Document:

Exhibit 4.18 

     

      

    
      
        	
                EXECUTION COPY

              

      

      

        Pursuant to Instruction 4(a) as to Exhibits of Form 20-F, certain identified information (marked by [*]) has been excluded from the exhibit because it is both not material and is the type that the
          registrant treats as private or confidential.

      

      

      

      AMENDMENT NO. 1 TO MASTER CLINICAL TRIAL
          COLLABORATION AGREEMENT

      

      

      THIS AMENDMENT NO. 1 TO MASTER CLINICAL TRIAL COLLABORATION AGREEMENT (this “Amendment”) is effective as of February 14, 2020 (“Amendment Effective Date”) by and between Compugen

          Ltd., an Israeli corporation with a place of business at Azrieli Center, 26 Harokmim Street, Building D, Holon 5885849, Israel (“Compugen”), and Bristol-Myers Squibb
          Company, a Delaware corporation, headquartered at 430 E. 29th Street, 14FL, New York, N.Y. 10016 (“BMS”).

       

      BACKGROUND

       

      A.          BMS and Compugen entered into that certain Master Clinical Trial Collaboration Agreement, dated as of October
          10, 2018 (the “Agreement”).

      

      

      B.          The Parties have mutually agreed to amend the Agreement as follows in accordance with
          Section 13.7 of the Agreement.

       

      NOW, THEREFORE, in consideration of the mutual covenants and undertakings contained herein, and on the terms and subject to the
        conditions set forth herein, the Parties hereby agree as follows:

      

      

      1.          Capitalized terms used and not otherwise defined herein shall have the meaning given to
          such terms in the Agreement.

       

      
        
          	

                	2.	
                   Section 1.34 shall be deleted in its entirety from the Agreement.

                

        

      

      

      

      3.          The definition of “Exclusive Collaboration Period” as set forth in Section 1.48 is hereby amended and restated
          in its entirety as follows:

       

      
        
          
            	“1.48	

                  	
                    
                      “Exclusive Collaboration Period” means the period commencing on the Effective Date and ending on the earliest of:

                    

                  

          

        

        

        

      

      
        
          	

                	(a)	
                  six (6) months after Study Completion of the Triple Study as set forth in Study Plan No. 2; or

                

        

      

       

      
        
          	

                	(b)	
                  the effective date of termination of this Agreement pursuant to Section 12.2, Section 12.3 or Section 12.4.”

                

        

      

      

      

      4.          Study Plan No. 1 previously attached to the Agreement is hereby replaced with the revised
          Study Plan No. 1 attached as Attachment A hereto.

       

      5.          Clause (a) of Exhibit E to the Agreement is hereby amended and restated in its entirety as follows:

       

      

      
        
          

      

      
      
        
          	
                  EXECUTION COPY

                

        

      

       

        

      “Neither Party is obligated to conduct additional studies of the Combined Therapy with the other Party upon completion of a Combined
        Therapy Study, subject to the following provisions of this Exhibit E; provided that the provisions of this Exhibit E are not applicable to any Combined Therapy Study other than the Triple Study. The provisions as set forth in this Exhibit E shall
        only be in effect (and the Parties will only have the rights set forth below in this Exhibit E) with respect to each Subsequent Study for which (x) the proposed protocol synopsis has been submitted by the Proposing Party to the Other Party (as set
        forth below) within the earlier of (i) [*] or (ii) [*]; provided that the proposed Subsequent Study must be commenced [*] within [*] of such protocol synopsis being provided to the Other Party and (y) at the time the proposed protocol synopsis has
        been submitted by the Proposing Party to the Other Party (as set forth below), the Other Party’s Compound is commercialized or in active development; provided that, in the case of BMS, both of the BMS
        Compounds included in the Triple Study must be commercialized or in active development. For clarity, a Subsequent Study may be conducted only for a Combined Therapy for which the Parties agreed to conduct a Combined Therapy Study under this
        Agreement; provided that neither Party has the rights or obligations set forth below in this Exhibit E with respect to any Combined Therapy Study other than the Triple Study. For clarity, if Compugen conducts a study of a therapy using both the
        Compugen Compound and the BMS Compound in addition to the Combined Therapy Study as described in Study Plan No. 1 and BMS does not supply any BMS Compound pursuant to this Agreement for such study, such study shall not be considered a Combined
        Therapy Study pursuant to this Agreement.

      

      

      6.          Clause (d)(iv) of Exhibit E to the Agreement is hereby amended and restated in its
          entirety as follows:

      

      

      “(iv) for the Subsequent Studies where Compugen is the non-Participating Other Party, [*]”

      

      

      7.          Clause (d)(v) of Exhibit E to the Agreement is hereby amended and restated in its
          entirety as follows:

      

      

      “(v) for the Subsequent Studies where BMS is the non-Participating Other Party, [*]

      

      

      8.          Except as amended by this Amendment, the Agreement shall continue in full force and
          effect pursuant to its terms.

      

      

      9.          This Amendment may be executed in two (2) or more counterparts, each of which shall be
          deemed an original, but all of which together shall constitute one (1) and the same instrument. This Amendment may be executed by facsimile or electronic (e.g., .pdf) signatures and such signatures shall be deemed to bind each Party hereto as if
          they were original signature.

      

      

      10.        This Amendment shall be governed and construed in accordance with the internal laws of the State of New York,
          USA, excluding any choice of law rules that may direct the application of the laws of another jurisdiction.

      

      

      [Signature page follows]

      
         

          

        
          2

          
            

        

      

      
        	
                EXECUTION COPY

              

      

       

      IN WITNESS WHEREOF, BMS and Compugen have duly executed this Amendment as of the Amendment Effective Date.

      

      

      	
              COMPUGEN LTD.

            	
              BRISTOL-MYERS SQUIBB COMPANY

            
	 	 
	
              By:/s/ Anat Cohen-Dayag

            	
              By:/s/ Jonath Cheng 

            
	
              Name: Anat Cohen-Dayag

            	
              Name: Jonathan Cheng, MD 

            
	
              Title: President & CEO

            	
              Title: SVP, Head of Oncology Development 

            

      

      

      
        3

        
          

      

      
        	
                EXECUTION COPY

              

         

      

      Attachment A

      STUDY PLAN NO. 1

      

      [*]

       

        

      
         

          

      

    

  

   
  4Exhibit 4.19

    

     

    
      
        Pursuant to Instruction 4(a) as to Exhibits of Form 20-F, certain identified information (marked by [*]) has been excluded from the exhibit because it is both not material and is the type that the
          registrant treats as private or confidential.

      

    

     

    
      Execution Version

       

      

    

    Amendment No. 2 to Master Clinical Trial Collaboration Agreement

     

    This Amendment No. 2 to Master Clinical Trial Collaboration Agreement (this “Amendment”)

      is effective as of February 19, 2021 (“Amendment Effective Date”) by and between Compugen Ltd., an Israeli corporation with a place of business at
      Azrieli Center, 26 Harokmim Street, Building D, Holon 5885849, Israel (“Compugen”), and Bristol-Myers Squibb Company, a Delaware corporation,
      headquartered at 430 E. 29th Street, 14FL, New York, N.Y. 10016 (“BMS”).

     

    Background

     

    A.          BMS and Compugen entered into that certain Master Clinical Trial Collaboration Agreement, dated as of October 10, 2018, as amended (the “Agreement”).

     

    B.          The Parties have mutually agreed to amend the Agreement as follows in accordance with Section 13.7 of the Agreement.

     

    Now, therefore, in consideration of the mutual covenants and undertakings contained herein, and on the terms and subject to the
      conditions set forth herein, the Parties hereby agree as follows:

     

    1.          Capitalized terms used and not otherwise defined herein shall have the meaning given to such terms in the Agreement.

     

    2.          The definition of “Exclusive Collaboration Period” as set forth in Section 1.48 is hereby amended and restated in its entirety as follows:

     

    “1.48          “Exclusive Collaboration Period” means the period commencing on the Effective Date and ending on the earliest of:

    

    

    	

          	(a)	
            the earlier of (i) six (6) months after Study Completion of both the Combination Therapy Study as set forth in Study Plan No. 1 and the Triple Study as set forth in Study Plan No. 2; or (ii) December 31, 2023.

          

     

    	

          	(b)	
            the effective date of termination of this Agreement pursuant to Section 12.2, Section 12.3 or Section 12.4.”

          

     

    3.          Study Plan No. 1 previously attached to the Agreement is hereby replaced with the Revised Study Plan No. 1 attached as Attachment A hereto.

     

    4.          Clause (a) of Exhibit E to the Agreement is hereby amended and restated in its entirety as follows:

     

    “Neither Party is obligated to conduct additional studies of the Combined Therapy with the other Party upon completion of a Combined Therapy Study, subject to the following
      provisions of this Exhibit E.  The provisions as set forth in this Exhibit E shall only be in effect (and the Parties will only have the rights set forth below in this Exhibit E) with respect to each Subsequent Study for which (x) the proposed
      protocol synopsis has been submitted by the Proposing Party to the Other Party (as set forth below) within the earlier of (i) [*] or (ii) [*]; provided that the proposed Subsequent Study must be commenced [*] within [*]of such protocol synopsis being
      provided to the Other Party and (y) at the time the proposed protocol synopsis has been submitted by the Proposing Party to the Other Party (as set forth below), the Other Party’s Compound is commercialized or in active development; provided that, in the case of BMS with respect to a Subsequent Study involving both of the BMS Compounds included in the Triple Study, both of such BMS Compounds must be commercialized or in active development. 
      For clarity, a Subsequent Study may be conducted only for a Combined Therapy for which the Parties agreed to conduct a Combined Therapy Study under this Agreement.

    
      
        

    

     
      Execution Version

       

      

    

    5.          The Parties have agreed on a press release having the content set forth in Attachment B hereto, which will be issued at a time agreed by the Parties.

     

    6.          Except as amended by this Amendment, the Agreement shall continue in full force and effect pursuant to its terms.

     

    7.          This Amendment may be executed in two (2) or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one (1) and the
      same instrument.  This Amendment may be executed by facsimile or electronic (e.g., .pdf) signatures and such signatures shall be deemed to bind each Party hereto as if they were original signature.

     

    8.          This Amendment shall be governed and construed in accordance with the internal laws of the State of New York, USA, excluding any choice of law rules that may direct the
      application of the laws of another jurisdiction.

     

    [Signature page follows]

    
      
        

    

     
      Execution Version

       

    

    In witness whereof, BMS and Compugen have duly executed this Amendment as of the Amendment Effective Date.

    

    

    	
            Compugen Ltd.

          	
            Bristol-Myers Squibb Company

             

            

          
	
            By: /s/ Anat Cohen-Dayag

          	
            By: /s/ Jonath Cheng 

          
	
            Name: Anat Cohen-Dayag      

          	
            Name: Jonathan Cheng, MD

          
	
            Title: President & CEO 

          	
            Title: SVP, Head of Oncology Development

          

    

    

    
      
        

    

    
      Execution Version

       

    

    Attachment A

    

    

    Revised Study Plan No. 1

    
      [*]

       

      

    

    
      
        

    

    
      Execution Version

       

    

    Attachment B

    

    

    
      

      

        

      

    

    FOR IMMEDIATE RELEASE

    
      

      

    

    
      Compugen Expands Clinical Collaboration Agreement with Bristol 

      Myers Squibb with Phase 1b Combination Study of COM701 with 

      Opdivo®

      

      

    

    
      Cohort expansion study expected to commence in the second quarter of 2021

      

      

    

    HOLON, ISRAEL – February 22, 2021 – Compugen Ltd. (Nasdaq: CGEN), a clinical-stage cancer immunotherapy company and a leader in predictive target discovery, announced today the expansion of its clinical
      collaboration agreement with Bristol Myers Squibb. Under the amended agreement, Bristol Myers Squibb will supply Opdivo® (nivolumab), its PD-1 inhibitor, for Compugen’s Phase 1b cohort expansion study designed to assess COM701, Compugen’s
      first-in-class anti-PVRIG antibody, in combination with Opdivo® in selected cancer indications. Study initiation is expected in the second quarter of 2021.

    

    

    “We are excited to further expand our clinical program evaluating COM701, our first-in-class anti PVRIG inhibitor,” said Anat Cohen-Dayag, Ph.D., President and CEO of Compugen. “While our triple checkpoint blockade study
      of COM701 combined with Bristol Myers Squibb’s PD-1 and TIGIT inhibitors currently advancing in the clinic offers the ultimate test of our science-driven hypothesis, translational research at Compugen suggests that certain patients may not require a
      triple therapy combination. With the enrollment in the dose escalation arm of COM701 in combination with Opdivo® completed and preliminary signs of antitumor activity previously disclosed, we are ready to continue our evaluation of this dual
      combination and move to the cohort expansion phase of the study. Testing COM701 in three settings – as a monotherapy, dual combination, and triple combination therapy – may provide additional insights on the contribution of components as well as the
      opportunity to broaden COM701 treatment options to address patients’ needs. We are proud to be moving quickly to initiate this biomarker and data-informed study in indications we believe are most likely to respond to dual PVRIG and PD-1 blockade,
      enhancing our leadership position in the DNAM-1 axis space.”

    
      
        

    

    
      Execution Version

       

    

    Dr. Cohen-Dayag continued, “Bristol Myers Squibb continues to be a valued partner for our COM701 clinical program as we advance the immunotherapy treatment landscape of patients with cancer .”

    

    

    Under the terms of the amendment, Bristol Myers Squibb will continue to supply Opdivo® to the Compugen-sponsored study. The Phase 1b study, a part of Compugen’s COM701 monotherapy and combination therapy dose escalation
      and expansion program (NCT03667716), will examine fixed doses of COM701 and Opdivo®, as determined by Compugen’s Phase 1a combination dose escalation study. Based on Compugen’s translational analyses and preliminary antitumor activity in dose
      escalation, the study will enroll patients with ovarian, breast, endometrial and microsatellite-stable colorectal cancers.

    

    

    Separately, Compugen and Bristol Myers Squibb are also investigating COM701 in a triple combination study with Opdivo® and BMS-986207,
      Bristol Myers Squibb’s investigational anti-TIGIT antibody.

    

    

    Opdivo® is a registered trademark of Bristol Myers Squibb.

    

    

    About Compugen

    Compugen is a clinical-stage therapeutic discovery and development company utilizing its broadly applicable, predictive computational discovery platforms to identify novel drug targets and develop therapeutics in the
      field of cancer immunotherapy. Compugen’s lead product candidate, COM701, a first-in-class anti-PVRIG antibody, for the treatment of solid tumors, is undergoing a Phase 1 clinical study. In addition, COM902, Compugen’s antibody targeting TIGIT, is in
      a Phase 1 clinical study. Compugen’s therapeutic pipeline also includes early stage immuno-oncology programs focused largely on myeloid targets. Compugen is headquartered in Israel, with offices in South San Francisco, CA. Compugen’s shares are
      listed on Nasdaq and the Tel Aviv Stock Exchange under the ticker symbol CGEN. For additional information, please visit Compugen’s corporate website at www.cgen.com.

    
      
        

    

    
      Execution Version

       

    

    Forward-Looking Statement

    This press release contains “forward-looking statements” within the meaning of the Securities Act of 1933 and the Securities Exchange Act of 1934, as amended, and the safe-harbor provisions of the Private Securities
      Litigation Reform Act of 1995. Such forward-looking statements are based on the current beliefs, expectations and assumptions of Compugen. Forward-looking statements can be identified by the use of terminology such as “will,” “may,” “expects,”
      “anticipates,” “believes,” “potential,” “plan,” “goal,” “estimate,” “likely,” “should,” “confident,” and “intends,” and similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain
      these identifying words. These forward-looking statements, including but not limited to statements about the initiation, procedures and potential results of the cohort expansion study, involve known and unknown risks and uncertainties that may cause
      the actual results, performance or achievements of Compugen to be materially different from any future results, performance or achievements expressed or implied by such forward-looking statements. Among these risks: Compugen’s operations could be
      affected by the outbreak and spread of COVID-19, clinical development involves a lengthy and expensive process, with an uncertain outcome and Compugen may encounter substantial delays or even an inability to begin clinical trials for any specific
      product, or may not be able to conduct or complete its trials on the timelines it expects; Compugen relies, and expects to continue to rely, on third parties to conduct its clinical trials and if these third parties do not successfully carry out
      their contractual duties, comply with regulatory requirements or meet expected deadlines (including as a result of the effect of the COVID-19), Compugen may experience significant delays in the conduct of its clinical trials; Compugen’s approach to
      the discovery of therapeutic products is based on its proprietary computational target discovery infrastructure, which is unproven clinically; Compugen does not know whether it will be able to discover and develop additional potential product
      candidates or products of commercial value; Compugen’s business model is substantially dependent on entering into collaboration agreements with third parties; and Compugen may not be successful in generating adequate revenues or commercializing
      aspects of its business model. These risks and other risks are more fully discussed in the “Risk Factors” section of Compugen’s most recent Annual Report on Form 20-F as filed with the Securities and Exchange Commission (SEC) as well as other
      documents that may be subsequently filed by Compugen from time to time with the SEC. In addition, any forward-looking statements represent Compugen’s views only as of the date of this release and should not be relied upon as representing its views as
      of any subsequent date. Compugen does not assume any obligation to update any forward-looking statements unless required by law.

    

    

    Company contact:

    Elana Holzman

    Director, Investor Relations and Corporate Communications Compugen Ltd.

    Email: elanah@cgen.com

    Tel: +972 (3) 765-8124

    

    

    Investor Relations contact:

    Bob Yedid

    LifeSci Advisors, LLC

    Email: bob@lifesciadvisors.com

    Tel: +1 (646) 597-6989

    

    

    Media contact:

    Josephine Belluardo, Ph.D.

    LifeSci Communications

    Email: jo@lifescicomms.com

    Tel: +1 (646) 751-4361

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