Document:

Unassociated Document

    [
* ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS
AMENDED.

    Exhibit
10.39

    Amendment
No. 1

     

    This
Amendment No. 1 (the “Amendment”) is entered into by and between ALNYLAM
PHARMACEUTICALS, INC., a corporation organized under the laws of the State of
Delaware having a principal office at 300 Third Street, Cambridge MA 02142
U.S.A. (“ALNYLAM”), and QUARK PHARMACEUTICALS, INC (previously known as Quark
Biotech, Inc.), a corporation organized under the laws of the State of
California having offices located at 6501 Dumbarton Circle Fremont, CA 94555
U.S.A. (“QUARK”).

     

    WHEREAS ALNYLAM and QUARK are
parties to a LICENSE AGREEMENT dated September 26, 2006 in respect of the target
identified as RTP801
and covering intellectual property of Alnylam identified as Kreutzer-Limmer (KL)
and Tuschl II (the “Agreement”);

     

    WHEREAS the Parties are
desirous to make certain additions and amendments to the Agreement as set forth
more fully below, to reflect their agreement to modify certain provisions of the
Agreement:

     

    NOW, THEREFORE the Parties
hereto agree as follows:

     

    
      	
               
      

            	
              1.

            	
              Section
      7.2 of the Agreement shall be deleted in its entirety and replaced by the
      following amended Section 7.2:

            

    

     

    “Insurance.  With
respect to its activities under this agreement, QUARK will secure and maintain
in full force and effect throughout the term of this Agreement (and for at least
[*] thereafter for claims made coverage), the following types and amounts of
insurance coverage with carriers having a minimum AM Best rating of A, with per
claim deductibles that do not exceed [*]:

     

    Comprehensive
General Liability and Personal Injury, including coverage for contractual
liability assumed by QUARK and coverage for QUARK independent contractor(s),
with limits of at least [*] per occurrence and a general aggregate limit of
[*].

     

    Umbrella
Liability, exclusive of the coverage provided by the policies listed above, with
a limit of at least [*], which shall be increased to a limit of at least [*]
upon [*].  Upon achievement of Net Sales of [*] in any given single
calendar year, the parties shall jointly determine and agree whether further
increase of the Umbrella Liability insurance coverage limit is
necessary.

     

    Products/Clinical/Professional
Liability, exclusive of the coverage provided by the Comprehensive General
Liability policy, with limits of at least [*] per occurrence and an aggregate
limit of at least [*], which shall be increased to limits of at least [*] per
occurrence, and an aggregate limit of [*] upon [*], with ALNYLAM to be named as
an additional insured party with respect to each Licensed RNAi Product under
such coverage.

    
      
         

      

      
        
        

        
          

        

      

      
         

      

    

     

    Notwithstanding
the above, the obligations under this Section 7.2 shall not apply to (i) QUARK
after such time that QUARK achieves aggregate annual revenues for all
pharmaceutical and diagnostic products in excess of [*], or (ii) any Affiliate
or Sublicensee that has aggregate annual revenues for all pharmaceutical and
diagnostic products in excess of [*]; provided, however, that QUARK
shall provide written notice to ALNYLAM at such time as it determines this
Section is in effect.”

     

    Other
than the changes above, the terms and conditions of the Agreement remain
unchanged and in full force and effect.

     

    The
effective date of this Amendment shall be the later of the two signature dates
below.

     

    
      
        	
                ALNYLAM
      PHARMACEUTICALS, INC.

              
	 
      	 
      
	
                By:

              	
                /s/ Barry Greene

              
	 
      	
                Name:  Barry
      Greene

              
	 
      	
                Title:    COO

              
	 
      	 
      
	
                QUARK
      PHARMACEUTICALS, INC.

              
	 
      	 
      
	
                By:

              	
                /s/ D. Zurr

              
	 
      	
                Name:  Danny
      Zurr

              
	 
      	
                Title:    CEO

              
	 
      	
                7/30/07                  
      

              

      

    

     

    [ * ] = CERTAIN CONFIDENTIAL
INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND
FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
406 OF THE SECURITIES ACT OF 1933, AS AMENDED.Unassociated Document

    [
* ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS
AMENDED.

    Exhibit
10.40

    Amendment
No. 1

     

    This
Amendment No. 1 (the “Amendment”) is entered into by and between ALNYLAM
PHARMACEUTICALS, INC., a corporation organized under the laws of the State of
Delaware having a principal office at 300 Third Street, Cambridge MA 02142
U.S.A. (“ALNYLAM”), and QUARK PHARMACEUTICALS, INC (previously known as Quark
Biotech, Inc.), a corporation organized under the laws of the State of
California having offices located at 6501 Dumbarton Circle Fremont, CA 94555
U.S.A. (“QUARK”).

     

    WHEREAS ALNYLAM and QUARK are
parties to a LICENSE AGREEMENT dated September 26, 2006 in respect of the target
identified as RTP801
and covering intellectual property of Cancer Research Technology Limited
(the “Agreement”);

     

    WHEREAS the Parties are
desirous to make certain additions and amendments to the Agreement as set forth
more fully below, to reflect their agreement to modify certain provisions of the
Agreement:

     

    NOW, THEREFORE the Parties
hereto agree as follows:

     

    
      	
               
      

            	
              1.

            	
              Section
      7.2 of the Agreement shall be deleted in its entirety and replaced by the
      following amended Section 7.2:

            

    

     

    “Insurance.  With
respect to its activities under this agreement, QUARK will secure and maintain
in full force and effect throughout the term of this Agreement (and for at least
[*] thereafter for claims made coverage), the following types and amounts of
insurance coverage with carriers having a minimum AM Best rating of A, with per
claim deductibles that do not exceed [*]:

     

    Comprehensive
General Liability and Personal Injury, including coverage for contractual
liability assumed by QUARK and coverage for QUARK independent contractor(s),
with limits of at least [*] per occurrence and a general aggregate limit of
[*].

     

    Umbrella
Liability, exclusive of the coverage provided by the policies listed above, with
a limit of at least [*] , which shall be increased to a limit of at least [*]
upon [*].  Upon achievement of Net Sales of [*] in any given single
calendar year, the parties shall jointly determine and agree whether further
increase of the Umbrella Liability insurance coverage limit is
necessary.

     

    Products/Clinical/Professional
Liability, exclusive of the coverage provided by the Comprehensive General
Liability policy, with limits of at least [*] per occurrence and an aggregate
limit of at least [*], which shall be increased to limits of at least [*] per
occurrence, and an aggregate limit of [*] upon [*], with ALNYLAM to be named as
an additional insured party with respect to each Licensed RNAi Product under
such coverage.

    
      
         

      

      
        
        

        
          

        

      

      
         

      

    

    Notwithstanding
the above, the obligations under this Section 7.2 shall not apply to (i) QUARK
after such time that QUARK achieves aggregate annual revenues for all
pharmaceutical and diagnostic products in excess of [*], or (ii) any Affiliate
or Sublicensee that has aggregate annual revenues for all pharmaceutical and
diagnostic products in excess of [*]; provided, however, that QUARK
shall provide written notice to ALNYLAM at such time as it determines this
Section is in effect.”

     

    Other
than the changes above, the terms and conditions of the Agreement remain
unchanged and in full force and effect.

     

    The
effective date of this Amendment shall be the later of the two signature dates
below.

     

    
      
        
          
            
              	
                      ALNYLAM
      PHARMACEUTICALS, INC.

                    
	 
	
                      By:

                    	
                      /s/ Barry Greene

                    
	 
      	
                      Name:  Barry
      Greene

                    
	 
      	
                      Title:    COO

                    
	 
      	 
      
	
                      QUARK
      PHARMACEUTICALS, INC.

                    
	 
	
                      By:

                    	
                      /s/ D. Zurr

                    
	 
      	
                      Name:  Danny
      Zurr

                    
	 
      	
                      Title:     CEO

                    
	 
      	
                      7/30/07           
      

                    

            

          

        

      

    

    

    [ * ] = CERTAIN CONFIDENTIAL
INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND
FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
406 OF THE SECURITIES ACT OF 1933, AS AMENDED.Unassociated Document

    [
* ] = CERTAIN CONFIDENTIAL INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY
BRACKETS, HAS BEEN OMITTED AND FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE
COMMISSION PURSUANT TO RULE 406 OF THE SECURITIES ACT OF 1933, AS
AMENDED.

    Exhibit
10.41

    Amendment
No. 1

     

    This
Amendment No. 1 (the “Amendment”) is entered into by and between ALNYLAM
PHARMACEUTICALS, INC., a corporation organized under the laws of the State of
Delaware having a principal office at 300 Third Street, Cambridge MA 02142
U.S.A. (“ALNYLAM”), and QUARK PHARMACEUTICALS, INC (previously known as Quark
Biotech, Inc.), a corporation organized under the laws of the State of
California having offices located at 6501 Dumbarton Circle Fremont, CA 94555
U.S.A. (“QUARK”).

     

    WHEREAS ALNYLAM and QUARK are
parties to a LICENSE AGREEMENT dated September 26, 2006 in respect of the target
identified as p53 and
covering intellectual property of Alnylam identified as Kreutzer-Limmer (KL) and
Tuschl II (the “Agreement”);

     

    WHEREAS the Parties are
desirous to make certain additions and amendments to the Agreement as set forth
more fully below, to reflect their agreement to modify certain provisions of the
Agreement:

     

    NOW, THEREFORE the Parties
hereto agree as follows:

     

    
      	
               
      

            	
              1.

            	
              Section
      7.2 of the Agreement shall be deleted in its entirety and replaced by the
      following amended Section 7.2:

            

    

     

    “Insurance.  With
respect to its activities under this agreement, QUARK will secure and maintain
in full force and effect throughout the term of this Agreement (and for at least
[*] thereafter for claims made coverage), the following types and amounts of
insurance coverage with carriers having a minimum AM Best rating of A, with per
claim deductibles that do not exceed [*]:

     

    Comprehensive
General Liability and Personal Injury, including coverage for contractual
liability assumed by QUARK and coverage for QUARK independent contractor(s),
with limits of at least [*] per occurrence and a general aggregate limit of
[*].

     

    Umbrella
Liability, exclusive of the coverage provided by the policies listed above, with
a limit of at least [*], which shall be increased to a limit of at least [*]
upon [*].  Upon achievement of Net Sales of [*] in any given single
calendar year, the parties shall jointly determine and agree whether further
increase of the Umbrella Liability insurance coverage limit is
necessary.

     

    Products/Clinical/Professional
Liability, exclusive of the coverage provided by the Comprehensive General
Liability policy, with limits of at least [*] per occurrence and an aggregate
limit of at least [*], which shall be increased to limits of at least [*] per
occurrence, and an aggregate limit of [*] upon [*], with ALNYLAM to be named as
an additional insured party with respect to each Licensed RNAi Product under
such coverage.

    
      
         

      

      
        
        

        
          

        

      

      
         

      

    

    Notwithstanding
the above, the obligations under this Section 7.2 shall not apply to (i) QUARK
after such time that QUARK achieves aggregate annual revenues for all
pharmaceutical and diagnostic products in excess of [*], or (ii) any Affiliate
or Sublicensee that has aggregate annual revenues for all pharmaceutical and
diagnostic products in excess of [*]; provided, however, that QUARK
shall provide written notice to ALNYLAM at such time as it determines this
Section is in effect.”

     

    Other
than the changes above, the terms and conditions of the Agreement remain
unchanged and in full force and effect.

     

    The
effective date of this Amendment shall be the later of the two signature dates
below.

     

    
      
        
          
            	
                    ALNYLAM
      PHARMACEUTICALS, INC.

                  
	 
	
                    By:

                  	
                    /s/ Barry Greene

                  
	 
      	
                    Name:  Barry
      Greene

                  
	 
      	
                    Title:    COO

                  
	 
      
	
                    QUARK
      PHARMACEUTICALS, INC.

                  
	 
	
                    By:

                  	
                    /s/ D. Zurr

                  
	 
      	
                    Name:  Danny
      Zurr

                  
	 
      	
                    Title:    CEO

                  
	 
      	
                    7/30/07           
      

                  

          

        

      

    

    

    [ * ] = CERTAIN CONFIDENTIAL
INFORMATION CONTAINED IN THIS DOCUMENT, MARKED BY BRACKETS, HAS BEEN OMITTED AND
FILED SEPARATELY WITH THE SECURITIES AND EXCHANGE COMMISSION PURSUANT TO RULE
406 OF THE SECURITIES ACT OF 1933, AS AMENDED.

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