Amendment No 3

AMENDMENT TO

LICENSE AND COLLABORATION AGREEMENT

THIS AMENDMENT TO LICENSE AND COLLABORATION AGREEMENT (this “Amendment”), is entered into this 21 day of December 2007 (the “Effective Date”) by and between Santaris Pharma A/S, a Danish corporation having its principal place of business at Hørsholm, Denmark (“Santaris”), and Enzon Pharmaceuticals, Inc., a Delaware corporation having its
principal place of business at Bridgewater, New Jersey 08807 (“Enzon”). Santaris and Enzon may be referred to herein individually as a “Party” or collectively, as the “Parties”.

BACKGROUND

WHEREAS, Enzon and Santaris entered into the License and Collaboration Agreement dated July 26, 2006 (the “Agreement”); and

WHEREAS, the Agreement was amended by Amendment No 1 dated 13th of June and Amendment No 2 dated 25th of June 2007.

WHEREAS, Enzon and Santaris desire to amend and restate certain provisions of the Agreement.

WHEREAS, Enzon and Santaris changed the discovery process activities to allow Enzon to make certain mini-tox studies.

NOW, THEREFORE, in consideration of the covenants and obligations expressed herein and intending to be legally bound, and otherwise bound by proper and reasonable conduct, the Parties agree as follows:

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

2. Section 5.4 of the Agreement is hereby amended and restated in its entirety as follows:

Compound Selection. Each LNA Compound delivered by Santaris to Enzon will be identified by Santaris pursuant to the selection process set forth in Schedule 5.4A (the “Compound Selection Process”) and shall satisfy the acceptance criteria set forth for such Additional Target in Schedule 5.4B (the “Compound Acceptance Criteria”). Following the Compound Selection Process, Santaris shall provide Enzon with written reports detailing the results of such process,
including its design, synthesis, first screening efforts, second screening efforts, as well as the sequences of any and all LNA Compounds resulting from such process that meet the Compound Acceptance Criteria. Upon Santaris’ delivery, at Santaris’ cost, of [**Redacted**] of each of 

 

 






Amendment No 3


[**Redacted**] LNA
    Compounds that meet the Compound Acceptance Criteria each of which is an “Accepted
    LNA Compound” for Enzon’s [**Redacted**] (which
    LNA Compounds shall satisfy the obligations of Santaris under Section 5.3),
    Enzon shall pay the required amount under Section 7.3; provided, however,
    in the event that Santaris elects to deliver the LNA Compounds to Enzon more
    frequently than with respect to [**Redacted**] Additional
    Target every [**Redacted**] pursuant
    to Section 5.3, Enzon  shall not be required to pay the amount required under
    Section 7.3 more than once in any [**Redacted**] period
    pursuant to the terms of Section 7.3. Following Enzon’s [**Redacted**],
    which shall last no longer than [**Redacted**],
    Santaris shall at Santaris’ cost provide Enzon with [**Redacted**] and [**Redacted**] of
    substance for [**Redacted**] LNA
    Compounds (identified by Enzon) meeting the applicable Compound Acceptance
    Criteria for an Additional Target (each of which is an Accepted LNA Compound).
    Enzon shall have the right to synthesize or have synthesized by a Third Party,
    at Enzon’s
sole cost, additional quantities of any and all LNA Compounds delivered by Santaris,
    as well as quantities of any additional LNA Compounds disclosed in the written
    reports provided by Santaris pursuant to this Section 5.4 that also meet
    the applicable Compound Acceptance Criteria (each such additional LNA Compound
    synthesized by or for Enzon, if any shall also be an Accepted LNA Compound).

3. Section 5.5 of the Agreement is hereby amended and restated in its entirety as follows:

In-Vitro
      and In-Vivo Profiling by Enzon.
      Enzon shall conduct such additional in-vitro and in-vivo testing
      as it deems appropriate in its sole discretion to select Accepted LNA Compounds
      for further Development. Enzon shall use its Diligent Efforts to determine,
      within [**Redacted**] after
      delivery of [**Redacted**] of
      substance for [**Redacted**] LNA
      Compounds (identified by Enzon) Accepted LNA Compound against each Additional
      Target from Santaris,  whether it wishes to select any Accepted LNA Compound
      to commence [**Redacted**];
      provided, however, if Santaris delivers the Accepted LNA Compound for more
      than [**Redacted**] Additional
      Target in any [**Redacted**] period,
      Enzon shall have an additional period of time equal to the amount of time
      such Accepted LNA Compound was delivered earlier than expected. For example,
      if Santaris delivers Accepted LNA Compound against the [**Redacted**] Additional
      Target on [**Redacted**],
      Enzon shall have [**Redacted**]  to
      determine whether it wishes to select any Accepted LNA Compound to commence
      pre-clinical toxicology studies for Target [**Redacted**] and [**Redacted**] for
      Target [**Redacted**].
      Further, for example if Santaris delivers Accepted LNA Compound against
      the [**Redacted**] Additional
      Targets on [**Redacted**],
      Enzon shall have [**Redacted**] to
      determine whether it wishes to select any 

 

 






Amendment No 3


Accepted LNA Compound to commence [**Redacted**] for Target [**Redacted**] and [**Redacted**] for Target [**Redacted**] from such delivery to make such determination. Each such Accepted LNA Compound selected by Enzon in writing to Santaris shall be designated a “Selected LNA Compound”.

4. The table in Section 6.1(a) of the Agreement is hereby amended and restated in its entirety as follows:

 


	
                        Development Milestone
 	
                         
 	
                        Time to Achieve
 
	
                        
 	
                         
 	
                        
 
	
       
 	
                         
 	
                        [**Redacted**] (or such longer period of time as extended pursuant to Section 5.5) after delivery of one and one-half (1-1/2) grams of substance for two (2) LNA Compounds (identified by Enzon) Accepted LNA Compound against each Additional Target from Santaris 
 
	
      [**Redacted**]
 	
                         
 	
                        (a) [**Redacted**] in respect of [**Redacted**];

            (b) [**Redacted**] after the [**Redacted**]; and 

            (c) in respect of other Selected LNA Compounds, [**Redacted**] after [**Redacted**]
 




5. Section 7.3 of the Agreement is hereby amended and restated in its entirety as follows:

Selected LNA Compound Acceptance Fees. Within thirty (30) days after the delivery by Santaris of [**Redacted**] of each of [**Redacted**] LNA Compounds that meet the Compound Acceptance Criteria for Enzon’s [**Redacted**] for an Additional Target pursuant to Section 5.4, Enzon shall pay US[**Redacted**] with respect to each of [**Redacted**] Additional Targets; provided, however, in the event that Santaris elects to deliver the LNA Compounds meeting the Compound Acceptance Criteria for more than [**Redacted**] Additional Target in any [**Redacted**] period, Enzon shall not be required to pay the amount required under this Section 7.3 more than once in any [**Redacted**] period. For example, if Santaris delivers 

 

 






Amendment No 3


[**Redacted**] of
    each of [**Redacted**] LNA
    Compounds that meet the Compound Acceptance Criteria for Enzon’s [**Redacted**] for [**Redacted**] Additional
    Targets on [**Redacted**] and
    delivers another [**Redacted**] of
    each of [**Redacted**] LNA
    Compounds that meet the Compound Acceptance Criteria for Enzon’s [**Redacted**] for [**Redacted**] Additional
    Target on [**Redacted**],
    Enzon shall owe Santaris a payment on [**Redacted**] for
    the [**Redacted**] Additional
    Target, a payment on [**Redacted**] for
    the second Additional Target, and a payment on [**Redacted**] of
    the [**Redacted**] for
    the [**Redacted**] Additional Target. If the first Event Milestone Payment
    payable under Section 7.4 in respect of any Additional Target is payable
    before the amount payable under this Section 7.3 in respect of such Additional
    Target is payable, such amount payable under this Section 7.3 shall be paid
    at the same time as such Event Milestone Payment is payable. For the purpose
    of Section 10.4(b)(ii), the amounts payable under this Section 7.3 shall
    accrue upon delivery of such quantities of LNA Compounds meeting the Compound
    Acceptance Criteria for an Additional Target, even if the payment may be
    deferred as provided above.

6. The fourth section of Schedule 5.4.A of the Agreement is hereby amended and restated in its entirety as follows:

[**Redacted**].

7. The last section of Schedule 5.4.A of the Agreement is hereby amended and restated in its entirety as follows:

[**Redacted**].

5. Except as set forth in this Amendment, the Agreement shall remain in full force and effect.

6. Resolution of all disputes arising out of or related to this Amendment or the performance, enforcement, breach or termination of this Amendment and any remedies relating thereto, shall be governed by and construed under the substantive Laws of the State of New York, without regard to conflicts of law rules that would provide for application of the Law of a jurisdiction outside New York. To the extent there is any such dispute, such dispute will be handled in accordance with the procedures set forth in Section 13 of the Agreement.

7. This Amendment may be executed in two or more counterparts (including by facsimile or pdf file) each of which shall be deemed an original, but all of which together shall constitute one and the same instrument.

 

 







Amendment No 3


IN WITNESS WHEREOF, the Parties have executed this Amendment in duplicate originals by their proper officers as of the date and year first above written.

 


	
                        SANTARIS PHARMA A/S
 	
                         
 	
                        ENZON PHARMACEUTICALS, INC.
 
	
                         
 	
                         
 	
                         
 
	
                         
 	
                         
 	
                         
 
	
                        By: 
 	
                         /s/ Keith McCullagh
 	
                         
 	
                        By: 
 	
                        /s/
                            Ivan Horak
 
	
                         
 	
                        
 	
                         
 	
                         
 	
                        
 
	
                        NAME: 
 	
                        Keith McCullagh
 	
                         
 	
                        NAME: 
 	
                        Ivan
                            Horak
 
	
                        TITLE: 
 	
                        Chief Executive Officer
 	
                         
 	
                        TITLE: 
 	
                        Chief
                            Scientific Officer
 




 


	
                        By: 
 	
                         Henrik Stage
 	
                         
 	
                        By: 
 	
                        /s/ Ralph
    del Campo
 
	
                         
 	
                        
 	
                         
 	
                         
 	
                        
 
	
                        NAME: 
 	
                        Henrik Stage
 	
                         
 	
                        NAME: 
 	
                        Ralph
                            del Campo
 
	
                        TITLE: 
 	
                        Chief Financial Officer
 	
                         
 	
                        TITLE: 
 	
                        EVP
                            Technical Operations