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





 


	
	Service Agreement 

      
Confidential 	7.2.1_GFOR_001/03
      
	Exp: end OCT 2016
      
	 Last Print Date: 7/07/2014
11:24:00	Page 1/17
  



 

Service Agreement 

between 

ORGENESIS Sprl 

and 

MASTHERCELL SA 

 


	   6.1.2_GFOR_002/04 	Drafting 	   Verification   	Approval 	Effective date 
	Initials + Dpt training 	SVE [ ] 	EMA [ ] 	PST [ ] 	NA [ ] 	 NA [ ]  	NA [ ]	NA [ ] 	NA [ ] 	SVE [ ] 	08 OCT 2013 











  	

          	Service Agreement 

          

      Confidential 	7.2.1_GFOR_001/03 
	Exp: end OCT 2016 
	 Last Print Date: 7/07/2014
        11:24:00	Page 2/17 




THIS AGREEMENT is made 

BETWEEN

	(1) 	
      ORGENESIS SPRL, ("ORGENESIS"), a
      company incorporated in Belgium, as company number 0540 866 555 and whose
      registered office is at 4 Avenue Professeur Henrijean, 4900 Spa,
      Belgium;

	 	 
	(2) 	
      MASTHERCELL SA, ("MASTHERCELL"), a
      company incorporated in Belgium, as company number 0840 843 708 and whose
      registered office is at B-6041 Gosselies (Belgium), rue Adrienne Bolland,
      8;



BACKGROUND: 

Orgenesis SPRL is a fully owned subsidiary of Orgenesis Ltd.,
an Israel based company. 

Orgenesis Ltd. is a development stage company with a novel
therapeutic technology that employs a molecular and cellular approach directed
at converting a patient’s own liver cells into functional insulin producing
cells, as a treatment for diabetes. 

Pancreatic islet cell transplantation is considered the only
available technology. However, it is extremely limited and impractical due to
shortages of donor tissue and unacceptable rejection rates by the patient's
immune system.

Orgenesis believes that converting the diabetic patients own
tissue into insulin-producing cells overcomes the problem of donor shortage and
removes the risk of transplant rejection. 

Orgenesis is looking for a partner to develop its process from
lab scale to clinical scale and to prepare for cGMP manufacturing of lots to be
used for a Phase I/II clinical trial to be initiated in 2015.

MASTHERCELL is a cell therapy dedicated contract development
& manufacturing company located in Gosselies, Belgium. 


  	   6.1.2_GFOR_002/04 	Drafting 	   Verification   	Approval 	Effective date 
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          	Service Agreement 

          

      Confidential 	7.2.1_GFOR_001/03 
	Exp: end OCT 2016 
	 Last Print Date: 7/07/2014
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NOW THEREFORE, in consideration of the preamble and mutual covenants, the parties hereto have hereby mutually agreed as follows: 

	
1. 		
Definitions

	
	 	 	 
		
1.1. 		
“Affiliates” means any company, corporation, firm, partnership or other entity which is directly or indirectly controlled by, or under common control with any of the parties, where control means the power,
direct or indirect, to direct or cause the direction of the management and policies of such entity, whether by contract, through the by-laws of the aforementioned entities or otherwise.

	
	 	 	 
		
1.2. 		
“Agreement” shall mean this services agreement including its Appendices.

	
	 	 	 
		
1.3. 		
“Appendix(ces)” shall mean an appendix to this Agreement.

	
	 	 	 
		
1.4. 		
“Confidential Information” has the meaning referred to in article 9.

	
	 	 	 
		
1.5. 		
“Consumable(s)” shall mean General Consumable(s) and/or Specific Consumable(s) that enter into the production process as well as is used for quality control purposes. Consumables are all components and
disposables that enter into the execution of the project. These comprise, but are not limited to, cell culture media, cell culture devices, quality control reagents and kits, pipets, tubes, and all small materials necessary to perform the activities
related to the execution of the project.

	
	 	 	 
		
1.6. 		
“Effective Date” shall mean the date referred to in article 14.

	
	 	 	 
		
1.7. 		
“Force Majeure” has the meaning referred to in article 12.

	
	 	 	 
		
1.8. 		
“Good Manufacturing Practice” or “GMP” shall mean practices required with respect to the manufacture of the Products by the provisions of EC Commission Directive 2003/94/CE together with any
implementing applicable legislation and with the Guide to Good Manufacturing Practice published by the EC Commission in 1992 (ISBN 92-82 6-3180-X) as well as with any other legislation, recommendations or guidelines (binding or non-binding) from the
competent authorities in Europe and all applicable rules, regulations, orders and guidance as the same may from time to time be amended.

	
	 	 	 
		
1.9. 		
“Material(s)” means all product produced by MASTHERCELL pursuant to the terms of this Agreement

	
	 	 	 
		
1.10. 		
“ORGENESIS Background Intellectual Property” shall mean all Intellectual Property which is in possession of ORGENESIS prior to the date of the signing of this Agreement (here included – but not limited to
- the Manufacturing Process), or which is developed by ORGENESIS in parallel with this Agreement.

	
	 	 	 
		
1.11. 		
“Intellectual Property Rights” shall mean any and all patents, patent applications, utility models, registered designs, unregistered design rights, know-how, copyright, database rights, trademarks, rights in
respect of confidential information, rights under data exclusivity laws, rights under orphan drug laws or under paediatric laws, property rights in biological or chemical materials, extension of the terms of any such rights (including supplementary
protection certificates), applications for and the right to apply any of the foregoing registered property and rights, and similar or analogous rights in any part of the world.

	
	 	 	 
		
1.12. 		
“JSC” shall mean the joint steering committee referred to in article 2.8

	
	 	 	 
		
1.13. 		
“SUPPLIER” shall mean the supplier of materials

	





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	 	1.14. 	“Production Facility(ies)”
      shall mean MASTHERCELL’s R&D facilities at Gosselies, Belgium
      where the development of the process will be carried out. 
	 	 	 
	 	1.15. 	“Project” shall include
      the following, as described more into details in this Agreement See
      Section 3) : 
	 	 	 
	 	1.16. 	“QC” shall mean quality
      control 
	 	 	 
	 	1.17. 	“Results” shall mean any
      data, methods, substances and/or materials produced, developed or
      collected by MASTHERCELL in the course of and relating to the Works
      (whether individually, collectively or jointly with ORGENESIS), including,
      without limitation, the Products as well as any and all reports and
      studies. 
	 	 	 
	 	1.18. 	“Work(s)” shall mean any
      works, services or tasks to be performed by MASTHERCELL under this
      Agreement. 



	2. 	
      General principles governing the performance of the
      Project

	 	 	 
		2.1. 	
      MASTHERCELL shall act as a Contract Development and
      Manufacturing Organization (“CDMO”) for ORGENESIS and shall diligently
      perform, in its Facility, the Project as ordered by ORGENESIS in this
      Agreement and its Appendices.

	 	 	 
		2.2. 	
      MASTHERCELL warrants and undertakes to ORGENESIS
    that:




	 	a. 	
      It will have all necessary authorizations for performing
      all its obligations under the Agreement;

	 	 	 
	 	b. 	
      The Works will be conducted in a professional manner,
      with reasonable professional skill and care;

	 	 	 
	 	c. 	
      It will perform the Project in strict compliance with the
      time schedules set out in Appendix 2.




	 	2.3. 	
      A summary report will be supplied to ORGENESIS after the
      completion of each main part of the Project. The summary reports will be
      sent to ORGENESIS at the latest one (1) month after the completion of each
      part of the Project.

	 	 	 
	 	2.4. 	
      Materials and procedures, background and previous
      experimental data will be made available to MASTHERCELL by ORGENESIS
      and/or SUPPLIER in due time to allow MASTHERCELL to perform the project.
      It is agreed that the biosafety level of the Materials transferred to
      MASTHERCELL will not exceed level 2, as defined in the Directive
      2000/54. ORGENESIS will provide, when applicable, any available
      safety data sheet and/or procedure related to the handling of the
      biological Material transferred to MASTHERCELL together with all
      information that the Belgian Biosafety Authorities might request.
      MASTHERCELL shall ensure that any biological Material shall be handled in
      accordance with the applicable legislation, here included this
      implementing Directive 2000/54/EC of the European Parliament and of the
      Council of 18 September 2000 on the protection of workers from risks
      related to exposure to biological agents at work.

	 	 	 
	 	2.5. 	
      Orgenesis will supply Masthercell with adequate
      recombinant adenovirus stocks that contain functional transgenes. These
      virus banks will have been tested for sterility and their functionality
      will have been demonstrated as driving transdifferentiation of human
      hepatic cells into pancreatic beta-cells before being used by
      Masthercell.




      
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	 	2.6. 	
      ORGENESIS shall retain ownership of the Materials at all
      times. MASTHERCELL shall in no circumstances use the Materials for
      purposes other than the performance of the Work or transfer the Materials
      to any third party. MASTHERCELL will ensure that the Materials are used in
      full compliance with all applicable legislation.

	 	 	 
	 	2.7. 	
      MASTHERCELL undertakes to communicate to ORGENESIS any
      available information or data which would be required in order to file any
      application with the competent authorities, including an application for
      being allowed to carry out preclinical and/or clinical trials.

	 	 	 
	 	2.8. 	
      Promptly after the Effective Date, the Parties will
      establish a joint steering committee (“JSC”) which will be in charge of
      overseeing the Parties’ activities under this Agreement and assessing the
      results of the Works carried out by MASTHERCELL. ORGENESIS and MASTHERCELL
      shall each appoint two (2) members as representatives in the JSC. Each of
      the parties represented in the JSC may replace its representatives at any
      time upon written notice to the other members.

	 	 	 
	 		
      The JSC will meet regularly and in any case at the end of
      each step of the Project. The representative of ORGENESIS will head the
      JSC and, if practicable, will send written notice of all meetings to all
      members of the JSC no less than fifteen (15) days before the date of each
      meeting. With the sole exception of specific items of the meeting minutes
      to which the members cannot agree and which are escalated as provided
      below, definitive minutes of the meetings shall be finalized no later than
      thirty (30) days after the meeting to which the minutes
pertains.

	 	 	 
	 		
      In the event the JSC is unable to reach a unanimous
      decision within fifteen (15) days after it has met, or if there is
      disagreement on the minutes, then either Party may, by written notice to
      the other, have such issue referred to the CEO of MASTHERCELL and the CEO
      of ORGENESIS, for resolution. If they are unable to determine a resolution
      in a timely manner, which shall in no case be more than thirty (30) days
      after the matter was referred to them, either Party may start an
      arbitration procedure as provided in article 14.2.

	 	 	 
	 		
      Notwithstanding the above, MASTHERCELL acknowledges that
      it is to conduct the Project as per the objectives of ORGENESIS, and no
      arbitration is required if ORGENESIS determines in its sole discretion
      that its objectives will not be met through MASTHERCELL’s intended or
      completed actions. In such case, ORGENESIS may terminate this Agreement
      under Article 0.




	3. 	
      Detailed steps of the Project

	 	 	 
		3.1. 	
      MASTHERCELL undertakes to carry out the Project in
      compliance with articles 3.3 to 3.8 provided demonstrated successful
      outcome of the small scale process developed by ORGENESIS and effective
      technology transfer of the process and of the existing analytical methods
      to MASTHERCELL.

	 	 	 
		3.2. 	
      Given the nature of the project, the duration and
      therefore the price given for each section here under are based on the
      assumptions that were used to prepare the Development plan submitted to
      the Walloon Region. If, for a reason not linked to the performance of
      Masthercell staff, the duration is extended, extra costs will be charged
      to Orgenesis.

	 	 	 
		3.3. 	
      Liver Cells sourcing from fresh liver tissue samples 

      Budget : 125,000 Euro




      
        	   6.1.2_GFOR_002/04 	Drafting 	   Verification   	Approval 	Effective date 
	Initials + Dpt training 	SVE [ ] 	EMA [ ] 	PST [ ] 	NA [ ] 	 NA [ ]  	NA [ ]	NA [ ] 	NA [ ] 	SVE [ ] 	08 OCT 2013 


      






  	

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	 	a. 	
      Obtain the authorization in Belgium to use fresh and
      frozen liver tissue sample

	 	 	 
	 		
      The goal is to obtain the authorization in Belgium to use
      fresh human liver tissue samples to develop GMP-compliant transfer of
      starting material, isolation, first culture steps, storage and transport
      of Liver Cells (in the absence of pen-strep)”. A dossier including
      clinical protocol, description of use of Human Corporal Material, Patient
      informed consent will be written and discussed with the Ethical Committee
      of the UCL. As an example, a convention could be signed with UCL (Prof.
      Sokal) in order to obtain the right to retrieve small pieces of donated
      organs that he harvests for the Hepatocyte Bank. Three months will be
      necessary on one hand to obtain approval from the Ethical Committee and on
      the other hand to negotiate sharing donated tissue and finalize a
      Convention with the Research Directorate of the UCL (0,25 FTE QP; few days
      of work for legal review of the contract for ORGENESIS).

	 	 	 
	 	b. 	
      Establish a protocol for harvesting fresh liver cells as
      source for the primary cell culture and banking

       Ideally 5 different donor
        tissues will be tested. 5 to 10 samples of equal or different sizes will
        be sampled from each liver to test stability of starting material and the
        smallest size compatible with full scale process (generation of
        109 cells). In average, five different donor livers can
    be collected over a period of 5 months.




	 	3.4. 	
      Comparison of cell expansion in CS CellBIND10 and
    CF10

	 	 	 
	 		
      Budget : 100,000 Euro

	 	 	 
	 		
      Preliminary tests at ORGENESIS have indicated that Cell
      Factories can support the proliferation of liver derived cells and the
      trans-differentiation process. Until the feasibility of
      transdifferentiation in Xpansion bioreactors is proven, Cell Factory
      systems will be used for cell production. The aim of this task is to
      identify the best cell factory system (CS CellBIND 10 from Corning and
      CF10 from Nunc) for cell proliferation and trans-differentiation. Decision
      to continue or abort development in cell factories will be taken after 6
      month work as preliminary data will be collected in parallel from a first
      series of experiments run in Xpansion 10 bioreactors at ATMI.

	 	 	 
	 		
      At the end of this work, MTC will evaluate all results
      obtained and, together with Orgenesis and ATMI, compare those with the
      results obtained by ATMI in bioreactors (XP10). The selection criteria
      (for the best system) will be defined with the 3 parties. These evaluation
      activities are estimated to take 3 weeks and are budgeted at 10,000€ (for
      MTC part of the work, on top of the 100k€ for the comparison
      activities)

	 	 	 
	 	3.5. 	
      Technology transfer from ATMI to MTC 

      Budget : 30,000 Euro

	 	 	 
	 		
      At the end of process development by ATMI, ATMI will
      perform 3 reproducibility runs in their lab. Masthercell will send some
      people to observe the execution of these runs in order to learn how to
      perform the process at large scale. This will allow to save time for
      technology transfer.




      
        	   6.1.2_GFOR_002/04 	Drafting 	   Verification   	Approval 	Effective date 
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	 	3.6. 	
      Full-scale non-GMP reproducibility and training runs 

      Budget : 250,000 Euro

	 	 	 
	 		
      3 Runs will be produced in the technology transfer lab
      for reproducibility and training. The success of these runs will conclude
      the technology transfer between ATMI and MTC and will be used to train all
      operators who will participate to the later clinical
  manufacturing.

	 	 	 
	 	3.7. 	
      Quality Control assay
development




	 	a. 	
      Final product stability 

    Budget : 75,000 euros

	 	 	 
	 		
      We will test various injectable formulation solutions at
      4°C (or RT) and measure cell viability, metabolic activity and cell
      potency at several time points. Viability should remain higher than 70%.
      As a general rule, metabolic activity and potency at the end of the
      stability phase will be considered sufficient for administration as long
      as they do not fall under 70% of the values achieved with the fresh
      product. Cells from at least three different donors will be tested.
      Finally, two formulation solution candidates will be used for comparison
      on full scale batches generated as reproducibility runs.

	 	 	 
	 	b. 	
      Quality Control on final product

	 	 	 
	 		
      Budget : 275,000 euros



•        Potency assay 

Optimization of the current GSIS and
Insulin ELISA assays will be carried out in order to increase the sensitivity of
the read-out. In addition, the assays have to be made GMP-compliant. They will
be evaluated for their suitability. Positive and negative controls from a secure
and stable source have to be incorporated in the assays. Linearity and
reproducibility (as referred to in the ICH Q2 (R1)) of the assays in the working
range have to be documented. The assay should be optimized using cells
transdifferentiated with the 3 current adenoviruses. Once the assay will be
optimized and controlled, it will be applied to cells transdifferentiated with
the three new humanized viruses.

•        Identity assay 

The identity assay will be based on
RT-PCR assays that are currently used to verify viral transduction efficacy in
addition to an insulin RT-PCR assay. It is essential to develop such an identity
assay in addition to the potency assay that measures the amount of insulin
released in order to verify expression of the exogenous transcription factors.
As a matter of fact cells that have received the three transcription factors
might be immature and not secrete insulin and still be able to
transdifferentiate in vivo thereby contributing to therapeutic efficacy.


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To set up these PCR assays, specific
probe and primer sets will be purchased from Applied Biosystems. Total RNA from
positive and negative cells will be purchased as positive and negative controls.
In parallel, a set of reference genes will be assessed in order to select the
two best ones to use in routine assays. The challenge in this assay development
will be to fix acceptance criteria on the expression levels that need to be
reached for each of the assessed mRNAs. This will require to collect a
statistically significant number of data and to acquire a good sense of assay
reproducibility and inter-individual variation.

•        Purity assays 

A cytometry assay will be used as the
principal purity assay to ensure that more than 90% of the cell population has a
mesenchymal phenotype. A relatively straightforward optimization of current
assays with the aim to analyze all markers in one tube with up to 8 colors and
measure viability and metabolic activity at the same time can be performed by
ImmuneHealth (or other partner) for cytometry assays. However, since
transdifferentiation into beta-like cells occurs in approximately 15% of the
total cell population, it will be essential to determine the fate of the other
85% of the cells and these subpopulations will need to be identified and
quantified. We will use the immunofluorescence assays developed while optimizing
the triple viral infection to quantify the subpopulations expressing or
co-expressing the various exogenous transcription factors.

Given the autologous character of the
process and the unknown inter-individual variability, approximately 6 months
will be needed to set up robust standardized assays for targeting the exogenous
transcription factors. Ideally, 3 assays will be designed but limitation might
come from the lack of availability of highly specific antibodies. Six additional
months will be required to make these assays GMP-compliant and to achieve
operator-independent quantification. 

•      
 Safety assays 

Safety assays are the only assays that
are required to be validated for phase I. Validation of sterility assays will be
outsourced. Validation of the assays measuring endotoxin and mycoplasma levels
are done routinely. 

Regulatory advice will be sought to
know if the titration of residual infectious viruses is an assay that requires
validation. This validation has been tentatively scheduled for 4 months after a
phase of tech transfer and GMP adaptations/optimizations.

	 	c. 	
      Genetic stability and potential tumorigenicity of the
      final product in vitro

	 	 	 
	 		
      Budget : 35,000 Euros

	 	 	 
	 		
      Genetic stability of cells maintained in culture for a
      few weeks will need to be confirmed via karyotyping and CGH (comparative
      genomic hybridization).




      
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In addition, at the end of the
process, even if it is expected that 15% of the cells will be fully mature and
post-mitotic, most of the cells present in the final product are still capable
of proliferating. If left in culture, these cells will take over and dilute the
mature cells. Demonstration that the cell product effectively reaches senescence
and stops proliferating will be required.

We plan to perform these assays on the
final product of full scale reproducibility batches. 

	 	3.8. 	
      Project management

	 	 	 
	 		
      During the execution of the project, a project manager
      will be appointed by MASTHERCELL to oversee Orgenesis’ Project. The cost
      for this activity is of 62,500€ as per the final offer made to Orgenesis
      and will be invoiced throughout the execution of the project. This person
      will ensure that the activities agreed with Orgenesis are executed in a
      timely manner, within the allocated budget. He/she will organize regular
      internal project meetings with the different persons working on the
      project and will report progresses to the customer on a regular
    basis.

	 	 	 
	 		
      The project manager will also prepare a final report at
      the end of the project.




	4. 	
      Trained personnel and supervision

	 	 	 
		4.1. 	
      MASTHERCELL’s trained personnel will perform the
      development activities described in this Agreement under the supervision
      of the MASTHERCELL’s Chief Operation Officer.

	 	 	 
		4.2. 	
      ORGENESIS may delegate, from its own personnel and under
      its own responsibility, a specialist to observe/support activities at
      MASTHERCELL. The Parties shall agree upon timing for the visits of
      ORGENESIS specialist at MASTHERCELL. Despite any intervention of the
      ORGENESIS specialist, MASTHERCELL remains in any case the sole responsible
      Party for any activity described in this Agreement.

	 	 	 
		4.3. 	
      MASTHERCELL shall remain responsible for any aspects of
      the employment of its personnel involved in activities carried out for
      ORGENESIS.

	 	 	 
	5. 	
      Compliance with legal
requirements

	 	 	 
		5.1. 	
      It is understood that activities performed by MASTHERCELL
      for the benefit of ORGENESIS will be carried out by MASTHERCELL in
      compliance with the applicable regulations.

	 	 	 
	6. 	
      Price and payment conditions

	 	 	 
		6.1. 	
      The Price of Work are listed in Annex 2 of this
      contract

	 	 	 
		6.2. 	
      Transportation costs are not included in the Price of the
      Work. If ORGENESIS requires MASTHERCELL to organize transportation,
      MASTHERCELL will charge ORGENESIS the transportation costs + 10% for
      administration and handling.

	 	 	 
		6.3. 	
      Outsourced quality control costs are not included in the
      Price of the Work. If they are required, they will be invoiced at their
      cost price, plus 10% for procurement, administration and handling.
      MASTHERCELL will not outsource any quality control without the prior
      consent of ORGENESIS.




      
        	   6.1.2_GFOR_002/04 	Drafting 	   Verification   	Approval 	Effective date 
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	 	6.4. 	
      Consumables are included in the Price of the Work, at the
      exception of disposable bioreactors and their accessories as well as
      serum. They will be invoiced at cost plus 5% for procurement,
      administration and handling.

	 	 	 
	 	6.5. 	
      The price of starting material (fresh or frozen hepatic
      cells or liver biopsies) and its transport and quality/safety testing is
      not included in this offer. These will be invoiced at their cost price,
      plus 10 % for procurement, administration and handling.

	 	 	 
	 	6.6. 	
      The payment of the Price of the Work shall be made
      according to the following timetable:




	 	– 	
      30 % of the Price of the Work (288,750 €, two hundred
      eighty-eight thousands seven hundred and fifty Euros) will be invoiced by
      MASTHERCELL upon (i) the signature of this Agreement and (ii) the official
      approval from the DG06. 

	 	  	     
	 	– 	
      MASTHERCELL shall then send to ORGENESIS, at the end of
      each month, an amount equal to the value of the Works actually performed
      during said month. Each month, and during 22 months, 13,150€ will be
      deducted from the monthly invoice. This amount corresponds to the initial
      payment (288,750€) divided by the amount of months planned for the project
      (22 months). 




	 	6.7. 	
      Invoices are payable within thirty (30) days from the end
      of month that the invoices were received by Orgenesis.

	 	 	 
	 	6.8. 	
      After due notice MASTHERCELL reserves the right to cease
      or suspend Works for which payment remains in arrear and to charge
      interest at the rate of one percent (1 %) per month on all overdue
      payments.




	7. 	
      Liabilities

	 	 	 
		7.1. 	
      MASTHERCELL agrees to indemnify and hold ORGENESIS
      harmless from and against any and all claims, demands, causes of action,
      actions or suits, judgements, decrees, damages or any liability whatsoever
      asserted or entered against ORGENESIS by or on behalf of any person, firm
      corporation or governmental bodies for bodily injury or damage to property
      arising out of or relating to the Products and/or the Project in case such
      damages are due to breach or negligence of MASTHERCELL.

	 	 	 
		7.2. 	
      ORGENESIS agrees to indemnify and hold MASTHERCELL
      harmless from and against any and all claims, demands, causes of action,
      actions or suits, judgements, decrees, damages or any liability whatsoever
      asserted or entered against MASTHERCELL by or on behalf of any person,
      firm corporation or governmental bodies for bodily injury or damage to
      property arising out of or relating to any use by ORGENESIS or other
      parties of any of the Products and/or the Project, in case such damages
      are due to breach or negligence of ORGENESIS.

	 	 	 
		7.3. 	
      In any case, neither Party shall be liable to the other
      for an amount exceeding the Price of the Work, except in case of gross
      negligence or wilful misconduct.

	 	 	 
		7.4. 	
      MASTHERCELL undertakes to be properly covered by an
      appropriate insurance policy for its liabilities under this
    Agreement.

	 	 	 
	8. 	
      Intellectual Property Rights

	 	 	 
		8.1. 	
      MASTHERCELL acknowledges that the Works will be performed
      exclusively based on the Manufacturing Process and other know-how coming
      from or derived from ORGENESIS Background Intellectual
  Property.




  
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	 	8.2. 	
      ORGENESIS Background Intellectual Property is and shall
      remain the exclusive property of ORGENESIS at all times. MASTHERCELL shall
      make no representation or do any act which may be taken to indicate that
      it has any right, title or interest in or to the ownership of the
      ORGENESIS Background Intellectual Property. ORGENESIS shall also retain
      ownership in all improvements and inventions in connection to ORGENESIS
      Background Intellectual Property and shall own any and all Intellectual
      Property Rights in improvements to ORGENESIS Background Intellectual
      Property that may arise during the course of the Work. MASTHERCELL
      acknowledges that nothing contained in this Agreement shall give it any
      right, title or interest in the ORGENESIS Background Intellectual Property
      or any improvements save as granted hereby.

	 	 	 
	 	8.3. 	
      ORGENESIS hereby grants to MASTHERCELL, which accepts, a
      non-exclusive, royalty- free license for use of the ORGENESIS Background
      Intellectual Property for the sole purpose of the performance of
      MASTHERCELL's Works on the Project at the Production Facility, subject to
      the other terms and conditions of this Agreement.

	 	 	 
	 	8.4. 	
      Any materials, including but not limited to all hard
      copies or other assets, including reports, notes, notebooks, summaries,
      tables presentations, graphics, databases, software produced by
      MASTHERCELL for ORGENESIS pursuant to the terms of this Agreement shall be
      the sole and exclusive property of ORGENESIS and MASTHERCELL hereby
      assigns and vests in ORGENESIS the entire rights, title and interest
      thereto.

	 	 	 
	 	8.5. 	
      MASTHERCELL shall promptly disclose to ORGENESIS all
      Results and upon ORGENESIS' request shall execute and deliver any and all
      instruments and documents and make such other acts as may be necessary or
      desirable to document such transfer or to enable ORGENESIS or any third
      Party identified by it, to prepare, apply for, prosecute, enforce and
      maintain patents, trademark registrations, copyrights or other
      Intellectual Property Rights in any jurisdiction with respect to any
      Results or to obtain any extension, validation, reissue, continuance or
      renewal of any such Intellectual Property related thereto. MASTHERCELL
      shall not prepare, file or cause to be prepared or filed, any patent,
      trademark or copyright applications in respect to any Results. ORGENESIS
      or any third party identified by it shall, at its sole discretion,
      prepare, file, prosecute and maintain patent, trademark or copyright
      applications for such Results.

	 	 	 
	 	8.6. 	
      MASTHERCELL warrants that any of its employees having
      access to ORGENESIS Background Intellectual Property: (i) shall be made
      aware of the confidentiality of the same; (ii) shall be bound by
      confidentiality agreements in place in substantially the same terms as the
      provisions in article 9 of this Agreement; (iii) will keep such ORGENESIS
      Background Intellectual Property in strict confidence; and (iv) will not
      disclose same to any third Party.




	9. 	
      Confidentiality

	 	 	 
		9.1. 	
      Each Party hereto understands that the other’s
      relationship with its ORGENESISs, officers and employees is one of
      confidence and that during the period of this Agreement between
      MASTHERCELL and ORGENESIS either Party may receive, or may have already
      received, knowledge of, or access to, information which relates to the
      materials, compounds, compound structures, compound synthesis information,
      technical and non-technical data, market information, sales, business
      plans, strategies, products, processes, specifications, techniques,
      testing procedures, research, developments, inventions, trade secrets, or
      know- how of the other or of its ORGENESISs and which is not known to the
      general public (“Confidential Information”).




      
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	 	9.2. 	
      The Parties are aware that Confidential Information may
      be disclosed in any manner including in writing, orally, electronically,
      or visually. Confidential Information disclosed in writing shall be
      clearly marked as “Confidential” when disclosed. To the extent possible,
      when Confidential Information is disclosed in a manner other than in
      writing, it shall be summarized and reduced to written form, marked
      “Confidential” and transmitted to the receiving party within thirty (30)
      business days of the initial disclosure.

	 	 	 
	 	9.3. 	
      Every information disclosed in the framework of the
      Technology Transfer, as well as every part of ORGENESIS Background
      Intellectual Property, falls automatically into the scope of the
      Confidential Information.

	 	 	 
	 	9.4. 	
      Except as necessary pursuant to the purpose of this
      Agreement, the receiving Party will not at any time, without the prior
      written consent of the disclosing Party, (a) use the Confidential
      Information for any purpose other than the purpose related to this
      Agreement, or (b) disclose any Confidential Information to any other
      person or entity, or (c) use any Confidential Information for the
      receiving Party's own benefit or the benefit of any other person or entity
      or (d) trade in the securities of any Party or its Affiliate while in
      possession of Confidential Information regarding the other
Party.

	 	 	 
	 	9.5. 	
      The foregoing obligations shall not apply to any portion
      of the Confidential Information that the receiving Party can demonstrate
      by documentary evidence: (i) was known to the receiving Party prior to
      receipt from the disclosing Party; (ii) is or lawfully becomes generally
      available to the public; (iii) is lawfully acquired from third parties who
      have a right to disclose such information; (iv) by mutual written
      agreement is released from a confidential status; (v) the receiving Party
      is required by law to release, provided, the disclosing Party is given
      prior written notice of such request to enable the disclosing Party to
      obtain a protective order or take other protective measures to protect its
      information; or (vi) is independently developed by the receiving Party
      without use of the Confidential Information of the other Party .

	 	 	 
	 	9.6. 	
      Confidential Information shall not be used by the
      receiving Party other than for the purpose of the Agreement. The Parties
      shall only disclose Confidential Information to employees who have a
      genuine need to access such information in order to fulfil the Party's
      obligations under this Agreement.

	 	 	 
	 	9.7. 	
      The receiving Party agrees that, at the other Party's
      request, the receiving Party shall forthwith return to the other Party any
      and all parts of the Confidential Information provided in documentary form
      and will return or destroy any copies or other tangible embodiments
      thereof made by the receiving Party; except for one copy that may be
      retained in a secure file for compliance purposes only.

	 	 	 
	 	9.8. 	
      These obligations of confidentiality and non-use are
      valid during the period of this Agreement and for a period of ten (10)
      years following the Effective Date.




	10. 	
      Assignment / Subcontracting

	 	 	 
		10.1. 	
      MASTHERCELL is not allowed to assign or subcontract all
      or part of its obligations under the Agreement without the prior written
      consent of ORGENESIS.

	 	 	 
		10.2. 	
      In any case, MASTHERCELL remains fully liable towards
      ORGENESIS for any activities of any of the
  sub-contractors.




  
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11. 		
Duration and termination of the Agreement

	
	 	 	 
		
11.1. 		
This Agreement shall be effective as from the Effective Date and shall remain in full force and effect until completion of the Works by MASTHERCELL.

	
	 	 	 
		
11.2. 		
Any Party shall be entitled to terminate the Agreement anticipatively upon immediate notice to the other Party in the event of material breach by the other Party which has not been remedied within thirty (30) days from receipt by
the defaulting Party of a written notice sent by the claiming Party with respect to such breach.

	
	 	 	 
		
11.3. 		
ORGENESIS may terminate this Agreement at any moment without cause, by sending a three (3) months prior written notice to MASTHERCELL. The termination will have effect at the end of this three (3) months period. ORGENESIS shall
own all Materials, in process materials, compounds and ORGENESIS information delivered to MASTHERCELL or arising under or otherwise resulting from the Works, or for which MASTHERCELL was reimbursed by ORGENESIS.

	
	 	 	 
			
When ORGENESIS terminates this Agreement in accordance with this provision, the Parties shall assess the value of all Works in progress or Works already completed by MASTHERCELL prior to the effective termination date, in
accordance with the invoicing of the Works actually performed and with the budget provided in Appendix 1. MASTHERCELL shall be entitled to moneys due for all such Works carried out until the actual termination date as well as to the reimbursement of
all non-refundable costs and expenses that it has actually incurred before the termination date, provided MASTHERCELL delivers to ORGENESIS all the Materials, information and process description used so that ORGENESIS can continue the Project with
another service provider.

	
	 	 	 
		
11.4. 		
Upon termination of this Agreement, MASTHERCELL shall, in full compliance with the applicable legislation, either destroy unused Materials or return them to ORGENESIS upon ORGENESIS' instructions.

	



	
12. 		
Force Majeure

	
	 	 	 
		
12.1. 		
If any Party hereto is delayed or prohibited from fulfilling its obligation or obligations under this Agreement by reason of fire, war, embargos, unavailability of raw materials, breakdown of or damage to machinery, or equipment,
strike, lock out or other labour dispute, any rule, order or regulation of any governmental authority, domestic or foreign, or any other cause of occurrence beyond the reasonable control of the Party (“Force Majeure”), and, if prompt
written notice of said delay or prohibition shall be given to the other Party, then performance of said obligation or obligations shall be excused for the period of time during which the cause of such delay or prohibition shall continue, provided
that the Party so impeded shall have made reasonable efforts to minimise any such delay.

	
	 	 	 
		
12.2. 		
If the performance by either Party of any of its obligations under this Agreement is prevented or delayed by Force Majeure for a continuous period in excess of thirty (30) working days, the Parties shall enter into bona fide
discussions with a view to alleviating its effects, or to agreeing upon such alternative arrangements as may be fair and reasonable in the circumstances.

	
	 	 	 
			
If the performance by either Party of any of its obligations under this Agreement is prevented or delayed by Force Majeure for sixty (60) days or more, consecutively or cumulatively, in any one year, then the other Party shall in
its discretion have the right to terminate this Agreement forthwith upon written notice.

	





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	13. 	
      Applicable law – Jurisdiction

	 	 	 
		13.1. 	
      This Agreement shall be entirely and exclusively
      interpreted and enforced in accordance with the laws of Belgium.

	 	 	 
		13.2. 	
      Any disputes arising out of or in relation with this
      Agreement shall be finally settled under the CEPANI Rules of Arbitration
      by one (1) arbitrator appointed in accordance with those Rules. The seat
      of the arbitration shall be Brussels (Belgium).

	 	 	 
		13.3. 	
      The arbitration shall be conducted in the English
      language.

	 	 	 
	14. 	
      Miscellaneous

	 	 	 
		14.1. 	
      It is understood and agreed between the Parties that no
      failure or delay by a Party in exercising any right, power or privilege
      hereunder shall operate as a waiver thereof, nor shall any single or
      partial exercise thereof preclude any other or further exercise thereof or
      the exercise of any other right, power or privilege hereunder.

	 	 	 
		14.2. 	
      All notices which are required to be given under this
      Agreement shall be deemed to have been sufficiently given if in writing
      and sent by registered mail or express courier with the requisite postage
      affixed, or if by fax, confirmed by registered mail or expressed courier
      addressed to the Party notified, at the address set forth in the head of
      this Agreement, or such other address as may hereinafter be given by such
      Party to the other for notice purpose. The date of such mailing or
      delivery shall be the date of service of such
notice.



For ORGENESIS:

[To the attention of Jacob BenArie,
CEO 

Orgenesis SPRL 

Avenue Professeur Henrijean, 4 

4900 Spa ] 

For MASTHERCELL: 

[To the attention of Hugues Bultot CEO


MASTHERCELL SA 

Avenue Auguste Piccard, 48 

6041 Gosselies ] 

	 	14.3. 	
      This Agreement together with the Appendices thereto which
      form an integral part thereof supersedes any previous understandings and
      constitutes the entire agreement between the Parties hereto relating to
      the subject matter hereof. Any amendments, modifications, variations, or
      waivers, including amendments and modifications to the Appendices, must be
      in writing and signed by both Parties hereto. In case of contradiction
      between the provisions of the Appendices and of these of this Agreement,
      the provisions of this Agreement will prevail.

	 	 	 
	 	14.4. 	
      If any provisions of this Agreement shall be held by a
      court of competent jurisdiction to be illegal, invalid or unenforceable,
      the remaining provisions shall remain in full force and effect. In such
      event, such provision will be changed and interpreted so as to best
      accomplish the objectives of such unenforceable or invalid provision
      within the limits of applicable law or applicable court
  decisions.




  
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	 	14.5. 	
      This Agreement shall not be construed to make either
      Party a legal representative of the other Party or to give either Party
      any right or power to bind the other Party to any contract or the
      performance of any obligation to or with any third Party.

	 	 	 
	 	14.6. 	
      Each Party shall conduct its operations as an independent
      contractor and no claims for taxes of any kind, nor claims arising out of
      labour laws, nor any other claims asserted against one Party may be
      asserted against the other as a consequence of this Agreement.

	 	 	 
	 		
      Made on June 23rd, 2014 in two original
      copies, each Party acknowledging having received one
  original.




	For and on behalf of MASTHERCELL: 	For and on behalf of
      ORGENESIS: 
	  	  
	Hugues Bultot 	Jacob BenArie 
	Print name 	Print name 
	  	  
	CEO 	CEO 
	Title 	Title 
	/s/ Hugues Bullot 	/s/ Jacob BenArie 
	............................................................... 	......................................................... 
	Signed July 3, 2014 	Signed July 3. 2014 



    
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APPENDIX 1 – PRICE OF WORK

Prices (ex-VAT) are given below for the individual stages of
the program at Masthercell.


	               
                         
         Activity 	Section 	Expected duration 	Total 
	Initiation activities 	See notes 	1 week 	15.000€ 
	Liver cell sourcing 	3.1 	15 months 	125.000 € 
	Comparison of cell expansion systems 	3.3 	5 months 	110.000 € 
	Tech transfer from ATMI 	3.4 	6 months 	30.000 € 
	Reproducibility and training runs 	3.5 	6 months 	250.000 € 
	Quality control assay development 	3.6 	17 months 	385.000 € 
	Project Management 	3.7 	Along the project 	62.500 € 
	  	  	 	 
	Total 	  	 	977.500 €
  



NOTES :

	1. 	
      Initiation activities at Orgenesis in Israel :

		
      Two persons from Masthercell will visit the lab and
      gather all available data/documents/procedures...

      During this visit
        Masthercell will also participate (observation and hands-on when possible)
    to process and QC experiments.

    
		
      The travel costs and reasonable out of pocket expenses
      will be invoiced to Orgenesis.

	2. 	
      These prices include the operator fees, overhead,
      documentation, project coordination, reports, internal meetings, regular
      conference calls with Orgenesis.

	3. 	
      The deliveries are quoted ex-works; the transport and
      related insurance will be paid by the customer but if requested can be
      organized by Masthercell.

	4. 	
      Transport and outsourced testing will be charged at cost
      plus 10% for procurement, administration and handling.

	5. 	
      These prices also include raw materials, consumables and
      disposables, at the exception of single use bioreactors and serum (these
      will be charged at cost plus 5% for procurement, administration and
      handling).



If regulatory support is required by our responsible
Pharmacist, Masthercell would charge this activity at an hourly rate of 150€
excl. VAT.


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APPENDIX 2 – PROJECT OVERALL TIMELINES (IN
MONTHS)

 





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