AMENDMENT
NO. 2

    TO

    REGISTRATION
RIGHTS AGREEMENT

    


    This
AMENDMENT TO REGISTRATION RIGHTS AGREEMENT (the “Amendment”) dated as
of February 11, 2009, 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 D
Holders”).

     

    WHEREAS,
the Company and the Series D Holders have entered into that certain Registration
Rights Agreement, dated as of May 2, 2007, as amended on April 11, 2008 (as so
amended, 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 D 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 by deleting the definition of
“Registrable Securities” therein and replacing it with the following
definition:

     

    “Registrable
Securities” shall mean 12,000,000 shares of Common Stock (subject to
adjustment in the event of stock splits, stock dividends or similar transactions
with respect to the Common Stock) issuable upon conversion of the Company’s
Series E Convertible Preferred Stock, $.00001 par value per share (the “Series E
Preferred Stock”), which Series E Preferred Stock was issued in exchange for
shares of the Company’s Series D Convertible Preferred Stock, $.00001 par value
per share, pursuant to that certain Consent and Exchange Agreement dated as of
the date hereof by and among the Company and the other parties thereto, the
offer and sale of which shares of Common Stock are currently registered under
the Securities Act pursuant a Registration Statement on Form S-1 (Registration
No. 333-143263); provided, that, a security
shall cease to be a Registrable Security upon sale pursuant to a Registration
Statement.

     

    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.


    
      
         


      

      
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    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
      D 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
      Special Opportunities Fund II Master

                                Fund,
      Ltd.

                              	 
      	
                                Hunt-BioVentures,
      L.P.

                              
	
                                Europa
      International, Inc. (1)

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

                              
	 
      	 
      	 
      	 
      	 
      	 
      	 
      
	
                                By:

                              	
                                /s/
      Fred Knoll

                              	 
      	 
      	
                                By:

                              	
                                /s/
      J. Fulton Murray, III

                              	 
      
	
                                Name: 

                              	
                                Fred
      Knoll

                              	 
      	 
      	
                                Name:

                              	
                                J.
      Fulton Murray, III

                              	 
      
	
                                Title:

                              	
                                Portfolio
      Manager 

                              	 
      	 
      	
                                Title:

                              	
                                Manager 

                              	 
      


                      

                    

                  

                

              

            

          

        

      

    

    


    (1)
Formerly Knoll Capital Fund II Master Fund Ltd.


    
      
         


      

      
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