Unassociated Document


    


    
      
        
          
            	
                    

                  	
                    8
      Hartom St, Jerusalem Israel 97775

                    Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                    www.biocancell.com
      info@biocancell.com

                  


          

        

      

    

    


    AGREEMENT

    


    Between

    


    BioCancell
Therapeutics Ltd.

    Beck
Science Center, 8 Hartom St.

    Jerusalem
97775, Israel

    (Hereinafter:
“BioCancell”)

    


    And
between

    


    Medical Research Infrastructure
Development and Health Services Fund by Chaim Sheba Fund, a non profit
organization incorporated under the Laws of the State of Israel, represented by
its authorized representative (the “Fund”);

    


    BioCancell
and the Fund shall be hereinafter collectively referred to in this Agreement as
“Parties”; each one of
which also referred to as “Party”.

    


    
      
        
          	
                  Whereas

                	 
      	
                  BioCancell
      has expressed its interest in carrying out, managing and funding the
      clinical trial the subject of which being “Phase 2b, Multicenter Trial of
      Intravesical DTA-H19/PEI in Patients with Intermediate-Risk Superficial
      Bladder Cancer”, bearing protocol no. BC-07-01, a copy of which is
      attached as Appendix A hereto (hereinafter: “the Trial”);
      and

                
	 
      	 
      	 
      
	
                  Whereas

                	 
      	
                  The
      Fund agrees to carryout the Study, employing the services of the
      Investigator;

                
	 
      	 
      	 
      
	
                  Whereas

                	 
      	
                  The
      Fund has declared it holds the proper facilities and staff required to
      perform the Trial, and that it is willing to put such facilities and staff
      at the disposal of BioCancell, for the purpose of performing the Trial;
      and

                
	 
      	 
      	 
      
	
                  Whereas

                	 
      	
                  The
      Parties agree that BioCancell shall maintain any and all management
      authorities with regard to the performance of the Trial in all of its
      stages; and

                
	 
      	 
      	 
      
	
                  Whereas

                	 
      	
                  BioCancell
      has agreed to pay the Fund the consideration, specified in Appendix C
      hereto, for the performance of all the undertakings of the Fund under this
      Agreement; all, according to the terms and conditions of this
      Agreement

                


        

      

    

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

      NOW, THEREFORE, it is hereby
declared and agreed between the parties as follows:

    

    


    
      	
              1.

            	
              General

            


    

    
      	
               
      

            	
              1.1.

            	
              The
      preface and appendices to this Agreement constitute an integral part
      hereof.

            


    

    
      	
               
      

            	
              1.2.

            	
              Titles
      of the sections in this Agreement shall be used for terms of reference
      only, and could not be used for the interpretation of this
      Agreement.

            


    

    
      	
               
      

            	
              1.3.

            	
              This
      Agreement contains the entire understanding of the Parties and the
      Principle Investigator with respect to the subject matter hereof, and
      supersedes all prior or pre-existing negotiations, declarations,
      presentations, commitments and/or agreements, whether written or oral,
      whether explicit or implied, between the Parties and the Principle
      Investigator, with respect to such subject
  matter.

            


    

    
      	
               
      

            	
              1.4.

            	
              In
      the event of a contradiction between this Agreement and any of the terms
      of its appendices, the terms and conditions of this Agreement shall
      prevail.

            


    

    
      	
               
      

            	
              1.5.

            	
              Anything
      in this Agreement denoting the singular shall also denote the plural, and
      anything denoting the feminine gender shall also denote the masculine
      gender, and vice versa, insofar as no other meaning is inferred by the
      context.

            


    

    


    
      	
              2. 

            	
              Appendices

            


    

    The
appendices to the Agreement are:

    
      	
               
      

            	
              2.1.

            	
              Appendix
      A: The Trial Protocol

            


    

    
      	
               
      

            	
              2.2.

            	
              Appendix
      B: The Trial Personnel Clearance

            


    

    
      	
               
      

            	
              2.3.

            	
              Appendix
      C: The Consideration

            


    

    
      	
               
      

            	
              2.4.

            	
              Appendix
      D: Schedule 4 of the Guidelines.

            


    

    
      	
               
      

            	
              2.5.

            	
              Appendix
      E: The Trial Documents and Related
Activities.

            


    

    


    
      	
              3.

            	
              Definitions

            


    

    In this
Agreement, the following terms shall have the specific meaning attributed to
them in the table below:

    
      
        
          	
                  The
      Agreement

                	 
      	
                  This
      agreement and its appendices.

                
	
                  Serious
      Adverse Event

                	 
      	
                  As
      defined in the Trial Protocol and in the Guidelines.

                
	
                  Monitors

                	 
      	
                  Any
      body or person/s nominated by, or representing BioCancell and/or any
      company of the BioCancell Group to monitor the Trial (i.e., conduct
      on-site audits for Good Clinical Practices compliance).

                
	
                  Completed
      CRF

                	 
      	
                  A
      CRF having, according to the sole and absolute discretion of BioCancell
      and/or any third party appointed by BioCancell, no discrepancies in its
      details and no unanswered queries.

                
	
                  CRF

                	 
      	
                  Case
      Report Forms containing any and all data of the Subjects, which has been
      gathered during the Trial. The CRF shall be in hardcopy
      format.

                
	      
                  The
      End of the

                  Trial

                	 	      
                  The
      point in time, in which a Completed CRF has been submitted to BioCancell
      by the Principal Investigator, as defined herein, for all the Subjects
      participating in the Trial, or the date of termination of the Trial
      according to the terms and conditions of the Agreement; the earlier of the
      two.

                


        

      

    

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    


    
      
        
          
            	
                    

                  	
                    8
      Hartom St, Jerusalem Israel 97775

                    Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                    www.biocancell.com
      info@biocancell.com

                  


          

        

      

    

     

    
      
        
          
            
              
                
                  	
                          FDA

                          The
      Guidelines

                        	 
      	
                          
                            The
      United States of America Food and Drug
      Administration. 

                          

                          Ministry
      of Health guidelines entitled “Clinical
      Trials of Human Subjects”
      as may be amended and modified from time to time.

                        
	
                          The
      Helsinki Declaration

                        	 
      	
                          The
      1964 Declaration of Helsinki regarding the recommendations guiding
      physicians in bio-medical research involving human beings, as amended in
      Tokyo, 1975.

                        
	
                          ICH-GCP

                        	 
      	
                          Harmonized
      Tripartite Guideline for Good Clinical Practice as may be amended and
      modified from time to time.

                        
	
                          IND

                        	 
      	
                          Investigational
      New Drug Application (US code of Federal Regulations 21 CFR Part
      312).

                        
	
                          Inspector/s

                        	 
      	
                          Any
      inspecting body legally authorized to perform inspections in clinical
      trials, including, inter alia, the MOH. FDA or any other state regulated
      medical authority.

                        
	
                          Invention
      Rights

                        	 
      	
                          Any
      and all intellectual property rights, relating to the Trial Data or to the
      BioCancell Data, including, inter alia, the right to register and/or own
      any inventions stemming directly or indirectly from the Trial Data and/or
      the BioCancell Data. Without derogating from the generality of the above,
      the Invention Rights shall include, inter alia, parents, information,
      data,  know-how, formulas, concepts, tests, drawings,
      specifications, applications, designs and trade secrets, methodologies,
      engineering and manufacturing processes and research processes, stemming
      directly or indirectly from the BioCancell Data and/or the Trial
      Data.

                        
	
                          Investigator
      Brochure

                        	 
      	
                          A
      document, which is submitted along with the Trial Protocol to the relevant
      Helsinki Committee and FDA, and the content of which is outlined in the
      GCP Guidelines.

                        
	 	 	 
	
                          The
      Medical Center

                        	 
      	
                          Chaim
      Sheba Medical Center.

                        
	 	 	 
	
                          Medical
      Center Helsinki Committee Ministry of Health Approval

                        	 
      	
                          A
      committee appointed pursuant to the National Health Regulations and whose
      role is to approve any and all medical experiments on humans conducted by
      the Medical Center. Approval from the Director General of the Ministry of
      Health, or whomever he/she has delegated the authority to for this
      purpose, for the performance of the Trial at the Medical Center, according
      to the National Health Regulations and the
  Guidelines.

                        


                

              

            

          

        

      

    

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    


    
      
        
          
            	
                    

                  	
                    8
      Hartom St, Jerusalem Israel 97775

                    Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                    www.biocancell.com
      info@biocancell.com

                  


          

        

      

    

     

    
      
        	
                Ministry
      of Health / MOH

              	 
      	
                The
      Israeli Ministry of Health.

              
	
                National
      Health Regulations

              	 
      	
                Israel
      National Health Regulations (Clinical Trials on Human Subjects), 5741-1980
      as may be amended from time to time.

              
	
                Publications

              	 
      	
                All
      publications, manuscripts, abstracts and papers relating directly or
      indirectly to the subject matter of the Trial, and which were initiated or
      composed directly or indirectly, in whole or in part, by the Principal
      Investigator and/or by the Fund and/or by any of the Trial
      Personnel.

              
	
                The
      BioCancell Data

              	 
      	
                Any
      and all information provided by BioCancell or by the BioCancell Group to
      the Fund, Principal Investigator or any member of the Trial Personnel with
      regard to the Trial, including, without limitation, the Trial Protocol and
      the Investigator Brochure which shall be the sole property of the
      BioCancell Group.

              
	
                The
      BioCancell Group

              	 
      	
                The
      group of companies consisting of BioCancell Therapeutics, Inc and
      BioCancell Therapeutics Ltd.

              
	
                The
      Guidelines

              	 
      	
                Ministry
      of Health guidelines entitled “Clinical Trials of Human Subjects”
      as may be amended and modified from time to time.

              
	
                The
      Product(s)

              	 
      	
                DTA-H19/PEI

              
	
                The
      Reports

              	 
      	
                Any
      and all reports required by BioCancell, by any state regulated medical
      authority, or by any applicable laws, rules, regulations or
      guidelines.

              
	
                The
      Subjects

              	 
      	
                A
      group of persons chosen by the Principal Investigator to participate in
      the Trial and who signed a written informed consent for the participation
      in the Trial, all according to the criteria established in the Trial
      Protocol.

              
	
                The
      Trial Data

              	 
      	
                Any
      and all clinical data, technical information, records, files and materials
      relating to the Trial, including the Trial Documents, case report forms,
      (such as subjects charts and physical notes), as well as other related
      data generated during or as a result of the Trial which shall be the sole
      property of the BioCancell Group.

              
	
                Trial
      Documents

              	 
      	
                Any
      and all documents required by BioCancell, the MOH, the Fund
      or any applicable laws, rules, regulations or guidelines, for the
      initiation, performance and completion of the Trial; without derogating
      from the generality of the above, the Trial Documents shall include any
      and all documents specified in Appendix E to this
    Agreement.

              


      

    

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    


    
      
        
          
            	
                    

                  	
                    8
      Hartom St, Jerusalem Israel 97775

                    Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                    www.biocancell.com
      info@biocancell.com

                  


          

        

      

    

     

    
      
        	
                Trial
      Personnel

              	 
      	
                The
      medical and administrative staff involved in the Trial, including those
      who shall be employed by the Medical Center and/or the Fund and cleared
      according to the undertaking attached to this Agreement as Appendix
      B.

              
	
                The
      Trial

                Protocol

              	 
      	
                A
      document that describes the objective(s), design, methodology, statistical
      considerations, and organization of the Trial. The Trial Protocol usually
      also gives the background and rationale for the trial, but these could be
      provided in other protocol referenced documents. Throughout this Agreement
      the term Trial Protocol refers to the protocol and its amendments, which
      are attached to this Agreement as Appendix
A.

              


      

    

    


    
      	
              4.

            	
              Precedent
      Condition

            


    

    The
Parties hereby agree and undertake that the Agreement shall not enter into
effect before both of following cumulative approvals have been granted
(hereinafter: “the Approvals”):

    
      	
               
      

            	
              4.1.

            	
              The
      approval of the Trial Protocol by the Medical Center Helsinki Committee
      and the MOH, if such latter approval is required by the Guidelines;
      and

            


    

    
      	
               
      

            	
              4.2.

            	
              The
      approval of the Agreement in general, its budget and Appendix C in
      particular, by the MOH and the committee of engagement with commercial
      companies in accordance Section 9 of the Guidelines;
  and

            


    

    
      	
               
      

            	
              4.3.

            	
              The
      approval of the Trial Protocol, Investigator Brochure and related
      documents by the FDA

            


    

    


    
      	
              5.

            	
              The
      Principal Investigator

            


    

    
      	
               
      

            	
              5.1.

            	
              Zohar
      A. Dotan MD, PhD of the Medical Center (hereinafter: “the Principal
      Investigator”) has agreed to serve as the principal investigator of
      the Trial

            


    

    
      	
               
      

            	
              5.2.

            	
              The
      Principal Investigator undertakes to perform the Trial in compliance with
      the following: (a) the Trial Protocol, (b) the Guidelines, (c) the
      instructions and the terms specified in the approval of the Medical Center
      Helsinki Committee, (d) the ICH-GCP, (e) the Helsinki Declaration, (f) the
      applicable laws, rules and regulations regulating such studies which are
      applicable in Israel, (g) written instructions and prescriptions issued by
      BioCancell regarding the Trial and/or the Product; all as may be amended
      from time to time, and (h). the requirements in accordance with the FDA
      Form 1572 “Statement of Investigator.” Every PI at each site must sign
      this form for submission to the FDA

            


    

    
      	
               
      

            	
              5.3.

            	
              The
      Principal Investigator has declared that he holds the professional ability
      and credentials required for performing the Trial in accordance with the
      Trial Protocol and any applicable laws, rules, regulations and guidelines,
      all as detailed above.

            


    

    
      
        	
                 
      

              	
                5.4.

              	
                In
      the event that the Principal Investigator, for any reason whatsoever,
      shall be unable to conduct the Trial, or shall cease to be available for
      the performance of the undertakings set forth in this Agreement, the Fund
      shall use its best efforts to appoint, within 20 days, a successor
      investigator whose identity shall be approved in advance by BioCancell
      (the “Successor
      Investigator”). Such
      Successor Investigator shall undertake all the duties and responsibilities
      of the Principal Investigator as detailed in the Agreement. Should
      the Fund not be able to appoint a Successor Investigator, or if the
      appointed Successor Investigator is not acceptable by BioCancell, either
      party shall be entitled to terminate this Agreement forthwith and without
      further liability.

              


      

    

     

    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    


    
      
        
          
            	
                    

                  	
                    8
      Hartom St, Jerusalem Israel 97775

                    Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                    www.biocancell.com
      info@biocancell.com

                  


          

        

      

    

     

    
      
      

    

    
      	
               
      

            	
              5.5.

            	
              In
      the event of the replacement of the Principal Investigator, as described
      under this Section 5, the Principal Investigator shall have no claim
      towards BioCancell and/or the Fund and/or any third party acting on their
      behalf in direct or indirect connection with such
    replacement.

            


    

    


    
      	
              6.

            	
              Fund
      undertaking

            


    

    
      	
               
      

            	
              6.1.

            	
              The
      Fund represents that it has the requisite skills, knowledge, experience
      and human resources to undertake and conduct the Trial in accordance with
      the provisions of this Agreement

            


    

    
      	
               
      

            	
              6.2.

            	
              The
      Fund undertakes to perform the Trial in compliance with the following: (a)
      the Trial Protocol, (b) the Guidelines, (c) the instructions and the terms
      specified in the approval of the Medical Center Helsinki Committee, (d)
      the ICH-GCP, (e) the Helsinki Declaration, (f) the applicable laws, rules
      and regulations regulating such studies which are applicable
      in  Israel, and (g) written instructions and prescriptions
      issued by BioCancell regarding the Trial and/or the Product; all as may be
      amended from time to time.

            


    

    
      	
               
      

            	
              6.3.

            	
              The
      Medical Center hereby undertakes to furnish BioCancell, the Principal
      Investigator and all of the Trial Personnel with the facilities and
      personnel necessary for the adequate performance of the Trial according to
      the terms and conditions of the Trial Protocol, and to fully collaborate
      with the Principal Investigator, BioCancell, and/or any other third party
      nominated by BioCancell, with regard to performing its duties
      hereunder.

            


    

    


    
      	
              7.

            	
              BioCancell
      Undertaking

            


    

    
      	
               
      

            	
              7.1.

            	
              BioCancell
      hereby undertakes to allow the Principal Investigator to use the
      BioCancell Data, exclusively for the purpose of performing the Trial,
      during the Term of This Agreement and according to the terms and
      conditions of this Agreement.

            


    

    The
Principal Investigator shall strictly abide by any and all instructions given to
him by BioCancell with regard to the BioCancell Data, while recognizing that
BioCancell or any other company from the BioCancell Group was and shall remain,
during the Term of this Agreement and thereafter, the sole and exclusive owner
of any and all rights in the BioCancell Data and the Trial Data, and the use
thereof.

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      	
               
      

            	
              7.2.

            	
              BioCancell
      shall remunerate the Fund, according to the terms of Appendix C hereto,
      for all services rendered.

            


    

    


    
      	
              8.

            	
              Consideration

            


    

    In
consideration for the performance of all of the tasks, duties and undertakings
of the Principal Investigator, the Trial Personnel and the Fund under this
Agreement, BioCancell hereby undertakes to pay the Fund the amount specified in
Appendix C hereto, according to the installments, timetable and manner specified
therein.

    


    
      	
              9.

            	
              Product
      Supply

            


    

    
      	
               
      

            	
              9.1.

            	
              BioCancell
      will, at its own expense, supply to the Fund all necessary quantities of
      the drugs to be used in the Trial, and only for the purposes as described
      in the Protocol. Any surplus shall be returned to BioCancell without
      delay, upon completion of the Trial or termination of this agreement for
      any reason whichever is the
earlier.

            


    

    
      	
               
      

            	
              9.2.

            	
              The
      Fund will ensure that the Product is managed and stored in accordance with
      GCP and with any special instructions issued by BioCancell. The Fund will
      maintain proper records of receipts, dispensing and returns of the
      Product.

            


    

    
      	
               
      

            	
              9.3.

            	
              BioCancell
      will continue to supply the Product after the termination of the Trial
      and/or Agreement to the patients participating in the trial in accordance
      with Appendix D.

            


    

     

    
      	
              10.

            	
              Trial
      Personnel Compliance and Clearance

            


    

    
      	
               
      

            	
              10.1.

            	
              The
      Fund and the Principal Investigator hereby undertake to exercise their
      best efforts so that the Trial Personnel shall abide by: (a) the Trial
      Protocol, (b) the Guidelines, (c) the instructions and the terms specified
      in the approval of the Fund Helsinki Committee, (d) the ICH-GCP, (e) the
      Helsinki Declaration, (f) the applicable laws, rules and regulations
      regulating such studies which are applicable in Israel, and (g) written
      instructions and prescriptions issued by BioCancell regarding the Trial
      and/or the Product; all as may be amended from time to
    time.

            


    

    
      	
               
      

            	
              10.2.

            	
              The
      Trial will also be conducted in accordance with the “Statement of
      Investigator” (FDA form no. 1572).

            


    

    
      	
               
      

            	
              10.3.

            	
              Trial
      Personal Clearance:

            


    

    
      
        	
              	
                10.3.1.

              	
                The
      Fund and the Principal Investigator shall deploy all possible efforts to
      see to it that none of the Trial Personnel (including the Principal
      Investigator and any other investigators) are debarred by the FDA or by
      the MOH in any capacity whatsoever, and that (1) none of the Trial
      Personnel appear in the FDA debarment list, detailing all firms or persons
      debarred pursuant to Section 306 (a) and (b) of the Federal Food, Drug,
      and Cosmetic Act (21 U.S.C. 335 (a) and (b)), as published in the Federal
      Registrar from time to time; and (2) none of the Trial Personnel are
      debarred according to the terms and conditions of the Israeli Physicians
      Ordinance [New Version], 1976 or pursuant to any other applicable
      law.

              


      

    

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      
        	
              	
                10.3.2.

              	
                The
      Fund and the Principal Investigator shall provide BioCancell with the
      written confirmation thereof, in a form attached as Appendix B
      hereto.

              


      

    

     

    
      	
              11.

            	
              Compliance
      with the Trial Budget and Cooperation with BioCancell
      Sub-Contractors

            


    

    
      	
               
      

            	
              11.1.

            	
              The
      Fund and the Principal Investigator hereby undertake to perform the Trial
      in accordance with the budget of the Trial, as such term is derived from
      Appendix C hereto (hereinafter: “the Trial Budget”) and not to deviate therefrom without
      the prior written approval of BioCancell in relation
    thereto.

            


    

    
      	
               
      

            	
              11.2.

            	
              The
      Fund hereby undertakes that any deviation from the Trial Budget without
      the prior written consent of BioCancell shall be born by the
      Fund.

            


    

    
      	
               
      

            	
              11.3.

            	
              The
      Fund and the Principal Investigator hereby undertake to fully cooperate
      with any and all sub-contractors nominated by BioCancell for the purpose
      of the Trial, including, inter alia, clinical research organizations,
      logistics companies, laboratories,
etc.

            


    

    


    
      	
              12.

            	
              Trial
      Documents

            


    

    
      	
               
      

            	
              12.1.

            	
              The
      Principal Investigator shall prepare and submit the Trial
      Documents.

            


    

    
      	
               
      

            	
              12.2.

            	
              The
      Principal Investigator shall perform all the activities specified in
      Appendix E hereto.

            


    

    
      	
               
      

            	
              12.3.

            	
              Any
      and all amendments to the Trial Protocol shall be performed only after
      securing the approval of BioCancell and the competent regulatory
      authority.

            


    

    


    
      	
              13. 

            	
              Confidentiality

            


    

    
      	
               
      

            	
              13.1.

            	
              The
      Parties and the Principal Investigator hereby agree and undertake that
      they are aware that the BioCancell Data and the Trial Data (hereinafter,
      jointly and severally “the Confidential
      Information”) are
      confidential information, and that BioCancell has disclosed such
      Confidential Information to the Fund and Principal Investigator for the
      sole purpose of conducting the
Trial.

            


    

    
      	
               
      

            	
              13.2.

            	
              The
      Parties and the Principal Investigator hereby agree and undertake that
      they are aware that the Confidential Information is the sole and exclusive
      property of BioCancell and/or any other company from the BioCancell Group.
      Accordingly, The Principal Investigator shall retain the Confidential
      Information under the strictest safeguarding and not use, disclose or
      divulge the Confidential Information in part or in whole, directly or
      indirectly, for a period of seven (7)
years.

            


    

    
      
        	
                 
      

              	
                13.3.

              	
                The
      Fund and the Principal Investigator shall maintain the confidentiality of
      the Confidential Information using the same degree of care used by them in
      relation to their own confidential information, and shall, without
      limitation, keep the Confidential Information in a safe and separate place
      and not make any copies thereof (whether in hardcopy or electronic file)
      unless first receiving BioCancell’s written
  consent.

              


      



    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      
      

    

    
      	
            	
              13.4.

            	
              The
      Fund and the Principal Investigator hereby further undertake to limit
      access to the Confidential Information to the Trial Personnel and any
      third parties on a “need to know basis” only, and cause such Trial
      Personnel and third parties to accept, in writing, the undertaking of the
      Principal Investigator in relation to the Confidential Information under
      this Agreement, as a condition precedent for receipt of any part of the
      Confidential Information.

            


    

    
      	
            	
              13.5.

            	
              At
      the request of BioCancell, the Fund and the Principal Investigator shall
      forthwith return to BioCancell the Confidential Information or any part
      thereof.

            


    

    
      	
            	
              13.6.

            	
              The
      Fund and the Principal Investigator hereby state that they are aware of
      the fact that any unauthorized disclosure or use of the Confidential
      Information shall cause immediate and/or irreparable injury to BioCancell,
      and that BioCancell cannot be adequately compensated for such injury in
      monetary damages. Thus, in order to safeguard BioCancell from any possible
      breach of confidentiality, the Principal Investigator and the Fund hereby
      undertake that BioCancell would be permitted to obtain, from any Court or
      Tribunal, any temporary or permanent injunction relief, necessary to
      prevent such unauthorized disclosure or use or peril thereof, and hereby
      renounce filing and/or submitting any objection to any request by
      BioCancell or by any company from the BioCancell Group, relating to such
      temporary or permanent injunction.

            


    

    
      	
            	
              13.7.

            	
              For
      the avoidance of any doubt, it is hereby clarified that such an
      undertaking is supplementary to and will not prejudice any right or
      remedy, which is or shall be available to BioCancell under any applicable
      law or agreement.

            


    

    
      
        	 	13.8.	
                The
      Fund and the Principal Investigator hereby undertake to exercise their
      best efforts to see to it that the Trial Personnel shall abide by the
      undertakings set forth in this Section 13.

              
	
              	
                13.9.

              	
                In
      the event that the Fund and the Principal Investigator are required by
      law, regulation, rule, act or order of any governmental authority or
      agency to disclose Confidential Information, they shall be entitled to do
      so provided that it shall first notify BioCancell of any such required
      disclosure, so that BioCancell may seek an appropriate protective order,
      and limit such disclosure as far as is possible under applicable law. The
      Fund and the Principal Investigator will reasonably cooperate with
      BioCancell in its efforts to seek such a protective order. Such disclosure
      shall, however, not relieve the Fund and Principal Investigator of their
      other obligations contained
herein.

              


      

    

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      	
              14. 

            	
              Invention
      Rights

            


    

    
      	
            	
              14.1.

            	
              The
      Fund and the Principal Investigator hereby acknowledge that the idea and
      initiative for the Trial were exclusively those of BioCancell, and that
      the involvement of the Fund and the Principal Investigator in the Trial is
      strictly the consequence of their nomination by
  BioCancell.

            


    

    
      	
            	
              14.2.

            	
              The
      Parties and the Principal Investigator hereby irrevocably agree and
      undertake that the Confidential Information, except for medical records of
      the Subjects, is the exclusive property of BioCancell, may be freely
      utilized by BioCancell in any manner it sees fit. Notwithstanding the
      above, BioCancell shall have the right to review Subjects’ medical records
      to verify entries in the CRF’s.
      BioCancell hereby undertakes full responsibility to ensure the safekeeping
      of patients’ confidentiality and personal data and shall be fully
      responsible for taking every measure to apply this
    commitment.

            


    

    
      
        	
              	
                14.3.

              	
                The
      Parties and the Principal Investigator hereby irrevocably agree and
      undertake that the Invention Rights shall be the absolute and exclusive
      property of BioCancell and that BioCancell shall have unrestricted free
      right to use such Invention
Rights.

              


      

    

    
      
        	  	14.4. 	
                The
      Fund and the Principal Investigator hereby undertake to disclose to
      BioCancell any and all applicable information relating to Invention Rights
      and exercise their best efforts with regards to registration of the
      Inventions Rights on the name of BioCancell and/or a name designated in
      writing by BioCancell, if and to the extent requested to do so by
      BioCancell.

              
	
              	
                14.5.

              	
                If
      by operation of law or for any reason, any Invention Rights to be owned by
      BioCancell pursuant to this Section 14 are not automatically deemed
      proprietary BioCancell upon their creation, the Fund and the Principal
      Investigator hereby further undertake to cause the Trial Personnel to,
      irrevocably grant and assign all such intellectual property rights to
      BioCancell.

              


      

    

    


    
      	
              15. 

            	
              Inspections

            


    

    
      	
            	
              15.1.

            	
              The
      Fund and the Principal Investigator hereby, undertake to allow the
      Monitors to perform monitoring visits in all sites related to the Trial,
      during or after the Trial, and assist the Monitors in their duties. For
      the avoidance of doubt, it is hereby clarified that the Monitors shall be
      entitled to monitor and/or inspect among others the Trial Documents and
      Trial Data as well as to insure compliance with the Trial
      Protocol.

            


    

    
      	
            	
              15.2.

            	
              The
      Fund and the Principal Investigator hereby undertake to allow the
      Inspectors to perform inspections of all sites related to the Trial,
      during or after the Trial (and each such inspection shall hereinafter be
      referred to as: “an Inspection”), and to assist the Inspectors in their
      duties, if and to the extent requested to do so by the
      Inspectors.

            


    

    
      	
            	
              15.3.

            	
              The
      Fund and the Principal Investigator shall immediately inform BioCancell in
      the event of an Inspection and/or upon gaining knowledge of any intention
      to perform an Inspection. The Fund and the Principal Investigator shall
      provide BioCancell with copies of any inquiries, correspondence or
      communications to or from any such
Inspectors.

            


    

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      	
              16. 

            	
              Publications

            


    

    
      	
               
      

            	
              16.1 

            	
              BioCancell
      covenants that it will not at any time, without first obtaining the
      consent in writing of the Medical Center (which consent may by refused or
      granted in its absolute discretion), use the Medical Center’s name or the
      name of the Principal Investigator or otherwise disclose the fact of their
      involvement in the performance of the Trial in any advertising, publicity
      or publication. However, BioCancell may use the name of the Fund and/or
      the Principal Investigator for listing the Trial on
      clinicaltrials.gov.

            


    

    


    
      	
               
      

            	
              16.2 

            	
              Publication
      of the Trial and/or its results, in whole or in part, shall be within the
      sole and absolute discretion of BioCancell. The Fund, the Principal
      Investigator or the Trial Personnel, and any employees and/or officers
      and/or representatives of any of the foregoing shall not publish or refer
      to the Trial and/or its results, in whole or in part, without obtaining
      the prior consent BioCancell in writing. BioCancell reserves the right to
      reject any such request, at its sole discretion. For the avoidance of
      doubt BioCancell has the right, at all times, to publish any article or
      data generated from the services rendered under this Agreement. Without
      derogating from this Section 16, BioCancell hereby undertakes to abide by
      the rules of publications issued by the MOH and set forth in Section 2 of
      Appendix D attached hereto.

            


    

    


    
      	
              17. 

            	
              Reports

            


    

    
      	
              
              

            	
              17.1.

            	
              The
      Fund and the Principal Investigator hereby undertake to submit the Reports
      to BioCancell and/or to competent authorities, whether Israeli or
      foreign.

            


    

    
      	
              
              

            	
              17.2.

            	
              The
      Fund and the Principal Investigator hereby undertake to disclose in the
      Reports any and all data provided to them by BioCancell, in accordance
      with any applicable laws, rules, regulations and guidelines, including,
      inter alia, safety data.

            


    

    
      	
              
              

            	
              17.3.

            	
              The
      Fund will cause the Principal Investigator to provide BioCancell, within
      45 (forty five) days of the end of each period of three (3) months during
      the period of the Trial, with a written report on the progress of the
      Trial in the said period.

            


    

    
      	
              
              

            	
              17.4.

            	
              45
      (forty five) days following the End of the Trial, the Principal
      Investigator shall submit to BioCancell a summary report, which shall
      include, in a full and detailed manner, a declaration regarding the
      activities performed during the Trial and the results obtained
      therein.

            


    

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      	
              18.

            	
              Serious
      Adverse Event

            


    

    
      	
              
              

            	
              18.1.

            	
              In
      the event one or more of the Subjects sustains any Serious Adverse Event
      related to the Trial, the Principal Investigator shall inform BioCancell
      and the Fund Helsinki Committee and/or the Fund management and/or the
      authorized national health
authorities.

            


    

    
      	
              
              

            	
              18.2.

            	
              The
      Principal Investigator shall report such Serious Adverse Event in the
      timetable and manner prescribed in the Trial Protocol and
      Guidelines.

            


    

    
      	
              
              

            	
              18.3.

            	
              In
      the occurrence of a Serious Adverse Event the Principal Investigator and
      the Fund Helsinki Committee shall be entitled to immediately cease the
      performance of the Trial, pending a prior notice of at least 24 hours to
      BioCancell regarding such decision and its
  execution.

            


    

    
      	
              
              

            	
              18.4.

            	
              In
      the occurrence of a Serious Adverse Event BioCancell will immediately take
      all measures at their disposal to evaluate the risk to the other patients
      and will instruct the Principal Investigator which measures to take with
      regard to that risk.

            


    

    
      	
              
              

            	
              18.5.

            	
              BioCancell
      has an obligation, as the trial sponsor, to notify each investigator of
      any Serious Adverse Events that are reported by any site during the trial
      that are submitted to the FDA in a safety report. Each Principal
      Investigator is obligated to provide these reports to the appropriate
      Helsinki Committee.

            


    

    
      	
              
              

            	
              18.6.

            	
              For
      the removal of doubt it is hereby clarified that should patients
      participating in the study are or shall be hospitalized in the course of
      the Study, then the Company shall reimburse the fund for any and all
      hospitalization expenses and hospitalization related expenses (“Hospitalization
      Expenses”), provided, however, that the sick funds of the patients
      did not cover such expenses. The Hospitalization expenses shall be paid to
      the Fund according to a detailed account provided to the Company by the
      Fund, within 30 days for receipt of the account by the
      Company.

            


    

    
      
         

        
          	
                  19.

                	
                  The
      Legal Status of the Fund and the Principal
  Investigator

                


        

      

    

    
      	
              
              

            	
              19.1.

            	
              The
      Parties and the Principal Investigator hereby agree that the relationship
      between BioCancell, on one hand, and the Fund and the Principal
      Investigator, on the other hand, are that of a client and an independent
      contractor, with the Fund and the Principal Investigator lacking any
      capacity whatsoever to legally bind BioCancell to a relationship of
      employer-employee, principal-agent or any other legal relationship
      differing from that of a client and an independent
    contractor.

            


    

    


    
      	
              20.

            	
              Term
      and Termination

            


    

    
      	
              
              

            	
              20.1.

            	
              This
      Agreement shall be in full force and effect as of the latter of either:
      (a) the date of its execution by the last Party or (b) the date the
      Approvals have been granted; and until the End of the Trial (and the
      period in which this Agreement shall be in full force and effect shall be
      referred to in this Agreement as “the Term of this
      Agreement”).

            


    

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

     

    
      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      
        	
                
                

              	
                20.2.

              	
                The
      Parties may bring this Agreement to an early end at any time, in writing,
      by prior notice of at least 30 (thirty) days, upon the occurrence of one
      (or more) of the following
events:

              


      

    

    
      
        	
                
                

              	
                20.2.1.

              	
                The
      MOH has voided its approval granted for the performance of the Trial or
      has conditioned the approval by conditions which the Fund and/or the
      Principal Investigator, as the case may be, have notified BioCancell that
      they are unable to comply
with.

              


      

    

    
      
        	
                
                

              	
                20.2.2.

              	
                The
      FDA has placed the Trial on clinical
hold.

              


      

    

    
      
        	
                
                

              	
                20.2.3.

              	
                BioCancell
      decides upon its sole and absolute discretion to bring the Trial to an
      end. For the sake of good order, the Parties and the Principal
      Investigator hereby state and undertake that they are aware, and agree,
      that BioCancell is entitled to terminate this Agreement, upon its sole and
      absolute discretion, at any moment whatsoever; and in this case no party
      hereto shall have any claim whatsoever towards BioCancell and/or any other
      company from the BioCancell Group with regard to such early
      termination.

              


      

    

    
      
        	
                
                

              	
                20.2.4.

              	
                A
      Party and/or the Principal Investigator is found to be in breach of this
      Agreement and does not cure such breach within a period of 30 (thirty)
      days following receipt of a notice in writing from any of the other
      Parties in relation thereto.

              


      

    

    
      
        	
                
                

              	
                20.2.5.

              	
                A
      Party and/or the Principal Investigator enter into bankruptcy or
      liquidation proceedings or a receiver is appointed over part or all of
      their assets, and such proceedings are not ceased within a period of 45
      (forty five) days following receipt by such Party of a written notice in
      relation thereto from any or all of the other
  Parties.

              


      

    

    
      	
               
      

            	
              20.3.

            	
              In
      the event of termination of this agreement the Parties and the Principal
      Investigator shall bring the Trial to an end as
  follows:

            


    

    
      
        	
                
                

              	
                20.3.1.

              	
                Any
      and all Confidential Information and remaining supply of Product shall be
      returned to BioCancell.

              


      

    

    
      
        	
                
                

              	
                20.3.2.

              	
                The
      Parties and the Principal Investigator shall cooperate in swiftly
      dispersing the Subjects and Trial Personnel, if the need arises, while
      preserving the latest Trial Data and providing as many Completed CRF’s as
      possible, and all to the satisfaction of
  BioCancell.

              


      

    

    
      	
               
      

            	
              20.4.

            	
              The
      obligation of the Parties and the Principal Investigator pursuant to
      sections 13, 14, 16, 17, and 21 shall survive termination of this
      Agreement.

            


    

    


    
      	
              21.

            	
              Insurance
      and Indemnification

            


    

    
      	
               
      

            	
              21.1.

            	
              BioCancell
      has agreed to insure, in accordance with the terms and conditions set
      forth in Appendix D attached hereto, the Subjects, the Trial Personnel,
      the Principal Investigator and the
Fund.

            


    

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      	
              
              

            	
              21.2.

            	
              BioCancell
      has agreed to indemnify the Trial Personnel the Principal Investigator,
      Medical Center and the Fund according to the terms of Sub-Section 21.3
      below (hereinafter each of them shall also be referred to as: the “Indemnitee”) for damages arising as a direct result
      of their involvement in the performance of the Trial (hereinafter: the
      “Damages”), provided that the damages are not as
      a result of an expected side effect of the Products and subject to the
      conditions detailed herein:

            


    

    
      
        	
                
                

              	
                21.2.1.

              	
                The
      Damages are not caused as a result of negligence or misconduct of the
      Indemnitee;

              


      

    

    
      
        	
                
                

              	
                21.2.2.

              	
                The
      lndemnitee performed the Trial in accordance with the Trial Protocol and
      the additional requirements set in this
  Agreement;

              


      

    

    
      	
              
              

            	
              21.3.

            	
              Promptly
      after receipt by the Indemnitee of a notice of the commencement of any
      claim, action, suit, proceeding or investigation in respect of which
      indemnity may be sought pursuant to this Section 21 (hereinafter: the
      “Claim”), the Indemnitee
      shall provide a notice to BioCancell, in writing, describing in reasonable
      detail the facts and circumstances upon which the asserted Claim for
      indemnification is based, and shall thereafter keep BioCancell reasonably
      informed with respect thereto, BioCancell shall have the right to assume
      the defense of any Claim, at its sole discretion. In any event, the
      Indemnitee shall cooperate with BioCancell in the defense of any Claim for
      which BioCancell assumes the defense. BioCancell shall not be liable for
      the settlement by the lndemnitee of any Claim affected without the consent
      of BioCancell. BioCancell shall be entitled to enter into any settlement
      of a Claim at its sole discretion.

            


    

    


    
      	
              22.

            	
              Notices.

            


    

    
      	
              
              

            	
              22.1.

            	
              Notices
      to be given by one Party to another shall be in the English language, and
      shall be deemed properly given if reduced to writing and transmitted to
      the Party’s address appearing on the first page of this Agreement, by air
      courier or by certified registered mail - all to be effective 3 (three)
      days after their sending date, or by facsimile with confirmation receipt -
      to be effective at the first business day following the date of
      transmission.

            


    

    
      	
              
              

            	
              22.2.

            	
              However,
      a notice shall be considered properly given, only in case a copy thereof
      was communicated as follows:

            


    

    


    
      
        
          
            
              
                	
                        Notice
      to BioCancell

                      	
                        Notice
      to Fund

                      
	
                        BioCancell
      Therapeutics Ltd.

                      	
                        Medical
      Research Development and

                      
	
                        Beck
      Science Center, 8 Hartom St.

                      	
                        Health
      services

                      
	
                        Jerusalem,
      97775 Israel

                      	
                        Sheba
      Medical Center

                      
	
                        Attn:
      Ran Vigdor

                      	
                        Tel
      Hashomer, 52621 Israel

                      
	
                        Director,
      Strategic Alliances

                      	
                        Attn:
      Prof Shlomo Noy,

                      
	
                        Telephone:       
      +972-2-548-6555

                      	
                        Deputy
      Director for R&D

                      
	
                        Facsimile:         
      +972-2-548-6550

                      	
                        Tel:
      03-5305754

                      
	 	Fax:
      03-5303800


              

            

          

        

      

    

     

    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      	
            	
              22.3.

            	
              The
      addresses of the Parties, listed in page 1 of this Agreement, shall be
      subject to any change of such address notified in writing by one Party to
      the other, according to the procedure stipulated in this
      Section.

            


    

    


    
      	
              23.

            	
              Miscellanies

            


    

    
      	
            	
              23.1.

            	
              Expenses
      of the Parties. Each Party and the Principal Investigator shall bear all
      its own expenses, including the expenses of its attorneys, in connection
      with the negotiation, execution and performance of this
      Agreement.

            


    

    
      	
            	
              23.2.

            	
              Waiver
      and forbearance. No rights of any Party shall be prejudiced or restricted
      by any indulgence or forbearance, to any other person or entity, and no
      waiver by any Party in respect of any breach shall operate as a waiver in
      respect of any subsequent breach.

            


    

    
      	
            	
              23.3.

            	
              Governing
      law and jurisdiction. This Agreement shall be exclusively governed by the
      Laws of the State of Israel. Any and all disputes arising hereunder shall
      be resolved by a competent court having jurisdiction over such matters in
      the Tel-Aviv Jaffn District, Israel

            


    

    
      	
            	
              23.4.

            	
              Assignment.
      This Agreement shall not be assigned, without the prior written consent of
      all of the other Parties, save for an assignment of rights by BioCancell
      to any company within the BioCancell
Group

            


    

    
      	
            	
              23.5.

            	
              Counterparts.
      This Agreement and any amendment hereto may be executed in multiple
      counterparts, each of which shall be deemed an original agreement and all
      of which shall constitute one and the same
  agreement.

            


    

    
      	
            	
              23.6.

            	
              Amendments.
      Modification or amendment to this Agreement shall only be valid if
      performed by a written instrument, signed by all Parties to this
      Agreement.

            


    

    
      	
            	
              23.7.

            	
              Severability.
      If any provision of this Agreement is determined by a court of competent
      jurisdiction to be invalid, illegal, or unenforceable, that determination
      shall not affect any other provision of this Agreement, and each such
      other provision shall be construed and enforced as if the invalid,
      illegal, or unenforceable provision were not contained
    herein.

            


    

    


    [Remainder
of page left intentionally blank. Signature page follows.]

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    IN
WITNESS WHEREOF, the parties hereto have caused this Agreement to be duly
executed and each of the undersigned hereby warrants and represents that he or
she has been and is, on the date of this Agreement, duly authorized by all
necessary and appropriate action to execute this Agreement.

    


    IN
WITNESS WHEREOF, the parties have executed this Agreement as at the date first
above written:

    


    
      
        
          
            
              
                
                  
                    
                      
                        
                          
                            
                              
                                
                                  	
                                          BioCancell
      Therapeutics Ltd.

                                        	 
      	
                                          Medical
      Research Development and

                                          Health
      Services, Sheba Medical

                                          Center

                                        
	 
      	 
      	 
      	 
      	 
      
	
                                          By:

                                        	
                                          /s/
      Avi Barak

                                        	 
      	
                                          By:

                                        	/s/
      Prof. S. Noy, M.D. Ph.D
	 
      	 
      	 
      	 
      	 
      
	
                                          Print
      Name: Avi Barak

                                        	 
      	
                                          Print Name:

                                        	Prof.
      S. Noy, M.D. Ph.D 
	 
      	 
      	 
      	 
      
	
                                          Title:
      CEO

                                        	 
      	
                                          Title:

                                        	
                                          Head
      - R & D

                                          Sheba
      Medical Center

                                          Tel
      Hashomer Israel

                                        
	 
      	 
      	 
      	 
      	 
      
	
                                          By:

                                        	
                                          /s/
      Patricia Ohana

                                        	 
      	
                                          By:

                                        	[Illegible]
	 
      	 
      	 
      	 
      	 
      
	
                                          Print
      Name: Patricia Ohana

                                        	 
      	
                                          Print Name:

                                        	[Illegible]
	 
      	 
      	 
      	 
      
	
                                          Title:
      VP Clinical Development

                                        	 
      	
                                          Title:

                                        	[Illegible]
	 	 	 	 
	 	 	 	14.7.08 


                                

                              

                            

                          

                        

                      

                    

                  

                

              

            

          

        

      

    

     

    I the
undersigned, Zohar A. Dotan, hereby declare and confirm that I have read and
understood the Agreement. I hereby agree to be appointed as the Principal
Investigator of the Trial on behalf of the Fund, and accept and undertake to
comply with all the terms, conditions, provisions, instructions and stipulations
set forth in the Agreement, including, without limitation, provisions referring
to the Parties.

    


    
      
        
          	/s/
      Z. A. Dotan
	
                  The
      Principal Investigator

                


        

      

    

     

    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

      Appendix
A

    

    


    The Trial
Protocol

    See attached
separately

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    Appendix
B

    


    The Trial Personnel
Clearance

    An
Undertaking with regard to a Clinical Trial’s Personnel

    


    We, the
undersigned, hereby warrant and undertake in relation of clinical trial bearing
protocol number BC-07-01, researching “Phase 2b, Multicenter Trial of
Intravesical DTA-H19/PEI in Patients with Intermediate-Risk Superficial Bladder
Cancer”, that we have not, we do not and we will not use nor employ, in any
capacity, the services of any person debarred under Section 306 (a) or (b) of
the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 335 (a) and (b)), or
debarred under the Israeli Physicians Ordinance [New Version], 1976 or pursuant
to any other applicable law.

    


    
      
        
          	
                  /s/ Z. A.
      Dotan

                	 
      	
                  Prof. S. Noy, M.D. Ph.D

                  
                    Head
      - R & D

                    Sheba
      Medical Center

                    Tel
      Hashomer Israel

                  

                
	
                  The
      Principal Investigator

                	 
      	
                  The
      Fund

                


        

      

    

    


    
      
        
          	
                  14.2.08

                
	
                  Date

                


        

      

    

     

    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

      Appendix
C

    

    


    The
Consideration

    


    
      	
              1.

            	
              Terms
      and Definitions

            


    

    In this
Appendix C terms shall have the meaning assigned to them in the Agreement.
The following terms shall have the meanings assigned to them
hereunder:

    
      
        	
                Complete

                Screening

              	 	
                A
      Screening of a Subject in which all examinations and/or tests and/or
      treatment and/or evaluations included in the Screening process, as
      detailed in the Trial Protocol, have been performed and the data collected
      and registered in the CRF

              
	
                Complete

                Evaluation
      Visit

                or
      Complete

                Treatment
      Visit

              	 	
                A
      Visit of a Participating Subject in which all examinations and/or tests
      and/or treatment and/or evaluations scheduled for the visit have been
      performed, as detailed in the Trial Protocol, and the data collected and
      registered in the CRF

              
	
                Evaluation
      Visit

              	 	
                Any
      Visit, as defined below, of visits 7, 11, 15, and 19 as these visits are
      numbered and defined in the Trial Protocol.

              
	
                Participating

                Subject

              	 	
                A
      Subject who that has undergone Screening, as defined below, and was
      determined to meet the requirements specified in the Trial protocol and
      who is participating in the Trial according to the terms and conditions of
      the Trial Protocol

              
	
                Screening

              	 	
                A
      series of tests and examinations as defined in table 4 of the Trial
      Protocol designed to evaluate a Subject’s suitability for participating in
      the Trial, as detailed in the Trial Protocol.

              
	
                Treatment
      Visit

              	 	
                Any
      Visit, as defined below, of visits 1-6, 8-10, 12-14, and 16-18 as these
      visits are numbered and defined in the Trial Protocol.

              
	
                Visit

              	 	
                Any
      one of the scheduled nineteen (19) visits of a Participating Subject as
      detailed in table 4 and 5 of the Trial
Protocol.

              


      

    

    


    
      	
              2.

            	
              The
      Consideration

            


    

    
      	
               
      

            	
              2.1.

            	
              In
      consideration for the performance, in good faith, by the Principal
      Investigator and the Fund, of all of their undertakings
      under  this Agreement, BioCancell hereby undertakes to pay to
      the Fund the following amounts:

            


    

     

    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      
        
          
            
              
                
                  
                    
                      
                        
                          
                            
                              
                                
                                  
                                    
                                      
                                        	
                                                Visit
      #

                                              	 	
                                                Procedure

                                              	 	
                                                Total
      costs per

                                                visit
      (NIS)

                                              
	
                                                Screening

                                              	 	
                                                Urine
      cytology

                                                Video
      cystoscopy

                                                Histology
      & Pathology

                                                Doctor’s
      fee

                                                Study
      nurse

                                                Study
      coordinator

                                                TUR

                                              	 	
                                                3,150

                                              
	 	 	 	 	 
	
                                                Visit
      # 1

                                              	 	
                                                 

                                                Doctor’s
      fee

                                                Study
      nurse (Drug administration & blood sampling)

                                                Study
      coordinator

                                              	 	
                                                1,250

                                              
	 	 	 	 	 
	
                                                Visit
      # 2

                                              	 	
                                                 

                                                Doctor’s
      fee

                                                Study
      nurse (Drug administration & blood sampling)

                                                Study
      coordinator

                                              	 	
                                                1,250

                                              
	 	 	 	 	 
	
                                                Visit
      # 3

                                              	 	
                                                 

                                                Doctor’s
      fee

                                                Study
      nurse (Drug administration & blood sampling)

                                                Study
      coordinator

                                              	 	
                                                1,250

                                              
	 	 	 	 	 
	
                                                Visit
      # 4

                                              	 	
                                                 

                                                Doctor’s
      fee

                                                Study
      nurse (Drug administration & blood sampling)

                                                Study
      coordinator

                                              	 	
                                                1,250

                                              
	 	 	 	 	 
	
                                                Visit
      # 5

                                              	 	
                                                 

                                                Doctor’s
      fee

                                                Study
      nurse (Drug administration & blood sampling)

                                                Study
      coordinator

                                              	 	
                                                1,250

                                              
	 	 	 	 	 
	
                                                Visit
      # 6

                                              	 	
                                                 

                                                Doctor’s
      fee

                                                Study
      nurse (Drug administration & blood sampling)

                                                Study
      coordinator

                                              	 	
                                                1,250

                                              
	 	 	 	 	 
	
                                                Visit
      # 7

                                              	 	
                                                Urine
      cytology

                                                Video
      cystoscopy

                                                Histology
      & Pathology

                                                Doctor’s
      fee

                                                Study
      nurse

                                                Study
      coordinator

                                                TUR

                                              	 	
                                                2,650

                                              
	 	 	 	 	 
	
                                                13,300

                                              	 	 
      	 	 
      


                                      

                                    

                                  

                                

                              

                            

                          

                        

                      

                    

                  

                

              

            

          

        

      

    

     

    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      
        
          
            
              
                
                  
                    
                      
                        
                          
                            
                              
                                	
                                        Visit
      # 8

                                      	 	
                                         

                                        Doctor’s
      fee

                                        Study
      nurse (Drug administration & blood sampling)

                                        Study
      coordinator

                                      	 	
                                        1,250

                                      
	 	 	 	 	 
	
                                        Visit
      # 9

                                      	 	
                                         

                                        Doctor’s
      fee

                                        Study
      nurse (Drug administration & blood sampling)

                                        Study
      coordinator

                                      	 	
                                        1,250

                                      
	 	 	 	 	 
	
                                        Visit
      # 10

                                      	 	
                                         

                                        Doctor’s
      fee

                                        Study
      nurse (Drug administration & blood sampling)

                                        Study
      coordinator

                                      	 	
                                        1,250

                                      
	 	 	 	 	 
	
                                        Visit
      # 11

                                      	 	
                                        Urine
      cytology

                                        Video
      cystoscopy

                                        Doctor’s
      fee

                                        Study
      nurse

                                        Study
      coordinator

                                      	 	
                                        1,510

                                      
	 	 	 	 	 
	
                                        Visit
      # 12

                                      	 	
                                         

                                        Doctor’s
      fee

                                        Study
      nurse (Drug administration & blood sampling)

                                        Study
      coordinator

                                      	 	
                                        1,250

                                      
	 	 	 	 	 
	
                                        Visit
      # 13

                                      	 	
                                         

                                        Doctor’s
      fee

                                        Study
      nurse (Drug administration & blood sampling)

                                        Study
      coordinator

                                      	 	
                                        1,250

                                      
	 	 	 	 	 
	
                                        Visit
      # 14

                                      	 	
                                         

                                        Doctor’s
      fee

                                        Study
      nurse (Drug administration & blood sampling)

                                        Study
      coordinator

                                      	 	
                                        1,250

                                      
	 	 	 	 	 
	
                                        Visit
      # 15

                                      	 	
                                        Urine
      cytology

                                        Video
      cystoscopy

                                        Doctor’s
      fee

                                        Study
      nurse

                                        Study
      coordinator

                                      	 	
                                        1,510

                                      
	 	 	 	 	 
	
                                        Visit
      # 16

                                      	 	
                                         

                                        Doctor’s
      fee

                                        Study
      nurse (Drug administration & blood sampling)

                                        Study
      coordinator

                                      	 	
                                        1,250

                                      


                              

                            

                          

                        

                      

                    

                  

                

              

            

          

        

      

    

     

    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      
        
          
            
              
                
                  
                    
                      
                        
                          	
                                  Visit
      # 17

                                	 	
                                   

                                  Doctor’s
      fee

                                  Study
      nurse (Drug administration & blood sampling)

                                  Study
      coordinator

                                	 	
                                  1,250

                                
	 	 	 	 	 
	
                                  Visit
      # 18

                                	 	
                                   

                                  Doctor’s
      fee

                                  Study
      nurse (Drug administration & blood sampling)

                                  Study
      coordinator

                                	 	
                                  1,250

                                
	 	 	 	 	 
	
                                  Visit
      # 19

                                	 	
                                  Urine
      cytology

                                  Video
      cystoscopy

                                  Doctor’s
      fee

                                  Study
      nurse

                                  Study
      coordinator

                                	 	
                                  1,150

                                
	 	 	 	 	 
	
                                  Total
      per continued treatment period (if no recurrence)

                                	 	 
      	 	
                                  15,780

                                
	 	 	 	 	 
	
                                  Total
      per first treatment period & continued treatment
period

                                	 	 
      	 	
                                  29,080

                                
	 	 	 	 	 
	
                                  General

                                	 	
                                  Unscheduled
      Video cystoscopy

                                	 	
                                  370

                                
	 	 	 	 	 
	
                                  General

                                	 	
                                  Unscheduled
      TUR

                                	 	
                                  960

                                
	 	 	 	 	 
	
                                  Pharmacy

                                	 	 
      	 	
                                  500
      US
$

                                


                        

                      

                    

                  

                

              

            

          

        

      

    

    


    * Blood
work and Urine analysis will be perform by an external central Lab (the costs
will be covered by the sponsor).

    


    
      	
              3.

            	
              Limitation
      of Payments

            


    

    
      	
               
      

            	
              3.1.

            	
              For
      the avoidance of doubt, it is hereby declared and agreed that BioCancell
      shall not pay any additional payments or any other amounts, which are not
      clearly mentioned and specified in section 2
  above.

            


    

    
      	
               
      

            	
              3.2.

            	
              It
      is further clarified that the amounts specified in section 2 above include
      payment by BioCancell for all services rendered from the Fund including
      but not limited to office services, Trial Personal required for performing
      the Trial including the Principal Investigator, physicians, nurses,
      receptionists and study coordinator, use of the Fund’s facilities, and all
      tests, procedures, examinations and evaluations as detailed in the Trial
      protocol.

            


    

    
      	
               
      

            	
              3.3.

            	
              The
      considerations do not include cost of analysis of hematology and chemistry
      samples which will be performed by BioCancell’s
      sub-contractor/s.

            


    

     

    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      	
              4.

            	
              Terms
      of Payment

            


    

    
      	
               
      

            	
              4.1.

            	
              The
      Fund shall send an invoice at the end of each calendar quarter (31/3,
      30/6, 30/9, and 31/12) detailing the Complete Screening, Complete
      Treatment Visits and Complete Evaluation Visits (together hereinafter:
      “Complete Visits”)
      performed as well as on which Subjects or Participating Subjects the
      relevant Complete Visit was
performed.

            


    

    
      	
               
      

            	
              4.2.

            	
              Payments
      detailed in section 2 shall be conditioned upon payment for Complete
      Visits and shall be included in the first invoice sent by the
      Fund.

            


    

    
      	
               
      

            	
              4.3.

            	
              Payment
      shall be maid by BioCancell within 30 (thirty) days of receipt of the
      Fund’s invoice.

            


    

    
      
        	
                 
      

              	
                4.4.

              	
                All
      Payments shall be performed in the last day of the calendar year during
      which the relevant payment date occurred. (Occurrence of the relevant
      payment date shall be at the termination and completion of the stage and
      conditions of which entitles the Fund for payment according to this
      Appendix C).

              
	 	4.5	Immediately
      upon receiving the payment as per the issued invoice the Fund will provide
      BioCancell with a receipt approving the
payment.


      

    

    


    
      	
              5.

            	
              Currency
      of Payments

            


    

    All of
the payments subject of this Appendix C shall be performed by BioCancell to the
Fund in NIS (New Israel Shekel).

    


    
      	
              6.

            	
              General
      Observations and Clarifications

            


    

    For the
sake of good order it is hereby clarified that, unless otherwise agreed upon in
writing by BioCancell:

    
      	
               
      

            	
              6.1.

            	
              No
      payment would be performed for any activities performed by the Principal
      Investigator and/or by the Fund, prior to the commencement of the
      Trial.

            


    

    
      	
               
      

            	
              6.2.

            	
              Without
      derogating from any right of BioCancell, in the event that no Completed
      CRF’s are provided to BioCancell, regarding a Subject, in relation to
      which BioCancell has performed payments to the Fund, BioCancell shall be
      entitled to perform one of the following three, according to its absolute
      discretion:

            


    

    
      
        	
              	
                6.2.1.

              	
                Write-off
      the amount paid by BioCancell in relation to Subject(s) for which no
      Completed CRF’s have been provided (hereinafter: “the Return Amount”) from
      the amount remaining due to the Fund by BioCancell according to this
      Agreement (hereinafter: “the Remaining
      Amount”)

              


      

    

    
      
        	
              	
                6.2.2.

              	
                Order
      the Fund, in writing, to pay BioCancell the Return Amount within a period
      no longer than 45 (forty-five) days from the End of the Trial. The Fund
      hereby undertakes that it shall pay the Return Amount, as specified above,
      and renounces any contentions and/or claims whatsoever in relation
      thereto.

              


      

    

    
      
        	
              	
                6.2.3.

              	
                In
      the event that the Return Amount shall exceed the Remaining Amount,
      BioCancell shall be entitled to exercise its rights under the above
      sub-sections 6.3.1 and 6.3.2 in concert, to the extent that BioCancell
      shall fully collect the Return Amount from the
  Fund.

              


      

    

    
      	
               
      

            	
              6.3.

            	
              No
      advance payments would be performed by BioCancell to the
    Fund.

            


    

     

    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

      Appendix
D

    

    


    Schedule
4 of the Guidelines

    


    
      
        	
                Title
      of the trial: “Phase 2b, Multicenter Trial of Intravesical DTA-H19/PEI in
      Patients with Intermediate-Risk Superficial Bladder
  Cancer”

              
	
                The
      protocol name and number: BC-07-01

              
	 
      
	
                Name
      of the investigational product: DTA-H19/PEI

              
	 
      
	
                Name
      of the Principal Investigator:

              	
                Department:

                Urology

              
	
                Name
      of the medical institution:

              
	
                The
      Sponsor’s name and address: BioCancell Therapeutics Ltd., Beck Science
      Center, 8
      Hartom St., Jerusalem 97775,
Israel

              


      

    

    


    
      	
              1.

            	
              Sponsor
      undertaking

            


    

    The
Sponsor undertakes to act in accordance with the local and international law for
clinical trials, and in particular with regard to the following
issues:

    
      	
               
      

            	
              1.1.1.

            	
              Responsibility
      for the safety and good order of the investigational
    product;

            


    

    
      	
               
      

            	
              1.1.2.

            	
              Supply
      of information regarding the trial;

            


    

    
      	
               
      

            	
              1.1.3.

            	
              Notice
      to the Ministry of Health regarding the performance of a multicenter trial
      in Israel;

            


    

    
      	
               
      

            	
              1.1.4.

            	
              Monitoring
      the trial process;

            


    

    
      	
               
      

            	
              1.1.5.

            	
              Safety
      reports;

            


    

    
      	
               
      

            	
              1.1.6.

            	
              Accountability
      in respect of the investigational
product;

            


    

    
      	
               
      

            	
              1.1.7.

            	
              Retention
      of documents.

            


    

    


    
      	
              2.

            	
              The
      Sponsor undertakes that if it shall decide to publish the results of the
      clinical trial in scientific literature, it shall publish them in full and
      without taking matters out of their
context.

            


    

    


    
      
        	
                3.

              	
                Insurance:

              


      

    

    
      	
               
      

            	
              3.1.

            	
              The
      Sponsor undertakes to insure its legal liability pursuant to the laws of
      the State of Israel against claims that may be filed by subjects in the
      clinical trial and/or third party claims - all in connection with the
      clinical trial, whether in the period of conducting the clinical trial or
      thereafter. The insurance shall be extended to include the legal liability
      of the medical institution and/or the clinical trial personnel and/or the
      Principal Investigator (hereinafter referred to as “the parties conducting the
      trial”) deriving from their involvement in the conduct of the
      clinical trial, subject to an exception of an act committed negligently or
      an intentional deviation from the clinical trial
  protocol.

            


    

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      	
               
      

            	
              3.2.

            	
              The
      Sponsor shall be given notice of any claim or any potential claim
      immediately after such comes to the knowledge of the medical institution
      or the Principal Investigator.

            


    

    
      	
               
      

            	
              3.3.

            	
              The
      Principal Investigator, the medical institution and its employees shall
      give the Sponsor, upon its written request, reasonable support in any
      event of a claim that may be filed against it as
  aforesaid.

            


    

    


    
      	
              4.

            	
              The
      Sponsor undertakes to supply the medical institution with the
      investigational product throughout the period of the clinical trial until
      the conclusion thereof, free of charge. Furthermore, the Sponsor
      undertakes to pay all additional costs deriving from the conduct of the
      clinical trial, provided that such costs do not derive from the regular
      medical treatment of the sickness.

            


    

    


    
      	
              5.

            	
              If
      after the termination of the clinical trial it is ascertained and
      recommended by the Principal Investigator that the welfare of the patient
      participating in the clinical trial necessitates continuation of his
      treatment with the investigational product and there is no other
      appropriate alternative medical treatment, the Sponsor undertakes to also
      continue supplying the investigational product, without charge, after the
      termination of the clinical trial for a period of three years, except in
      one of the following cases:

            


    

    
      	
               
      

            	
              5.1.

            	
              The
      investigational product was approved for marketing in the State of Israel
      after its registration for its requested scope and it can be obtained from
      the sick fund with which the patient is
insured.

            


    

    
      	
               
      

            	
              5.2.

            	
              The
      development of the product was discontinued or the results of the clinical
      trials were unsuccessful.

            


    

    
      	
               
      

            	
              5.3.

            	
              The
      administration of the investigational product for the said protracted
      period is likely to harm the patient’s health, since there is insufficient
      information regarding the safety of the product administered over the long
      term.

            


    

    
      	
               
      

            	
              5.4.

            	
              Where
      the investigational product is not a medical preparation, such as:
      cosmetic products / food / food additive / herbal
  remedy.

            


    

    


    The
decision as to the continuation of administering the investigational product is
given to the medical institution’s Helsinki Committee (“the Helsinki
Committee”), that is entitled to
re-examine its determination from time to time. The Principal Investigator and
the Sponsor have a right of appeal against such decision to the Ministry of
Health’s director-general or such person as empowered by him in such
regard.

    


    
      	
              6.

            	
              The
      continued administration of the investigational product after termination
      of the clinical trial is subject to the following terms and
      conditions:

            


    

    
      	
               
      

            	
              6.1.

            	
              The
      continued treatment shall be given within the context of an orderly
      monitoring protocol that shall be written by the Principal Investigator
      and approved by the Sponsor and the Helsinki
  Committee.

            


    

    


    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      	
               
      

            	
              6.2.

            	
              The
      Principal Investigator is responsible for continuing to routinely monitor
      the subject’s medical condition and to report to the Helsinki Committee
      any exceptional events that occur during the ongoing treatment, as is the
      norm in clinical trials.

            


    

    The
principal investigator shall report to the Helsinki Committee at least once a
year as to the progress of the subject’s treatment.

    The
medical institution in which the ongoing treatment shall be given shall attend
to appropriate insurance cover for the liability of the medical institution and
the Principal Investigator vis-a-vis the patient, in respect of the continuation
of administering the investigational product after the termination of the
clinical trial.

     

    
      	
              7.

            	
              This
      Appendix constitutes an integral part of the agreement between the company
      sponsoring the clinical trial and the medical
  institution.

            


    

    


    
      
        
          
            
              
                
                  
                    
                      
                        
                          
                            
                              
                                
                                  	
                                          BioCancell
      Therapeutics Ltd.

                                        	 
      	
                                          Sheba
      Medical Center, Tel Hashomer

                                        
	 
      	 
      	 
      	 
      	 
      
	
                                          By:

                                        	
                                          /s/
      Avi Barak

                                        	 
      	
                                          By:

                                        	
                                          /s/
      Prof. S. Noy, M.D. Ph.D

                                        
	 
      	 
      	 
      	 
      	 
      
	
                                          Print
      Name: Avi Barak

                                        	 
      	
                                          Print Name:

                                        	
                                          Prof.
      S. Noy, M.D. Ph.D

                                        
	 
      	 
      	 
      	 
      
	
                                          Title:
      CEO

                                        	 
      	
                                          Title:

                                        	
                                          Head
      - R & D

                                          Sheba
      Medical Center

                                          Tel
      Hashomer Israel

                                        
	 
      	 
      	 
      	 
      	 
      
	
                                          By:

                                        	
                                          /s/
      Patricia Ohana

                                        	 
      	
                                          By:

                                        	 
      
	 
      	 
      	 
      	 
      	 
      
	
                                          Print
      Name: Patricia Ohana

                                        	 
      	
                                          Print Name:

                                        	 
      
	 
      	 
      	 
      	 
      
	
                                          Title:
      VP Clinical Development

                                        	 
      	
                                          Title:

                                        	 
      
	 	 	 	 
	 	 	 	14.2.08


                                

                              

                            

                          

                        

                      

                    

                  

                

              

            

          

        

      

    

    


    I the
undersigned,   
Z. A. Dotan     , hereby declare and confirm that I
have read and understood this Appendix D.

    


    
      
        
          	      
                  /s/ Z. A. Dotan
      

                
	
                  The
      Principal Investigator

                


        

      

    

     

    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    Appendix
E

    


    The Trial Documents and
Related Activities

    


    The Trial
Documents shall include, inter alia, all the documents set forth in the
Guidelines, as well as the documents specified hereunder.

    


    Any and
all terms not specifically defined in this Appendix shall have the meaning
attributed to them in the Agreement.

    


    Prior
to the initiation of the Trial:

    
      	
              1.

            	
              The
      executed signature page of the Trial Protocol;
  and

            


    

    
      	
              2.

            	
              Investigator
      Brochure; and

            


    

    
      	
              3.

            	
              The
      current curriculum vitae of the Principal Investigator;
  and

            


    

    
      	
              4.

            	
              The
      list of all sub-investigators, all of which necessarily being listed on
      either the FDA form no. 1572, or on the Principal Investigator’s Statement
      Form; and

            


    

    
      	
              5.

            	
              The
      written approval of the Medical Center Helsinki Committee, indicating that
      it has reviewed and approved the Trial Protocol;
  and

            


    

    
      	
              6.

            	
              The
      written approval of the MOH with regards to the content of all publicity
      and advertisements, related to the Trial, which are to be performed prior
      to the commencement of the Trial;
and

            


    

    
      	
              7.

            	
              A
      list of all participants in the Helsinki Committee, convened in relation
      to the Trial (hereinafter: “the Helsinki
      Committee”);
      and

            


    

    
      	
               
      

            	
              7.1.

            	
              Should
      the Principal Investigator be a member of the Helsinki Committee, the
      written Statement of the chairman of the Helsinki Committee confirming
      that the Principal Investigator did not participate in the voting,
      relating to the Trial, during the hearing of the said Helsinki Committee;
      and

            


    

    
      	
               
      

            	
              7.2.

            	
              A
      financial disclosure form, confirming that the Principal Investigator
      holds no financial interests in
BioCancell.

            


    

    


    While
conducting the Trial:

    
      	
              1.

            	
              A
      review of all the Trial Documents and verification the accuracy and
      completeness thereof in relation to the source documents, on which the
      above documents were based; and

            


    

    
      	
              2.

            	
              Report
      to the Medical Center Helsinki Committee of any Severe Adverse Events, as
      such terms are defined in the Trial Protocol, to the Subject(s), in
      accordance with the Guidelines; and

            


    

    
      	
              3.

            	
              Report
      to the Medical Center Helsinki Committee of any deviation from the Trial
      Protocol; and

            


    

    
      	
              4.

            	
              Maintain
      adequate records of Subjects identification, clinical observations, as
      well as study drug receipt and dispensation (hereinafter: “the Records”), in
      accordance with any applicable laws, rules, regulations and guidelines, as
      amended from time to time. In any event, the Principal Investigator and
      BioCancell shall maintain the Records for a period of no less than 15
      (fifteen) years following the end of the
Trial.

            


    

     

    
      
        
           


        

        
           


          
            

          

        

        
           


        

      

    

    
      


      
        
          
            
              	
                      

                    	
                      8
      Hartom St, Jerusalem Israel 97775

                      Phone:
      +972-2-548-6555 Fax: +972-2-548-6550

                      www.biocancell.com
      info@biocancell.com

                    


            

          

        

      

       

    

    
      	
              5.

            	
              Compare
      the data in the CRF with the source documents relating to each subject
      participating in the Trial, and confirm the accuracy of the CRF;
      and

            


    

    
      	
              6.

            	
              Maintain
      a log, documenting the Product(s) provided to each subject during the
      Trial; and

            


    

    
      	
              7.

            	
              Report
      no later than 7 (seven) days before additional quantities of Product(s)
      are required to proceed with the
Trial.

            


    

    
      	
              8.

            	
              Complete
      all CRFs

            


    

    
      	
              9.

            	
              Re-validate
      the approval of the relevant Helsinki Committee to the Trial, within a
      reasonable time prior to its expiration
date.

            


    

    
      	
              10.

            	
              A
      written detailed periodic report on the progress of the Trial in the said
      period (section 17.3 of the
Agreement).

            


    

    


    At
the end of the Trial:

    
      	
              1.

            	
              All
      Completed CRFs;

            


    

    
      	
              2.

            	
              A
      summary report, which shall include, in a full and detailed manner, a
      declaration regarding the activities performed during the Trial and the
      results obtained therein (section 17.4 of the
  Agreement).