SECOND OMNIBUS AMENDMENT

Exhibit 10.3

SECOND OMNIBUS AMENDMENT

This SECOND OMNIBUS AMENDMENT (this “Second Amendment”) is made and entered into as of March 5, 2012, by and among Tang Capital Partners, LP, RTW Investments, LLC, Galena Biopharma, Inc. (formerly RXi Pharmaceuticals Corporation) and RXi Pharmaceuticals Corporation (formerly RNCS, Inc.).

WHEREAS, the parties entered into a Securities Purchase Agreement dated as of September 24, 2011 (the “Securities Purchase Agreement”) and the Ancillary Agreements related thereto, including the Bridge Notes;

WHEREAS, the parties entered into an Omnibus Amendment dated as of February 6, 2012 (the “First Amendment”), amending certain provisions of the Securities Purchase Agreement and the Bridge Notes;

WHEREAS, the Securities Purchase Agreement, as amended by the First Amendment, in Section 8.01(c) thereof provides that the Agreement may be terminated by either the Company or the Investors if the Closing has not occurred on or before 5:00 p.m., Eastern Standard Time, on March 5, 2012, which date may be extended from time to time by mutual written consent of the Company and the Investors;

WHEREAS, the Bridge Notes dated September 24, 2011 held by the Investors, as amended by the First Amendment, in Section 1.1 thereof each provide for a Maturity Date (as defined in the Bridge Notes) of the earlier of (i) March 5, 2012 or (ii) an Event of Default (as defined in the Bridge Notes);

WHEREAS, the parties desire to amend such provisions of the Securities Purchase Agreement and the Bridge Notes to extend the March 5, 2012 date;

WHEREAS, the parties also desire to amend other provisions of the Securities Purchase Agreement as set forth below;

NOW, THEREFORE, in consideration of the premises and mutual covenants herein, and for other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the parties agree as follows:

1. Securities Purchase Agreement Amendment. The Securities Purchase Agreement, as amended by the First Amendment, is hereby amended as follows:

(a) Section 8.01(c) is hereby amended to replace “March 5, 2012” with “March 31, 2012.

(b) The following new section is added to ARTICLE V:

Section 5.16 Advirna Confirmation. The Company shall have received from Advirna written confirmation, in a form satisfactory to the Investors in their

sole discretion, that the Advirna Amendment remains in full force and effect and that the Company’s rights arising thereunder as of the date of execution remain intact as of the date of such confirmation.

2. Bridge Notes Amendment. The Bridge Notes, as amended by the First Amendment, are hereby amended to replace references to “March 5, 2012” with “March 31, 2012.”

3. Miscellaneous. Capitalized terms used herein and not defined shall have the meanings set forth in the Securities Purchase Agreement or in the Bridge Notes, in each case, as amended, as applicable. The terms and conditions set forth in Article X of the Securities Purchase Agreement are incorporated herein by reference. Nothing herein shall constitute a waiver of any provision of the Securities Purchase Agreement or any of the Ancillary Documents pursuant to Section 10.03 of the Securities Purchase Agreement.

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IN WITNESS WHEREOF, the parties hereto have executed this Second Amendment as of the date first above written.

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