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Mail Stop 6010          November 26, 2007   Tod Woolf, Ph.D.  Chief Executive Officer  RXi Pharmaceuticals Corporation  One Innovation Drive  Worcester, Massachusetts 01605
 Re: RXi Pharmaceuticals Corporation
  Registration Statement on Form S-1
  Filed October 30, 2007
  File No. 333-147009

Dear Dr. Woolf:
  We have reviewed your filing and have the following comments.  Where indicated, we think you should re vise your document in response to these comments.  If
you disagree, we will consider your explanation as to why our comment is inapplicable or
a revision is unnecessary.  Please be as deta iled as necessary in your explanation.  In
some of our comments, we may ask you to provi de us with information so we may better
understand your disclosure.  After reviewing th is information, we may raise additional
comments.   Please understand that the purpose of our re view process is to assist you in your
compliance with the applicable disclosure  requirements and to  enhance the overall
disclosure in your filing.  We look forward to  working with you in these respects.  We
welcome any questions you may have about our comments or any other aspect of our review.  Feel free to call us at the telephone numbers listed at the end of this letter.

FORM S-1

 General

1. We note that you are submitting a number of docum ents in a conf idential treatment
request.  Please note that you will be r eceiving comments to the confidential
treatment request under separate cover and that all conf idential treatment issues
must be resolved before we will consider a request for acceleration of the registration statement.

Tod Woolf, Ph.D.
RXi Pharmaceuticals Corporation  November 26, 2007 Page 2

2. Please file as promptly as possible al l exhibits required by the Exhibit Table
provided in Item
 601(a) of Re gulation S-K.  We note, fo r example, that you have
not filed the opinion or cons ent of your legal counsel.

3. Please note that where we provide exampl es to illustrate what we m ean by our
comments, they are examples and not exhaustive lists.   If our comments are
applicable to portions of th e filing that we have not cited as examples, make the
appropriate changes in acco rdance with our comments.

4. Unless otherwise stated, all comments are ap p licable to the dist ribution prospectus,
award prospectus and resale prospectus.

5. Throughout the registration statement, you c ite various estim ates, statistics and
other figures.  For example:

a. The statement that “The potential market for RNAi therapeutics is substantial” which is found on page 50
b. Information included under the “N eurology – Market Opportunity”
subheading on page 52;
c. The first sentence included under th e “Metabolic Disease – Market
Opportunity” subheading on page 53; and
d. Information included under the “Oncology – Market Opportunity”
subheading on page 53.

In the prospectus, please attribute these st atem
 ents and other similar statements to
the source from which you obtained the in formation. In addition, where you cite
your own estimates, please explain ho w you arrived at those estimates and
disclose any third-part y sources you relied upon.

6. Throughout the registration statement, you s hould clearly articulate the basis of
the various beliefs and assertions you m
ake.  As a non-exclusive example, on
page 1, you state, “It is believed that this  inhibition may potentia lly treat diseases
by ‘turning off’ genes that lead to di sease.”  In this and each similar case
throughout the filing, you should disclose who has expressed the belief and the basis for the belief.  If any of your assertions of beliefs are not supported by ample evidence or knowledge, you should dele te them.  Also, given that you are a
discovery-stage company and none of your therapeutics are in the pre-clinical or clinical stages, you should not  make any assertions rega rding the effectiveness of
any of your therapeutics.

7. Please update your financial information th roughout the filing in accordance with
Rule 3-12 of Regulation S-X.

Tod Woolf, Ph.D.
RXi Pharmaceuticals Corporation  November 26, 2007 Page 3
Prospectus Cover Pages

8. The cover pages of the respective prosp ectuses should contain the information
required by Item
 501(b) of Regulation S-K and not include the other information
you provide.  While we recognize that the information regarding taxation and the
particulars of the distribution are important  to investors, you should articulate that
information more prominently at the beginning of the Summary, rather than on
the cover page.
 Prospectus Summary, page 1

9. We note that you state here on page A-1 that  all share data in these prospectuses
assum
es no effect to any possible resale of your shares by CytRx pursuant to the
resale prospectus.  We further note that  on page B-80 of the resale prospectus, you
state that CytRx intends to sell all of it s remaining 49% ownership interest in the
company.  Please revise the disclosure throughout the distribution prospectus and
award prospectus to reflect that CytRx plans to sell all of its shares.  You should
also disclose what specific arrangements,  if any, that CytRx has initiated to
facilitate the sale of its remaining shares.
 RXi Pharmaceuticals Corporation, page 1

10. Since you are still a discove ry-stage com pany, please remove all references to
commercialization from your business de scription here, pages 5 and 48 and
elsewhere as appropriate.

11. We note that the information provided in  “Our Business” and  “Our Competitive
Strengths” is identical to the information provided on pages 48-29 and the information provided in “Business Strate gy” is identical to the information
provided on pages 54-55.  Please revise this  discussion to high light the key points
of these topics rather than re peating the same disclosure.

12. Throughout the Summary and rest of the pr ospectus you m
 ention the contributions
of your scientific advisory board members.  Please clarify briefly in the Summary and in more detail in the rest of the pr ospectus exactly what role each of these
advisors will have in the development of your therapeutics.  Also, clarify how
much time they will devote to the co mpany, as opposed to other professional
endeavors.
 13. You state throughout the filing that some of your advisory board members are “lead
ing” researchers.  In each case, please explain the basis for these assertions or
delete them.

Tod Woolf, Ph.D.
RXi Pharmaceuticals Corporation  November 26, 2007 Page 4
The Distribution, page 5

14. Please provide more information on why you believe the partial distribution of the
com
pany’s common stock will establish your company as one of the leading
companies dedicated to developing RXi ther apeutics as stated  here and on page
27.

15. Please revise the section entitled “Relationship w ith CytRx after the Distribution,”
pages 23 and 30 and elsewhere as appr opriate to state that following the
distribution, CytRx intends to sell all of its remaining 49% ownership interest in
the company under the Resale Pros pectus as stated on page B-80.

16. In the Summary, and in more detail later in the prospectus, explain why CytRx is not distributing all of the RXi shares it owns, and why it has decided to offer for
resale the 49
% stake it will own i mmediately after the distribution.
 Risk Factors, page 11

 “We may be unable to achieve some or all of the benefits that we expect to achieve…”
page 11

17. It appears from the last sentence of this  risk factor that the com pany faces
additional risks other than “not achieving some or all of the benefits” that it
expects to achieve.  For example, please expand the risk factor  or add separate
risk factors to discuss why the company may not be able to raise funds as a
separate company that might have been available to a combined company.  Also,
we note from your disclosure on page 44 that the company has and will continue to have significant increased expenses as a separate company.  Please describe and quantify these increased expenses.  In addition, please revi se the heading of
this risk factor to accurately describe this risk, highlighting that, as a separate company, it not be able to receive the same amount of benefits it currently has as a combined company.
 “You may have difficulty evaluating our business…” page 11

 18. Please separate into a separate risk factor  the last paragraph of this section which
discusses th
e risk that the company may not be able to effectively operate as a
separate company.  Please use the last sent ence of the current risk factor heading
as the heading of this new risk factor.
 “We may not be able to obtain financing…” page 12

19. Please separate into a separately headed risk factor the last paragraph of this
section which discusses the risks asso
ciated with the company’s issuance of debt

Tod Woolf, Ph.D.
RXi Pharmaceuticals Corporation  November 26, 2007 Page 5
or equity in the future.  Please expa nd your discussion to thoroughly discuss the
risks associated with these possible issuances.
 “We expect to continue to incur significant research and development expenses…” page
12

20. Please delete the statement, “If the actual  funds required exceed  our estimates” as
this appears to be inconsistent with your  statem
ent in the prior sentence that you
are unable to estimate the actual funds re quired to develop and commercialize the
products.

21. Please delete the reference to “lower than anticipated revenues” as it appears from
your disclosure on page 10 that you do not currently have any anticipated
revenues.
 “We will no longer be able to rely on CytRx…” page 13

22. We note your reference to “commercializing”  your products in the last paragraph
of this risk f
actor.  Since you are still in the developing stage, please revise this to
be “developing” your products.

23. You state that following the distribution, you will be m ore susceptible to specific
risks relating to RNAi technologies.  Pleas e add separate risk factors to explain
these specific risks to the extent there are any additional risks that you have not
disclosed in the other risk factors.

“We will rely upon third parties for the manufacture of our clinical product candidates.”
page 14

24. Please name the specialty organic chem istry synthesis com pany with which you
intend to manufacture nanotransporters.

25. In addition, please describe how th e com pany intends to use these
nanotransporters once they are manufactured.  For example, does the company
intend to use these to identify lead compounds?

26. To the extent the company is aware of  any litig ation, threat ened litigation or
challenge to the company’s intellectual pr operty, please revise to describe here
and in the first complete risk factor on page 19.
 “Any drug candidates we develop may fail in development…” page 14

27. Please separate into a separately headed ri sk factor the fact th at the company has
not yet any nominated lead compounds fo r therapeutic development nor has the

Tod Woolf, Ph.D.
RXi Pharmaceuticals Corporation  November 26, 2007 Page 6
company begun any pre-clinical trials .  Please expand your discussion to
thoroughly discuss the risks associated with  the fact that no lead compounds have
been identified.
 “We are dependent on technologi es we license…” page 19

28. Please file a copy of your license ag reem ent with Caregie Institution of
Washington as discussed here and on page 37.
 “We use biological and hazardous materials…” page 21

29. Please disclose your level of workers’  com pensation insurance coverage and
briefly describe what potential liabilities  are and are not covered.  Please also
disclose the cost to you of such coverage, if material.
  “The market price of our common stock…” page 22

30. If any of the factors you have  listed in the bullets in this risk factor represent
m
aterial risks to investors in your common stock, you should discuss them in
more detail in separate prope rly captioned risk factors.
 The Founding and Initial Fundiong of RXi, page 28

31. Please clarify here who will own the remaining 14% of the company.
 Results of the Distribution, page 29

32. Please clarify whether the approximate num ber of holders that you will dis close
represents record or beneficial ownership.
 Management’s Discussion and Analysis of Financial Condition and Results of
Operations, page 35
 Strategic Licenses and Alliances, page 36

 33. Please revise to discuss the company’s planned product research and developm
 ent
over the next 12 months, including, but not limited to, any development within the
scope of the described strategic relationships.

34. It appears that your license  agreem ent with TriLink is a material agreement
pursuant to Item 601(b)(10) of Regulati on S-K.  Please file a copy of this
agreement with your next amendment.  A lternatively, if you do not believe this is
a material agreement, please provide an analysis of why you believe this is not a material agreement.

Tod Woolf, Ph.D.
RXi Pharmaceuticals Corporation  November 26, 2007 Page 7

Basis of Presentation, page 37

35. It appears that your sponso red research agreem ent with Massachusetts General
Hospital is a material agreement pursuant to Item 601(b)(10) of Regulation S-K.
Please file a copy of this agreement with your next amendment.  Alternatively, if you do not believe this is a material agreem ent, please provide an analysis of why
you believe this is not a material agreement.
 Liquidity and Capital Resources, page 45

36. We note that you state that you have ad equate working capital to support your
currently planned level of operations through the first quarter of 2009.  Please
expand your discussion to disclose your  sources of working capital and your
m
aterial commitments.
 Quantitative and Qualitative Disclosu res About Market Risk, page 47

37. To the extent material, please include the inform ation required by Item 305(a) of
Regulation S-K.  Note that this item lists three possible disclosure alternatives from which you may present this informa tion.  Alternatively, if you believe the
risk is not material, please revise to so indicate.
 Business, page 48

 License Agreements, page 59

38. Please revise the first sentence of this  paragraph to indicate that the UM MS
license agreements which were assign ed by CytRx included four exclusive
licenses, one co-exclusive license and one non-exclusiv e license.  In addition,
please revise the name of Exhibit 10. 13 in your exhibit index accordingly.

39. Please revise your discussion of your agreement with Cold Spring Harbor Laboratory to discuss the m
aterial terms of this agreement, including, but not
limited to any payment provisions, the ex istence of royalty provisions, aggregate
milestones, usage restrictions, exclusivity  provisions, obligations/rights to defend,
other rights obtained and material obliga tions that must be met to keep the
agreement in place, duration and termination provisions.
 Government Regulation, page 62

40. Please define cGMP the first tim e you use the acronym.

Tod Woolf, Ph.D.
RXi Pharmaceuticals Corporation  November 26, 2007 Page 8
Executive Compensation, page 72

41. We note your disclosure that the compa ny did not pay any compensation or grant
any equity awards to any em
ployee pr ior to 2007, however, pursuant to Item
402(a)(2) of Regulation S-K, the Item re quires “disclosure of all plan and non-
plan compensation awarded to, earned by, or  paid to the named executive officers
designated under paragra ph (a)(3) of this Item, and directors covered by
paragraph (k) of this Item, by any person for all services rendered in all
capacities to the registrant and its subsidiaries, unless otherwise specifically
excluded from disclosure in this Item.”  (emphasis added).  Please provide the
required information for any of the persons covered in Item 402(a)(3) in the last
fiscal year.  Alternately, if  the direct or indirect expenses for such persons
render