Document:

Unassociated Document

CONFIDENTIAL
TREATMENT REDACTED VERSION

	 
      Cobra
      Biomanufacturing Plc

      The
      Science Park,

      Keele,

      U.K.

      ST5
      5SP

       

 

Executive
Summary

Advaxis
has developed a recombinant attenuated L.
monocytogenes for
vaccination against HPV E7 expressing tumors. Advaxis will require the
production of approximately [ * ] cfu of
L.
monocytogenes non-cGMP
preclinical material and [ * ] cfu for
clinical trial use produced following cGMP guidelines. The program will involve
the following phases:

Phase
I

	·  	
      Transfer
      of current Listeria
      culture and analysis methods 

	·  	
      Two
      month feasibility study and process development
program

	·  	
      Animal
      component free growth media recommendation

	·  	
      Analytical
      methods development and host characterization methods

Phase
II

	·  	
      cGMP
      Master Cell Bank production

	·  	
      Toxicology
      material

	·  	
      Manufacture
      of clinical material

	·  	
      Development
      of product stability tests 

	·  	
      Quality
      assurance review 

	·  	
      Bulk
      product release for fill/finish

To
achieve these goals, Advaxis will require the collaboration of a partner
with:

	·  	
      Specialized
      facilities for plasmid DNA manufacture

	·  	
      Experience
      in plasmid DNA manufacture according to cGMP

	·  	
      Successful
      track record producing material for clinical trials in the
    USA

	·  	
      Experience
      in meeting regulatory requirements in facilities and
      documentation

Cobra
has both the expertise and the facilities available to meet the project
deliverables required by Advaxis in the timescales attached.

Cobra
Biomanufacturing Plc

Cobra is
a full
service, world class Contract Manufacturing Organization that manufactures and
supplies DNA-based therapeutics for the pharmaceutical and biotechnology
industries. Cobra provides contract services spanning pre-clinical to early
Phase III scale production and supply of biological products. These services
include the cGMP manufacture of DNA, recombinant protein, viruses, mammalian
cell products and cell banking.  

Currently,
four clinical trials in the USA are being conducted using products manufactured
at Cobra. Additionally, there are clinical trials in Europe, Africa, China, and
Australia using products manufactured at Cobra.

Cobra has
a Type II Drug Master File (DMF) lodged with the FDA covering DNA manufacture.
We were last inspected by the MCA in August 2002 and found to be cGMP compliant.
Cobra provides a comprehensive analytical and documentation package for
regulatory filing.

	
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Introduction

Cobra
Biomanufacturing
is a full service, world class Contract Manufacturing Organization that
manufactures and supplies DNA-based therapeutics for the pharmaceutical and
biotechnology industries. Cobra provides contract services spanning pre-clinical
to early Phase III scale production and supply of biological products. These
services include the cGMP manufacture of DNA, recombinant protein, viruses,
mammalian cell products and cell banking. The company also undertakes process
development programs for recombinant protein and gene therapy products.

Company
History

Cobra was
founded in 1992 as a start up biotechnology company specializing in gene therapy
and has been operating from facilities at the Keele Science Park for the past 8
years. The manufacturing division was originally established in order to
expedite Cobra Therapeutics own R & D programs. Investments were made in
cGMP manufacturing facilities and the development of technology for scaleable
manufacture of DNA and protein based pharmaceuticals. In 1998 the manufacturing
division began to offer cGMP manufacturing services to the pharmaceutical
industry. Cobra Therapeutics became a wholly owned subsidiary of ML Laboratories
in 2000. 

In June
2002, following a successful IPO on London’s AIM, Cobra Biomanufacturing was
established as an independent company
with an exclusive focus on custom manufacturing of bio
therapeutics.

Cobra’s
corporate objective is to continue to grow as a major contract supplier of DNA,
virus and protein based therapeutics for clinical trials and of licensed
biopharmaceutical products for commercial sale.

Manufacture
of DNA Therapeutics for Clinical Trials

Cobra has
established a worldwide reputation in the manufacture of plasmid DNA
therapeutics and is supporting clinical trials in the USA, Europe, Africa,
China, and Australia.

Every
project undergoes a technology transfer of your existing expression system to
utilize our scale-up expertise before initiating the cGMP manufacturing program.
During the evaluation stage genetic stability and relative productivity will be
determined in shake flask experiments. The fermenter productivity of the
transformed host strain will then be evaluated in a scale down (5L)
evaluation.
This
initial optimisation is to achieve the maximum productivity in the fermentation,
ensure yield and product purity throughout the purification process. It is
essential for the identification
of potential difficulties with your plasmid. The process development work is
necessary because in our experience there can
often be a 5-10 fold difference in productivity between strains (even with
similar plasmid backbones) and genetic instability is observed with some
plasmids. By assessing the plasmid at the beginning of the program, we can
accurately estimate the yields of clinical material that you will
obtain.

	
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Cobra has
substantial experience working with Kanamycin and Tetracycline resistant
plasmids and has also developed and been granted patents covering an
antibiotic-free plasmid DNA manufacturing process, the Operator Repressor
Titration (ORT) System. A Type II
DMF (Drug Master File) has been lodged with the FDA covering DNA
manufacture.

Facilities

Cobra has
over 11,000 square feet of space used for a process development facility,
separate QA/QC laboratories, and dedicated cGMP manufacturing facilities. The
existing cGMP manufacturing facility includes 4,500 square feet of EU Grade C
Clean Room space required for key stages in the manufacture of biopharmaceutical
products. The cGMP facility has two microbial production suites. The [ * ]
fermenter suite ([ * ] working volume) is for Phase I and II clinical trial
material. There is a [ * ] fermenter ([ * ] working volume) that is used to
provide an inoculum for the larger fermenter. The [ * ]fermenter suite ([ * ]
working volume) is for Phase II and III clinical trial material. 

Additionally,
there are two virus production suites with [ * ] and [ * ] fermenters ([ * ] and
[ * ] working volume) utilising adenovirus and baculovirus expression systems
for manufacture of Phase I and II clinical trial material.

Quality

Cobra is
committed to conducting its manufacturing activities in accordance with
appropriate current Good Manufacturing Practice (cGMP) and Good Control
Laboratory Practice (GLP) regulations and/or guidelines. The latest inspection
from the UK Medicines Control Agency (MCA) was in August 2002 with a compliance
statement received several weeks later. Cobra’s QA group ensures that the
products manufactured by the division meet appropriate standards of safety,
quality, and efficacy. The QA group oversees manufacture at all stages and is
responsible for testing, release, storage, and arranges shipment of the drug
product. Overseas shipping and safe passage 

through
Customs is easily co-ordinated and sub-contracted to BioCair, Inc or World
Courier.

Key
Personnel 

Cobra’s
belief that quality individuals result in quality products is reflected in the
key personnel that will be involved in the manufacture of Advaxis’ L.
monocytogenes for
clinical trials.

	
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Julian
Hanak B.Sc.
(Hons), MSc.,
Director
of Production

After
gaining an honours degree in Biochemistry at University College London, Julian
obtained an MSc at the University College of North Wales and then trained in
cell culture and microbial fermentation at the National Institute of Medical
Research. He then moved to the Bioproducts Laboratory (Elstree) where his duties
involved the pilot scale production of human monoclonal antibodies for clinical
trials. He was also responsible for running a sterile fill operation and
supervising the commissioning of a new cGMP production suite.

In 1992,
Julian moved to Zeneca Pharmaceuticals where he was involved with the process
development of several immunotherapy products and the development of virus
expression systems for protein production. He joined Cobra in 1994 and took over
responsibility for production in 1995.

Geoff
Sharpe BSc.,
PhD., CChem, MRSC.,
Director
of Quality
Assurance 

Geoff has
over 25 years experience in pharmaceutical biotechnology with over 12 years
experience in Quality Assurance. After having gained a degree in Applied
Chemistry at Liverpool, Geoff trained as a research chemist working for ICI
Corporate Laboratory. He later worked at the ICI Corporate Bioscience Group and
went on to complete a PhD in molecular biology at Leicester University.

In 1991
he transferred to ICI Pharmaceuticals (now AstraZeneca) where he was involved
with the cloning and expression of recombinant proteins and managed the
corporate DNA sequencing laboratory. In 1993, he moved to Zeneca
Pharmaceuticals. In the pharmaceutical department Geoff managed a team involved
in the development, manufacture, and release of both small molecule and
biotechnology based therapeutics. In 1996 he joined Cobra as their Quality
Assurance Manager and has been trained as a Qualified Person under Article 23 of
Directive 75/319/EEC.

Amanda
Weiss BSc.,
MSc.,
Section
Head Fermentation

Amanda
was trained at the University of Birmingham, Centre for Biochemical Engineering
before joining Cobra in 1996 as a fermentation scientist. Amanda has expertise
in microbial and mammalian cell culture, scale-up design and large-scale
manufacture
of biopharmaceuticals. She was also involved with the exemplification and
publication of Cobra’s ORT technology. Amanda has successfully managed the
fermentation aspect of Cobra’s manufacturing operations for over 5
years.

Tony
Hitchcock BSc,
Section
Head Microbial Products

Tony has
over 19 years’ experience in the large-scale manufacture of biopharmaceuticals.
Tony has held positions in the Blood Products Laboratory (Elstree) and at Zeneca
Pharmaceuticals in the protein process development department. Tony was a
founding staff
member of Cobra and has been responsible for the development of much of Cobra’s
DNA manufacturing technology. Tony has published several papers in the field and
is an inventor on two families of Cobra’s process patents.

	
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Roy
Cowell BSc.
(Hons), CChem, MRSC,
Section
Head Quality
Control 

Roy has
16 years’ experience of analytical development and quality control of
pharmaceuticals within the associated regulatory framework. Ten years employed
by Zeneca (now AstraZeneca) Pharmaceuticals working on new chemical entities and
candidate biotherapeutics and six years employed at Cobra working on candidate
DNA products. Roy is currently undergoing training leading to eligibility for
Qualified Person status.

Joy
Manley BSc, Senior
QA Microbiologist

Joy is
currently responsible for developing, validating, and applying suitable testing
regimes that help to assure clean room suitability and equipment cleanliness.
New test methods are designed and validated for plant systems and for cleaning
as required. Both standard and novel microbiological methods are developed and
used to characterize cell banks. She has experience in working with
microorganisms from both pharmaceutical and clinical backgrounds, previously
working for Fisons and The Public Health Laboratory.

David
Thatcher, Chief Executive

David was
trained as a protein chemist at the Universities of Newcastle on Tyne and
Edinburgh. In 1981 he moved to Biogen SA in Geneva where he worked on the
isolation of recombinant cytokines. In 1985 he became Director of Process
Development of Biogen, Inc. in Cambridge, MA, where he was responsible for the
development of large-scale processes for the production of gamma interferon,
GM-CSF and several other products. 

In 1988
he left Biogen and joined Zeneca Pharmaceuticals as head of their Protein
Production Lab where he was responsible for the production of a number of
biopharmaceutical products for clinical evaluation. In 1994 he joined Cobra and
has been responsible for managing the evolution of Cobra’s manufacturing
technology and developing the contract manufacturing business into an
independent company with a successful initial public offering.

	
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Quotation
O422

Description                        Price

Phase
I

[
* ] 

Phase
II

[
* ]

Notes:

Stage
I

 

	1.	Execution
      of Material Transfer Agreement. Advaxis methods for recombinant
      Listeria
      culture and analysis will be transferred to Cobra. This will include
      plasmid isolation, plasmid and host identity, plasmid and host stability,
      cryopreservation, and protocol for plasmid
isolation.

 

	2.	Characterization and strain history of the
      untransformed L.
      monocytogenes
      will be addressed by Advaxis. Advaxis will also be responsible for plasmid
      sequence and/or detailed restriction maps. Host and plasmid information is
      required for the GMO risk assessment. A letter from Dr. Paterson
      addressing the mobility of L.
      monocytogenes is
      requested.

 

	3.	Advaxis
      will supply [ * ] vials of a transformed research cell bank (mid log
      phase) of L.
      monocytogenes
      with documentation sufficient to make the research bank suitable for
      generation of the cGMP Master Cell Bank.

	4.	A
      two-month feasibility study will be undertaken to determine the growth
      kinetics of Listeria
      (latest
      harvest point) in various growth media. The study will also involve
      bioreactor growth, analysis of log phase, determination of yield, and
      number of cell doublings in vivo before maintenance of virulence is lost.
      We suggest running Stage II at the same time as Stage I to reduce the
      timeline to cGMP manufacture. 

Stage
II

	4.	An
      animal component free growth media will be recommended following
      evaluation
      of the existing media formulations with suitable alternatives. The media
      evaluated will be from published references for media used in Listeria
      culture.

	
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	5.	Development
      of a cryopreservation media suitable for administration to
    patients.

	6.	Analytical
      methods will be developed to meet FDA regulatory requirements for a
       live
      attenuated bacterial vaccine. Methods developed will include:

	o  	
      host
      identity

	o  	
      plasmid
      identity (restriction mapping or
sequencing)

	o  	
      culture
      purity (monosepsis)

	o  	
      viable
      count.

	7.	Host
      characterization methods will be developed for the
following:

	o  	
      phenotype
      auxotrophies and markers

	o  	
      morphology

	o  	
      specific
      media for identification

	o  	
      gram
      strain

	
      8.
	
      Cobra
      will supply Dr. Paterson with [ * ] of log phase culture for a hemolysin
      assay. Additionally, Cobra will supply Dr. Paterson with three samples of
      [ * ] for a mouse tumor challenge to study maintenance of
      virulence.

	9.	The
      following documentation will be provided:

Technical
Report

	10.	Confirmation
      of price estimates for cGMP manufacture at this point, dependent upon
      successful technology transfer, feasibility study and process development.
      

Stage
III

	
      11.
	
      Cell
      banking will only proceed based upon the feasibility study achieving cell
      densities of at least [ * ] viable
      cells per litre of culture. The Master Cell Bank will be manufactured
      under cGMP in accordance with the latest CPMP guidelines and MCA guidance.
      A Type II Drug Master File has been lodged with the FDA covering these
      procedures. Cells will be cryopreserved in mid log growth at a density of
      between [ * ] to [ * ] cfu/ml. 

Pricing
for the Working Cell Bank is based on production immediately following the
Master Cell Bank. Characterization for the Working Cell Bank is free of charge
if concurrent with Master Cell Bank testing.

	
      12.
	
      A [
      * ]-vial cGMP Master Cell Bank and Working Cell Bank will be released
      according to the agreed program. 

	
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      13.
	
      The
      Master Cell Bank and Working Cell Bank will be characterised using the
      following range of tests:

	·  	
      Confirmation
      of species (API Listeria)

	·  	
      Confirmation
      of strain by partial genotyping 

	·  	
      Plasmid
      stability by serial sub-culture

	·  	
      Counter
      selection for monosepsis

	·  	
      Plasmid
      identity by restriction digest

	·  	
      DNA
      sequence of the plasmid (to be invoiced
separately).

	14.	The
      non-cGMP material for use in toxicology studies, stability testing, and
      quality control
      lot release will produced at the [ * ] scale with a yield of [ * ]
      based
      upon the feasibility study achieving cell densities of at least [ * ]
      viable cells per litre of culture.

	15.	The
      following documentation will be provided to support a Regulatory
      filing:

Certificates
of Analysis 

Analytical
Reports

 

Stage
IV

	16.  	
      cGMP
      Manufacture:
      Prices are estimates without knowledge of the results of the Phase I
      Feasibility Program and may require variances to this proposal. If the
      productivity of the strain cannot be developed to achieve cell densities
      of at least [ * ] viable cells per litre of culture the delivery of [ * ]%
      of final bulk material cannot be guaranteed. The expected quantity of bulk
      and scale required will be advised as soon as it is determined during the
      Phase I Feasibility and Development Program and prior to initiation of the
      Phase II cGMP manufacturing program. If cell densities of [ *
      ] cells
      per litre are obtained in the feasibility study then a [ * ] fermentation
      should yield the requested [ * ] clinical material. If the desired cell
      densities of [ * ] cells per litre are not achieved, then the cGMP
      manufacturing program will be renegotiated.

Stage
V

	17.	Product
      Stability Testing will be required, but will be negotiated as a separate
      contract once the methods have been developed and the protocol agreed by
      Advaxis after FDA discussions. Stability tests for genetic stability; cell
      bank stability and bulk drug stability will be developed once a program is
      agreed upon. The figure provided is for budgetary
purposes.

Stage
VI

18.
Documentation.

	
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The
following documentation will be provided:

Certificate
of Analysis

Technical
Summary to support regulatory filing

A copy of
the completed BMR will be provided. 

	19.	Specifications

Cobra
warrants that upon delivery of the Product to Advaxis, Inc. the Product
shall:

	·  	
      Have
      been manufactured in accordance with cGMP. 

	·  	
      Be
      in conformity with the provisional draft specifications as attached to
      this document.

	·  	
      That
      Cobra will provide Product of sufficient quality for human clinical
      use.

	·  	
      In
      the event the Product fails to meet any of the specification described
      above, the final determination as to the suitability of the product for
      human clinical use shall be determined by Advaxis, Inc., who may consult
      with the appropriate offices of the US FDA or other regulatory
      agencies.

Stage
VII

	
      20.
	
      Fill/Finish
      will be subcontracted to BioReliance. A quote cannot be provided until the
      type of container, number of vials and other variables have been
      determined. The figure provided is for budgetary purposes.
  

	20.	The
      costs of consumables have not been included in this quotation and will be
       
      billed directly to the customer without additional charge.

	21.	The
      cost of subcontracted work has not been included in this quotation and
      will be billed
      directly to the customer (plus a [ * ]% handling
charge).

	
      22.
	
      Cobra
      will take responsibility for shipment. The price of shipment of bulk,
      dosage forms and samples and insurance thereof is excluded from this
      contract. Shipping will be arranged in consultation with the customer and
      will be billed directly to the customer (plus a [ * ]% handling
      charge).

	23.	Cobra
      and/or Advaxis, Inc. may wish to issue a press release relating to this
      contract. However, prior to any information being disclosed written
      approval must be obtained from the other party.

 

	24.	The
      Customer agrees to pay reasonable travel expenses connected with Cobra
      staff attending
      meetings, other than those on Company premises and requested by the
      Customer.
      

	
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      25.
	
      Cobra
      Bio-Manufacturing plc’s O422 Phase I Terms and Conditions and O422 Phase
      II Terms and Conditions apply to this work and acceptance of this
      quotation implies acceptance of these Terms and Conditions.
    

How
to Proceed

Please
return a signed copy of the enclosed contract with your formal Purchase Order to
Cobra Biomanufacturing. 

Cobra
Biomanufacturing Plc

The
Science Park

Keele,
United Kingdom ST5 5SP

Phone:
011 44 1782 714181

Fax: 011
44 1782 714168

When
timing is critical a faxed version is acceptable, but an original must be signed
and returned within fourteen days. Upon receipt Cobra will notify the client of
acceptance within 72 hours.

	
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Advaxis,
Inc.

212
Carnegie Center, Suite 206

Princeton,
NJ 08540 USA

July 7,
2003

Contract
O422

Determination
of Manufacturing Parameters, Process Development and cGMP Manufacture
of L.
monocytogenes

  

(a)
Phase I: Two-month Feasibility Study and Development
Program

Price 

(Line
items: a + b + c):

Total:               $[
* ]

Terms
of Payment

The
following payment terms will apply: On receipt of a signed copy of the Contract,
Cobra Biomanufacturing Plc. will begin Phase I. Upon commencement of the work
program, Advaxis will be invoiced for $[ * ] net 30 days and will be invoiced
the remaining $[ * ] appropriately on a monthly basis for the length of the
program. The final invoice will be sent before [ * ]. 

This
phase of the program is governed by the Terms and Conditions set out in the
attached document “ O422 Phase I Terms and Conditions”.

Phase
II: Pre-Clinical and GMP Manufacture

Price
Estimate is based on [ * ] cGMP manufacture: 

(Line
items: d + e + f + g + i +k + l + m + n + o)

Total:               $[
* ] (excluding Fill/Finish)

Terms
of Payment

The
following payment terms will apply: On receipt of a signed copy of the Contract,
Cobra Biomanufacturing Plc. will hold a slot for Advaxis without a deposit.
Advaxis will be notified of any request for the slot and may reserve the slot
with a [ * ]% deposit. Receipt of this payment will reserve the production slots
as per the agreed program. On commencement of the work program, [ * ]% of the
cost will be appropriately invoiced on a monthly
basis for the length of the program, with the remaining [ * ]% due upon the
delivery and acceptance of the Certificate of Analysis by the Customer’s QA
Department (less
deposit if required). There is an intention by Advaxis and Cobra to agree on %
royalties of final commercial products utilizing the current Listeria
monocytogenes platform and variations thereof for various indications in
exchange for a reduction in price of the Phase II cGMP manufacturing campaign of
proposal 0422.

	
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This
phase of the program is governed by the Terms and Conditions set out in the
attached document “ O422 Phase II Terms and Conditions”.

Contract
O422

Determination
of Manufacturing Parameters, Process Development and cGMP Manufacture
of L.
monocytogenes

  

 

	For Advaxis, Inc.	 	 	For Cobra Biomanufacturing Plc
	 	 	 	 
	Accepted by: J. Todd
    Derbin	 	 	David R. Thatcher
	 	 	 	 
	Signature: /s/ J. Todd Derbin	 	 	/s/
      David R. Thatcher
	 	 	 	 
	Date: 7/7/03	 	 	8th
      July 2003

	
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CTL.0422.S.1.1

Provisional
Draft Specification

Test        Method          Specification

[ *
]

Identity

API
Listeria                             Profile
number conforms, typically >0.95

Growth on
selective media                     Good
growth

Gram
strain                             Gram
positive

Colony
morphology                          Complies
with that for L.
monocytogenes

Quantity

[ *
]

Purity

[ *
]

	
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COBRA
BIO-MANUFACTURING PLC

 

O422
PHASE II - TERMS AND CONDITIONS

 

	1.	Definitions

 

In these
conditions the following words have the following meanings unless the context
requires otherwise:

 

 

		“Agreement”	means
      these conditions of business; 

	 	 	 

	 	“Background”	means all Intellectual Property Rights
      belonging to Cobra existing prior to the date of this Agreement or which,
      if created subsequent to the date of this Agreement, are created outside
      of any work with Advaxis under this Agreement or the scope of any
      Contract;

	 	 	 

	 	“Cobra”	
      means
      Cobra Biomanufacturing Plc, a corporation located at The Science Park,
      Keele, United Kingdom ST5 5SP;

	 	 	 

	 	“Confidential
      Information”	means, in relation to a party to the Contract,
      any and all confidential and/or proprietary information relating its
      business methods, customers, suppliers, finances, ideas, strategies,
      concepts, methodologies, protocols, inventions, processes, specifications,
      materials, marketing plans, formulae, products, software and other
      matters, including but not limited to its Intellectual Property Rights,
      and, in the case of Advaxis, including the Results, but excluding all
      information described in clause 15.8;

	 	 	 

	 	“Contract”	means any contract relating to Phase II of
      Proposal 0422 dated 7th July 2003 by and between Cobra and Advaxis
      incorporating the conditions of business set forth in this Agreement for
      the sale of Products and/or the provision of the Services and agreed to in
      writing by an authorized representative of each of Advaxis and
      Cobra;

 

 

	 	“Contract
      Price”	means, with respect to a Contract, the total
      sums payable to Cobra by Advaxis under the Contract for Phase II of
      Proposal 0422 dated 7th July 2003;

	 	 	 

	 	“Deposit”	means, with respect to a Contract, the sum of
      10% of the Contract Price;

	 	 	 

	 	“Foreground”	means all Intellectual Property Rights
      conceived or made by or on behalf of either Cobra or Advaxis, or jointly
      by Cobra and Advaxis, as a result of work under any letter of intent
      executed by the parties or under this Agreement or the performance of any
      Contract, other than general laboratory or manufacturing know-how that is
      not specifically related to any Materials;

	 	 	 

	 	“GMP”	
      means
      the current good manufacturing practices (under U.S. 21 CFR Part 211, as
      amended and supplemented from time to time, or the equivalent EU good
      manufacturing practices as confirmed at inspection by the UK Medicines
      Control Agency) for the methods to be used in, and the facilities and
      controls to be used for, the manufacture, processing, packing and holding
      of Products, as applicable under a
Contract;

	 		 

	 	“Intellectual
      Property Rights”	means any or all intellectual property rights
      including, without limitation, patents, registered and/or unregistered
      design rights, registered and/or unregistered trade marks and/or trade
      names, logos, copyright, know-how and any other similar industrial or
      intellectual property rights subsisting anywhere in the world together
      with any application for such rights and/or the right to make any such
      application;

	 	 	 

	 	“Liability”	means liability for damages, claims,
      proceedings, actions, awards, expenses, costs (including reasonable
      attorneys’ fees and expenses) and any other losses and/or liabilities in
      any way related to this Agreement or any
Contract;

	
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	 	“Materials”	means any products, DNA, protein, cell lines,
      biological matter and/or other materials which are supplied by Advaxis and
      used by Cobra in performing its obligations under a
Contract;

	 	 	 

	 	“Products”	means any protein, DNA, biological matter,
      cell lines, materials, products, goods and/or other matter ordered from
      Cobra by Advaxis or to be supplied by Cobra to Advaxis and/or such items
      which are to be provided to Advaxis in the performance of the
      Services;

	 	 	 

	 	“Results”	means any results from any Services carried
      out by Cobra for Advaxis;

	 	 	 

	 	“Services”	means the research, evaluation, development,
      scale up, manufacturing services and/or any other services to be performed
      by Cobra for Advaxis;

	 	 	 

	 	“Specification”	means the manufacturing procedures specified
      for a Product and/or the acceptance criteria for such Product;
  

	 	 	 

	 	“Advaxis”	Means Advaxis, Inc., located at 212 Carnegie
      Center, Princeton, NJ
08540;

 

	
      2.
	
      Basis
      Of Contract

 

	
      2.1
	
      This
      Agreement shall govern each Contract “Phase II” of the Quotation detailed
      in proposal O422 between Cobra and Advaxis and shall supersede and replace
      any conflicting terms or conditions included therein.

 

	
      2.2
	
      No
      order placed by Advaxis shall be accepted by Cobra unless it is a Contract
      which incorporates these conditions.

 

	
      2.3
	
      This
      Agreement supersedes all previous terms and conditions relating to Phase
      II of Proposal O422 and shall replace any terms and conditions previously
      notified to Advaxis.

	
      Confidential
      Document
	
      July
      7, 2003

3

	
      2.4
	
      No
      variation to this Agreement shall be binding on Cobra or Advaxis unless
      agreed to in writing between an authorised representative of each of
      Advaxis and Cobra. 

 

	
      2.5
	
      Cobra’s
      employees, sub-contractors and/or agents are not authorised to make any
      representations or warranties concerning the Products and/or Services
      unless confirmed by Cobra in writing. 

 

	
      2.6
	
      Advaxis
      acknowledges that Advaxis does not rely on any representation and/or
      warranty which has not been made in this Agreement or a Contract or other
      writing signed by an authorized representative of
Cobra.

 

	
      3.
	
      Orders
      And Contract

 

	
      3.1
	
      Quotations
      (unless stated otherwise) are not binding or capable of acceptance and are
      estimates only. A binding quotation issued by Cobra shall be binding for
      10 business days unless withdrawn by Cobra by oral or written notice given
      to Advaxis at any time before the expiry of the 10-business-day period.
      Advaxis may place an order based on a binding quotation issued to Advaxis
      at any time before the expiry of the 10-business-day period or earlier
      withdrawal of the quotation by Cobra (whichever is the first to
      occur).

 

	
      3.2
	
      A
      Contract between Cobra and Advaxis shall come into effect when it has been
      executed and delivered (whether in one or more counterparts) by an
      authorized representative of each party. 

 

	
      4.
	
      Samples
      and Additional Work

 

	
      4.1
	
      The
      production of any additional samples or test work not detailed in a
      Contract shall, unless otherwise agreed to in writing, be delayed until
      such production is covered by a Contract or Contract amendment entered
      into in accordance with this Agreement. 

 

	
      4.2
	
      If
      Advaxis approves in writing any sample Product produced or test Services
      performed by Cobra under a Contract, then, unless and until Advaxis
      withdraws such approval in writing, Advaxis shall have no claim in respect
      of, nor any right to reject, Products or Services provided under the
      Contract if the Products and/or the Services in question are of the same
      description, Specification, quality and fitness for purpose as the
      approved sample and/or test work as appropriate. If Advaxis withdraws its
      approval of any sample Product or test Services, then from and after
      receipt by Cobra of such written withdrawal by Advaxis, Advaxis shall not
      be required to accept any additional Products or Services of the same
      description, and the parties shall promptly amend the terms of the
      applicable Contract reflect mutually agreed upon changes resulting from
      such withdrawal (e.g., designation of such withdrawal as a production
      variation under Section 8, a cancellation under Section 9 or otherwise,
      provision of alternate supply and pricing terms).

	
      Confidential
      Document
	
      July
      7, 2003

4

	
      5.
	
      Materials

 

	
      5.1
	
      Any
      Materials supplied by or on behalf of Advaxis to Cobra in respect of any
      Contract shall at all times remain Advaxis’s
property.

 

	
      5.2
	
      Risk
      in the Materials shall pass to Cobra whilst such Materials are in the
      power, possession and/or control of Cobra. 

 

	
      5.3
	
      Cobra
      shall not transfer, or permit the transfer of any Materials to a third
      party except to a sub-contractor of Cobra. Cobra shall limit access to the
      Materials to employees or sub-contractors of Cobra who have a need to
      access the Materials in connection with the production of Products and/or
      the provision of Services for Advaxis, and shall take all other reasonable
      measures to protect the Materials from destruction, theft or loss whilst
      in the possession and/or control of Cobra.

 

	
      5.4
	
      Cobra
      shall use the Materials only for the production of Products and/or the
      provision of Services for Advaxis under a Contract, and for no other
      purpose, except with the specific written consent of
    Advaxis.

 

	
      5.5
	
      Advaxis
      shall ensure that Cobra has the right to use in the performance of the
      Services and/or production of the Products any Materials provided by
      Advaxis

 

	
      5.6
	
      Advaxis
      shall provide to Cobra storage, handling, health and safety and/or
      utilisation information regarding any Materials, to the extent known to
      Advaxis, at the time of delivery of the Materials to Cobra, or upon
      request by Cobra in writing, in advance of such
  delivery.

 

	
      5.7
	
      If
      any Materials are lost, damaged and/or destroyed, Cobra shall promptly
      inform Advaxis and shall re-imburse Advaxis for (or Advaxis, at its
      option, may credit against any amounts due to Cobra) the cost of replacing
      any Materials lost, damaged and/or destroyed. This shall not apply to any
      Materials which are properly utilised in and/or natural wastage arising
      from the performance of the Services and/or production of the Products.
      

 

	
      6.
	
      Sub-Contracting

 

	
      6.1
	
      Cobra
      may not sub-contract all or any part of a Contract to a third party
      without the prior written approval of Advaxis (such consent not to be
      unreasonably refused or delayed). In the event that Advaxis allows any
      such sub-contracting, Cobra shall remain liable for any non-performance of
      the Contract due to the acts and/or omissions of a third party
      sub-contractor.

	
      Confidential
      Document
	
      July
      7, 2003

5

	
      6.2
	
      If
      Cobra sub-contracts work to a sub-contractor, Cobra shall ensure that,
      prior to entering into the sub-contract, the sub-contractor enters into a
      separate agreement with Cobra obligating the sub-contractor to protect
      Advaxis’s Confidential Information and Materials at least to the same
      degree as they are protected by the obligations of Cobra under this
      Agreement, and Cobra shall not disclose to the sub-contractor any Advaxis
      Confidential Information and shall not provide to the sub-contractor any
      Materials except as required to permit the sub-contractor to perform the
      sub-contract approved by Advaxis. 

 

	
      7.
	
      Production
      Slot Timetable and Deposit

 

	
      7.1
	
      In
      any quotation for the provision of Products and/or Services submitted by
      Cobra to Advaxis, Cobra shall provisionally allocate to Advaxis a
      production slot.

 

	
      7.2
	
      No
      order for Products and/or Services placed by Advaxis shall become binding
      until a Contract has been entered into by the parties
      therefor.

 

	
      7.3
	
      Upon
      the execution and delivery of a Contract for Products and/or Services and
      the receipt of the Deposit by Cobra from Advaxis, Cobra shall firmly
      allocate the production slot(s) for the Products and/or Services specified
      in the Contract.

 

	
      8.
	
      Production
      Variations and
      Deposit

 

	
      8.1
	
      Cobra
      has agreed to hold a production slot without requiring pre-payment of a
      deposit from Advaxis providing no other customers compete for that slot.
      If another customer requests the same production slot agreed upon with
      Advaxis, then Advaxis will be required to secure the slot with a deposit
      of 10% ($51,100) of the Phase II portion of Proposal 0422. If Advaxis has
      secured the production slot and requests any change to a production slot
      for Products to be manufactured under this Contract less than 30 calendar
      days prior to the commencement of such production slot, Advaxis shall pay
      Cobra an amount of $50,000. 

 

	
      8.2
	
      If
      Advaxis requests a change to a secured production slot for Products to be
      manufactured under this Contract and the change is requested 30 to 60 days
      prior to the commencement of such production slot, then Advaxis shall
      forfeit an amount of $20,000, 

 

	
      8.3
	
      If
      Advaxis requests a change of more than one month to a secured production
      slot for Products to be manufactured under this Contract and the change is
      requested more than 90 days prior to the commencement of such production
      slot, then Advaxis shall forfeit 25% of the Deposit allocable to the
      production slot (calculated as provided in clause 8.1) with the remaining
      75% being carried forward and allocated to the alternative production
      slot. Cobra shall firmly allocate to Advaxis the requested rescheduled
      production slot, unless that slot has been filled prior to receipt of 25%
      of the Deposit allocable to the production slot from Advaxis under this
      clause 8.3, in which case Cobra will secure for Advaxis the next available
      production slot.

	
      Confidential
      Document
	
      July
      7, 2003

6

	
      8.4
	
      Cobra
      shall use its reasonable endeavours to accept any request to change to a
      production slot for Products provided that the requested new production
      slot is available. All such requests will be considered in good
      faith.

 

	
      8.5
	
      Cobra
      shall consider in good faith any request by Advaxis for Cobra to waive
      Cobra’s right to treat all or any portion of the Deposit allocated to the
      production slot as forfeited under this Section
8.

 

	
      9.
	
      Cancellation

 

	
      9.1
	
      If
      Advaxis cancels or terminates a Contract without cause, or refuses to
      accept delivery of conforming Products and/or performance of Services
      rendered in accordance with a Contract:

 

	 	
      9.1.1
	
      The
      Deposit paid by Advaxis under the Contract shall be forfeited and shall
      not be refundable to Advaxis. Under circumstances where cancellation
      occurs after commencement of the programme and the Deposit has been
      waived, Advaxis will pay an equivalent sum to the value of the Deposit;
      and

 

	 	
      9.1.2
	
      Advaxis
      will pay Cobra for all Services rendered in accordance with the Contract
      and conforming Products attempted to be delivered in accordance with the
      Contract through the date of cancellation, on a percentage of completion
      basis, if and to the extent that their value exceeds the Deposit and the
      Deposit paid by Advaxis shall be creditable against any payment due for
      such Services.

 

	
      10.
	
      Delivery
      and Performance

 

	
      10.1
	
      Cobra
      will use its reasonable commercial efforts to ensure delivery and/or
      performance on the dates specified in each Contract and shall keep Advaxis
      promptly informed of any delivery and/or performance that may be delayed.
      The delivery and/or performance dates specified in a Contract are Cobra’s
      best estimates only and are not guaranteed. Time is not of the essence in
      relation to such dates. They are also subject to clause
    24.4.

 

	
      10.2
	
      Advaxis
      shall have no right to rescind or terminate a Contract for late delivery
      and/or performance, or to reject Products and/or Services as
      non-conforming unless the due date for delivery and/or performance has
      passed and Advaxis shall have provided notice to Cobra requiring the
      delivery to be made, the Services to be performed and/or delivery of
      conforming Products and giving Cobra not less than 14 days in which to do
      so and the notice shall not have been complied
with.

	
      Confidential
      Document
	
      July
      7, 2003

7

	
      10.3
	
      Cobra
      shall arrange for the delivery of the Products to Advaxis’s premises or to
      an agreed delivery address provided that Advaxis confirms that such a
      location is appropriately equipped to store and handle the Products,
      otherwise Cobra shall keep and store the Products at its own expense for
      45 days. Cobra shall consult with Advaxis as to any and all delivery
      arrangements. Delivery generally will be made between 9.00am and 5.00pm on
      days when Advaxis is open for business.

 

	
      10.4
	
      Advaxis
      shall procure during normal working hours that Cobra and/or its appointed
      representatives have free right of access to the address for delivery for
      the purpose of delivering the Products between 9.00am and 5.00pm on any
      working day for Advaxis.

 

	
      10.5
	
      If
      the parties agree that the Products are to be collected from Cobra’s
      premises, then Advaxis shall collect the Products within 30 working days
      of being notified that the Products are ready for collection. If the
      Products are not collected by Advaxis or its agent within the specified
      period, Cobra shall provide notice thereof to Advaxis and at any time
      commencing three business days after Advaxis receives such notice, the
      parties will negotiate in good faith as to the appropriate steps to be
      taken. 

 

	
      10.6
	
      If
      Advaxis refuses to take delivery of any Products and/or to allow
      performance of the Services without cause, then after providing a notice
      to Cobra in writing 45 days in advance. Cobra shall be entitled to
      withhold delivery and/or performance of any other Products and/or Services
      and to treat this Agreement or any Contract as repudiated by Advaxis and
      Cobra shall have the right to rescind this
Contract.

 

	
      11.
	
      Price
      

 

	
      11.1
	
      The
      price of the Products and/or the Services shall be as set forth in the
      applicable Contract.

 

	
      11.2
	
      Unless
      expressly stated in a Contract, Cobra’s prices are exclusive of costs of
      importation, transport, insurance, packaging and/or freight of Products
      and/or Materials which shall be payable by Advaxis in
      addition.

 

	
      11.3
	
      The
      parties will negotiate in good faith an increase a Contract Price to take
      into account of any changes in methodology and/or additional work that are
      requested by Advaxis or are reasonably deemed necessary by Cobra in light
      of any Results or are required to comply with changes in
    GMP.

 

	
      11.4
	
      Advaxis
      will be informed in writing by Cobra of any increases in a Contract Price
      to be made pursuant to clause 11.3 or 11.4, not less than 30 days before
      such increase takes effect.

	
      Confidential
      Document
	
      July
      7, 2003

8

	
      11.5
	
      If
      the increase in Contract Price cannot be agreed between Cobra and Advaxis,
      Cobra may cease working on the Contract, and Advaxis may cease making
      payments on the Contract (except as required under clause 11.7), until any
      increase is agreed.

 

	
      11.6
	
      Advaxis
      may cancel without Liability any Contract in relation to which the price
      is to be increased and such increase cannot be agreed provided that Cobra
      receives notice of cancellation from Advaxis within 30 days after receipt
      by Advaxis of Cobra’s notice of the price increase. In such cases, Advaxis
      will pay Cobra for all Services rendered and conforming Products produced
      in accordance with the Contract up to the date of cancellation, on a
      percentage of completion basis, if and to the extent that their value
      exceeds the Deposit. 

 

	
      11.7
	
      If
      the Contract Price is to be increased as provided in clause 11.3 or 11.4
      and Advaxis does not cancel the Contract within the 30-day period
      specified in clause 11.6, then the price increase shall take effect for
      the Products and/or Services provided by Cobra under the Contract after
      the end of the 30-day period unless Advaxis has notified Cobra that it
      does not agree with such increase.

 

	
      11.8
	
      Advaxis
      shall reimburse Cobra for its out-of-pocket costs in connection with
      reasonable travel and accommodation expenses involved in the provision of
      the Services, provided that such travel is specified in the Contract or
      otherwise approved in advance by Advaxis in writing.

 

	
      12.
	
      Payment

 

	
      12.1
	
      The
      balance of the Contract Price shall be
payable:

 

	 	
      12.1.1
	
      85%
      paid as equal monthly payments over the length of the Contract as detailed
      in the Contract; and

 

	 	
      12.1.2
	
      15%
      on receipt of the certificate of analysis and/or acceptance/deemed
      acceptance by Advaxis of the Products and/or Services under the
      Contract.

 

	
      12.2
	
      Cobra’s
      terms of payment are net cash within 30 days after Advaxis receives
      Cobra’s duly issued invoice, except as otherwise provided in clauses 12.1
      and 12.8. Cobra shall have no right to terminate a Contract for failure by
      Advaxis to make timely payment of any amount due thereunder unless Cobra
      provides Advaxis a written notice specifying the unpaid amount and
      requiring such payment and giving Advaxis not less than three business
      days in which to make such payment and the notice shall not have been
      complied with. 

 

	
      12.3
	
      If
      Advaxis fails to make any undisputed payment in full on the due date,
      Advaxis will be extended 90 days free of interest, after 90 days Cobra may
      charge Advaxis interest (both before and after judgment) on the amount
      unpaid at the annual rate of 2% above the prime, compounded monthly.
      

	
      Confidential
      Document
	
      July
      7, 2003

9

	
      12.4
	
      Any
      monies received by Cobra from Advaxis may be applied by Cobra at its
      option against any interest charged prior to application against any
      principal sums due from Advaxis against which it may be applied in any
      order.

 

	
      12.5
	
      Payment
      shall not be deemed to be made until Cobra has received either cash or
      cleared funds in respect of the full amount outstanding.
  

 

	
      12.6
	
      If
      any undisputed payment is not made in full to Cobra when due, then Cobra
      may withhold or suspend future or current deliveries of the Products
      and/or performance of the Services and delivery and/or performance under
      any other Contract. 

 

	
      12.7
	
      If
      any Contract is cancelled or terminated under clause 9.1, Cobra shall
      invoice Advaxis for all amounts due in accordance with clause 9.1, and
      Advaxis shall pay the amount of such invoice within 15 days after
      receipt.

 

	
      13.
	
      Specification

 

	
      13.1
	
      Any
      Specification for Products supplied by Cobra to Advaxis shall only be
      approximate unless the Specification applies to the production of Products
      under GMP, the Specification is marked “Final” and signed by authorized
      representatives of Cobra and Advaxis, or the Contract provides
      otherwise.

 

	
      13.2
	
      The
      quantity, quality, description and/or Specification for the Products
      and/or the Services shall be that set out in the Contract unless otherwise
      agreed in writing by the parties. 

 

	
      13.3
	
      It
      is the responsibility of Advaxis to verify and check any Specification for
      the Products. 

 

	
      13.4
	
      Cobra
      shall have no Liability for errors in any Specification unless Cobra has
      been negligent and/or in breach in relation to the Specification.
      

 

	
      13.5
	
      Advaxis
      shall indemnify and keep indemnified Cobra against any and all liability,
      loss, costs and expenses arising out of or in any way connected with any
      third party claim relating to Cobra’s use of Materials and/or information
      supplied by Advaxis under a Contract or any Specification approved in
      writing by Advaxis, subject to the limitations set forth in clause 21.6.
      

 

	
      13.6
	
      Subject
      to Advaxis’ written approval Cobra reserves the right to make changes to
      the Specification of any Products and/or Services as required from time to
      time by good laboratory practice, GMP, law, and/or applicable safety
      requirements, provided that they do not have a material adverse effect on
      the quality and/or performance of the Products and/or the Services and
      that they shall not be put into effect until 5 business days after receipt
      by Advaxis of a description and explanation of any such
      changes.

	
      Confidential
      Document
	
      July
      7, 2003

10

	
      13.7
	
      If
      Cobra does make changes to the Specification of any Products and/or
      Services in violation of clause 13.6, then Advaxis shall have the right to
      cancel the Contract without Liability.

 

	
      14.
	
      Intellectual
      Property Rights 

 

	
      14.1
	
      The
      Background shall remain the absolute and unencumbered property of Cobra.
      Advaxis shall not obtain any license in respect of Cobra’s Background.
      Advaxis shall not be obligated to pay any royalties in respect of the use
      of the Background in connection with the performance of any Contract by
      Cobra or for any use of Background to the extent it is embedded in the
      Advaxis products. It is understood that any consideration for the use of
      the Background in connection with the performance of any Contract by Cobra
      is already included in Contract O422.

 

	
      14.2
	
      All
      Foreground relating to process and manufacturing technology shall belong
      to Advaxis. Cobra will promptly make full written disclosure to Advaxis in
      the form of summary reports, will hold in trust for the sole right and
      benefit of Advaxis, and hereby assigns, transfers and conveys to Advaxis,
      or its designee, all use Foreground covered by this clause.
    

 

	
      14.3
	
      All
      Foreground not covered by clause 14.2 shall belong to Advaxis. Cobra shall
      provide regular reports to Advaxis describing the Foreground and shall
      promptly reply to Advaxis’s reasonable requests for information regarding
      the Foreground. Cobra hereby assigns and agrees to assign to Advaxis all
      of its rights, title and interest in and to the Foreground not covered by
      clause 14.2, and upon request by Advaxis, Cobra shall promptly execute
      such documents and perform such other acts as may be reasonably requested
      by Advaxis, at Advaxis’s expense, to obtain, perfect and enforce the
      rights of Advaxis under this clause 14.3 and the assignment
      thereof.

 

	
      14.4
	
      Advaxis
      grants to Cobra a licence to use such of Advaxis’s Intellectual Property
      Rights (including, without limitation, any Foreground) as are necessary to
      enable Cobra to carry out its obligations under a Contract, and Cobra may
      sub-licence such Intellectual Property Rights to any sub-contractors
      approved by Advaxis in accordance with Section 6, solely for the purpose
      of performing the Contract.

 

	
      14.5
	
      Advaxis
      agrees to indemnify and keep Cobra indemnified against any and all
      Liability suffered by Cobra arising from and/or due to any claim that the
      use by Cobra of any or all of Advaxis’s Intellectual Property Rights in
      performing a Contract infringes any third party’s Intellectual Property
      Rights.

	
      Confidential
      Document
	
      July
      7, 2003

11

	
      14.6
	
      Cobra
      warrants that Cobra has the right to use the Background to perform its
      obligations in accordance with this Agreement and any
      Contract.

 

	
      14.7
	
      Cobra
      agrees to indemnify and keep Advaxis indemnified against any and all
      Liability suffered by Advaxis arising from or due to any claim that the
      use of any or all of the Background in performing a Contract infringes any
      third party’s Intellectual Property Rights.

 

	
      14.8
	
      Advaxis
      warrants that Advaxis has the right to grant the license and any permitted
      sub-license of the Intellectual Property Rights required under clause 14.4
      above.

 

	
      15.
	
      Confidentiality

 

	
      15.1
	
      Each
      party shall use the other party’s Confidential Information disclosed to
      and/or acquired by it only for the purposes of this Agreement, any
      Contract, and any other purpose for which the other party gives its prior
      written consent.

 

	
      15.2
	
      Each
      party shall maintain as confidential all of the other party’s Confidential
      Information which has come into and/or may come into its possession under
      this Agreement or any Contract.

 

	
      15.3
	
      Each
      party shall not directly and/or indirectly use and/or disclose any of the
      other party’s Confidential Information in whole or in part except in
      accordance with this Agreement.

 

	
      15.4
	
      Each
      party shall at the other party’s request made at any time deliver up to
      the other party all documents, material and/or other media which may be in
      its possession, power or control which comprises or contains any part of
      the other party’s Confidential Information except that it may retain one
      complete copy solely for archive purposes.

 

	
      15.5
	
      Each
      party shall allow access to the other party’s Confidential Information
      only to those employees who need to see and use such Confidential
      Information in order to perform their obligations under this
      Agreement.

 

	
      15.6
	
      Each
      party shall be responsible for the acts and/or omissions of its employees
      and/or representatives (whether or not they remain its employees and/or
      representatives) as if they were its own acts and/or omissions under this
      Agreement.

 

	
      15.7
	
      The
      obligations of confidentiality and non-use in relation to the other
      party’s Confidential Information and/or Materials shall have retrospective
      force and effect and apply to any of the other party’s Confidential
      Information disclosed prior to the date of this Agreement and shall
      continue indefinitely.

	
      Confidential
      Document
	
      July
      7, 2003

12

	
      15.8
	
      A
      party’s Confidential Information shall not include any information which:
      

 

	 	
      15.8.1
	
      the
      receiving party can prove by documentary evidence was information already
      in its possession and at its free disposal when received by it under this
      Agreement or any Contract; 

 

	 	
      15.8.2
	
      is
      after the date of this Agreement disclosed to the receiving party in
      writing without any obligations of confidentiality by a third party who is
      not in breach of any duty of confidentiality in doing so;
  

 

	 	
      15.8.3
	
      is
      or becomes generally available to the public in printed publications in
      general circulation through no act or default on the part of the receiving
      party; or 

 

	 	
      15.8.4
	
      is
      required to be disclosed by law, provided that the party required to make
      such disclosure gives the other party prompt notice of such requirement so
      that the other party may seek a protective order or other appropriate
      remedy or waive compliance with the provisions of this Agreement, and
      provided, further, that the party required to make such disclosure
      cooperates with all reasonable efforts of the other party to obtain
      confidential treatment of, or to otherwise limit, the required
      disclosure.

 

	
      15.9
	
      The
      exceptions in clause 15.8 above shall not apply
to:

 

	 	
      15.9.1
	
      Confidential
      Information merely because it is embraced by more general information
      which falls within any one or more of such exceptions;
    and/or

 

	 	
      15.9.2
	
      any
      combination of features merely because individual features (but not the
      combination itself) fall within any one or more of such
      exceptions.

 

	
      16.
	
      Property
      And Risk

 

	
      16.1
	
      Risk
      in and title to the Products shall pass to Advaxis at the time of delivery
      to Advaxis. Delivery shall be deemed to
occur:-

 

	 	
      16.1.1
	
      at
      the time when the Products arrive at the place of delivery if Cobra
      delivers the Products by its own transport and/or it arranges transport
      for Advaxis; or

 

	 	
      16.1.2
	
      after
      the expiration of 10 working days after Advaxis has been notified of that
      the Products are available for collection from Cobra in accordance with
      clause 10.6.

	
      Confidential
      Document
	
      July
      7, 2003

13

	
      16.2
	
      If
      any Products are to be utilised in the Services, risk of damage to or loss
      of such Products shall pass to Advaxis once utilised in the performance of
      the Services. Cobra will replace free of charge any Products in which risk
      has passed to Advaxis if it can be shown that they were damaged or lost
      due to the neglect or default of Cobra, its employees or other
      representatives.

 

	
      17.
	
      Default

 

	
      17.1
	
      If
      Advaxis:-

 

	 	
      17.1.1
	
      fails
      to make any payment to Cobra 30 days after due
date;

 

	 	
      17.1.2
	
      breaches
      the terms of this Agreement or any Contract and, if the breach is capable
      of remedy, has not remedied the breach within 14 days of receiving notice
      requiring the breach to be remedied;

 

	 	
      17.1.3
	
      persistently
      breach any one or more terms of this Agreement;
or

 

	 	
      17.1.4
	
      pledges
      any Products which remain the property of Cobra, or ceases or threatens to
      cease to carry on business, applies for an interim order under Section 252
      Insolvency Act 1986 or has a Bankruptcy Petition presented against
      Advaxis, enters into voluntary or compulsory liquidation, has a receiver,
      administrator or administrative receiver appointed over all or any of its
      assets, or takes or suffers any similar action in any jurisdiction;
      

 

then
Cobra shall have the right, without prejudice to any other remedies, to exercise
any or all of the rights set out in clause 17.2 below.

 

	
      17.2
	
      If
      any of the events set out in clause 17.1 above occurs in relation to
      Advaxis then:-

 

	 	
      17.2.1
	
      Cobra
      may withhold delivery of any undelivered Products and stop any Products in
      transit;

 

	 	
      17.2.2
	
      Cobra
      may withhold the performance of any Services and cease any Services in
      progress;

 

	 	
      17.2.3
	
      Cobra
      may cancel, terminate and/or suspend any Contract with Advaxis without
      Liability to Advaxis for such cancellation, termination or suspension;
      and/or

 

	 	
      17.2.4
	
      All
      monies owed by Advaxis to Cobra shall immediately become due and
      payable.

 

	
      18.
	
      Archiving

 

	
      18.1
	
      On
      termination or completion of a Contract, Cobra shall, within 30 days of
      Advaxis’s written request, either return and/or destroy any and all
      Materials in Cobra’s possession supplied by or on behalf of Advaxis under
      this Agreement together with any Results provided that Advaxis has paid to
      Cobra all monies due and payable to Cobra under the Contract, except that
      Cobra shall be entitled to retain in its archive one copy of such
      Materials, Results and/or other information to enable it to comply with
      GMP and/or Good Laboratory Practice and any and all other applicable
      legislation, regulations and/or best practice from time to time in force.
      No charge is made for such archive storage.

	
      Confidential
      Document
	
      July
      7, 2003

14

	
      18.2
	
      If
      Cobra does not receive a request from Advaxis in accordance with clause
      18.1 above, Cobra shall retain in its archives for a period of 10 years
      (or such other period as Cobra determines based on the quality of the
      matters to be archived) following either the date of termination of the
      Contract or from the date of completion of the Contract all of the
      Materials, Results and other information arising out of that Contract
      whether or not Cobra is obliged to archive such matters under clause 18.1.
      At the end of the ten-year period Cobra shall contact Advaxis for further
      instructions as to the disposal and/or storage of the archived information
      held by Cobra. If Advaxis does not respond within 30 days of such
      notification, Cobra may either return the archived matter to Advaxis at
      Advaxis’s own expense or destroy the archived
matter.

 

	
      19.
	
      Warranties

 

	
      19.1
	
      Cobra
      warrants that the Products and/or
Services:-

 

	 	
      19.1.1
	
      will
      be free from substantial defects in materials and/or
      workmanship;

 

	 	
      19.1.2
	
      are
      manufactured and/or performed with all proper and reasonable skill,
      competence, care and attention; 

 

	 	
      19.1.3
	
      are
      produced and/or performed in accordance with GMP and Medicines Control
      Agency and/or FDA guidelines where specified or
    appropriate;

 

	 	
      19.1.4
	
      will
      at the time of delivery and/or performance conform with any final
      Specification (for the avoidance of doubt this warranty does not extend to
      draft or provisional Specification);

 

	 	
      19.1.5
	
      comply
      with all applicable legal and regulatory standards from time to time;
      and

 

	 	
      19.1.6
	
      are
      manufactured, packaged, handled and stored in accordance with the terms of
      the applicable Contract and all appropriate legislation rules and other
      requirements of the appropriate regulatory authorities in force at the
      time of the Contract.

	
      Confidential
      Document
	
      July
      7, 2003

15

	
      19.2
	
      The
      warranties in clause 19.1 above are given by Cobra subject to the
      following conditions:-

 

	 	
      19.2.1
	
      Cobra
      shall be under no Liability in respect of any defect in the Products
      and/or Services arising directly from any information and/or
      specifications supplied to Cobra by
Advaxis;

 

	 	
      19.2.2
	
      Cobra
      shall have no Liability in respect of any faults arising after risk in the
      Products has passed to Advaxis that are caused by any subsequent
      mechanical, chemical, biological, electrolytic or other damage not due to
      a defect in the Products and/or Services or the neglect or default of
      Cobra; and/or

 

	 	
      19.2.3
	
      Cobra
      shall be under no Liability in respect of any faults or defects caused by
      wilful damage, abnormal working or operating conditions, failure to follow
      Cobra’s instructions, misuse or alteration of Products and/or Services
      without Cobra’s approval, improper maintenance, storage or negligence on
      Advaxis’s part and/or by a third party.

 

	
      19.3
	
      Cobra
      does not guarantee that the Services to be carried out by Cobra under this
      Agreement or any Contract will be successful and/or will achieve any
      objectives outlined by Advaxis in Advaxis’s
order.

 

	
      19.4
	
      If
      Cobra is in breach of any of the warranties given in clause 19.1 with
      respect to a Contract, Advaxis may suspend the due date for payment of any
      unpaid amounts under the Contract until Cobra
promptly:

 

	 	
      19.4.1
	
      replaces
      the defective Products; and/or

 

	 	
      19.4.2
	
      re-performs
      the Services;

 

and
thereafter all outstanding amounts shall become due and payable.

 

	
      19.5
	
      Cobra
      shall have no liability under the warranties given in clause 19.1 unless
      it has received written notification of non-conformance from Advaxis
      within 21 days of discovery by Advaxis of the
    non-conformance.

 

	
      20.
	
      Repairs
      And Replacements

 

	
      20.1
	
      Cobra
      will at its option, promptly, either refund the price or re-perform any
      defective Services and/or replace any defective Products where the defect
      is apparent on inspection, provided that the defect is notified to Cobra
      within 21 working days of delivery of such Products or performance of the
      Services.

 

	
      20.2
	
      If
      Advaxis fails to notify Cobra of any defect in the Products and/or
      Services under clause 20.1 within 21 working days of delivery and/or
      performance, Advaxis will be deemed to have accepted the Products and/or
      Services.

	
      Confidential
      Document
	
      July
      7, 2003

16

	
      20.3
	
      A
      sample of any defective Products must where reasonable be returned to
      Cobra for inspection if requested by Cobra before Cobra will have any
      Liability for defective Products. If the sample proves to be defective,
      then Cobra shall reimburse Advaxis for the cost of returning the sample of
      the defective Products to Cobra.

 

	
      20.4
	
      Cobra,
      if it requests and where reasonable, shall have the right to inspect the
      subject-matter of any allegedly defective Services at a mutually
      convenient time, and Cobra will not have any Liability for any such
      defective Services until it has been allowed to make such
      inspection.

 

	
      20.5
	
      Cobra
      will replace and/or re-perform defective Products and/or Services which
      are not notified to Cobra within the time limit specified in clause 20.1
      where the defect would not have been ascertainable on inspection and has
      been notified to Cobra as soon as reasonably practicable after discovery
      by Advaxis. 

 

	
      20.6
	
      Cobra
      will at its option either refund the price of or replace free of charge
      any Products missing from a delivery of Products provided that the missing
      items are notified to Cobra within five working days after receipt of the
      shipment or, in the event of total non-delivery, this fact is notified to
      Cobra within five working days after receipt by Advaxis of Cobra’s invoice
      for such Products. 

 

	
      20.7
	
      If,
      on investigation, it is found that any claimed defects in the Products
      and/or Services are not the responsibility of Cobra under this Agreement
      or the applicable Contract, Cobra may charge Advaxis for all reasonable
      costs and expenses it has incurred in the course of and/or in consequence
      of the investigation.

 

	
      21.
	
      Limitations
      On Liability

 

	
      21.1
	
      Cobra
      shall have no Liability for defective Products and/or Services where the
      defect has been caused by Advaxis.

 

	
      21.2
	
      Cobra
      shall have no Liability to Advaxis for defective Products and/or Services,
      Products not despatched or Products damaged or lost in transit unless the
      event is notified to Cobra within the appropriate time limit set out in
      this Contract.

 

	
      21.3
	
      Cobra
      shall have no Liability for additional damage, loss, liability, claims,
      costs or expenses caused by Advaxis’s continued use of defective Products
      and/or Services after a defect has become apparent to
    Advaxis.

 

	
      21.4
	
      Advaxis
      shall where reasonable give Cobra a reasonable opportunity to remedy any
      matter for which Cobra is liable before Advaxis incurs any costs and/or
      expenses in attempting to remedy the matter independently. If Advaxis does
      not do so, Cobra shall have no liability to Advaxis for any damages caused
      by Advaxis, which could have been avoided if Advaxis had permitted Cobra
      the opportunity to remedy the matter first.

	
      Confidential
      Document
	
      July
      7, 2003

17

	
      21.5
	
      Neither
      party shall have any Liability to the other party for
  any:-

 

	 	
      21.5.1
	
      consequential
      losses; 

 

	 	
      21.5.2
	
      loss
      of profits (other than direct loss of profit under a Contract in relation
      to work to be and/or already performed by Cobra under that Contract)
      and/or damage to goodwill; 

 

	 	
      21.5.3
	
      economic
      and/or other similar losses; 

 

	 	
      21.5.4
	
      special
      damages and indirect losses; and/or

 

	 	
      21.5.5
	
      business
      interruption, loss of business, contracts, opportunity and/or
      production;

 

suffered
by the other party, and this shall apply whether or not it has been informed by
the other party of the possibility of such matters.

 

	
      21.6
	
      Each
      party shall be under a duty to mitigate any loss, damage, costs or
      expenses that it may suffer. 

 

	
      21.7
	
      Cobra’s
      total Liability to Advaxis in relation to any Contract shall not exceed
      the
      amount paid by Advaxis to Cobra in relation to that
    Contract.

 

	
      21.8
	
      Each
      of the limitations and/or exclusions in this Agreement shall be deemed to
      be repeated and apply as a separate provision for each of:
  

 

	 	
      21.8.1
	
      Liability
      for breach under any Contract and/or under this Agreement;
  

 

	 	
      21.8.2
	
      Liability
      in tort (including negligence);

 

	 	
      21.8.3
	
      Liability
      for breach of statutory duty; and

 

	 	
      21.8.4
	
      Liability
      for breach of Common Law.

 

except
clause 21.8 which shall apply once only as to any Contract in respect of all the
said types of Liability under the Contract.

 

	
      21.9
	
      Nothing
      in this Agreement or any Contract shall exclude or limit the Liability of
      Cobra for death or personal injury due to its negligence or any Liability
      which is due to Cobra’s fraud or any other liability which it is not
      permitted to exclude or limit as a matter of
law.

 

	
      22.
	
      Reporting
      

 

	
      22.1
	
      Cobra
      shall provide prompt and regular updates to Advaxis as the progression of
      work under each Contract and shall disclose all Results to Advaxis on a
      regular basis.

	
      Confidential
      Document
	
      July
      7, 2003

18

	
      22.2
	
      All
      Results and any and all Intellectual Property Rights in the Results shall
      belong to Advaxis and shall form part of Advaxis’s Confidential
      Information under the Contract. Cobra may only use the Results with
      Advaxis’s prior written consent.

 

	
      22.3
	
      Cobra
      shall provide Advaxis with a final report within 30 working days of
      completion of the Services under any Contract, the contents of which
      include but will not be limited to the Results. Further copies of the
      final report shall be made available to Advaxis on Advaxis’s request and
      at Advaxis’s own expense.

 

	
      23.
	
      Restrictions

 

	
      23.1
	
      Advaxis
      shall not, during the term of any Contract and for a period of 12 months
      immediately following the termination of the Contract, whether on
      Advaxis’s own behalf or in conjunction with or on behalf of any person,
      firm, company, business entity or other organisation and whether as
      employee, director, principal, agent, consultant, shareholder or in any
      other capacity whatsoever, directly or
indirectly:-

 

	 	
      23.1.1
	
      solicit
      or procure any person who is or was an employee, agent and/or
      representative of Cobra to cease working for Cobra or accept into
      employment or otherwise engage or use the services of any person where
      that person:-

 

	 	
      23.1.1.1
	
      is
      an employee, agent and/or representative of Cobra at that time;
      and/or

 

	 	
      23.1.1.2
	
      has
      been an employee, agent and/or representative of Cobra at any time during
      the immediately preceding three months.

 

	
      23.2
	
      Whilst
      each of the restrictions in clause 23.1 are considered by the parties to
      be reasonable in all the circumstances as at the date of this Contract, it
      is agreed and declared that if any one or more of such restrictions shall
      be judged to be void as going beyond what is reasonable in all the
      circumstances for the protection of the interests of Cobra but would be
      valid if the restrictions were reduced in scope, the restrictions shall be
      deemed to apply with such modification.

 

	
      23.3
	
      Any
      restriction or part of a restriction found in any event to be void shall
      not affect the validity of any other restriction contained in this
      Agreement.

 

	
      23.4
	
      Cobra
      may by written notice at any time reduce the duration and/or scope of any
      of the restrictions in clause 23.1 above.

	
      Confidential
      Document
	
      July
      7, 2003

19

	
      24.
	
      General

 

	
      24.1
	
      Advaxis
      agrees to indemnify and keep indemnified Cobra against any and all
      liability, loss, costs and expenses arising out of (i) any third party
      claim relating to this Agreement, (ii) any third party claim relating to
      the use of Products by Advaxis or by any third party, or (iii) the breach
      by Advaxis of any of its obligation or covenants under any Contract, in
      each case, subject to the limitations set forth in clause 21.6.
      

 

	
      24.2
	
      Cobra
      agrees to indemnify and keep indemnified Advaxis against any and all
      liability, loss, costs and expenses arising out of (i) any third party
      claim relating to this Agreement, (ii) any third party claim relating to
      the use of Products by Cobra or by any third party, or (iii) the breach by
      Cobra of any of its obligation or covenants under any Contract, in each
      case, subject to the limitations set forth in clause 21.6.
  

 

	
      24.3
	
      

 

	
      24.4
	
      No
      waiver by a party of any breach of this Agreement or any Contract shall be
      considered as a waiver of any subsequent breach of the same provision or
      any other provision.

 

	
      24.5
	
      If
      any provision of this Agreement or any Contract is held by any competent
      authority to be invalid or unenforceable in whole or in part, the validity
      of the other provisions thereof and the remainder of the affected
      provision shall be unaffected and shall remain in full force and
      effect.

 

	
      24.6
	
      Neither
      party shall have any Liability to the other party for any delay in
      performance of any Contract to the extent that such delay is due to any
      events outside its reasonable control including but not limited to acts of
      God, war, flood, fire, labour disputes, subcontractor delays, strikes,
      lock-outs, riots, civil commotion, malicious damage, explosion,
      governmental actions and any other similar events. If a party is affected
      by any such event, then time for performance shall be extended for a
      period equal to the period that such event or events delayed such
      performance, provided that the party uses all reasonable efforts to
      minimize the duration of such effect. This shall not apply to any decision
      by the Medicines Control Agency that the Products have, where required,
      been produced without appropriate GMP and/or Good Laboratory Practice
      controls and/or documentation.

 

	
      24.7
	
      Neither
      party may assign this Agreement or any Contract without the written
      consent of the other party, except to a wholly owned subsidiary or to any
      successor in interest by merger or purchase of all or substantially all of
      its assets.

	
      Confidential
      Document
	
      July
      7, 2003

20

	
      24.8
	
      All
      third party rights are excluded and no third party shall have any right to
      enforce this Agreement or any Contract. 

 

	
      24.9
	
      Any
      dispute arising out of or in connection with the Contract shall be
      referred to the arbitration in London of a single arbitrator appointed by
      agreement between the parties or, in default of agreement, nominated on
      the application of either party by the President for the time being of The
      Law Society. The arbitration shall be carried out in accordance with the
      Rules of Arbitration of the International Chamber of Commerce in force as
      at the date of the dispute. This Agreement shall be governed by and
      construed in all respects in accordance with the Laws of England. This
      shall not prevent either party seeking interim injunctive relief from any
      court of law.

 

	
      24.10
	
      Ongoing
      Relationship and Commercial Supply

 

	 	
      24.10.1
	
      Cobra
      acknowledges that drug development is a lengthy and risky process and
      accordingly:

 

	 	
      24.10.2
	
      Advaxis
      may wish to amend or terminate the Development Program at any time it
      reasonably considers the manufacture and/or marketing to the public at
      large of Formulated Product or Listeria monocytogenes ceases to be
      commercially viable; or

 

 

	 	
      24.10.3
	
      Advaxis
      may require Cobra to be a long-term collaborator in the production of
      Formulated Product or Listeria monocytogenes suitable for toxicological
      studies, stability studies, human clinical trials and marketing to the
      public at large.

 

 

	 	
      24.10.4
	
      Upon
      Advaxis’s written request, the Parties will negotiate in good faith an
      agreement on the terms under which Cobra will manufacture and supply to
      Advaxis quantities of Formulated Product or Listeria monocytogenes
      required by Advaxis on a commercial scale for marketing to the public at
      large.

 

 

	 	
      24.10.5
	
      Notwithstanding
      clause 24.8.4, Cobra acknowledges that Advaxis has made no representation
      that Advaxis will, intends to or is likely to, issue a request to Cobra
      for the manufacture and supply of Formulated Product or Listeria
      monocytogenes in quantities on a commercial scale for marketing to the
      public at large.

	
      Confidential
      Document
	
      July
      7, 2003

21Redacted
Version

Confidential
Treatment Sought

with
respect to certain portions of the Agreement indicated 
by a [ *
]

 

 

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

 

Advaxis
Clinical Research Agreement

April 6,
2005

Page 1 of
16

 

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. 

 

Advaxis
Clinical Research Agreement

April 6,
2005

Page 2 of
16

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.

 

Advaxis
Clinical Research Agreement

April 6,
2005

Page 3 of
16

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.

 

Advaxis
Clinical Research Agreement

April 6,
2005

Page 4 of
16

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.

 

Advaxis
Clinical Research Agreement

April 6,
2005

Page 5 of
16

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.

Advaxis
Clinical Research Agreement

April 6,
2005

Page 6 of
16

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, 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.

 

Advaxis
Clinical Research Agreement

April 6,
2005

Page 7 of
16

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.

 

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.

Advaxis
Clinical Research Agreement

April 6,
2005

Page 8 of
16

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.

 

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Clinical Research Agreement

April 6,
2005

Page 9 of
16

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. 

 

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 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.

 

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Clinical Research Agreement

April 6,
2005

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16

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:

Advaxis
Clinical Research Agreement

April 6,
2005

Page 11 of
16

(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 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. 

Advaxis
Clinical Research Agreement

April 6,
2005

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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 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. 

Advaxis
Clinical Research Agreement

April 6,
2005

Page 13 of
16

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.

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.

 

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Clinical Research Agreement

April 6,
2005

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16

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.

 

15.10   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

 

Advaxis
Clinical Research Agreement

April 6,
2005

Page 15 of
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
	
      [ *
      ]

	
      Special
      Protocol Assessment meeting with FDA
	
      [ *
      ]

	
      Submit
      to Ethics Committee and RA, [ * ]
	
      [ *
      ]

	
      Submit
      IND with FDA
	
      [ *
      ]

	
      Approval
      [ * ]
	
      [ *
      ]

	
      Approval
      [ * ]
	
      [ *
      ]

	
      First
      patient in to study [ * ]
	
      [ *
      ]

	
      Last
      patient in to study
	
      [ *
      ]

	
      Interim
      report
	
      [ *
      ]

	
      Last
      patient out of study
	
      [ *
      ]

	
      Close
      database
	
      [ *
      ]

	
      Statistical
      analysis complete
	
      [ *
      ]

	
      Study
      draft Final Report 
	
      [ *
      ]

	
      CRO
      Total Grant
	
      $[
      * ]
	 

 Excluding
pass-through costs

Payment
Schedule for Services:

	
      [ *
      ]
	
      [ *
      ]

	
      [ *
      ]
	
      [ *
      ]

	
      [ *
      ]
	
      [ *
      ]

	
      [ *
      ]
	
      [ *
      ]

	
      [ *
      ]
	
      [ *
      ]

	
      [ *
      ]
	
      [ *
      ]

	
      [ *
      ]
	
      [ *
      ]

* these
payments are subject to the closing of an equity financing equal or greater to
$[ * ]

Advaxis
Clinical Research Agreement

April 6,
2005

Page 16 of
16

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:

Attachment
IA
 

Pass-throughs

 

	
      Item
	
      Cost
      ($)
	
      Notes

	[ *
      ]
	[ *
      ]
	[ *
      ]

	[ *
      ]
	[ *
      ]
	[ *
      ]

	[ *
      ]
	[ *
      ]
	[ *
      ]

	[ *
      ]
	[ *
      ]
	[ *
      ]

	[ *
      ]
	[ *
      ]
	[ *
      ]

	[ *
      ]
	[ *
      ]
	[ *
      ]

	[ *
      ]
	[ *
      ]
	[ *
      ]

	[ *
      ]
	[ *
      ]
	[ *
      ]

	Total
	
      $181,080
      
	 

[ *
]

 

Advaxis
Clinical Research Agreement

April 6,
2005

Page 17 of
16

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, [ * ]

	6.  	
      Submit
      IND with FDA

	7.  	
      Obtain
      Approval for Phase I in Lovaxin C in [ * ]

	8.  	
      Obtain
      Approval for Phase I in Lovaxin C in [ * ]

	9.  	
      Recruit
      2 Phase I study sites In [ * ]

	10.  	
      Recruit
      2 Phase I study sites In [ * ]

	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.

Advaxis
Clinical Research Agreement

April 6,
2005

Page 18 of
16

Attachment
III

Protocol

 

Not yet
finalized.

 

 

 

 

 

 

 

Advaxis
Clinical Research Agreement

April 6,
2005

Page 19 of
16

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