SecProbe.io

August 16, 2010
 Russell H. Ellison, M.D. Chief Executive Officer Ventrus Biosciences, Inc.
Re: Ventrus Biosciences, Inc.
Registration Statement on Form S-1 Filed July 20, 2010
  File No. 333-168224

Dear Dr. Ellison:

We have reviewed your registration statem ent and have the following comments.  In
some of our comments, we may ask you to provi de us with information so we may better
understand your disclosure.
 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

General
 1. Please provide us proofs of all graphic, visual, or photographic information you will provide
in the printed prospectus prior to its use, fo r example in a preliminary prospectus.  Please
note we may have comments regarding these materials.
 2. Please note that where we provide examples to illustrate what we mean by our comments,
they are examples and not complete lists.  If our comments are applicab le to portions of the
filing that we have not cited as examples, pleas e make the appropriate changes in accordance
with our comments.
 3. Please update the discussion in your prospect us to the most recent date practicable.
 4. Please note that our comments on your request for confidential treatment will be provided
under separate cover.  Please be advised that we will not be in a position to consider a request

Dr. Russell H. Ellison Ventrus Biosciences, Inc. August 16, 2010 Page 2

 for acceleration of effectiveness of the regist ration statement until we resolve all issues
concerning the confidential treatment request.
 5. Please note that when you file a pre-eff ective amendment containing pricing-related
information, we may have additional comments.  As you are likely aware, you must file this
amendment prior to circ ulating the prospectus.
 6. Please note that when you file a pre-effectiv e amendment that include s your price range, it
must be bona fide.  We interpret this to m ean that your range may not exceed $2 if you price
below $20 and 10% if you price above $20.
 Prospectus Cover Page

 7. Please revise the reference to possible listing to simply state whether you  expect to apply for
listing or, if true, that you have applied for lis ting.  In addition, until your listing application
is approved, the disclosure s hould indicate that you have not received approval of your listing
application.
 Industry and Market Data, page 1

8. We note your statements concerning the lack of any guarantee for the accuracy of third party
data, that you have not verified the informati on contained in the third party sources you have
used, and the accuracy of the results and estima tes of your research has not been verified by
independent sources.  One may infer from these statements that you do not take responsibility for information from third pa rties you include in the prospectus.  Please
remove this language, or expand the disclosure  to clearly state that  you are liable for the
information in your prospectus.
 Company Overview, page 2

 9. Please include a separate section describing your business strategy and how you intend to
develop and commercialize your proposed products .  In this regard, we note you currently
have no employees.
 10.  Please reconcile your referen ce to your development of VEN 309 and 308 with the fact you
have no employees, i.e. how did you “develop” these candidates.
 11.  Please provide the basis for your statements concerning the size of the global market for
gastrointestinal disorders a nd the number of people in th e United States suffering from
hemorrhoids, fecal incontinence, and anal fissures, respectively.
 12. Please expand the discussion to clarify what portion of the $31 billion mark et is attributed to
each of the specific type of products and servi ces you provide or intend to provide.  If you do

Dr. Russell H. Ellison Ventrus Biosciences, Inc. August 16, 2010 Page 3

 not intend to serve the global market, the disc ussion of your anticipated  market should be
revised accordingly.
 13.  Please disclose whether and when you filed applications with the FDA for your proposed
products.
 14.  The prospectus summary section should provide a balanced presentation of the information
presented in the body of the filing.  As curre ntly written, your summary focuses only on the
positive attributes of the compa ny.  Please balance the current discussion with a discussion of
the challenges and risks you f ace, at least as prominent and detailed as your current
discussion of your positive attrib utes, including a discussion of:
• The lack of revenues from your development stage operations;
• The challenges you face to obtai n FDA approval of your products;
• The fact your independent auditors expre ss substantial doubt about your ability to
continue as a going concern;
• Your dependence on third parties; and
• The fact you have in-licensed all of your product candidates and these licenses
can be terminated on short notice if you are unable to make substantial up-front,
milestone, and royalty payments.
 Iferanserin Ointment, page 2

 15. We note your reference to the absence of FDA approved prescription drugs for the treatment
of hemorrhoids, conventional hemorrhoid ther apies, and the comparison of VEN 309 to
placebo.  Please expand the discussion to id entify the conventiona l therapies and the
comparison, if any, between VEN 309 and c onventional therapies or over the counter
products.
 16.  Please state when the SPA was filed with the FDA and the nature of any ongoing
discussions or negotiati ons regarding the SPA.
 17.  Please expand the discussion to clarify you ha ve licensed the product and from whom the
product was licensed.  We note you already provide similar disclo sure with respect to your
other pipeline products.
 Diltiazem Cream, page 2

 18.   Please clarify whether the uniqueness, if any, of VEN 307 compared to diltiazem cream
already prescribed by gastroente rologists is that th e VEN 307 is already formulated and/or
that VEN 307 includes nitroglyceri n.  In addition, since diltiazem cream is already available,
please discuss whether the product is patentable  and has been patented by S.L.A. Pharma
AG.

Dr. Russell H. Ellison Ventrus Biosciences, Inc. August 16, 2010 Page 4

 Phenylephrine Gel, page 3

 19.   Please expand the discussion to briefly descri be the options currently available to treat
IPAA.
 Risk Factors

 “We have had negative cash fl ows from operations….” Page 7

 20.  Please expand the discussion to indicate the amount of indebtedne ss you will have after
conversion of the $11.9 million of convertible no tes, identify the obligors, and explain how
they are affiliated with the registrant.
 “We have an aggregate of $1,720,165 in prin cipal and accrued interest….” Page 7

 21.  Please reconcile the statement in this risk factor indicating you in tend to negotiate the
obligation with the disclosure in the fourth paragraph on page  79 that indicates Paramount
Credit Partners has agreed verbally to waive the repayment obligation upon the closing of the
offering.
22.  We note that if you are unable to renegotiate  the maturity date of  the indebtedness to
Paramount, the obligation will be due when the offering occurs.  Please revise the use of
proceeds section to provide alternative disclosu re to cover the situations where you are able
and unable to renegotiate the maturity date.
 “Our failure to meet our substantial obligations to our licensors….” Page 8

 23.  Please expand the discussion to discuss the amount of aggregate clinical and regulatory
milestone payments you may be required to make to S.L.A. Pharma.
 “Preclinical and clinical trials required for our products are expensive….” page 13

 24.  We note that one of the factors you cite th at may delay the comme ncement and rate of
completion of clinical trials is “the emergen ce of unforeseen safety issues.”  If you have
identified any safety issues, please revise your di sclosure to include an additional risk factor
to address the safety issues you have encountered  to date in preclinical  studies and clinical
trials.
 “If we lose key management or scientific personnel….” Page 16

 25.  Please expand your disclosure to state whether you have any non-competition or
confidentiality agreemen ts with your current or former employees and whether you intend to
obtain such agreements in the future in connec tion with the hiring and re tention of personnel.

Dr. Russell H. Ellison Ventrus Biosciences, Inc. August 16, 2010 Page 5

 “We might be exposed to liability claims asso ciated with the use of hazardous materials and
chemicals.” Page 19
 26.  Please expand the disclosure to state whether you  currently maintain liability insurance with
respect to your use of hazardous materials.  If so, briefly describe the potential liabilities that
are and are not covered and, if material, the cost of such c overage.  If you do not have
coverage for the use of hazardous materials, pleas e revise the risk factor discussion to include
the lack of coverage for poten tial contamination expenses.
 “Our license with S.L.A. Pharma is  subject to termination….” Page 19

 27.  We note the license may be terminated if this offering is not completed by September 30,
2010.  We also note the disclosure that your li cense may be terminated upon 30 days notice if
a third party wishes to enter into an agreemen t for the products if you ha ve not paid all then
required payments under the agreement.  Please clarify whether the licen se agreement can be
terminated on the basis of such third party in terest even if the offering is completed by
September 30, 2010.  In addition, please discu ss whether you are undergoing, and the current
status of, any negotiations to extend the current deadline for co mpletion of the offering.  In
this regard, we note the probability the o ffering may not be completed by September 30,
2010.

“If we infringe the rights of third parties….” Page 21

 28.  To the extent you have experienced problems in the past or are aware of any claims
regarding infringement of intellectual prope rty rights, please expa nd the discussion to
describe these problems or claims.  Similarl y, please expand the risk  factor on page 19
entitled “A patent has not been issued for VEN 307 and might never be issued” to include
specific disclosure of any potential claims  regarding infringement of your licensed
intellectual property.
 “There are interlocking relationships am ong us and certain affiliates….” Page 21

 29.  Please expand the discussion to state the appr oximate percentage Dr. Rosenwald would own
in the event the warrants and promissory notes you refer to  are exercised or converted.
 Use of Proceeds, page 27

 30.  Please expand the discussion with respect to th e first bullet point to indicate the specific
amount allocated to Phase III clinical trial, carcinogenicity testing, and the development of
new intellectual property, respectively.
 31.  Please clarify whether you anticipate the amount allocated to Phase II I clinical trial is
sufficient to complete the Phase III trial.

Dr. Russell H. Ellison Ventrus Biosciences, Inc. August 16, 2010 Page 6

 32.  Please clarify whether the carcinoge nicity testing is in addition to any testing usually related
to Phase III trials.  If you have reason to be believe your product poses cancer risks, please
expand the risk factor section and busi ness sections to a ddress these risks.
 33.  Please explain what you mean by the term “developing new intellectual property.”  For
example, are you considering other uses fo r VEN 309 in addition to the treatment of
hemorrhoids, is the “new intellectual property” a reference to the filing and/or receipt of a
patent, etc.
 34.  Please expand the discussion in the second bullet to indicate th e specific amount allocated to
pay S.L.A. Pharma for your li censing obligations with resp ect to diltiazem cream and
phenylephrine gel, respectively.  Please rec oncile this discussion with the obligations
described in the risk factor entitled “Our failu re to meet our substant ial obligations to our
licensors….”  If the phe nylephrine gel is VEN 308, so state.  In addition, please indicate the
amount of proceeds allocated to the developmen t of an improved formulation and preparation
of a Phase II clinical trial, respectively.  Also, please clarif y whether the amount allocated to
the Phase II trial is sufficient to complete the Phase II trial.
 Capitalization, page 30

35. Please revise the first sentence to state that th e table sets forth your cash and cash equivalents
as well as your capitalization.

36. Please confirm whether the pro forma information will reflect the effects of the beneficial
conversion feature once an estimated o ffering price has been established.

Management’s Discussion and Analysis of Financ ial Condition and Results of Operations, page
32
 37. Please include a caption in this section to addr ess the impact that the material weaknesses
over internal controls discussed on page 11 had on the financial reporting process.  Please
include how the material weaknesses were iden tified, whether the material weaknesses were
corrected and the steps the company has ta ken to remedy the material weaknesses.
 Financial Operations Overview

 Critical Accounting Policies

 Stock-Based Compensation, page 33

 38. Please refer to your disclosure on convertible de bt.  In a separate caption please disclose your
accounting policy for the issuance of convertible debt and warrant s issued in connection with
debt.  Also expand your disclosure  to describe how the proceeds from the debt instrument are

Dr. Russell H. Ellison Ventrus Biosciences, Inc. August 16, 2010 Page 7

 allocated between the convertible debt and any detachable free-standing instruments.  This
comment also applies to your disclosure in Note 2 to the financial statements.
 Research and Development Expense, page 34

 39. You disclose on page 43 that you are unable to determine the completion costs of your
product candidates.  However, on page 10 you disc lose that “we anticipat e that to complete
the clinical trial proc ess and commercialize our product ca ndidates will cost approximately
$15 million for VEN 307, $15 million for VEN 308 and $40 million for VEN 309”.
Therefore, please disclose the nature, timing a nd estimated costs of the efforts necessary to
complete VEN 307, VEN 308 and VEN 309.
 40. The total amount of research and development pa yments disclosed in the table on page 34 for
VEN 307 and VEN 309 for Q1 2010 is $521,600.  Pl ease explain why this amount is higher
than research and development expense for the three months ended March 31, 2010 disclosed
in the statement of operations of $413,746. Simila rly, the amount in the table for YE 2009 is
$3,209,147 which is higher than the amount disclo sed on the statement of operations for the
year ended 2009 of $2,942,992.  Please explain an d revise the disclosure if necessary.
 Liquidity and Capital Resources

41. Please include a discussion of cash used in operating activities and cash provided by
financing activities for the three months ended March 31, 2010 compared to March 31, 2009.
 Notes Payable, page 36

 42.  We note the PCP notes will mature upon consu mmation of this offering.  In addition, it
appears that the PCP notes will not automatically  convert into equity upon completion of the
offering.  If this is correct, pl ease clarify this aspect of the PCP notes in this  section and the
“Certain Relationships and Related Transacti ons” section and describe how you intend to pay
off the PCP notes.
Net Cash Used in Operating Activities, pag