SecProbe.io

October 19, 2010
 Russell H. Ellison, M.D. Chief Executive Officer Ventrus Biosciences, Inc.
Re: Ventrus Biosciences, Inc.
Registration Statement on Form S-1 Amendment  No. 1 filed October 4, 2010
  File No. 333-168224

Dear Dr. Ellison:

We have reviewed your amended registra tion statement and have the following
comments.
 Please respond to this letter by amending your registration statement and providing the
requested information.  If you do not believe  our comments apply to your facts and
circumstances or do not believe an amendment is appropriate, please tell us why in your
response.
 After reviewing any amendment to your re gistration statement and the information you
provide in response to these comments, we may have additional comments.
 FORM S-1

Company Overview – General, page 2

1. Please briefly expand the discussion to desc ribe the status of VEN 307 and VEN 308 in
the FDA approval process, when you had meetings with the FDA concerning VEN 307 and VEN 308, and the specific nature of these meetings.  Please provide more detailed
information pertaining to meetings with  the FDA concerning VEN 307 and VEN 308 and
FDA approval process status in the business section.
2. Please expand the discussion to explain what  you mean by the statement that VEN  307
“is essentially ready for Phase III studies….”   Please clarify whether additional approval or work is required prior to the commencement of Phase III studies.

Our Products and Development Strategy, page 2

3. Please update the disclosure to indicate wh ether you filed a revi sed SPA after March
2010 and describe the response, if any, you received from the FDA.

Dr. Russell H. Ellison Ventrus Biosciences, Inc. October 19, 2010 Page 2

 Diltiazem Cream, page 4

4. We note your response to comment 18 and the additional disclosure concerning the
patent application status, speci fically that S.L.A.’s patent application has not yet been
issued.  We also note the statement that “if the continued prosecution of this patent is
unsuccessful, or, if successful, a nd the issued patent is invalidated, we would then have
three years of market exclusivity after appr oval.”  Please expand the discussion to explain
why you would have three years of  exclusivity even if no patent  is ultimately issued.
 “We have had negative cash fl ows from operations…,” page 14

5. We note your response to comments 21 and 22.  Please file the credit agreement with
Paramount Credit Partners and the subsequent wa iver agreement as exhibits or provide an
analysis as to why these agreem ents do not need to be filed.
 “We have issued convertible notes that have a maturity date of December 31, 2010,” page 15

6. The risk factor should speak as of the latest  practicable date and not just June 30, 2010.
Please update the disclosure to reflect any modi fication with respect to the maturity date
or other material terms.  It appears that if the offering is not completed by December 31,
2010, the automatic conversion will not occur and the offering proceeds may be used to
repay this indebtedness.  In  addition, we note the underwri ting agreement has not yet
been filed and there is a 45 day option to cover over-allotm ents.  These factors may tend
to indicate the offering may not be comp leted by December 31, 2010.  In addition to
updating the disclosure, please describe the mate rial effects on the offering, shareholders,
and the company’s financial condition in the event the offering is not completed by
December 31, 2010.
 Management’s Discussion and Analysis of Fi nancial Condition and Results of Operations

Critical Accounting Policies
Accounting for Convertible Debt and Debt Issu ed with Stock Purchase Warrants, page 44

7. Please refer to your response to our prior co mment 38.  Please move the third paragraph
under your accounting policy titled ‘Stock-Bas ed Compensation’ to  the new caption you
added for Convertible Debt.  In addition, pl ease include the new disclosure regarding
how the proceeds from your financing arrangem ents are allocated to  the warrants in your
notes to the financial statements.
 Research and Development Expense, page 44

8. Please refer to your response to our prior comment 40.  We note that you removed the
disclosures for research and developmen t expenses for 2007.  Please revise your
disclosure to include the inception to date  amounts for each project in the table.

Dr. Russell H. Ellison Ventrus Biosciences, Inc. October 19, 2010 Page 3

 Financial Statements

Notes to Financial Statements
 Note 2 – Summary of Significant Accounting Policies:

Warrants – Convertible Notes:, page F-8

9. Please refer to your response to our prior co mment 94.  Please revise your table to
disclose the assumptions used for each pe riod presented.  Please explain why the
volatility percentage used increased from 104.78% to 163%.  This comment also applies
to your disclosure in Note 2 to the interim financial statements.

10. Please revise your disclosure to quantify the a ssumptions used to determine the fair value
of the other warrants disclosed in  other sections of the filing.
 Note 3 – Related Party Transactions:

Notes Payable:, page F-9
Subsequent Event (2010 Senior Convertible Notes):, page F-11

11. Please refer to your response to our prio r comment 93.  If the number of warrants
issuable under a Qualified Financing cannot be calculated revise your disclosure to
quantify the number shares i ssuable under the warrants if  the Qualified Financing does
not occur. Also, please explain to us the assumptions, including the number of warrants
issuable, used to determine the amount allocat ed to the warrants.  This comment also
applies to your disclosure in Note 3 to the interim financial statements.
 Note 7 — License Agreements:, page F-16

12. You disclose that the “Company shall issue to S.L.A. that number of  additional shares of
common stock so that the number of shares fo llowing such issuance have a fair market
value equal to $500,000.”  Please explain to us how you accounted for this obligation
under the license  agreement.
 Note 9 – Subsequent Events:

2010 Senior convertible  notes, page F-19

13. Please refer to your response to our prior comme nt 97.  Your disclosure  is still not clear
regarding the potential adjustments to the number of shares of common stock to be
received upon exercise of the warrants.  Pl ease revise your disclosure to include the
potential adjustments as provided in Section 3 of the Warrant agreements.

Dr. Russell H. Ellison Ventrus Biosciences, Inc. October 19, 2010 Page 4

 Note 10 — Pro Forma Effects of Ce rtain Transactions:, page F-20

14. It appears that your revised disclosure in re sponse to our prior comment 92 will present
the pro forma effect of certain transactions  that are already included in the weighted
average common shares outstanding, such as the issuance of shares, or will include
transactions that will be anti -dilutive to net loss per common share, such as the issuance
of warrants and options.  Please revise your disclosure as appr opriate.  This comment also
applies to your disclosure in Note 8 to the interim financial statements.
 Notes to Unaudited Condensed Financial Statements

 Note 3 – Related Party Transactions:

Notes payable:, page F-27

15. Please refer to your response to our prior comme nt 98.  You disclose that the convertible
secured notes are convertibl e into common stock at a 70%  discount.  Please clarify
whether this should be a 30% discount si milar to your disclosure on page F-36.

16. Please revise your disclosure throughout the document to clarify the expiration date of
your warrants. Your disclosure on pages F-27 an d F-36 state that the warrants expire on
June 30, 2015.  However, your disclosure on page F-11 states that the warrants expire on
March 31, 2015. The disclosure on page II-3 st ates that the warrants expire on February
26, 2015.
 Note 4 – Stockholders’ Deficiency

Common stock options a nd warrants, page F-30

17. Please update the table for warrant activity to in clude all of the warrants outstanding as of
June 30, 2010 as noted in your disclosure  on page 100.  Based on your disclosure
included on page 75 of the original S-1 it a ppears that many of these warrants were
outstanding as of June 30, 2010 and s hould be included in the table.

We urge all persons who are responsible for th e accuracy and adequacy of the disclosure
in the filing to be certain that the filing incl udes the information the Securities Act of 1933 and
all applicable Securities Act rules require.  Since the company and its management are in
possession of all facts relating to a company’s disc losure, they are responsible for the accuracy
and adequacy of the disclosures they have made.
Notwithstanding our comments, in the event you request acceleration of  the effective date
of the pending registration statement please pr ovide a written statement from the company
acknowledging that:

Dr. Russell H. Ellison Ventrus Biosciences, Inc. October 19, 2010 Page 5

 • should the Commission or the staff, acting purs uant to delegated authority, declare the
filing effective, it does not foreclose the Co mmission from taking any action with respect
to the filing;

• the action of the Commission or the staff, acting pursuant to delegated authority, in
declaring the filing effective, does not relieve the company from its full responsibility for
the adequacy and accuracy of the disclosure in the filing; and

• the company may not assert staff comments a nd the declaration of effectiveness as a
defense in any proceeding initiated by the Commission or any person under the federal securities laws of the United States.

 You may contact Vanessa R obertson, Staff Accountant, at (202) 551-3649 or Don
Abbott, Review Accountant, at (202) 551-3608 if you have questions regarding comments on the
financial statements and related matters.  Plea se contact John Krug, Se nior Counsel, at (202)
551-3862, or me at (202) 551-3715 with any other questions.

Sincerely,
     Jeffrey Riedler
Assistant Director

          cc: Alexander M. Donaldson, Esq.      W. David Mannheim, Esq.      Wyrick Robbins Yates & Ponton LLP      4101 Lake Boone Trail, Suite 300      Raleigh, North Carolina 27607