Final Execution Version

       

      

    

    Exhibit 10.69

    

    

    CONFIDENTIAL TREATMENT REQUESTED

    UNDER 17 C.F.R. §§ 200.80(b)(4), 240.24B-2

     

      

    AMENDMENT NO. 1

     

    This Amendment No. 1 (the “Amendment”) to the Strategic Collaboration Agreement dated July 31st, 2015 (the “Agreement”), is made by and between

     

    
      
        	

              	(1)	
                ASTRAZENECA AB, a company incorporated in Sweden under no. 556011-7482 with its registered office at SE-151 85 Södertälje, Sweden (“AstraZeneca”) and

              


      

    

     

    
      
        	

              	(2)	
                IONIS PHARMACEUTICALS, INC., a Delaware corporation, (formally known as Isis Pharmaceuticals, Inc.) having its principal place of business at 2855 Gazelle Court, Carlsbad,
                    California 92010 (“Ionis”),

              


      

    

     

    and is made effective as of October 18th, 2018 (the “Amendment Effective
        Date”).

     

    Recitals

     

    WHEREAS, the Parties desire to further amend and restate certain terms and conditions of the Agreement.

     

    Agreement

     

    NOW, THEREFORE, in consideration of the mutual covenants contained in this Amendment, and other good and valuable consideration, the receipt and sufficiency
        of which are hereby acknowledged, the Parties, intending to be legally bound, agree as follows:

     

    
      
        	

              	1.	
                Definitions

              


      

    

     

    Any capitalized term not separately defined in this Amendment shall have the meaning ascribed to it in the Agreement.

     

    
      
        	

              	2.	
                Modifications

              


      

    

     

    
      Section 5.1.2. of the Agreement is hereby deleted in its entirety and replaced by the following:

       

        

    

    
      
        


    

    
      Final Execution Version

    

     

    “5.1.2. Integrated Product Plans.  For
        each Licensed Program, AstraZeneca will prepare a global integrated Product plan or a comparable document consistent with AstraZeneca’s then current internal practices for AstraZeneca’s internal programs outlining key aspects of the Development of
        the Product being Developed from such Program through all Approvals as well as, as Development proceeds and when such information is available, key aspects of worldwide regulatory strategy, pricing and market access strategy, market launch, and
        Commercialization (each plan or other such document, an “Integrated Product Plan” or “IPP”).  On a Product-by-Product basis, AstraZeneca will prepare each IPP no later than [***] for the relevant Product, and the IPP will contain high level
        information consistent with AstraZeneca’s development and commercialization plans for its similar products at similar stages of development and commercialization in the same AstraZeneca franchise, including without limitation a status update,
        timelines, goals, and the criteria AstraZeneca will use to make internal decisions, but excluding information that AstraZeneca is required not to share even under confidentiality pursuant to restrictions imposed by any Third Party.  Once
        AstraZeneca has prepared an IPP, AstraZeneca will update it consistent with AstraZeneca’s standard practice (including if the IPP is updated and presented to an AstraZeneca internal committee) but at least Annually and will provide such updates to
        Ionis.  AstraZeneca and Ionis will meet (through the JSC or as the Parties may otherwise agree) on a yearly basis to discuss the draft of the IPP and AstraZeneca will consider, in good faith, any proposals and comments made by Ionis or
        incorporation in the IPP.  AstraZeneca and Ionis will [***], to discuss the status of execution of the IPP.  Additionally, subject to AstraZeneca’s confidentiality obligations to any Third Party, AstraZeneca may provide more frequent updates in the
        case of extraordinary material events (e.g. approvals, regulatory feedback, etc.) as deemed appropriate by AstraZeneca.  For the avoidance of doubt, information provided by AstraZeneca to Ionis pursuant to this Section 5.1.2 shall be treated by Ionis as AstraZeneca’s Confidential Information subject to the provisions in Article 11.”

     

    
      
        	

              	3.	
                Amendment Effective Date

              


      

    

     

    This Amendment shall become effective on the Amendment Effective Date.

     

    
      
        	

              	4.	
                Entire Agreement

              


      

    

     

    This Amendment, together with the Agreement, constitutes the entire agreement between the Parties with respect to the subject matter of the
        Agreement.  The Agreement together with this Amendment supersedes all prior agreements, whether written or oral, with respect to the subject matter of the Agreement, as amended.  Each Party confirms that it is not relying on any representations,
        warranties, or covenants of the Party except as specifically set out in the Agreement as amended.  Nothing in this Amendment is intended to limit or exclude any liability or fraud.  The Parties hereby agree that subject to the modifications
        specifically stated in this Amendment, all other terms and conditions of the Agreement shall remain in full force and effect.

     

    
      
        	

              	5.	
                Execution

              


      

    

     

    THIS AMENDMENT IS EXECUTED by the authorized representatives of the parties as of the date first written above.

     

    	 	
            ASTRAZENECA AB (publ.)

          	 	
            IONIS PHARMACEUTICALS, INC.

          
	 	 	 	 	 	 	 
	 	
            Signature:

          	
            /s/ Regina
                    Fritsche Danielson

                

          	 	
            Signature:

          	

          	
            /s/ Brett Monia

                

          	 
	 	 	 	 	 	 	 
	 	
            Name:

          	
            Regina Fritsche Danielson

          	 	
            Name:

          	
            Brett Monia

          	 
	 	 	 	 	 	 	 
	 	
            Title:

          	
            VP and Head of IMED CVRM

          	 	
            Title:

          	
            Chief Operating Officer