Document:

Exhibit 10.5

 

AMENDMENT NO. 4

 

AMENDMENT TO

LICENSE AND COLLABORATION AGREEMENT

 

THIS AMENDMENT TO LICENSE AND COLLABORATION
AGREEMENT (this “Amendment”), is entered into this 8th day of July, 2009 (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 2007, Amendment No. 2 dated 25th of June 2007, and Amendment No. 3 dated 21st
of December 2007; and

 

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

 

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 8.1 (c) of the Agreement is hereby amended and restated in its entirety as follows:

 

(c) In Respect of all LNA Compound Patents:

 

(i)      Santaris and Enzon shall jointly own the right, title
and interest in and to all provisional and other priority LNA Compound Patent applications regardless of inventorship; and without
the need for any further action by a Party and subject to the licenses granted hereunder.

  

(ii)     At the time of filing of each international patent
application filed under the Patent Cooperation Treaty (a “PCT Application”), if not already jointly owned, Santaris
and Enzon shall jointly own the right, title and interest in and to such PCT Application, regardless of inventorship; and without
the need for any further action by a Party and subject to the licenses granted hereunder. Santaris agrees to assign, and herby
does assign, such right, title and interest in and to any LNA Compound Patents to Enzon so that Santaris and Enzon shall jointly
own such LNA Compound Patents. For clarity, such a PCT Application shall be filed in both Santaris and Enzon names.

 

(iii)     At the time each PCT Application enters the national
or regional phase in any country or region in the Santaris Territory, Enzon agrees to assign, and hereby does assign, such right,
title and interest in and to any such LNA Compound Patent to Santaris so that Santaris shall

 

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(iv)     At the time each PCT Application enters the national
or regional phase in any country or region in the Enzon Territory, Santaris and Enzon shall continue to jointly own such LNA Compound
Patent in all countries in the Enzon Territory.

  

(v)     Promptly after the Effective Date, Santaris shall
assign and hereby does assign, to Enzon such right, title and interest in and to all existing LNA Compound Patents listed on Schedule
1.57 that are PCT Applications or have entered the national phase in any country in the Enzon Territory so that Santaris and Enzon
shall jointly own such LNA Compound Patents, except for those that have already entered the national or regional phase in any country
or region in the Santaris Territory so that Santaris shall continue to own those LNA Compound Patents in the Santaris Territory.

 

(vi)     If any given LNA Compound is not selected as
a Selected LNA Compound by the latest date required by the Agreement, Enzon agrees to assign, and herby does assign, such right,
title and interest in and to any LNA Compound Patents covering such LNA Compound to Santaris.

 

(vii)     If Enzon discontinues all Development or
Commercialization activities of all Selected LNA Compounds claimed under an LNA Compound Patent jointly owned by the Parties,
Enzon shall then assign its entire, right, title and interest in such LNA Compound Patent to Santaris.

 

(viii)     Except to the extent permitted under Section
2.4 or with the prior written consent of Santaris, Enzon shall not assign, license, grant, suffer, permit or otherwise transfer
any license, rights, security interest, lien or other encumbrance, or other interest of any kind in such LNA Compound Patents
(except in connection with an assignment pursuant to Section 14.8).

  

		3.	Section 8.2 (c) of the Agreement is hereby amended and restated in its entirety as follows:

 

(c) LNA Compound Patents. With respect to inventions
made with no inventive contribution by Santaris’ employees, Enzon shall initially file and prosecute all provisional and
other priority patent applications which at least shall be filed in the United States. The parties shall jointly prepare the PCT
Applications derived from such provisional and other priority patent applications and each of Santaris and Enzon shall have the
right to approve the initial filing of the PCT Applications. Enzon shall file, prosecute and maintain such PCT Applications for
the benefit of both Parties.

 

With respect to inventions made with inventive contribution
by Santaris’ employees, Santaris shall initially file and prosecute all provisional and other priority patent applications
which at least shall be filed in the United States. The parties shall jointly prepare the PCT Applications derived from such provisional
and other priority patent applications and each of Santaris and Enzon shall have the right to approve the initial filing of the
PCT Applications. Santaris shall file, prosecute and maintain such PCT Applications for the benefit of both Parties.

 

At the time each such PCT Application enters the national
or regional phase in any country in the Santaris Territory, Santaris shall thereafter direct the filing, prosecution (including
any interferences, oppositions, reissuance, and re-examinations) and maintenance of all LNA Compound Patents in countries in the
Santaris Territory.

 

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At the time each such PCT Application enters the national
or regional phase in any country in the Enzon Territory, Enzon shall thereafter direct the filing, prosecution (including any interferences,
oppositions, reissuance, and re-examinations) and maintenance of all LNA Compound Patents in countries in the Enzon Territory.

  

The Party having the right to prosecute in accordance
with the foregoing is referred to as the “Prosecuting Party”. Prosecuting Party shall provide the other Party promptly
with copies of all patent applications, correspondences and other communications relating to LNA Compound Patents to and from patent
offices and provide the other Party at least sixty (60) days to offer comments. Prosecuting Party shall consider in good faith
any comments the other Party may have with regard to the preparation, filing, prosecution and/or maintenance of the patent applications
and patents related to such LNA Compound Patents. Prosecuting Party shall provide the other Party, a reasonable time prior to taking
or failing to take action that would affect the scope or validity of rights under any LNA Compound Patent (including substantially
narrowing or canceling any claim without reserving the right to file a continuing or divisional application, abandoning any patent
or not filing or perfecting the filing of any patent application in any country), with notice of such proposed action or inaction
so that the other Party has a reasonable opportunity to review and make comments, and take such actions as may be appropriate in
the circumstances. However, the foregoing three sentences shall not apply to the prosecution of national or regional phase applications
in the Santaris Territory, except that Santaris shall keep Enzon informed of the material progress of such prosecution and shall
provide such documents and take such actions as may be reasonably required to facilitate the prosecution of corresponding Patents
in the Enzon Territory.

 

The Parties and their patent counsel shall establish
such procedures as may be desired to carry out the mutual review and consultation procedure contemplated under this Section 8.2
(c) without imposing unreasonable burdens and delays on the prosecution of the LNA Compound Patents. If Enzon, as the Prosecuting
Party, determines not to file, prosecute, defend or maintain any LNA Compound Patent (including failing to defend any interference
or opposition proceedings) in any country, and providing that no other patent applications or patents containing the same claims
are pending or issued in that same country, then Enzon shall provide Santaris with thirty (30) days prior written notice of such
determination and Santaris shall have the right and opportunity to file, prosecute, defend and/or maintain such patent or patent
application at Santaris’ sole cost and expense.

 

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

 

5.     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 Jurisdiction outside of 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.

  

6.     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.

 

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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/SENZON PHARMACEUTICALS, INC.

 

 

	By: /s/Soren Tulstrup	By: /s/Ivan Horak
	Name: Soren Tulstrup	Name: Ivan Horak
	Title: President & CEO	Title: EVP – R&D, CSO
	 	 
	 	 
	 	 
	By: /s/Maja Boyko	By: /s/Paul Davit
	Name:  Maja Boyko	Name: Paul Davit
	Title: Director - IP	Title: EVP - HR

 

    	4Exhibit 10.6

 

AMENDMENT NO. 5

 

AMENDMENT TO

LICENSE AND COLLABORATION AGREEMENT

 

THIS
AMENDMENT TO LICENSE AND COLLABORATION AGREEMENT (this “Amendment”), is entered into this 2nd day
of October 2009 (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”.

 

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, Amendment No 2 dated 25th of June 2007 and Amendment No
3 dated 21st of December 2007.

 

WHEREAS, Enzon and
Santaris desire to amend and restate certain provisions of the Agreement to provide for substitution of targets for purposes of
certain development milestones.

 

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.  A new Section 6.1(j) is hereby
added to read in its entirety as follows:

 

Interchange
of Targets. Notwithstanding the provisions of Section 6.1(a), Enzon shall have the right to accelerate the Development of one
Accepted LNA Compound and delay the Development of another Accepted LNA Compound by substituting one Accepted LNA Compound for
another for purposes of achieving the first development milestones set forth in Section 6.1(a); provided that if Enzon exercises
this right, it shall not have the right to extend pursuant to Section 6.1(b) the first development milestone for the Accepted LNA
Compound for which Development was advanced. Upon substitution of the first development milestone, the second development milestone
shall be accordingly substituted (so that the second development milestone date is 18 months after the first development milestone
date for such Accepted LNA Compound). For illustration purposes only, if compound 1 has a first development milestone (i.e. select
an Accepted LNA Compound for Development and commence pre-clinical toxicology study) on September 1, 2009 and a second development
milestone (i.e. filing of an IND) on April 1, 2011 and compound 2 has a first development milestone on February 1, 2010 and a second
development milestone on August 1, 2011, Enzon may elect to achieve the compound 1 first development milestone with compound 2.
Upon such substitution, the second milestone date for compound 1 shall become August 1, 2011 and the second milestone date for
compound 2 shall become April 1, 2011. Thereafter, Enzon could not elect to extend the first development milestone for compound
2 (i.e. the compound which was advanced) pursuant to Section 6.1(b); however, Enzon could elect to extend the first milestone for
compound 1 or the second milestone for compound 1 or compound 2 pursuant to Section 6.1(b). Any payments required by Enzon for
the achievement of milestones pursuant to Section 7.4(a)(i) or 7.4(a)(ii) shall reflect any substitution of Accepted LNA
Compounds pursuant to this Section 6.1(j).

 

3.The Parties have agreed that the
contractual milestone start dates for the LNA Lead Candidates that Santaris Pharma has delivered to Enzon on the six novel discovery
targets shall be the following:

 

	Clock start for Next Milestone	Milestone Due Date: Select
	(Delivery of 2 LNA compounds)	Preclinical Lead

 

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	HER3	April 3, 2008	October 3. 2009
	Beta-Catenin	June 3, 2008	February 3, 2010
	AR	October 15, 2008	April 15, 2010
	PIK3CA	October 15, 2008	August 15, 2010
	HSP27	December 17, 2008	August 17, 2010
	Gli2	April 20, 2009	October 20, 2010

 

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

 

5.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.

 

6.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.

 

 

 

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/Soren Tulstrup	By: /s/Ivan Horak
	 	 
	NAME: Søren Tulstrup	NAME: Ivan Horak
	TITLE: Chief Executive Officer	TITLE: EVP – R&D, CSO
	 	 
	 	 
	By: /s/Henrik Stage	By: ______________________
	 	 
	NAME: Henrik Stage	NAME:
	TITLE: Chief Financial Officer	TITLE:

 

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