Document:

Orgenesis Inc.: Exhibit 10.1 - Filed by newsfilecorp.com

Work proposal and offer for

Exploration of key process parameters for

the production of liver derived human 
autologous cells 

 

 

	For: 
	  
	Orgenesis Ltd. 
	70 Denya street 
	Haifa, Israel, 34980 
	  
	  
	  
	From: 
	Markus Schandar 
	Fraunhofer IGB, Nobelstraße 12 
	70569 Stuttgart 
	  
	  
	Stuttgart, 08. November 2012 

	Fraunhofer IGB 	1 
	Work package offer 	  

1 Background

The Fraunhofer IGB has a strong
background to develop manufacturing processes for Advanced Medicinal Therapy
Products (ATMPs) like for example autologous transplants in regenerative
medicine, to apply for manufacturing authorizations and to manufacture
cell-based therapeutics in their certified GMP manufacturing unit in a pilot
clinical scale (according to the German Drug Law). 

Orgenesis is developing an ATMP for
the treatment of type I diabetes based on adenovirus transduced autologous liver
cells. The existing research scale production process has to be up scaled and
adopted to GMP requirements in order to deliver up to 2x109
autologous liver derived cells per patient that subsequently can be
transduced with an adenovirus. About 1x107 liver cells (i.e., before
AD transduction) should be bio-banked or cryo-preserved for future use.

The Fraunhofer IGB will perform
experiments to explore the most critical production process parameters as
described in the work plan section. The results of these studies should deliver
the basis for the initial planning and set up of an GMP compliant production
process in order to obtain a production authorization for clinical grade
material to be used in a first in man study.

2 Description of work plan

The major goal of the planned work is
to explore the key process parameters for the up scaled production of the liver
derived autologous cells in order to deliver the required cell numbers, purity
& functionality and in parallel reduce the cost for materials &
media.

The existing production methods will
be transferred to the Fraunhofer GMP facility. The most critical parameters for
up scaling of the cell culture process will be explored and pilot studies for
the sampling, storage and transport of biopsies and amplified cells will be
performed. Functional assays for characterizing the produced cells (GSIS assay)
will be established at the Fraunhofer IGB. An initial set up of QC methods and
documentation according to GMP requirements will be implemented.

Orgenesis will provide the Fraunhofer
IGB with all required information and sufficient amounts of human liver cells to
perform the work packages described in the following sections. Orgenesis will be
responsible for testing of the cells produced by the Fraunhofer IGB for their
functionality concerning transducibility with Adenoviruses, cell reprogramming
and insulin production (GSIS assay) until
these functional assays are established at the Fraunhofer IGB, as defined in
Work Package 1.

	Fraunhofer IGB 	2 
	Work package offer 	  

	2.1 	
      Work package 1: Method transfer to the Fraunhofer GMP
      facility

	Methods from Orgenesis Inc. will be transferred
      to the Fraunhofer GMP facility. In order to facilitate this process an
      onsite visit at the laboratories of Orgenesis Inc. in Israel is planned.
      The existing process will be used as a starting point for: 
	  	  
	Exploring different growth media 
	  	  
	o 	Test used media and supplements for GMP
      compliance 
	o 	Test alternative ATMP media, serum free media
    
	o 	Test the feasibility of autologous human serum
      and/or platelet lysate 
	  	  
	Defining cell seeding parameters 
	  	  
	o 	Optimal starting seeding density 
	o 	Maximum cell density to be reached 
	o 	Doubling times 
	  	  
	Cells from at least three different donors will
      be compared for their growth properties under selected conditions.
      Orgenesis Inc. will test selected batches of the produced cells for their
      functionality until these analytical methods are established at the
      Fraunhofer IGB. 
	  	  
	Analytical methods for functional
      characterization of the trans differentiated cells will be transferred to
      and established at the Fraunhofer IGB including: 
	  	  
	o 	Transduction of liver cells with adenoviruses
      serotype 5 
	o 	Trans differentiation of cells 
	o 	Setup of non RIA assays for the quantification
      of insulin storage and secretion as well as C-peptide secretion from trans
      differentiated cells 
	o 	Setup of GSIS functional assay 
	o 	Setup of GS-GFP assessment 
	  	  
	Methods will be transferred to the Fraunhofer IGB
      with the help of an Orgenesis employee working for a certain time at the
      Fraunhofer facility. During the experiments Orgenesis will provide
      sufficient amounts of Adenoviruses and liver cells. Currently it is
      assumed, that work with this viruses can be performed under S1 conditions
      to be approved by the local authorities. 

	2.2 	
      Work package 2: Parameters for up scaling of the cell
      culture process

The major goal of the work package is
to define and optimize the most critical process parameters and establish the
first in process controls for setting up a plate process aiming to the cost efficient
      production of 2*109 adherent cells. Based on the results
obtained in work package 1 the following topics will be addressed: 

	Fraunhofer IGB 	3 
	Work package offer 	  

	Compare different plate materials 
	  	  
	o 	Tissue factories from Nunc 
	o 	CellStack & HyperFlask from Corning 
	  	  
	Optimize plate process 
	  	  
	o 	Select optimal material that results in maximal
      number of cells in minimal time in a cost effective manner 
	o 	Adopt cell seeding & growth conditions  
	o 	Define maximal cell density to be reached
	  	  
	Establish methods 
	  	  
	o 	For sampling of QC probes (Sterility,
      mycoplasma, endotoxins, etc.) 
	o 	For splitting and final harvesting of the cells    
	o 	GS-GFP assessment (minimum 15%) 
	  	  
	
      Cells from at least three different donors will be
      compared for their growth and functional properties under selected
      conditions. Fraunhofer will test selected batches of the produced cells
      for their functionality (GSIS assay). Unless the supply of liver cells
      from a German hospital and the initial liver cell isolation protocol in
      work package 4 is not established, Orgenesis will provide sufficient
  amounts of liver cells to run the experiments in this work package.  

	2.3 	
      Work package 3: Set up of QC
  methods

	
      The work package covers the setup of analytical methods
      testing the quality of the produced cells: 

	  	  
	o 	For identity and purity (preferred are FACS
      assays) 
	o 	Vitality & sterility 
	o 	Genetic stability (Karyotyping) 
	o 	Endotoxin & Mycoplasma burden

	2.4 	
      Work 4: Biopsy
sampling

	
      This work package covers the initial setup of a liver
      biopsy supply from a German clinic to the Fraunhofer IGB and the transfer
      of the initial process of cell isolation and primary amplification to the
      Fraunhofer IGB. It includes: 

	  	  
	o 	Establish protocols for shipment and income
      control of liver biopsies 
	o 	Implement method for cell isolations from
      biopsies 
	o 	Implement method for primary amplification
  
	o 	Test stability of biopsies in different
      transport media 

	Fraunhofer IGB 	4 
	Work package offer 	  

Methods will be transferred to the
Fraunhofer IGB with the help of an Orgenesis employee working for a certain time
at the Fraunhofer facility. The start of this work package depends on the
approval of the collaborating clinical side for taking human tissue samples.

	2.5 	
      Work package 5: Storage and Transport of AIP
      cells

	
      The work package is designed to test for possible effects
      of cell storage & transport on the cell viability and function (GSIS
      assay): Storage in primary packaging material for transport 

	 
	o 	Stability of cells in different transport media
    
	o 	Effects of primary packaging materials (mainly
      bags) 
	 	 
	Cell density in the final product 
	o 	Density dependent cell stability &
      viability 
	o 	Optimal application volume 
	o 	Frozen storage 
	o 	Appropriate temperature 
	 	 
	Effects on viability & function 
	 
	Initial stability studies 
	 
	Fraunhofer will test at least 3 batches of the
      stored and shipped cells for their functionality (GSIS assay).
  

	2.6 	
      Work package 6:
Documentation

	
      During the work the following draft versions for the
      first core process documents will be compiled: 

	  	 
	o 	Forms for production SOPs and protocols 
	o 	Forms for storage SOPs and protocols 
	o 	Forms for transport SOPs and protocols 
	o 	Forms for QC testing SOPs and protocols
  

3 Time lines, costs & deliverables

	3.1 	
      Time lines

The figure below summarizes the
possible work flow and anticipated time lines of the planned work packages.
Packages 2-4 build on package 1 but can be performed in parallel. Packages 5 should be
addressed after packages 1-4. Work package 6 could be done at the end of the
project but ideally is performed during the work up of the different work
packages.

	Fraunhofer IGB 	5 
	Work package offer 	  

Time lines dependent on a close
collaboration with Orgenesis providing sufficient amounts of cells in time,
method transfer and performing functional studies with cells produced by the
Fraunhofer IGB.

Orgenesis can access and pay for the
work packages case by case. In general it is possible to agree on new work
packages to be included during the project and to eliminate packages that have
not been started. Modifications to running packages have to be discussed case by
case and reduction ore increase of costs has to be agreed on by the two
parties.

The project could start 2 weeks after
singing of the contract.

	3.2 	
      Costs

	The following costs applies to performing the different
      work packages: 
	 
	Work package 1: 70.000 € 
	 
	Work package 2: 50.000 € 
	 
	Work package 3: 45.000 € 
	 
	Work package 4: 35.000 € 
	 
	Work package 5: 35.000 € 
	 
	Work package 6: 25.000 €

	Fraunhofer IGB 	6 
	Work package offer 	  

Total costs: 260.000 €

Payments by Orgenesis Inc. are due to
the receipt of the final work package reports from the Fraunhofer IGB.

Costs cover the estimated expenses for
personal and materials. Depending on the final production scale tested in work
package 2 additional material costs for plates and media might apply, will be
agreed on by the two parties and should be covered by Orgenesis Inc. Orgenesis
Inc. will cover all costs for the shipment of all samples from Orgenesis
facilities to the Fraunhofer IGB and from the Fraunhofer IGB to Orgenesis Inc.
facilities. Project travel costs of Fraunhofer and Orgenesis employees are
covered by Orgenesis.

Costs do not cover third party
expenses like for example karyotyping studies and possible
investments in special equipment. 

	3.3 	
      Deliverables

The Fraunhofer IGB will provide
Orgenesis Inc. with a written final report at the end of each work package.
During the work updates of the project will be given in regular telephone calls
and experimental data will be provided by E-Mail. At the end of the project
Orgenesis Inc. will receive all data, protocols and documents generated during
the collaboration. During the work the Fraunhofer IGB will transfer samples of
cells produced with data sheets describing the cell batch to Orgenesis Inc. for
further evaluation. Whenever possible aliquots of cells and other materials will
be archived for later use and/or transfer to Orgenesis Inc.

Orgenesis Inc. will provide the
Fraunhofer IGB with sufficient amount of cell material to perform the
experiments described in the work packages. The cells derived from liver tissue
of human donors should have the quality required to perform the planned
experiments. Samples should be sent with data sheets describing the most
important features of the cell batch and of the donor. In particular Orgenesis
should not send material from donors that have no or a positive serum test for
infection with HIV, hepatitis virus A B C, lues virus. Donors must have given a
written consent to Orgenesis Inc. to use their cells for research or commercial
use and Orgenesis shall indemnify Fraunhofer from any claim of any donor arising
in connection with Fraunhofer IGB's work under this offer. During the project
Orgenesis Inc. should provide the Fraunhofer IGB with all data generated with
the cells produced by the Fraunhofer IGB.

	Fraunhofer IGB 	7 
	Work package offer 	  

4 Contractual Basis

The enclosed »General Terms &
Conditions for Research and Development contracted to Fraunhofer-Gesellschaft
zur Förderung der angewandten Forschung e.V., version 2002/II« as well as the
"Addendum to General Terms and Conditions for Research and Development" dated
October 12th, 2012, form a part of this offer.

	Encl.: 	- 	»General Terms & Conditions« 
	  	- 	»Addendum to General Terms & Conditions«  

	Fraunhofer IGB 	8 
	Work package offerInfrastructure Materials Corp.: Exhibit 10.1 - Filed by newsfilecorp.com

Exhibit 10.1

AMENDMENT TO CONSULTING AGREEMENT 

This Amendment is made and entered into as of the 1st day of
October, 2012 by and between Infrastructure Materials Corp., a Delaware
corporation (the “Corporation”) and 1408943 Alberta Ltd., an Alberta corporation
(“Consultant”). 

WHEREAS, the Corporation and Consultant entered into a
Consulting Agreement as of the 23rd day of June, 2008 (the
“Consulting Agreement”); and 

WHEREAS, the Corporation and Consultant desire to amend the
Consulting Agreement under the terms and conditions as described herein. 

NOW, THEREFORE, in consideration of the premises and mutual
agreements herein, the Corporation and Consultant agree as follows: 

1.     Section 1 of the Consulting Agreement “DEFINITIONS” shall be
amended to include the following defined term: “Principal Executive Officer
means President and Chief Executive Officer of the Corporation.” 

2.     Effective as of the date of this Amendment, wherever the
term “President” is used in the Consulting Agreement, it shall be replaced with
term “Principal Executive Officer.” 

3.     Section 3, paragraph 5 of the Consulting Agreement is
amended to include the following statement: “The Corporation and Consultant
confirm that Mr. Douglas may, at his discretion, carry out his responsibilities
as Principal Executive Officer of the Corporation from his office in Canada.”

4.     Section 4(a) of the Consulting Agreement is hereby revised
in its entirety to read as follows: “The Corporation agrees to pay Consultant
annual compensation of $155,000.00, payable in 12 equal monthly
installments.”

5.     Except as otherwise provided in this Amendment, all other
terms, covenants and conditions of the Consulting Agreement remain in full force
and effect on the date hereof without modification or amendment.

6.     This Amendment may be signed by facsimile or electronic
signature, and in one or more counterparts, each of which shall be deemed to be
an original, but which together shall constitute one agreement. 

[THIS SPACE INTENTIONALLY LEFT BLANK] 

IN WITNESS WHEREOF, the parties have duly executed this
Amendment effective as of the day and year first above written. 

INFRASTRUCTURE MATERIALS CORP. 

By: /s/Anne
Macko              
 
      Anne Macko, Secretary 

1408943 ALBERTA LTD. 

By: /s/Mason
Douglas          
 
       Mason Douglas, President

2

Source: [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00209-of-00352.parquet"}, [{"source": "alea-institute/alea-institute/kl3m-data-edgar-agreements/train-00209-of-00352.parquet"}]]