedule, Budget, pass through and Timelines Schedule
|
|
|
Attachment
II
|
APOTHECARIES
Clinical Research Services and APOTHECARIES
deliverables
|
|
|
Attachment
III
|
Protocol
and Schedule of Procedures
|
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
1 of
23
This Clinical Research Services Agreement (this Agreement) is made and entered into effective as of 28 Oct. 2006, by and between Advaxis, Inc. (hereafter “THE COMPANY”), a Delaware Company with its principal office at 000 Xxxxx 0, Xxxxx Xxxxxxxxx, Xxx Xxxxxx 00000, and APOTHECARIES LIMITED. (hereafter “APOTHECARIES ”), a corporation organized under the laws of India, with its principal office at 000, Xxxxx, Xxxx Xxxxxx Xxxxx, Xxx Xxxxx 000000, Xxxxx.
RECITALS
WHEREAS,
THE COMPANY is a biotech company that develops biological vaccines to cure
cancer; and
WHEREAS,
APOTHECARIES is a contract research organization that plans, implements, and
manages clinical trials; and
WHEREAS,
THE COMPANY desires to engage APOTHECARIES to assist THE COMPANY in planning,
implementing, and managing regulatory and conduct of a phase I clinical trial
on
an Investigational Biological Product Lovaxin C, as hereafter defined;
and
WHEREAS,
APOTHECARIES 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 Synopsis, 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;
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
2 of
23
|
1.2
|
“Clinical
Laboratory Agreement” means the Agreement between THE COMPANY 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 APOTHECARIES to
monitor one or more Study Sites.
|
|
1.4
|
“Clinical
Trial Agreement” means the agreement between APOTHECARIES and an
Investigator that details the respective rights and obligations of
both
parties in relation to the Study;
|
|
1.5
|
“Clinical
Trial Materials” means the Investigational Product, printed Case Report
Forms, competitor substances, CRF monitoring conventions, the Protocol,
the investigational drug brochure, informed consent form, guidelines
for
use of the Investigational Product, and all other materials provided
by
THE COMPANY to conduct the Study.
|
|
1.6
|
“Closeout
Services” means those services described in Section 14 to be performed by
APOTHECARIES upon termination of this Agreement.
|
|
1.7
|
“Company
Obligations” means the obligations of THE COMPANY under this
Agreement.
|
|
1.8
|
“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
APOTHECARIES Group or of THE COMPANY, 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 or information
developed or generated in the course of performance of this Agreement.
Publication of the fact that THE COMPANY and APOTHECARIES have entered
into a clinical trials 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.
|
| The parties acknowledge that they have already executed a confidentiality agreement. (“CDA”) In the event of a conflict or a contradiction between this Agreement and the CDA, the terms of the CDA shall control. |
Advaxis
Clinical Research Agreement
October
18, 2006
Page
3 of
23
|
1.9
|
“CRO
Compensation” means the compensation to be paid by THE COMPANY to
APOTHECARIES as set out in Attachment
1.
|
|
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” 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.
|
|
1.13
|
“Good
Clinical Practice” means the clinical standards established by the FDA,
counterpart agencies of each country in which the Study will take
place,
and ICH treaties designed to regulate the activities of THE COMPANY’s
investigators, monitors, and Institutional Review Boards (“IRBs”) involved
in clinical drug testing.
|
|
1.14
|
“Institutional
Review Board” 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 THE COMPANY
with the FDA requesting the FDA to allow human testing on the
Investigational Product.
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
4 of
23
|
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
|
“APOTHECARIES
Group” means the following persons and entities, as constituted at the
date of this Agreement or subsequently: (i) APOTHECARIES; 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 APOTHECARIES.
For the purpose of this definition, Investigators identified and
deployed
by Apothecaries shall be treated as Contractors of
Apothecaries.
|
|
1.19
|
“APOTHECARIES’
Obligations” means the obligations of APOTHECARIES under this
Agreement.
|
|
1.20
|
“Project
Manager” means the manager assigned by APOTHECARIES to be the primary
contact person between APOTHECARIES and THE COMPANY during the
Study.
|
| 1.21 | “Protocol” means the plan that describes the objectives, study design, and methodology and any approved amendments thereto, which is attached as Attachment III, and 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 APOTHECARIES in connection
with the
Study as set out in this Agreement and the list of deliverable specified
in Attachment
II.
|
|
1.26
|
“Staff”
means the staff assigned to the Study by THE COMPANY either directly
or
indirectly through the Clinical Trial
Agreement.
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
5 of
23
|
1.27
|
“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.
|
|
1.28
|
“Study”
means the clinical trial of the Investigational Product, the details
of
which are set out in the Attachments I, II and III and the
Protocol..
|
|
1.29
|
“Study
Documents” means the documents produced by APOTHECARIES in connection with
the Study that are, in the sole discretion of APOTHECARIES, necessary
for
the production of the Final Study Report.
|
|
1.30
|
“Term”
means the duration of this Agreement as set out in Section
13.
|
|
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
Attachment I are to the sections of, and Attachment I to, this Agreement.
Attachment I is 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.
|
|
3.
|
APPOINTMENT
AND RELATIONSHIP OF PARTIES
|
|
3.1
|
THE
COMPANY hereby engages the services of APOTHECARIES, and APOTHECARIES
accepts such engagement, to perform the Study and the Services, under
the
terms and conditions contained in this
Agreement.
|
|
3.2
|
During
the Term, APOTHECARIES shall at all times be the independent contractor
of
THE COMPANY, and nothing in this Agreement is intended, nor shall
be
construed, to create between THE COMPANY and APOTHECARIES the relationship
of principal and agent, employer and employee, partnership, or joint
venture, and the parties shall not represent themselves
otherwise.
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
6 of
23
|
3.3
|
THE
COMPANY 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
COMPANY’s
employees. Likewise, APOTHECARIES 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 APOTHECARIES’ employees.
|
|
3.4
|
If
the Internal Revenue Service or any other government authority shall,
at
any time, question or challenge the independent contractor status
of
APOTHECARIES, 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
|
APOTHECARIES
warrants to THE COMPANY that it has the authority to enter into this
Agreement.
|
|
4.2
|
THE
COMPANY warrants to APOTHECARIES that (i) it has the authority to
enter
into this Agreement; and (ii) all consents and approvals required
for the
Study (except for the consent of the individuals who will participate
in
the Study) have been, or will be obtained prior to initiation of
the
Study.
|
|
5.
|
APOTHECARIES’
OBLIGATIONS
|
|
In
addition to APOTHECARIES’s Obligations set forth in Attachment I and II
and elsewhere in this Agreement, APOTHECARIES shall have the following
obligations:
|
|
5.1
|
Before
commencement of the Study, APOTHECARIES shall assign to the Study
a
Project Manager and sufficient personnel, including CRAs, with suitable
experience and training to fulfill APOTHECARIES’ obligations under this
Agreement.
Any change in the Project Manager thereafter must be reasonably acceptable
to THE COMPANY.
|
|
5.2
|
APOTHECARIES
shall apply to the Study systems of quality control designed to ensure
that, as far as is reasonably practicable, THE COMPANY and the
Investigators conduct the Study; generate data; and record and report
data, all in compliance with the Regulatory Requirements, Good Clinical
Practice, the Protocol, and this Agreement, in that
order.
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
7 of
23
|
5.3
|
APOTHECARIES
shall use its best efforts to perform the Services and deliverables
within
the time frames specified in Attachment
I.
|
|
5.4
|
APOTHECARIES
shall procure and maintain consents, approvals, licenses, and operating
certificates as required.
|
|
5.5
|
APOTHECARIES
shall retain all material Study Documents, as determined by APOTHECARIES
in its sole discretion, until this Agreement has terminated and all
Closeout Services has been performed. All
Study Documents and relevant copies of CRF pages will be forwarded
to THE
COMPANY after the Study is completed. CRF pages containing personal
information of patients shall not be forwarded to the
Company.
|
|
5.6
|
Company
shall have the right to visit and co-monitor a Study Site or inspect
and
audit any of the Study Documents maintained by APOTHECARIES. All
such
visits and inspections must be conducted during normal working hours
on
regular business days, unless otherwise agreed. APOTHECARIES
shall arrange access to the Study Site as soon as reasonably practicable
following notification by THE
COMPANY.
|
|
5.7
|
APOTHECARIES
will provide THE COMPANY with written status reports in accordance
with
either THE COMPANY or APOTHECARIES
SOPs.
|
|
5.8
|
APOTHECARIES
shall notify THE COMPANY by phone immediately after becoming aware
of a
Serious Adverse Event and shall submit an initial written report
to THE
COMPANY regarding that Serious Adverse Event via facsimile within
24 hours
after APOTHECARIES becomes aware of any such event, and shall file
the
appropriate documentation as required under local statutes in a timely
manner.
|
|
5.9
|
APOTHECARIES
shall indemnify and save harmless THE COMPANY, its officers, agents,
and
employees from all 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 for 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 APOTHECARIES (or its agents or
employees), in connection with its execution or performance of this
Agreement. The Investigators are not and shall not be deemed the
agents of
APOTHECARIES for purposes of this Section 5.9. THE COMPANY will notify
APOTHECARIES 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. APOTHECARIES shall have the sole right to control
and
settle any such claim or suits, and THE COMPANY shall make all reasonable
efforts to cooperate (at APOTHECARIES’ expense) as requested by
APOTHECARIES in handling any such claim or
suit.
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
8 of
23
|
5.10
|
For
the removal of any doubt, subject to the Company providing APOTHECARIES
with the materials necessary for APOTHECARIES to complete and write
the
Investigational Product, APOTHECARIES shall be responsible to obtain
all
approvals, construct all the necessary written materials submit any
and
all applications as necessary, and cause the Phase I clinical trial
to be
conducted and completed in accordance with the Protocol (a draft
of which
is attached hereto as Attachment
III)
and in a form and manner acceptable to the US Food and Drug
Administration.
|
|
5.11
|
APOTHECARIES
shall follow the Special Protocol Assessment procedure of the US
Food and
Drug Administration and seek the feedback or approval of the US Food
and
Drug Administration to the
Protocol.
|
|
5.12
|
Outside
regulatory consultant:
APOTHECARIES may work with a third party regulatory consultant pre
approved by THE COMPANY.
|
|
5.13
|
APOTHECARIES
shall be responsible for the list of services and deliverables specified
in Attachment
II.
APOTHECARIES as the contracted research organization agrees to conduct
the
proposed phase trial for Advaxis with the highest quality of care
and in
compliance with accepted standards of Good Research Practice and
Good
Laboratory Practice. Without derogating from the generality of the
foregoing statement, the standards of management mentioned in Attachment
II shall
apply.
|
|
5.14
|
APOTHECARIES
understands that as the aforementioned clinical trial is ongoing
and
coordinated through a central site in Belgrade Serbia. Apothecaries
agrees
to collaborate with this site, adhere to all appropriate monitoring
and
other SOPs, including monitoring, remote data entry, and all necessary
forms completion and
communications.
|
|
6.
|
THE
COMPANY’S OBLIGATIONS
|
|
In
addition to THE COMPANY’s Obligations set forth in the Attachment I and
elsewhere in this Agreement, THE COMPANY shall have the following
obligations:
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
9 of
23
|
6.1
|
THE
COMPANY shall provide APOTHECARIES, at no expense to APOTHECARIES
(i) with
all information and documentation reasonably necessary for APOTHECARIES
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 APOTHECARIES to fulfill its duties under
this
Agreement.
|
|
6.2
|
Except
for the APOTHECARIES obligations in Paragraph 5.4, or as otherwise
specifically provided herein, THE COMPANY shall procure and maintain
all
consents, approvals, licenses, and operating certificates required
to
conduct the Study. THE COMPANY shall also develop, comply with, and
require Staff 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.
|
|
6.3
|
THE
COMPANY shall indemnify and save harmless APOTHECARIES, its officers,
agents, and employees from all 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, 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 the Staff or THE COMPANY (or its agents
or
employees), in connection with the Study or their execution or performance
of this Agreement. APOTHECARIES will notify THE COMPANY of any claim
or
suit which may be subject to the provisions of this Section 6.3 as
soon as
reasonably practicable after receiving notice of the claim. THE COMPANY
shall have the sole right to control and settle any such claims or
suits,
and APOTHECARIES shall make all reasonable efforts to cooperate (at
THE
COMPANY’s expense) as requested by THE COMPANY in handling any such claim
or suit.
|
|
7.
|
CRO
COMPENSATION
|
|
7.1
|
THE
COMPANY shall pay APOTHECARIES the amounts set forth in Attachment
I
for all services provided and expenses incurred by APOTHECARIES pursuant
to this Agreement, according to the payment schedule set forth in
Attachment I. Upon early termination of this Agreement pursuant to
Sections 13.2, 13.3, or 13.4, THE COMPANY shall continue to pay
APOTHECARIES the amounts set forth in Attachment I for all services
provided by APOTHECARIES prior to the termination of this Agreement
and
for the Closeout Services furnished by APOTHECARIES after the termination
of this Agreement, provided that in no event will the amount owed
to
APOTHECARIES exceed the maximum amounts specified in Attachment
I.
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
10
of 23
|
7.2
|
APOTHECARIES
shall submit invoices to THE COMPANY upon the completion of each
payment
milestone event set forth in Attachment I. THE COMPANY shall make
full
payment of such sums by electronic transfer to such bank account
in the
India as APOTHECARIES may reasonably specify from time to time, upon
receipt of invoice (“Due Date”), without any deduction, set off or
withholding except any tax which THE COMPANY is required by law to
deduct
or withhold. Any amounts which remain unpaid for thirty (30) days
or more
after the Due Date shall bear interest at the rate equal to 6% per
annum.
Interest shall be computed on the basis of a 365 or 366-day year,
as the
case may be, subject to the provisions hereof limiting interest to
the
maximum rate of interest allowed by applicable law.
If
any amounts remain unpaid for Thirty (30) days or more after the
Due Date,
APOTHECARIES shall have the right to discontinue all work and services
under this Agreement until such amounts are paid in
full.
|
|
7.3
|
If
THE COMPANY is required by law to make any tax deduction or withholding,
THE COMPANY shall provide reasonable assistance as requested by
APOTHECARIES to assist APOTHECARIES 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. THE COMPANY shall
also
supply APOTHECARIES from time to time with proper evidence as to
the
deduction or withholding and payment over of the tax deducted or
withheld.
|
|
8.
|
INSURANCE
|
|
8.1
|
THE
COMPANY and APOTHECARIES 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.
|
|
8.2
|
Upon
request by either party, the other party shall provide evidence of
that
party’s compliance with this Section.
|
|
9.
|
CONFIDENTIALITY
|
|
9.1
|
Except
as specified in the following Section, 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; 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 Information
comply with these non-disclosure obligations.
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
11
of 23
|
9.2
|
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, and will be directed by the
respective party not to disclose to any other person any Confidential
Information; and (ii) the FDA, an IRB, 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 6.1.
|
|
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.
|
|
10.
|
INTELLECTUAL
PROPERTY
|
|
10.1
|
APOTHECARIES
acknowledge that, as between THE COMPANY and APOTHECARIES, any and
all
intellectual property rights that may arise in the Study itself shall
belong solely to THE COMPANY, including without limitation all data
generated in the course of the Study, and all Clinical Trial
Materials.
|
|
10.2
|
THE
COMPANY acknowledges that, as between APOTHECARIES and THE COMPANY,
any
and all intellectual property rights in works authored by APOTHECARIES
before the Effective Date of this Agreement and works authored by
APOTHECARIES independent of the Study shall belong to
APOTHECARIES.
|
|
11.
|
ARBITRATION
|
|
11.1
|
Any
controversy or claim between the parties arising out of or relating
to
this Agreement, shall be finally determined and settled pursuant
to
arbitration in Princeton, NJ, by one arbitrator whom (i) shall have
at
least 5 years of experience as an arbitrator and (ii) shall be associated
with the American Health Lawyers Association ADR Service or the American
Arbitration Association. .
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
12
of 23
|
11.2
|
The
arbitration proceedings shall be conducted in accordance with the
Commercial Arbitration Rules of the American Arbitration Association.
A
determination, award, or other action shall be considered the valid
action
of the arbitrators if supported by the affirmative vote of two or
three of
the three arbitrators. The costs of arbitration (exclusive of a party’s
own costs incurred in attending the arbitration, and of the fees
and
expenses of legal counsel to such party, all of which shall be borne
by
such party) shall, in the discretion of the arbitrators, be ordered
to be
paid by the one or both of the parties either equally or in such
proportions as may be decided by the arbitrators. The arbitration
award
shall be final and binding, and judgment upon such award may be entered
in
any court having jurisdiction. Notwithstanding any
other provision hereof, no party shall be awarded punitive or exemplary
damages in any arbitration
hereunder.
|
|
12.
|
NON-SOLICITATION
OF STAFF
|
|
During
the term of this Agreement and for a period of thirty-six months
following
its termination or expiration, THE COMPANY shall not directly or
indirectly (i) solicit or entice any employee or contractor of
APOTHECARIES 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.
|
|
13.
|
TERM
AND TERMINATION
|
|
13.1
|
This
Agreement shall commence on the Effective Date and, unless terminated
pursuant to this Section 13, shall
continue until such time as the Services and Closeout Services have
been
completed.
|
|
13.2
|
This
Agreement may be terminated upon the mutual, written consent of both
parties.
This Agreement may also be terminated by THE COMPANY without cause
upon
thirty (30) days prior written notice to the other
party.
|
|
13.3
|
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:
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
13
of 23
|
13.3.1
|
Termination
by APOTHECARIES. APOTHECARIES
may terminate this Agreement for cause upon the occurrence of any
of the
following events:
|
|
(i)
|
THE
COMPANY fails to maintain the insurance coverage required by Section
8.1;
|
|
(ii)
|
The
FDA, IRB, 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)
|
If
on behalf of the COMPANY, APOTHECARIES
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
THE
COMPANY may cure any such deficiency by removing the affected individual
from providing services under this
Agreement;
|
|
(iv)
|
THE
COMPANY breaches any material provision of this Agreement, other
than
those specifically referenced in this Section 13.3.1, and fails to
remedy
that breach within 30 days after receiving notice of such breach;
or
|
|
(v)
|
THE
COMPANY 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 THE COMPANY files a petition for the appointment of a
receiver
in liquidation or a trustee with respect to THE COMPANY 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 THE COMPANY’s receiving
notice of such petition.
|
|
13.3.2
|
Termination
by THE COMPANY. THE
COMPANY may terminate this Agreement for cause upon the occurrence
of any
of the following events:
|
|
(i)
|
The
FDA, IRB, or any regulatory authority with jurisdiction over the
Study
suspends or revokes any consent, approval, license, or operating
certificate required to conduct the
Study;
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
14
of 23
|
(ii)
|
The
occurrence of a Serious Adverse Event which should cause the Study
to be
terminated due to safety concerns
|
|
(iii)
|
APOTHECARIES
breaches any material provision of this Agreement, other than those
specifically referred to in this Section 13.3.2, and fails to remedy
that
breach within 30 days after receiving notice of such breach;
or
|
|
(iv)
|
APOTHECARIES
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
APOTHECARIES 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 APOTHECARIES files a petition for the appointment of a
receiver
in liquidation or a trustee with respect to APOTHECARIES 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 APOTHECARIES ’s receiving notice of the petition.
|
|
13.4
|
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.
|
|
14.
|
CONSEQUENCES
OF TERMINATION
|
|
14.1
|
The
termination of this Agreement for any reason shall not affect any
right or
remedy existing hereunder prior to the effective date of
termination.
|
|
14.2
|
Without
limiting the foregoing, upon termination of this Agreement, THE COMPANY
shall, in addition to all CRO Compensation then due, compensate
APOTHECARIES as specified in Attachment I, 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
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
15
of 23
|
15.
|
GENERAL
PROVISIONS
|
|
15.1
|
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.
|
|
15.2
|
Any
amendment of or modification to this Agreement shall become effective
only
if it is in writing and executed by the
parties.
|
|
15.3
|
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.
|
|
15.4
|
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 THE COMPANY shall be addressed to:
Dr.
Xxxx
Xxxxxxx, VP Clinical Development
Advaxis
Inc., USA
000,
Xxxxx 0, Xxxxx Xxxxxxxxx,
XX
00000,
XXX
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 THE COMPANY shall be placed and
facsimiles
to THE COMPANY shall be sent to the following numbers:
Phone:
000 000 0000 Fax: 000 000 0000.
Advaxis
Clinical Research Agreement
October
18, 2006
Page
16
of 23
All
notices to APOTHECARIES shall be addressed to:
Apothecaries
Limited
000,
Xxxxx, Xxxx Xxxxxx Xxxxx, Xxx Xxxxx 000000, Xxxxx
Email:
Xxxxxxxxx@Xxxxxxxxxxxx.xxx
Phones:
x00-00000 00000, x00-00000 00000
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 APOTHECARIES shall be placed and
facsimiles
to APOTHECARIES shall be sent to the following numbers:
Phone:
+91-11-2450 2451/52/53
Fax:
x00-00-00000000
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.
|
15.5
|
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
6.3, and Sections 7 through 12, and 14, shall survive such termination
or
expiration hereof and shall not be
merged.
|
| 15.6 | The waiver by any party of a 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. |
| 15.7 | 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. |
| 15.8 | No party may assign this Agreement or its rights and duties hereunder, without the prior written consent of the other party, except that THE COMPANY may assign this Agreement to a purchaser or acquirer of substantially all of the business to which this Agreement relates. Apothecaries, may, however assign certain site management related tasks to the CRCs retained by Clinical Research Academy, New Delhi, India. Apothecaries will be entirely responsible for the conduct and management of all such CRCs / staff members. |
Advaxis
Clinical Research Agreement
October
18, 2006
Page
17
of 23
| 15.9 | 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. |
| 15.10 | 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. |
| 15.11 | 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, 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. |
| 16. | APPLICABLE LAW |
| This Agreement shall be governed by and be construed under the laws of the New Delhi India, 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 India.. |
IN
WITNESS WHEREOF, this Agreement is executed by the parties hereto and is
effective as of the day and year first above written.
Advaxis, Inc.
By: ____________________________________
Apothecaries
Limited
By: ____________________________________
Advaxis
Clinical Research Agreement
October
18, 2006
Page
18
of 23
Attachment
I
Timelines
and Payment Schedule
Timelines:
|
Event
|
Date
|
|||||
|
Contract
and transfer of funds
|
Day
0
|
|||||
|
Site
Assessment for 6-8 sites
|
Day
30
|
|||||
|
Site
Feasibility Reports
|
Day
30
|
|||||
|
List
of probable investigator sites and investigators
|
Day
30
|
|||||
|
Estimated
enrolment rates
|
Day
45
|
|||||
|
Preparation
of regulatory dossiers for
|
||||||
|
conducting
clinical trials on Lovaxin C
|
Day
30
|
|||||
|
Submission
to Indian Regulatory Authorities
|
Day
40
|
|||||
|
Obtaining
regulatory approvals in India (likely)
|
Day
130-160
|
|||||
|
First
patient in to study India
|
Day
145-175
|
|||||
|
Last
patient in to study India
|
To
be decided
|
|||||
Advaxis
Clinical Research Agreement
October
18, 2006
Page
19
of 23
Payment
Schedule for Services:
|
Execution
of Clinical Research Services Agreement, and initiation of compilation
of
dossier for Indian regulatory submission
|
$
|
6,500
|
||
|
Site
assessment report - first 4 sites
|
$
|
1,500
|
||
|
Each
additional site assessment report
|
$
|
1,500
|
||
|
Submission
for regulatory approval in India
|
$
|
4,000
|
||
|
Upon
obtaining regulatory approval in India
|
$
|
6,500
|
||
|
Upon
enrollment of each qualified patient
(institutional
cost)
|
$
|
1,500
|
||
|
Upon
enrollment of each qualified patient
(management
cost)
|
$
|
750
|
||
|
Upon
completion of each qualified patient
(institutional
cost)
|
$
|
3500
|
||
|
Upon
completion of each qualified patient
(management
cost)
|
$
|
750
|
||
|
Completion
of report for India patients (per patient)
|
$
|
1,000
|
All
the
following expenses are included in the above cost:
Administrative
cost (telephones, faxes, mail, etc)
Site
visits as follows: monthly and as required to comply with safety review panel
meetings, site initiation and closing, and in the event of reportable adverse
events.
CRF
preparation and printing
Investigator
fees estimated from protocol synopsis
Above
costs are based on INR-US$ conversion rate of 46 INR = 1US$. Any fluctuations
in
the conversion rate shall be to the Sponsor’s account.
Service
tax, if and when chargeable according to Govt. of India rules, shall be payable
by the clients over and above the indicated costs. At present, service tax
is
not applicable to overseas clients who do not have their offices in India.
However, for those overseas clients who have established an office in India
the
service tax may be chargeable @ 12.24% even if the assignment is carried out
for
the overseas office of the client.
Pass-throughs:
Invoices
will be sent to Advaxis, Inc for all pass-through cost.
The
parties agree that the pass-through costs shall not exceed the cost structure
detailed in Attachment
IA:
Advaxis
Clinical Research Agreement
October
18, 2006
Page
20
of 23
Attachment
IA
|
Pass-throughs
|
||
|
Item
|
Cost
($)
|
Notes
|
|
Plasma
sample shipment for titers
|
To
be decided
|
|
|
Import/Export
Fees
|
To
be decided
|
Vaccine
shipment into India & samples for assay to Serbia
|
|
Medical
Insurance
|
To
be decided
|
|
|
Laboratory
expenses
|
||
|
EC
Fees
|
||
Advaxis
Clinical Research Agreement
October
18, 2006
Page
21
of 23
Attachment
II
Clinical
Research Services and APOTHECARIES’s deliverables
APOTHECARIES
Deliverables
|
1.
|
Protocol,
Investigators Brochure and CRF
translations
|
|
2.
|
Provide
site assessment reports, 8 sites
|
|
3.
|
Submit
to Ethics Committee and RA, India
|
|
4.
|
Obtain
Approval for Phase I in Lovaxin C in
India
|
|
5.
|
Recruit
6-8 Phase I study sites In India
|
|
6.
|
Remote
data entry into Advaxis existing study database and all necessary
collaboration.
|
|
7.
|
Management
and reporting of all adverse experiences Grade 3 or
higher
|
Quality
of Study Management
|
1.
|
A
site screening visit that assures each site has the appropriate facilities
and personnel to conduct the proposed study. This includes approved
and
certified physicians, a dedicated study nurse, and adequate clerical
personnel necessary facilities for patient visits, diagnostic devices,
and
so forth.
|
|
2.
|
A
study initiation visit for previously screened sites in which the
specific
details of the protocol are reviewed in detail and instruction is
given to
the site personnel as to the correct methods for conducting the study.
Specific attention is paid to following the study plan and schedule,
collecting information, completing case report forms (CRF) and assuring
their veracity when compared with the patient
charts.
|
|
3.
|
A
monitoring schedule which assures that CRFs are audited on a timely
basis.
Weekly calls with the sponsor to the site to track patient enrollment
and
visits at least once per month to assure adequate patient enrollment,
enrolled patients are being treated in compliance with the protocol
as
written, auditing of CRF against original documents (patient charts,
scans, X-rays, lab reports, etc). The retrieval of all CRF, or portions
of
CRF, which are completed, audited, and ready for data
entry.
|
|
4.
|
Verification
of data entered into the analytic database against the CRF data forms
to
assure the reliability of the data to be
analyzed.
|
Advaxis
Clinical Research Agreement
October
18, 2006
Page
22
of 23
Attachment
III
Protocol
Advaxis
Clinical Research Agreement
October
18, 2006
Page
23
of 23
