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REITLER
BROWN &
ROSENBLATT LLC 800 Third Avenue, 21st Floor
- ----------------------- New York, NY 10022-7604
ATTORNEYS AT LAW Tel (212) 209-3050
Fax (212) 371-5500
June 1, 2005
CONFIDENTIAL
VIA OVERNIGHT COURIER
The Secretary
Securities and Exchange Commission
450 Fifth Street, N.W.
Washington, D.C. 20549
RE: Advaxis, Inc. - Amendment No. 3 to Form SB-2
(Registration No. 333-122504)
Objection to Public Disclosure of Information
---------------------------------------------
Dear Sir:
In connection with the filing by Advaxis, Inc., a Colorado corporation
(the "Company"), of its Amendment No. 3 to Form SB-2 under the Securities Act of
1933, as amended (the "Form SB-2"), the Company hereby applies for an order of
the Securities and Exchange Commission (the "Commission"), pursuant to Rule
24b-2 ("Rule 24b-2") promulgated under the Securities Exchange Act of 1934 as
amended (the "Act"), granting confidential treatment to selected portions
(hereinafter referred to as the "Confidential Information") of that certain
Clinical Research Services Agreement, dated April 6, 2005, between Pharm-Olam
International Ltd., a Texas limited partnership, and the Company. The Agreement
was filed as Exhibit 10.26 to the Form SB-2.
Enclosed is a copy of Exhibit 10.26 clearly marked "CONFIDENTIAL
TREATMENT" with the specific portions the Company desires to keep confidential
bracketed and highlighted to identify where confidential treatment is requested.
With the exception of the Confidential Information, the Agreement has been filed
in its entirety as Exhibit 10.26. A copy of Amendment No. 3 to the Form SB-2 is
also enclosed for your review.
In accordance with subsection (b) of Rule 24b-2, Exhibit 10.26 was
filed with the Form SB-2 with asterisks to indicate that the omitted material
was filed separately with the Commission.
The paragraphs below set forth the following:
(I) An explanation of the basis for the Company's request for
confidential treatment with respect to the Confidential Portions of the
Agreement;
(II) An item by item presentation of the information for which the
Company is requesting confidential treatment;
(III) An explanation of why disclosure of this information is not
necessary to protect investors;
(IV) The time period for which confidential treatment is requested with
respect to the Agreement and an explanation of the basis for such request;
(V) A representation by the Company of its willingness to permit
disclosure to other governmental agencies, offices or bodies (including, without
limitation, the Congress) of the Confidential Portions;
(VI) An objection to public disclosure of this letter; and
(VII) The name, address and telephone number of the person to whom all
notices and orders issued under this rule at any time should be directed.
I. Basis of Confidential Treatment Request.
Legal Background
Rule 24b-2 of the Act provides that the Commission may grant
confidential treatment if it determines that such treatment is justified under
the Freedom of Information Act, 5 U.S.C. ss.552 (the "FOIA"). Subsection (b)(4)
of 5 U.S.C. ss.552 ("Exemption 4") exempts from the broad public disclosure
requirements of the FOIA "trade secrets and commercial or financial information
obtained from a person and privileged or confidential." This exemption is
intended to protect both the interests of commercial entities that submit
proprietary information to the government and the interests of the government in
receiving continued access to such data.
According to the decision in Public Citizen Health Research Group v.
Food and Drug Administration, 704 F.2d 1280, 1286 (D.C. Cir. 1983), there are
two alternative tests under which information could be found to fall within
Exemption 4: (i) the information can be found to consist of "trade secrets," in
which case no further inquiry is necessary, or (ii) the information can be found
to consist of commercial or financial information, in which case the exemption
will apply only if such information was obtained on a privileged or confidential
basis.
"Trade secret," for purposes of Exemption 4, is a secret, commercially
valuable plan, formula, process, or device that is used for making, preparing,
compounding, or processing trade commodities and that can be said to be the end
product of either innovation or substantial effort. Burnside-Ott Aviation
Training Center. Inc. v. United States, 617 F. Supp. 279 (S.D. Fla. 1985).
"Commercial or financial information" has been construed by the courts
in accordance with its plain meaning, and broadly encompasses information
relating to commerce or compiled in pursuit of profit. Critical Mass Energy
Project v. Nuclear Regulatory Commission, 644 F. Supp. 344 (D.D.C. 1986),
vacated on other grounds, 830 F.2d 278 (D.C. Cir. 1987). Commercial or financial
information is confidential within the meaning of Exemption 4 if it is not
customarily released to the public from the person from whom it was obtained,
and is likely to impair the Government's ability to obtain necessary information
in the future or to cause substantial harm to the competitive position of the
person from whom the information was obtained. S.Rep. No. 813, 89th Cong., 1st
Sess. 9 (1965); National Parks and Conservation Association v. Morton, 498 F.2d
765 (1974); Burke Energy Corporation v. Department of Energy, 583 F. Supp. 507
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(1984). Evidence revealing actual competition and the likelihood of substantial
competitive injury is sufficient to classify commercial information as
confidential. Public Citizen, 704 F.2d at 1291.
Company Background and Competitive Environment
The Company is a development stage biotechnology company utilizing
multiple mechanisms of immunity with the intent to develop cancer vaccines that
are more effective and safer than existing vaccines. To that end, the Company
has licensed rights from The Trustees of the University of Pennsylvania ("Penn")
to use a patented system to engineer a live attenuated Listeria monocytogenes
bacteria (the "Listeria System") to secrete a protein sequence containing a
tumor-specific antigen. Using the Listeria System, the Company believes it will
force the body's immune system to process and recognize the antigen as if it
were foreign, creating the immune response needed to attack the cancer. The
Company's licensed Listeria System, developed at Penn over the past 10 years,
provides a scientific basis for believing that this therapeutic approach induces
a significant immune response to a tumor. Accordingly, the Company believes that
the Listeria System is a broadly enabling platform technology that can be
applied to many types of cancers. In addition, the Company believes there may be
useful applications in infectious diseases and auto-immune disorders.
Reference is also made to the following sections of the Form SB-2,
filed with the Commission on February 3, 2005, as amended on April 7, 2005 and
as further amended on May __, 2005, as it may be further amended: PROSPECTUS
SUMMARY, RISK FACTORS ("We are dependent upon our license agreement with Penn,
as well as proprietary technology of others."; "We have no manufacturing, sales,
marketing or distribution capability and we must rely upon third parties for
such."; "The biotechnology and biopharmaceutical industries are characterized by
rapid technological developments and a high degree of competition. We may be
unable to compete with more substantial enterprises.") and BUSINESS
("Partnerships and Agreements"; "Manufacturing" and "Competition").
General Basis for Confidential Treatment Request
A. Protectable Trade Secrets.
The Company requests confidential treatment of the Confidential
Portions contained in the Agreement on the basis that such Confidential Portions
contain confidential and commercially valuable technical information of the
Company. Specifically, some of the Confidential Portions may describe the range
of functions provided by the Company's proprietary technologies, and the plans
and processes by which such technologies are applied to address customer
specifications - each of which make the Company's services unique and
protectable under state and federal intellectual property rights laws. To the
extent that the Company is required to publicly disclose Confidential Portions
relating to the functions of its proprietary technologies, the Company's
competitive advantages vis-a-vis its competitors - who provide similar services
using different technologies applied in accordance with different plans and
processes - would be materially compromised.
B. Protectable Commercial Information.
The Company has expended considerable time and effort in negotiating
the terms of the Agreement. If the Confidential Portions are made public, the
Company's competitors will gain an advantage since such competitors will seek to
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negotiate similar or more advantageous terms with potential joint development
parties, licensors or licensees. This is particularly true with respect to the
provisions regarding pricing and commissions paid to such parties. Public
disclosure of the Confidential Portions of the Agreement would provide
competitors of the Company with a reference to offer marginally more attractive
terms to potential clients thereby undercutting the Company's ability to enter
into agreements with others or greatly reducing the competitive position of the
Company.
C. Material Adverse Effect on the Formation of New Business Relationships.
Public knowledge of the Confidential Portions of the Agreement would
also place the Company in an adverse negotiating position with respect to
potential clients. The Company would have great difficulty negotiating similar
future agreements on more favorable terms because each potential contracting
party, aware of the terms of the Agreement, would be disinclined to accept terms
less attractive than those accepted by our current clients and business partners
in the Agreement. Further, such potential contracting parties would know what
concessions the Company was previously willing to bear. Thus, the Company may be
unable to negotiate terms more favorable to it than are present in the Agreement
if the Confidential Portions are disclosed.
Public disclosure of the Confidential Portions of the Agreement could
also make it very difficult for the Company to enter into similar agreements
with third parties in the future, because such entities may be reluctant to
contract with the Company if there is a strong likelihood that the sensitive
terms of such contracts would be publicly disclosed by the Company. Such
potential business partners may be more likely to seek a more substantial
partner that would not consider the contract sufficiently material to merit
public disclosure (as might be the case with a larger company) or a partner that
is not subject to such disclosure obligations.
D. General Considerations.
The Company's Agreement would be worth little to the Company or the
other parties to the Agreement if, by reducing their arrangements to writing,
they made the public dissemination of commercially sensitive information more
likely. Written contracts ensure against future misunderstandings. Public
disclosure of such confidential commercial material could be a disincentive to
reduce agreements to writing, with a consequent increase in risk to both
parties. Additionally, such an approach would impair the government's ability to
obtain necessary information in the future.
Finally, disclosure of the Confidential Portions of the Agreement is
wholly unnecessary for the protection of investors since such disclosure would
not contribute at all to an understanding of the Company's business, and would,
for the reasons described above in Sections A-D of this Article I, only
compromise the future prospects of the business in which such investors are
considering investing.
II. Itemization of Confidential Portions of the Agreement.
The Company requests confidential treatment of the following
Confidential Portions of the Agreement, as marked on the enclosed copy. Such
Confidential Portions are deal specific negotiated terms which disclosure would
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have a material adverse affect on the business, operations and financial
condition of the Company. For a more complete discussion of the reasons that the
Confidential Portions require protection, see Articles I and III hereof.
Exhibit 10.26; Agreement. The Agreement is an agreement between the Company and
Pharma-Olam International Ltd. ("POI").
Page and Section Reason
---------------- ------
Attachment I Confidential pricing and fee information and
confidential commercial information and deal
specific negotiated terms
Attachment II Confidential commercial information
III. Investors' Interests Protected without Disclosure.
In addition to the foregoing, the Company further believes that
disclosure of this information is not necessary for the protection of investors
in light of the broad disclosure as to the Company's overall commercial and
financial status and the disclosure of a substantial portion of the Agreement in
the Form SB-2. Confidential treatment is not requested for the material terms of
the Agreement taken as a whole in that the Confidential Portions are
specifically limited to proprietary technical and pricing and other commercial
provisions. Indeed, the material for which confidential treatment has been
requested is limited, and substantially all of the Agreement would otherwise be
available for public inspection.
The Confidential Portions of the Agreement are deal specific negotiated
terms between the parties and such disclosure would have a material adverse
affect on the business, operations and financial conditions of the Company. The
Company believes that the only parties that would benefit from public disclosure
of such information would be actual and potential competitors of the Company
and/or its corporate partners and third parties who could use the Confidential
Portions to the substantial detriment of the Company's business interests. For
these reasons, the Company believes that disclosure would harm its stockholders
and prospective investors. In contrast, knowledge of the Confidential Portions
of the Agreement would demonstrate little to an investor with respect to his or
her decision to purchase securities.
For the above reasons, the Company believes that disclosure of the
Confidential Portions of the Agreement would substantially harm the competitive
position of the Company. The information contained in the Confidential Portions
is not generally available to the public and the Company maintains a substantial
program to protect its confidentiality, including requiring employees to execute
confidentiality agreements with respect to the Company's proprietary
information. Thus, the only way that the Company's competitors could gain access
to this confidential, commercial information is through mandatory disclosure. To
avoid the substantial harm inherent in such disclosure, the Company respectfully
requests that the Confidential Portions of the Agreement be granted confidential
treatment.
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IV. Duration of Confidential Treatment.
Exhibit 10.26: Agreement. The Company believes that the Confidential Information
will remain sensitive and likely to cause substantial harm to the competitive
position of the Company if disclosed prior to the expiration of the term of the
Agreement. Therefore, the Company requests that the Commission grant an order
providing confidential treatment for the Confidential Information contained in
the Agreement until termination of the Agreement. At the expiration of this
period, the Confidential Information may be disclosed unless the Company then
requests and is granted continued confidential treatment for any information the
disclosure of which could have significant commercial consequences adverse to
the Company. The Company believes that such periods represent a reasonable
balance between the policy of full public disclosure and the Company's
legitimate commercial and competitive needs and concerns.
V. Disclosure to Other Government Agencies.
The Company consents to disclosure of the Confidential Portions of the
Agreement to other governmental agencies, offices or bodies (including, without
limitation, the Congress). The Company has voluntarily submitted the information
for which confidentiality is sought to the Commission and no prior
determinations by the Commission, other federal agencies or a court concerning
confidential treatment have been made. Further, the Company will disclose in its
future filings all material information about the Agreement required to be
disclosed under the federal securities laws, rules and regulations in light of
changing facts and circumstances, including, if appropriate, provisions
regarding limitations on liability and time periods for bringing legal claims.
VI. Objection to Public Disclosure of this Letter.
The Company also hereby objects to public disclosure of the following
because disclosure of such information would defeat the effectiveness of any
confidential treatment granted hereunder:
1. This transmittal letter;
2. Any memoranda, notes, correspondence, or other writings made by
any member or employee of the Commission or by the Company, or by any
representative on their behalf relating to the Agreement, this transmittal
letter, or any of the foregoing documents or any conference or telephone call
with respect thereto; and
3. Any copies or extracts of any of the foregoing.
VII. Name of Contact Person.
All notices and communications with respect to this application for
confidential treatment should be addressed to:
Advaxis, Inc.
212 Carnegie Center
Suite 206
Princeton, NJ 08540
Telephone: (609) 895-7150
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With a copy to:
Reitler Brown & Rosenblatt LLC
800 Third Avenue
21st Floor
New York, NY 10022
Attn: Gary Schonwald
Telephone: (212) 209-3090
It is the Company's understanding that if the Commission grants this
application, a notation to that effect will be made at the appropriate place in
the Agreement as filed with the Commission. It is also the Company's
understanding that if the Commission determines that this application will be
denied in whole or in part, it will so inform the Company, which may petition
the Commission for a review of such denial.
If you have any questions, please contact me at (212) 209-3090.
Please stamp the enclosed copy of this letter with the date of filing,
and return it to the undersigned in the self-addressed, stamped envelope
provided. Thank you for your attention to this matter.
Very truly yours,
/s/ Gary Schonwald
Gary Schonwald, Esq.
(Enclosure)
cc: Freedom of Information Act Officer (Securities and Exchange Commission)
Jeffrey Riedler Assistant Director (Securities and Exchange Commission)
Albert Lee (Division of Corporate Finance)
J. Todd Derbin (Advaxis, Inc.)
Roni Appel (Advaxis, Inc.)
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CONFIDENTIAL TREATMENT REQUESTED
BRACKETED AND HIGHLIGHTED VERSION
CLINICAL RESEARCH SERVICES AGREEMENT
BETWEEN
ADVAXIS, INC
AND
PHARM-OLAM INTERNATIONAL LTD.
TABLE OF CONTENTS
RECITALS 1
1. DEFINITIONS 1
2. INTERPRETATION 5
3. APPOINTMENT & RELATIONSHIP OF PARTIES 5
4. REPRESENTATIONS & WARRANTIES 6
5. POI's OBLIGATIONS 6
6. THE COMPANY's OBLIGATIONS 7
7. CRO COMPENSATION 8
8. INSURANCE 9
9. CONFIDENTIALITY 9
10. INTELLECTUAL PROPERTY 10
11. ARBITRATION 10
12. NON-SOLICITATION OF STAFF 11
13. TERM & TERMINATION 11
14 CONSEQUENCES OF TERMINATION 13
15. GENERAL PROVISIONS 13
16. APPLICABLE LAW 15
Attachment I and IA Payment Schedule, Budget, pass through and Timelines
Schedule
Attachment II POI Clinical Research Services and POI deliverables
Attachment III Protocol and Schedule of Procedures
2
This Clinical Research Services Agreement (this Agreement) is made and
entered into effective as of April 4, 2005, by and between Advaxis, Inc.
(hereafter "THE COMPANY"), a Colorado Company with its principal office at
212 Carnegie Center, Suite 206, Princeton, New Jersey 08540, and PHARM-OLAM
INTERNATIONAL LTD. (hereafter "POI"), a Texas limited partnership, with its
principal office at 450 N Sam Houston Pkwy, Suite 450, Houston, TX 77060,
United States.
RECITALS
WHEREAS, THE COMPANY is a biotech company that develops biological
vaccines to cure cancer; and
WHEREAS, POI is a contract research organization that plans,
implements, and manages clinical trials; and
WHEREAS, THE COMPANY desires to engage POI 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, POI is willing to accept such engagement on the terms and
conditions set forth herein;
NOW, THEREFORE, in consideration of the premises and the mutual
covenants and obligations set forth herein, and for other good and valuable
consideration, the receipt and sufficiency of which are acknowledged, the
parties agree as follows:
1. DEFINITIONS
For purposes of this Agreement and the Protocol 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;
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 POI to monitor one or more Study Sites.
3
1.4 "Clinical Trial Agreement" means the agreement between POI
and an Investigator that details the respective rights and obligations of both
parties in relation to the Study;
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 POI 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 POI 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 POI 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.
1.9 "CRO Compensation" means the compensation to be paid by
THE COMPANY to POI 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.
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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 and counterpart agencies of each country in which the
Study will take place, 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.
1.16 "Investigational Product" means the product (drug,
device, or biologic) described in the Protocol that will be evaluated in this
Study.
1.17 "Investigator" means an individual who actually conducts
a clinical investigation, i.e., under whose immediate direction the
Investigational Product is administered or dispensed to, or used involving a
subject, or, in the event of an investigation conducted by a team of
individuals, is the responsible leader of that team.
1.18 "POI Group" means the following persons and entities, as
constituted at the date of this Agreement or subsequently: (i) POI; and (ii) any
person or entity that directly, or indirectly through one or more
intermediaries, controls, is controlled by, or is under common control with POI.
1.19 "POI's Obligations" means the obligations of POI under
this Agreement.
1.20 "Project Manager" means the manager assigned by POI to be
the primary contact person between POI and 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.
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1.22 "Regulatory Requirements" means those laws, regulations,
and professional and ethical standards and guidelines then in effect in the
countries in which the Study is conducted that apply to the Investigational
Product or clinical trials in general.
1.23 "Related Products" means any product (drug, device, or
biologic), other than the Investigational Product, administered or utilized as
part of this Study.
1.24 "Serious Adverse Event" shall take the meaning given this
term in the Protocol.
1.25 "Services" means the services to be furnished by POI in
connection with the Study as set out in this Agreement 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.
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 POI in
connection with the Study that are, in the sole discretion of POI, 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.
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3. APPOINTMENT AND RELATIONSHIP OF PARTIES
3.1 THE COMPANY hereby engages the services of POI, and POI
accepts such engagement, to perform the Study and the Services, under the terms
and conditions contained in this Agreement.
3.2 During the Term, POI 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 POI the relationship of
principal and agent, employer and employee, partnership, or joint venture, and
the parties shall not represent themselves otherwise.
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 COMPANYs employees. Likewise, POI shall be liable for its own debts,
obligations, acts or omissions, including but not limited to the payment of all
required compensation, withholding, social security and other taxes or benefits
for POI's 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 POI, upon receipt by either party of notice from the Internal Revenue
Service or any other governmental authority, the receiving party shall promptly
notify the other party and afford the other party the opportunity to participate
in any discussion or negotiation with the Internal Revenue Service or other
government authority, regardless as to who initiates such discussions or
negotiations.
4. REPRESENTATIONS AND WARRANTIES
4.1 POI warrants to THE COMPANY that it has the authority to
enter into this Agreement.
4.2 THE COMPANY warrants to POI 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. POI'S OBLIGATIONS
In addition to POI's Obligations set forth in Attachment I and II and
elsewhere in this Agreement, POI shall have the following obligations:
5.1 Before commencement of the Study, POI shall assign to the
Study a Project Manager and sufficient personnel, including CRAs, with suitable
experience and training to fulfill POI's obligations under this Agreement. Any
change in the Project Manager thereafter must be reasonably acceptable to THE
COMPANY.
5.2 POI 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,
7
all in compliance with the Regulatory Requirements, Good Clinical Practice, the
Protocol, and this Agreement, in that order.
5.3 POI shall use its best efforts to perform the Services and deliverables
within the time frames specified in Attachment I.
5.4 POI shall procure and maintain consents, approvals,
licenses, and operating certificates as required.
5.5 POI shall retain all material Study Documents, as
determined by POI in its sole discretion, until this Agreement has terminated
and all Closeout Services has been performed. All Study Documents and CRF's will
be forwarded to THE COMPANY after the Study is completed.
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 POI.
All such visits and inspections must be conducted during normal working hours on
regular business days, unless otherwise agreed. POI shall arrange access to the
Study Site as soon as reasonably practicable following notification by THE
COMPANY.
5.7 POI will provide THE COMPANY with written status reports
in accordance with either THE COMPANY or POI SOP's.
5.8 POI 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 POI becomes aware of any such event.
5.9 POI 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 POI (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 POI for purposes of this Section 5.9. THE
COMPANY will notify POI of any claim or suit which may be subject to the
provisions of this Section 5.9 as soon as reasonably practicable after receiving
notice of the claim. POI shall have the sole right to control and settle any
such claim or suits, and THE COMPANY shall make all reasonable efforts to
cooperate (at POI's expense) as requested by POI in handling any such claim or
suit.
5.10 For the removal of any doubt, subject to the Company
providing POI with the materials necessary for POI to complete and write the
Investigational Product, POI 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.
8
5.11 In the event the Phase I study is conducted out of the
US, POI 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: POI will work with a third
party regulatory consultant pre approved by THE COMPANY.
5.13 POI shall be responsible for the list of services and
deliverables specified in Attachment II. POI as the contracted research
organization agrees to conduct the proposed phase 1b 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.
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:
6.1 THE COMPANY shall provide POI, at no expense to POI (i)
with all information and documentation reasonably necessary for POI to perform
its duties hereunder, including but not limited to, all Clinical Trial
Materials; and (ii) with all advice, guidance, and assistance reasonably
requested by POI to fulfill it duties under this Agreement.
6.2 Except for the POI 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 POI, 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. POI 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 POI shall make all reasonable efforts to cooperate (at THE
COMPANY's expense) as requested by THE COMPANY in handling any such claim or
suit.
9
7. CRO COMPENSATION
7.1 THE COMPANY shall pay POI the amounts set forth in
Attachment I for all services provided and expenses incurred by POI 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 POI the amounts set forth in Attachment
I for all services provided by POI prior to the termination of this Agreement
and for the Closeout Services furnished by POI after the termination of this
Agreement, provided that in no event will the amount owed to POI exceed the
maximum amounts specified in Attachment I.
7.2 POI 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 check or in cleared funds to
such bank account in the United States as POI may reasonably specify from time
to time, upon receipt of invoice ("Due Date"), without any deduction, set off or
withholding except any tax 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 8% 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 ninety (90) days or
more after the Due Date, POI shall have the right to discontinue all work and
services under this Agreement until such amounts are paid in full.
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 POI to assist POI to claim exemption from, or if that is not
possible a credit for, the deduction or withholding under any applicable double
taxation or similar agreement. THE COMPANY shall also supply POI from time to
time with proper evidence as to the deduction or withholding and payment over of
the tax deducted or withheld.
8. INSURANCE
8.1 THE COMPANY and POI shall each maintain, at its sole cost
and expense, insurance coverage with a reputable insurer (which shall be either
occurrence based or claims made coverage) in an amount usual and customary for
companies engaged in activities as contemplated by this Agreement. All such
insurance shall be in place before the first patient is enrolled in the Study.
Each shall designate the other party as an additional named insured on all such
policies, and an endorsement shall be made on each such policy prohibiting the
insurer from canceling the policy for any reason or substantially modifying its
terms without first giving the other party at least twenty-eight (28) days
written notice of its intention to do so.
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
10
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.
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 POI acknowledges that, as between THE COMPANY and POI,
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 POI and THE
COMPANY, any and all intellectual property rights in works authored by POI
before the Effective Date of this Agreement and works authored by POI
independent of the Study shall belong to POI.
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 three disinterested arbitrators
each of 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. One arbitrator shall be
appointed by THE COMPANY, one arbitrator shall be appointed by POI, and one
arbitrator shall be appointed by such party-appointed arbitrators. The third
arbitrator shall be an attorney and shall act as chairman. Should either party
fail to appoint an arbitrator as contemplated in this Section within 10 days
after that party has received such written request, or if the two arbitrators
appointed by or on behalf of the parties as contemplated in this Section fail to
appoint a third arbitrator, then upon application by either party, the remaining
arbitrator(s) shall be appointed pursuant to the Commercial Arbitration Rules of
11
the American Arbitration Association, which arbitrator(s) shall fill such
position with the same force and effect as though such arbitrator(s) had been
appointed as contemplated in this Section.
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 twelve months
following its termination or expiration, THE COMPANY shall not directly or
indirectly (i) solicit or entice any employee or contractor of POI with whom it
comes into contact as a result of participation in the Study, to be employed by
it or any other person or entity; or (ii) approach any such employee or
contractor for such purpose or authorize or approve the taking of such action by
any other person.
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:
13.3.1 Termination by POI. POI 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;
12
(iii) If THE COMPANY 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;
(ii) The occurrence of a Serious Adverse
Event which should cause the Study to be terminated due to safety concerns
(iii) POI 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) POI files a petition for the
appointment of a receiver in liquidation or a trustee with respect to itself or
any of its property; any entity POI controls makes a voluntary assignment for
the benefit of creditors or files a petition in bankruptcy or insolvency or for
reorganization, compromise, adjustment, or other relief; or if any person other
than POI files a petition for the appointment of a receiver in liquidation or a
trustee with respect to POI or any entity it controls in bankruptcy, insolvency,
or reorganization, compromise, adjustment or other relief relating to the relief
of debtors, and such involuntary petition is not vacated or set aside or stayed
within 60 days from POI's receiving notice of the petition.
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
13
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 POI, 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
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:
Mr. Todd Durbin
Advaxis, Inc.
212 Carnegie Center, Suite 206
Princeton, N.J. 08540
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: 609 895 7150 Fax: 801 459 3596.
14
All notices to POI shall be addressed to:
John Hovre
Executive Vice President
Pharm-Olam International Ltd.
450 N. Sam Houston Pkyw. Ste 250
Houston, TX 77060
If notices or communications by telephone or facsimile are
specifically authorized in this Agreement or otherwise agreed
to by the parties in writing, calls to POI shall be placed and
facsimiles to POI shall be sent to the following numbers:
Phone: (713) 463-8075
Fax: (713) 463-8281
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.
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
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
State of New Jersey, 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 NJ,
United States.
IN WITNESS WHEREOF, this Agreement is executed by the parties hereto and is
effective as of the day and year first above written.
Adavaxis, Inc.
By: ____________________________________
Pharm-Olam, Int'l.
By: ____________________________________
John Hovre, its Executive Vice President
16
Attachment I
Timelines and Payment Schedule
Timelines:
Event Date
Protocol Completion and Investigator Brochure Completed and attached
Submitting request for Special
Protocol Assessment meeting with FDA [May 1, 2005]
Special Protocol Assessment meeting with FDA [June 1, 2005]
Submit to Ethics Committee and RA, [Mexico and Serbia] [June 15, 2005]
Submit IND with FDA [August 1, 2005]
Approval [Serbia] [August 15, 2005]
Approval [Mexico].........................................[October 1, 2005]
First patient in to study [Serbia] [September 15, 2005]
Last patient in to study [December 15, 2005]
Interim report [February 15, 2006]
Last patient out of study [April 15, 2006]
Close database [April 30, 2006]
Statistical analysis complete [May 15, 2006]
Study draft Final Report [May 30, 2006]
- --------------------------------------------------------------- ----------------
CRO Total Grant $430,000
- --------------------------------------------------------------- ----------------
Excluding pass-through costs
Payment Schedule for Services:
- --------------------------------------------------------------- ----------------
[10% at execution of Clinical Research Services Agreement] [$ 43,000 ]
- --------------------------------------------------------------- ----------------
[10% upon Protocol and IB completion] [ $ 43,000 ]
- --------------------------------------------------------------- ----------------
[15% Minister of Health Approval in both countries] [ $ 64,500 ]
- --------------------------------------------------------------- ----------------
[15% 10 patients in] [ $ 64,500]
- --------------------------------------------------------------- ----------------
[10% Last patient in*] [ $ 43,000 ]
- --------------------------------------------------------------- ----------------
[20% Last patient out*] [ $ 86,000 ]
- --------------------------------------------------------------- ----------------
[20% Signed Final Report*] [ $ 86,000 ]
- --------------------------------------------------------------- ----------------
[* these payments are subject to the closing of an equity financing equal or
greater to $[5 million on or after March 31, 2005.]
Pass-throughs:
Invoices will be sent to Advaxis, Inc for all pass-through cost.
The parties agree that the pass-through costs shall not exceed the cost
structure detailed in Attachment IA:
17
Attachment IA
Pass-throughs
- ----------------------------------------------------------------------------------------------------------
Item Cost ($) Notes
- ----------------------------------------------------------------------------------------------------------
[Administrative cost (telephones, [$30,100] [Will be billed monthly over first 12 month
faxs, mail, etc. 7% of clinical period]
service cost]
- ----------------------------------------------------------------------------------------------------------
[Project manager one site visit] [$1,200 ] [flight, hotel and food]
- ----------------------------------------------------------------------------------------------------------
[CRA travel and expenses] [$4,680 ] [At 400 miles per visit at $0.40 per mile
and $120 for hotel and food for 18 trips to
site]
- ----------------------------------------------------------------------------------------------------------
[CRF preparation and printing] [$2,500 ] [30 CRFs at $75.00 each]
- ----------------------------------------------------------------------------------------------------------
[Investigator fees estimated from [20 completed patients @ $6,000]
protocol synopsis] [$120,000 **]
- ----------------------------------------------------------------------------------------------------------
[Plasma sample shipment for titers ] [$10,000 ] [20 shipments @ $500 each]
[Import fee] [$600 ] [Vaccine shipment into Mexico]
[Medical Insurance] [$12,000 ] [20 patient @ 600 per patient]
- ----------------------------------------------------------------------------------------------------------
Total [$181,080 ]
- ----------------------------------------------------------------------------------------------------------
[Cost all study specific immunogenic lab test not include in investigator fee.]
[** POI to provide a detailed breakdown if these fees.]
18
Attachment II
Clinical Research Services and POI's deliverables
POI Deliverables
1. Protocol Completion
2. Investigator Brochure completion
3. Submitting request for Special Protocol Assessment meeting with FDA
4. Special Protocol Assessment meeting with FDA
5. Submit to Ethics Committee and RA, [Mexico and Serbia]
6. Submit IND with FDA
7. Obtain Approval for Phase I in Lovaxin C in [Serbia]
8. Obtain Approval for Phase I in Lovaxin C in [Mexico]
9. Recruit 2 Phase I study sites In [Serbia]
10. Recruit 2 Phase I study sites In [Mexico]
11. Provide an Interim study report after 10 patients have completed the
treatment
12. Create and manage a database accessible to Advaxis at all times.
13. Perform and complete statistical analysis
14. Study draft Final Report
15. Study final report
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 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.
19
Attachment III
Protocol
20