Document:

AMENDMENT
      

    TO
      

    REGISTRATION
      RIGHTS AGREEMENT

    

    This
      AMENDMENT TO REGISTRATION RIGHTS AGREEMENT (the “Amendment”)
      dated
      as of April 11, 2008, is entered into by and between Novelos Therapeutics,
      Inc.,
      a Delaware Corporation (the “Company”)
      and
      the entities listed on the signature pages hereto (collectively, the “Series B
      Holders”). 

     

    WHEREAS,
      the Company and the Series B Holders have entered into that certain Registration
      Rights Agreement, dated as of May 2, 2007 (the “Registration
      Agreement”);

     

    WHEREAS,
      pursuant to Section 7(a) of the Registration Agreement, the Registration
      Agreement may be amended with the written consent of the Company and the
      Requisite Holders (as defined in the Registration Agreement);

     

    WHEREAS,
      the Company and the Series B Holders, which holders include the Requisite
      Holders, desire to amend the Registration Agreement as hereinafter set
      forth.

     

    NOW,
      THEREFORE, in consideration of the premises and the mutual covenants herein
      contained, the parties hereto agree as follows:

     

    1. Amendment.
      The
      Registration Agreement is hereby amended as follows:

     

    (a) The
      definition of “Holders” in Section 1 is hereby deleted in its entirety and
      replaced with the following:

     

    “Holders”
shall
      mean the Investors,
      the
      Lead
      Investors and any Affiliate or permitted transferee thereof who is a subsequent
      holder of any Registrable Securities or shares of Preferred Stock convertible
      into Registrable Securities.

     

    (b) The
      definition of “Registrable Securities” in Section 1 is hereby deleted in its
      entirety and replaced with the following:

     

    “Registrable
      Securities”
shall
      mean up to 12,000,000 shares of Common Stock issuable upon conversion of the
      Company’s Series D Convertible Preferred Stock, $.00001 par value per share (the
“Series D Preferred Stock”), which Series D Preferred Stock was issued in
      exchange for the Registered Preferred Stock (as defined below) pursuant to
      that
      certain Securities Purchase Agreement dated as of March 26, 2008, as amended
      on
      April 9, 2008, by and among the Company and the investors set forth on Schedule
      I thereto; provided,
      that,
      a
      security shall cease to be a Registrable Security upon sale pursuant to a
      Registration Statement. For purposes hereof, “Registered Preferred Stock” is
      Preferred Stock that was convertible into 12,000,000 shares of Common Stock,
      the
      offer and sale of which is, as of the date hereof, registered pursuant to
      Amendment No. 3 to the Registration Statement on Form SB-2 (Registration No.
      333-143263) filed with the SEC on August 29, 2007.

     

    (c) Section
      3(a) is amended by deleting “two years from the Closing Date” in subsection (ii)
      and replacing it with “three years from the Closing Date.”

     

    
      
        
        

      

      
        
        

        
          

        

      

      
        
        

      

    

     

    2. Applicable
      Law.
      This
      Amendment shall be governed by, and construed and enforced in accordance with,
      the substantive laws of the State of New York, without regard to its principles
      of conflicts of laws.

     

    3. Effect
      on Registration Agreement.
      Except
      as modified hereby, the Registration Agreement shall remain in full force and
      effect.

     

    4. Counterparts.
      This
      Amendment may be executed in any number of counterparts, each of which shall
      be
      an original, but all of which together shall be deemed to constitute one
      instrument.

     

    
      
        
        

      

      
        -
          2
          -

        
          

        

      

      
        
        

      

    

    IN
      WITNESS WHEREOF the undersigned have executed this Amendment to the Registration
      Rights Agreement as of the date first above written.

    

    
      	
              NOVELOS
                THERAPEUTICS, INC.

            
	 	 
	
              By:
                

            	
              /s/
                Harry S. Palmin

            	
            
	
              Name:
                 Harry S. Palmin

            
	
              Title:   
                President and CEO

            

    

    

    

    
      	
              SERIES
                B HOLDERS:

            	 	 	 
	 	 	 	 	 
	
              Xmark
                Opportunity Fund, Ltd.

            	 	
              Caduceus
                Capital Master Fund Limited

            
	
              Xmark
                Opportunity Fund, L.P.

            	 	
              Caduceus
                Capital II, L.P.

            
	
              Xmark
                JV Investment Partners, LLC

            	 	
              UBS
                Eucalyptus Fund, L.L.C.

            
	
               

            	 	
              PW
                Eucalyptus Fund, Ltd.

            
	 	 	 	 	 	 	 
	
              By:
                

            	
              /s/
                Mitchell D. Kaye

            	 	 	
              By:
                

            	
              /s/
                Samuel D. Isaly

            	 
	Name:	Mitchell
              D. Kaye	 	 	Name: 	Samuel
              D. Isaly	 
	Title:	Authorized
              Signatory	 	 	Title: 	Managing
              Partner, Orbimed Advisors	 
	 	 	 	 	 	 	 
	
              Knoll
                Capital Fund II Master Fund, Ltd. 

            	 	
              Hunt-BioVentures,
                L.P.

            
	
              Europa
                International, Inc.

            	 	
              By :
                HBV GP, L.L.C, its General Partner

            
	 	 	 	 	 	 	 
	
              By:
                

            	
              /s/
                Fred Knoll

            	 	 	
              By:
                

            	
              /s/
                J. Fulton Murray, IIII

            	 
	Name: 	Fred
              Knoll	 	 	Name:	J.
              Fulton Murray, III	 
	
              Title:

            	Portfolio
              Manager 	 	 	Title:	Manager 	 

    

    

    
      
        
        

      

      
        -
          3
          -WARRANT
      AMENDMENT AGREEMENT

    

    THIS
      WARRANT AMENDMENT AGREEMENT (“Amendment”)
      is
      made as of this 11th day of April, 2008 by and among Novelos Therapeutics,
      Inc.,
      a Delaware corporation (the “Company”)
      and
      the undersigned holders of warrants to purchase 7,500,000 shares of the
      Company’s common stock dated May 2, 2007 (the “Series
      B Warrants”)
      issued
      pursuant a certain Securities Purchase Agreement, dated as of April 12, 2007,
      by
      and among the Corporation and the Investors signatory thereto (as amended on
      May
      2, 2007, the “Series
      B Purchase
      Agreement”).
      All
      capitalized terms used but not defined herein shall have the meanings ascribed
      thereto in the Series B Warrants.

     

    WHEREAS,
      pursuant
      to Section 21 of the Series B Warrants, the Series B Warrants may amended with
      the written consent of the Company and the Requisite Holders (as such term
      is
      defined in the Series B Purchase Agreement) and any such amendment shall apply
      to all of the Series B Warrants; and

    

    WHEREAS,
      the
      Company and the undersigned holders of Series B Warrants, which holders include
      the Requisite Holders, desire to amend the Series B Warrants; 

    

    NOW,
      THEREFORE,
      for good
      and valuable consideration, the receipt and sufficiency of which is hereby
      acknowledged, the parties hereto agree that the Series B Warrants are hereby
      amended as follows: 

    

    1) The
      Expiration Date, as defined in Paragraph 1, is hereby changed to April 11,
      2013
      from May 2, 2012. 

    

    2)
       The
      Warrant Price, as defined in Paragraph 1 is hereby reduced to $0.65 from $1.25.
      

    

    3)
       Section
      7
      is amended and restated as follows: 

    

    Section
      7. Reservation
      of Common Stock.
      The
      Corporation hereby represents and warrants that there have been reserved, and
      the Corporation shall at all applicable times keep reserved until issued (if
      necessary) as contemplated by this Section 7, out of the authorized and unissued
      shares of Common Stock, 100% of the number of shares issuable upon exercise
      of
      the rights of purchase represented by this Warrant. The Corporation agrees
      that
      all Warrant Shares issued upon due exercise of the Warrant shall be, at the
      time
      of delivery of the certificates for such Warrant Shares, duly authorized,
      validly issued, fully paid and non-assessable shares of Common Stock of the
      Corporation.

     

    
      
         

      

      
         

        
          

        

      

      
         

      

    

     

    4)
       Section
      15 is amended and restated as follows: 

    

    Section
      15. Registration
      Rights.
      The
      initial holder of this Warrant is entitled to the benefit of certain
      registration rights with respect to the shares of Common Stock issuable upon
      the
      exercise of this Warrant as provided in the Registration Rights Agreement dated
      April 11, 2008, by and between the Warrantholders and the Corporation, and
      any
      subsequent holder hereof shall be entitled to such rights to the extent provided
      in the Registration Rights Agreement.

    

    
      
        5) 
          Section
          19 is hereby amended by deleting the first sentence thereof and replacing
          it
          with the following:

         

      

    

    Cashless
      Exercise.
      If, at
      any time after the six-month anniversary of the Original Issue Date, there
      is no
      effective registration statement covering all or any part of the Warrant Shares
      filed under the Securities Act, the Warrantholder may elect to receive, without
      the payment by the Warrantholder of the aggregate Warrant Price in respect
      of
      the shares of Common Stock to be acquired upon exercise hereof, shares of Common
      Stock equal to the value of this Warrant or any portion hereof being exercised
      pursuant to this Section 19 by the surrender of this Warrant (or such portion
      of
      this Warrant being so exercised) together with the Net Issue Election Notice
      annexed hereto as Appendix
      B
      duly
      executed, at the office of the Corporation. 

    

    6) Section
      20 is amended and restated as follows: 

    

    Section
      20. Redemption.
      If
      the
      registration statement covering the resale of all of the Warrant Shares
      underlying all of the Warrants is declared effective by the SEC, and is then
      effective, and
      the
      daily VWAP of the Common Stock for twenty (20) consecutive trading days exceeds
      $2.50 per share (subject to appropriate adjustment from time to time in the
      event of any stock dividend, stock split, reverse stock split, reclassification,
      stock combination or other recapitalization affecting the Common Stock), and
      the
      Company has provided the Warrantholder notice that this redemption provision
      of
      this Warrant has been triggered, then Warrantholders shall have up to thirty
      (30) days to exercise this Warrant in accordance with Section 3 at the Warrant
      Price then in effect. On and after the thirty-first day, this Warrant, to the
      extent unexercised, shall no longer be exercisable and shall be converted into
      a
      right to receive $.01 per share for the number of shares for which the Warrant
      had been exercisable at the end of the thirtieth day.

     

    [The
      remainder of this page is intentionally left blank.]

     

    
      
         

      

      
         

        
          

        

      

      
         

      

    

     

    IN
      WITNESS WHEREOF, the undersigned have executed this Warrant Amendment Agreement
      or caused its duly authorized officers to execute this Warrant Amendment
      Agreement as of the date first above written.

    

    
      	
              NOVELOS
                THERAPEUTICS, INC.

            
	 
	
              By:

            	
              /s/
                Harry S. Palmin

            
	
              Name:

            	
              Harry
                S. Palmin

            
	
              Title:

            	
              President
                and CEO

            

    

     

    
      	
              WARRANTHOLDERS

            	 	 
	 	 	 
	
              Xmark
                Opportunity Fund, Ltd.

            	 	
              Caduceus
                Capital Master Fund Limited

            
	
              Xmark
                Opportunity Fund, L.P.

            	 	
              Caduceus
                Capital II, L.P.

            
	
              Xmark
                JV Investment Partners, LLC

            	 	
              UBS
                Eucalyptus Fund, L.L.C.

            
	 	 	
              PW
                Eucalyptus Fund, Ltd.

            
	 	 	 
	
              By:

            	
              /s/
                Mitchell D. Kaye

            	 	
              By:

            	
              /s/
                Samuel D. Isaly

            
	
              Name:

            	
              Mitchell
                D. Kaye

            	 	
              Name:

            	
              Samuel
                D. Isaly

            
	
              Title:

            	
              Authorized
                Signatory

            	 	
              Title:

            	
              Managing
                Partner, Orbimed Advisors

            
	 	 	 
	
              Knoll
                Capital Fund II Master Fund, Ltd. 

            	 	
              Hunt-BioVentures,
                L.P.

            
	
              Europa
                International, Inc.

            	 	
              By :
                HBV GP, L.L.C, its General Partner

            
	 	 	 
	
              By:
                

            	
              /s/
                Fred Knoll

            	 	
              By:

            	
              /s/
                J. Fulton Murray, IIII

            
	
              Name:
                

            	
              Fred
                Knoll

            	 	
              Name:

            	
              J.
                Fulton Murray, III

            
	
              Title:

            	
              Portfolio
                Manager

            	 	
              Title:

            	
              Manager

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