<SUBMISSION>
<ACCESSION-NUMBER>0000950123-09-017224
<TYPE>424B3
<PUBLIC-DOCUMENT-COUNT>1
<FILING-DATE>20090625
<DATE-OF-FILING-DATE-CHANGE>20090625
<FILER>
<COMPANY-DATA>
<CONFORMED-NAME>RXI PHARMACEUTICALS CORP
<CIK>0001390478
<ASSIGNED-SIC>2834
<IRS-NUMBER>000000000
</COMPANY-DATA>
<FILING-VALUES>
<FORM-TYPE>424B3
<ACT>33
<FILE-NUMBER>333-158968
<FILM-NUMBER>09909443
</FILING-VALUES>
<BUSINESS-ADDRESS>
<STREET1>60 PRESCOTT  STREET
<CITY>WORCESTER
<STATE>MA
<ZIP>01605
<PHONE>508-767-3861
</BUSINESS-ADDRESS>
<MAIL-ADDRESS>
<STREET1>60 PRESCOTT  STREET
<CITY>WORCESTER
<STATE>MA
<ZIP>01605
</MAIL-ADDRESS>
</FILER>
<DOCUMENT>
<TYPE>424B3
<SEQUENCE>1
<FILENAME>b76044rxe424b3.htm
<DESCRIPTION>RXI PHARMACEUTICALS CORPORATION
<TEXT>
<HTML>
<HEAD>
<TITLE>e424b3</TITLE>
</HEAD>
<BODY bgcolor="#FFFFFF">
<!-- PAGEBREAK -->
<DIV style="font-family: 'Times New Roman',Times,serif">


<DIV align="right" style="font-size: 10pt; margin-top: 12pt"><B>Filed pursuant to Rule&nbsp;424(b)(3)<BR>
Registration No.&nbsp;333- 158968</B>
</DIV>


<DIV align="left" style="font-size: 10pt; margin-top: 12pt"><B>PROSPECTUS SUPPLEMENT NO. 1</B>
</DIV>


<DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>RXi PHARMACEUTICALS CORPORATION</B>
</DIV>


<DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;This prospectus supplement amends the prospectus included in the registration statement on
Form S-3 filed May&nbsp;4, 2009 and declared effective May&nbsp;22, 2009, related to the resale from time to
time by a stockholder of up to 500,000 shares of common stock of RXi Pharmaceuticals Corporation
(the &#147;Company&#148;) and the offer and sale from time to time by the Company of up to $30,000,000 of
securities of the Company which may take the form of equity, debt or warrants (the &#147;Prospectus&#148;).
</DIV>

<DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;This prospectus supplement provides supplemental information to the Prospectus concerning the
Plan of Distribution. The fifth paragraph in the section &#147;Plan of Distribution &#150; Secondary
Securities&#148; on page 7 of the Prospectus is replaced with the following:
</DIV>
<DIV align="left" style="font-size: 10pt; margin-top: 6pt">&#147;CytRx and any broker-dealers or agents that participate in the sale of the Secondary Securities
may be deemed to be &#147;underwriters&#148; within the meaning of Section&nbsp;2(11) of the Securities Act. Any
discounts, commissions, concessions or profit they earn on any resale of the shares may be
underwriting discounts and commissions under the Securities Act. Under no circumstances will any
fees, discounts, commissions or concessions received by any FINRA member or independent
broker-dealer exceed eight percent of the gross proceeds to CytRx in any offering in the United
States of the Secondary Securities covered by the prospectus. CytRx is subject to the prospectus
delivery requirements of the Securities Act.&#148;
</DIV>


<DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;This prospectus supplement should be read in conjunction with the Prospectus which is to be
delivered with this prospectus supplement.
</DIV>

<DIV align="left" style="font-size: 10pt; margin-top: 6pt">&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;NEITHER THE SECURITIES AND EXCHANGE COMMISSION NOR ANY STATE SECURITIES COMMISSION HAS
APPROVED OR DISAPPROVED OF THESE SECURITIES OR DETERMINED IF THIS PROSPECTUS SUPPLEMENT OR THE
PROSPECTUS IS ACCURATE OR COMPLETE. ANY REPRESENTATION TO THE CONTRARY IS A CRIMINAL OFFENSE.
</DIV>

<DIV align="center" style="font-size: 10pt; margin-top: 18pt"><B>June&nbsp;25, 2009</B>
</DIV>



<P align="center" style="font-size: 10pt"><!-- Folio --><!-- /Folio -->
</DIV>




</BODY>
</HTML>
</TEXT>
</DOCUMENT>
</SUBMISSION>
