FIRST SUPPLEMENTAL INDENTURE

Exhibit 4.1

FIRST SUPPLEMENTAL INDENTURE

ENZON PHARMACEUTICALS, INC.,

AS ISSUER

AND

WILMINGTON TRUST COMPANY,

AS TRUSTEE

FIRST SUPPLEMENTAL INDENTURE
DATED AS OF AUGUST 25, 2008

     FIRST SUPPLEMENTAL INDENTURE, dated as of August 25, 2008, between Enzon Pharmaceuticals, Inc., a corporation incorporated under the laws of the State of Delaware (the “Company”), as issuer and Wilmington Trust Company, a Delaware banking corporation (the “Trustee”), as trustee.

     WHEREAS, the Company and the Trustee are parties to an Indenture, dated as of May 23, 2006 (the “Indenture”), pursuant to which the Company issued its 4.0% Convertible Senior Notes Due 2013 (the “Notes”);

     WHEREAS, the Board of Directors of the Company has determined that it is in the best interests of the Company to authorize and approve amendments (the “Proposed Amendments”) to the Indenture;

     WHEREAS, Section 10.2 of the Indenture provides that the Company and the Trustee may amend the Indenture and the Notes with the written consent of the Holders of not less than a majority in aggregate principal amount of the Notes then outstanding;

     WHEREAS, the Company has distributed a Consent Solicitation Statement, dated August 11, 2008 as amended on August 12, 2008 and August 18, 2008 (as so amended, the “Solicitation Statement”), and accompanying Consent Letter to the Holders of the Notes in connection with the Proposed Amendments as described in the Solicitation Statement;

     WHEREAS, the Holders of not less than a majority in aggregate principal amount of the Notes outstanding have approved the Proposed Amendments to the provisions of the Indenture; and

     WHEREAS, the execution and delivery of this instrument have been duly authorized and all conditions and requirements necessary to make this instrument a valid and binding agreement have been duly performed and complied with;

     NOW, THEREFORE, for and in consideration of the premises and other good and valuable consideration, receipt and sufficiency of which are hereby acknowledged, it is mutually covenanted and agreed, for the equal proportionate benefit of all Holders of the Notes, as follows:

ARTICLE 1. AMENDMENT OF SECTION 1.1, 3.10, ARTICLE IV AND SECTION 6.5

     Section 1.01. The definition of “Fundamental Change” in Section 1.1 of the Indenture is hereby deleted and replaced in its entirety as follows:

     ““ Fundamental Change ” will be deemed to have occurred at the time after the Notes are originally issued that any of the following occurs:

(1) the Common Stock (or other common stock into which the Notes are convertible) is neither traded on NASDAQ or the NYSE or another U.S. national securities exchange or quoted on another established automated over-the-counter trading market in the United States; or

(2) any Person acquires Beneficial Ownership, directly or indirectly, through a purchase, merger or other acquisition transaction or series of transactions, of shares of the Company’s Capital Stock entitling such Person to exercise 50% or more of the total voting power of all shares of the Company’s Capital Stock entitled to vote generally in elections of directors, other than an acquisition by the Company, any of its Subsidiaries or any of the Company’s employee benefit plans; or

(3) the Company merges or consolidates with or into any other Person (other than a Subsidiary), or another Person (other than a Subsidiary) merges with or into the Company, other than any transaction:

(a) that does not result in a reclassification, conversion, exchange or cancellation of the Company’s outstanding Common Stock; or

     (b) pursuant to which the holders of the Common Stock immediately prior to the transaction have the entitlement to exercise, directly or indirectly, 50% or more of the voting power of all shares of Capital Stock entitled to vote generally in the election of directors of the continuing or surviving corporation immediately after the transaction; or

     (c) which is effected solely to change the Company’s jurisdiction of incorporation and results in a reclassification, conversion or exchange of outstanding shares of the Common Stock solely into shares of common stock of the surviving entity; or

(4) the Company conveys, sells, transfers or leases all or substantially all of the Company’s assets to another Person; or

(5) at any time the Continuing Directors do not constitute a majority of the Company’s Board of Directors (or, if applicable, a successor Person to the Company).

(6) For purposes of this definition and Section 3.10 hereof, “Person” includes any syndicate or group that would be deemed a person under Section 13(d)(3) of the Exchange Act.”

     Section 1.02. Section 3.10 of the Indenture is hereby amended as follows:

               (a) The words “under clause (2) or (3)” in subsection (b)(2) are replaced by the words “under clause (2), (3) or (4)”.

               (b) The words “identified in clauses (2), (3) or (4)” in the first paragraph of subsection (f) are replaced by the words “identified in clauses (2), (3), (4) or (5)”.

               (c) The words “under clauses (3) or (4)” in subsection (f)(1)(B) are replaced by the words “under clauses (3), (4) or (5)”.

               (d) The words “under clause (2) a