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Russell H. Ellison, MD, MSc
Chief Executive Officer and Chairman of the Board
Forward Looking Statements
This material contains estimates and forward-looking statements. The words “believe,” “may,” “might,” “will,” “aim,”
“estimate,” “continue,” “would,” “anticipate, ”“intend,” “expect,” “plan” and similar words are intended to identify
estimates and forward-looking statements. Our estimates and forward-looking statements are mainly based on our current
expectations and estimates of future events and trends, which affect or might affect our businesses and operations.
Although we believe that these estimates and forward-looking statements are based upon reasonable assumptions, they
are subject to many risks and uncertainties and are made in light of information currently available to us. Our estimates
and forward-looking statements may be influenced by the following factors, among others: risks related to the costs,
timing, regulatory review and results of our studies and clinical trials; our ability to obtain FDA approval of our product
candidates; differences between historical studies on which we have based our planned clinical trials and actual results
from our trials; our anticipated capital expenditures, our estimates regarding our capital requirements, and our need for
future capital; our liquidity and working capital requirements; our expectations regarding our revenues, expenses and
other results of operations; the unpredictability of the size of the markets for, and market acceptance of, any of our
products, including VEN 309; our ability to sell any approved products and the price we are able realize; our need to obtain
additional funding to develop our products, and our ability to obtain future funding on acceptable terms; our ability to
retain and hire necessary employees and to staff our operations appropriately; our ability to compete in our industry and
innovation by our competitors; our ability to stay abreast of and comply with new or modified laws and regulations that
currently apply or become applicable to our business; estimates and estimate methodologies used in preparing our
financial statements; the future trading prices of our common stock and the impact of securities analysts’ reports on these
prices; and the risks set out in our filings with the SEC, including our Annual Report on Form 10-K. Estimates and forward-
looking statements involve risks and uncertainties and are not guarantees of future performance. As a result of known and
unknown risks and uncertainties, including those described above, the estimates and forward-looking statements discussed
in this material might not occur and our future results and our performance might differ materially from those expressed in
these forward-looking statements due to, including, but not limited to, the factors mentioned above. Estimates and
forward-looking statements speak only as of the date they were made, and, except to the extent required by law, we
undertake no obligation to update or to review any estimate and/or forward-looking statement because of new
information, future events or other factors.



  1
Company Overview

 A Phase III biopharmaceutical company focused exclusively on gastroenterology;
  specifically, anal disorders - a neglected area of drug development
 Development risk stratified across three late-stage products
   NCE and 505(b)2 registration pathways
   Two pivotal Phase III read-outs for two separate products expected in 2Q 2012
       Possible validation of two lead programs
       Range of co-promotion/partnership opportunities could follow data

 Products address large, underserved, and untapped markets
   3 of the top 10 GI disorders
   Significant market potentials in specialty pharma and primary care

 Well funded through key milestones
        Cash and cash equivalents of $ 53.3 Mil (Sept. 30, 2011)
        $20 mm IPO (with overallocation) in Dec 2010; $50 mm follow-on in July 2011


 2
Pipeline

                  Late Stage Pipeline with Two Pivotal Phase III Read-outs
                 Expected in 2Q 2012 for Validation of Two Lead Programs

      Program                              Clinical Phase         Potential    Commercial
                      Indication
     (Pathway)                       I           II         III   NDA Filing     Rights

VEN 309                                                                        World Wide,
                     Hemorrhoids                                    2014
Iferanserin (NCE)                                                              Unpartnered


VEN 307                                                                          North
Diltiazem            Anal Fissures                                  2013        America,
(505(b)2)                                                                      Unpartnered

                                                                                 North
VEN 308                  Fecal
                                                                    2015        America,
(505(b)2)            Incontinence
                                                                               Unpartnered




 3
VEN 309: Iferanserin
 NCE for Hemorrhoids
Hemorrhoids: A Large, Underserved Market
 10,000 consumer surveyed, 1,125 report suffering from hemorrhoids1:
         Past two years                             11.0%                 25.8 million2
         Past year                                   9.3%                 21.7 million2
         Day of survey                               2.9%                  6.7 million2

 Current treatment options:
         Invasive procedures: banding, sclerosing agents, surgery for prolapsed hemorrhoids
         Rx: No FDA approved Rx drugs
             4+ million prescriptions of non-approved and non-DESI intra-anal steroids3
             Minimal to no reimbursement; No other known drugs in dev. in US, EU* or Japan
         OTC: 20-22 million3,4 OTC units sold annually in US (e.g., Preparation H®)
           85% reported using OTC or Rx treatment at least once (86% OTC/14% Rx)^
          10% of all patients reported having an invasive procedure (61% surgery) with
                      75% reporting recurrence of symptoms after surgery^
 1. Princeton Brand Econometrics Survey 2011. 2: calculated from the 2010 US Adult population – 234,564,000 (2010 US census)
 3. IMS 2003 4. IMS 2009 * Oral Daflon has a hemorrhoid indication in France ^ PBE survey of 10,202 consumers 2011

  5
Physiology of Hemorrhoids

  Primary Symptoms:
                                                                    Increased intra-pelvic
Bleeding, Itching & Pain
                                                                          pressure



      Efferent venous                                                  Dilatation of the
       constriction &                                               hemorrhoidal plexus,
          platelet                                                   increased pressure,
        aggregation                                                        swelling




      5HT2a receptor                                                     Local serotonin
        activation External hemorrhoid                                    (5HT) release
                                                   Internal hemorrhoid

                                         VEN 309



  6
                                         
VEN 309 (iferanserin) Summary
                          Topical rectal ointment applied intra-anally
                     BID x 2 weeks (with proprietary single-use applicator)

                          Selective 5HT2a antagonist
Mechanism
                          Does not cross the blood brain barrier except at doses much higher than to be
of Action
                           used therapeutically


                          Systemic exposure is < 10%
Preclinical Safety
                          Therapeutic ratio is > 17x


Clinical                  Metabolized by CYP2D6 in liver
Pharmacology              No accumulation of the drug on twice daily dosing


                          Seven clinical trials in 359 subjects (220 exposures)
                          No SAEs, limited AEs (mainly GI), similar AE profile vs. placebo
Clinical Data
                          Significant improvements in symptoms related to hemorrhoids including
                           bleeding, pain and itching


 7
Efficacy Phase IIb (German study1)

                                                                                            Primary endpoint
                                                                                      BLEEDING (n=111 patients)
    121 patients randomized to
     VEN 309 (iferanserin) BID vs.
     placebo ointment x 14 days
                                                                                                        P < 0.05
    Weekly visits for 2 week
     treatment; follow-up at 45

                                                         Mean (Bleed)
     days                                                                                                p<0.0001            p < 0.0075
    Symptoms recorded in daily
     diaries (scale of 1-10; 1 = no
     symptoms)
    Statistically significant
     improvement in symptoms:
     bleeding, itching, pain




    1. Herold A, Dietrich J, Aitchison R. Intra-anal iferanserin 10 mg BID for hemorrhoid disease:                 VEN 309           PLACEBO
    a prospective, randomized, double-blind, placebo-controlled trial. Clin Ther. 2012;34(2):329-340.

      8
Efficacy Phase IIb (German study1)
                                     Secondary endpoints: rapid, sustained effect



                    ITCHING (n=60 patients)                                                         PAIN (n=40 patients)


                       DAY 7 P < 0.0008; DAY 14 P < 0.02

                                                                                                           * = P < 0.05




                                                                             Mean (Pain)
Mean (Itch)




                                      P < 0.05
                                                                                                    * *




1. Herold A, Dietrich J, Aitchison R. Intra-anal iferanserin 10 mg BID for hemorrhoid disease:              VEN 309        PLACEBO
a prospective, randomized, double-blind, placebo-controlled trial. Clin Ther. 2012;34(2):329-340.

         9
Modeling of Phase IIb1 Data for Phase III Endpoints*
                                      Absence of symptom Day 7 through Day 14

                                   PRIMARY ENDPOINT:
                 No Bleeding from Day 7 to Day 14 (2nd week of Treatment)
           60%                 57%                                                                    Secondary Endpoints
           50%                                                  P = ≤ 0.0001                              Itching:
                                                                                                            59% vs. 32%
           40%                                                                                              p<0.034
Response




           30%
                                                                                                          Pain:
                                                                                                            50% vs. 18%
                                                                          20%
           20%                                                                                              p<0.032


           10%

           0%
                           Iferanserin                                  Placebo

                                Majority of responders in the treatment arm respond by Day 3
 1. Herold A, Dietrich J, Aitchison R. Intra-anal iferanserin 10 mg BID for hemorrhoid disease:
 a prospective, randomized, double-blind, placebo-controlled trial. Clin Ther. 2012;34(2):329-340.                         *Post hoc
     10
Robust, Disciplined Phase III Trial
 Endpoints   Meaningful improvement (proposed by FDA)
              • Primary endpoint: cessation of bleeding day 7 – 14 (>99% powered)
              • Secondary endpoints: cessation of pain, itching day 7 – 14 (>95% powered)

 Design      Three arms:
              • 7 day / 14 day / placebo
              • 200 pts per arm
              • Open label extension to 1 year to treat recurrence

 Sites       70 US sites
 Inclusion   Meaningful symptoms (bleeding, itching, pain for 2 days) to clearly
 criteria    demonstrate therapeutic effect
 Progress     •   Discussion with FDA on all major elements of the protocol
              •   Enrolling correct patients
              •   Continuous data review (blind)
              •   Minimal loss of key outcome data
              • Reporting of top line results expected June 2012

 11
Development Plan: Next Steps

 Chronic repeated use product (FDA definition, may not apply in Japan/EU)

 1,500 subjects needed for complete safety profile (US and possibly EU)
        7 clinical trials in 359 subjects (220 exposures)
        600 patients in Phase III study designed to provide program validation
        Second pivotal Phase III trial planned (double blind Phase III recurrence trial to
         determine safety/efficacy and treatment for recurrence for the US)
 Clinical pharmacology program including: DDI, PK in poor metabolizers
  (results expected Q2), QT and special populations
 Preclinical: Chronic Tox and Carcinogenicity studies (two species for 2 yrs)
 Carcinogenicity is critical path for NDA, clinical trials can be done serially




12
Patient/Prescriber Response to VEN 3091


 Strong willingness to ask their doctor for VEN 309 at the next visit
        For patients who are having symptoms now, (estimated at 6.7 mm)
            80% would* request a prescription
        In the whole sample:
            66% receiving a prescription would fill the Rx at a $35 out-of-pocket co-pay*
            78% with household income above $50k/year would fill the Rx at a $35 copay*

 Health care providers showed high willingness to prescribe and minimal
  co-pay price sensitivity
        Probability of HCPs to grant a patient Rx request ranged from .88 - .92*




     1. Princeton Brand Econometrics Survey 2011. * PBE factored


13
VEN 307: Diltiazem Cream
Novel Treatment for Anal Fissures
Anal Fissures: Cause and Management

         Cause                                                       Treatment options
 Increased sphincter                                                 Control constipation,
        tone                                                            topical steroids

                                                                      Reduce sphincter
                                                                            tone
     Local ischemia

                                                                        Compounded
                                                                        Topical drugs:
     Tear (fissure) in                                                 • GTN*
       anal canal                                                      • diltiazem
                             Sphincters                    Anal
                             (muscles)                    fistula

                                          Anal fissure              Botox              Surgery
     Severe pain on                  1.1 mm office visits/year
       defecation

               *Rectiv (topical GTN) recently approved by FDA but not yet launched

15
VEN 307 (diltiazem) Summary
                                   2% topical diltiazem cream
                                     applied peri-anally TID


Mechanism               Calcium channel blocker
of Action                    Relaxes the internal anal sphincter, reducing pain and increasing tissue blood flow




Preclinical Safety      Preclinical topical safety with 2% diltiazem twice daily for ninety days



                        Topical has < 10% systemic exposure as oral dose but significantly greater effect
Clinical
                         on sphincter tone – i.e., blood levels do not predict activity. Low exposure =
Pharmacology             better tolerability than oral diltiazem


                        Ten clinical trials in 453 individuals
Clinical Data           Infrequent mild AEs reported
                        Similar or better reduction in pain, significantly better tolerability than GTN


16
Pivotal Phase III Trial
 FDA (analgesia division) pre-IND meeting conducted in August 2007
   Achieved clarity on primary endpoint: reduction in pain
   Confirmed safety database and tox requirement
   NDA filing possible 2013


 Phase III trial conducted by SLA (Ex-NA licensor)
   3 arms, 155 pts per arm: 2% 4% diltiazem TID, and placebo in 31 sites in Europe
   Primary endpoint: reduction in pain on defecation using a validated scale (Likert, NRS)
   Ventrus review of blinded data and study operations 10/2011: Correct patients enrolled,
    data compliance and GCRP are good, data are being reviewed continuously
   Enrollment completed; data readout expected in May 2012


 Planned Second Phase III trial(s):
   Developing 4 possible extended release formulations: may test some or all in human
    manometry trial in 2012. Next phase could be 2 PH III trials with extended release
    formulation if one is acceptable, or 1 with original formulation




 17
Competitive Treatments for Anal Fissure

    Rectiv™ 0.4% GTN               Approved in the US for moderate and severe pain of chronic anal fissure, launched
    ointment BID                   March 2012
    (Topical
                                   Priced at $730 WAC per 8 week course
    Nitroglycerine)
                                   Extensive literature reporting improved pain but difficult side effect profile: high
                                   rate of headaches (64% of patients, often severe), flushing, nausea and dizziness
                                   Medical associations’ guidelines have consistently directed physicians to topical
                                   diltiazem over GTN as 1st line therapy1, 2
    Calcium Channel                Compounded nifedipine is used to a lesser extent than diltiazem
    Blockers                       Less literature available
    Botox                          Out of pocket cost for patients

    Surgery                        Forcible dilatation and sphincterotomy
                                   Most often curative, but fecal incontinence is a problem


      Diltiazem is the recommended first-line treatment for anal fissures among GIs and CRS
The launch of Rectiv™ could allow cost effective targeting of prescribers and increase AF awareness
     With our AE advantage, VEN 307 could rapidly establish market dominance once launched

1    Cross, KLR., et al., (2008) The Management of Anal Fissure: ACPGBI Position Statement. Colorectal Disease, 10 (Suppl. 3), 1-7.
2    Madoff, RD., & Fleshman, JW. (2003) AGA Technical Review on the Diagnosis and Care of Patients With Anal Fissure. Gastroenterology, 124, 235–245

    18
Business Overview, Milestones
Target Markets Provide Optimal Strategic Flexibility

 Specialty sales force and DTC can be highly effective
       Diltiazem is the recommended first-line treatment in focused market of specialists
       50% of current hemorrhoid scripts (4 million) are concentrated in 21,000 prescribers
             No data to support the use of intra anal steroids as effective treatment; not approved

         Direct To Consumer (DTC) advertising could be highly impactful for VEN 3091
 Partnerships
         We intend to seek a marketing partner for VEN 309 for ex-US territories
         Co-promotion opportunities exist for broader PCP coverage of VEN 309
 Pricing and Reimbursement
       VEN 309: No other drugs in class or indication: Medicare Part D and managed care
        implications
       VEN 307: Parity pricing to Rectiv® ($730 two month supply) is possible; Expect major
        share of existing compounded Rx, new Rectiv™ patients, plus additional patients



1:Princeton Brand Econometrics forecast model 2012

 20
Rights and Exclusivity

                                           VEN 309
Rights               Ventrus has all rights and title, World-wide, paying royalties between 1% and 4%

                     New concentration range patent filed with USPTO & PTC (August 2010)
                     Composition of matter expires August 2015
Market and Data
                     5 years and 10 years of data exclusivity in the US under Hatch-Waxman Act and
Exclusivity
                      EU, respectively
                     Topical GI Product with low bioavailability


                                           VEN 307
Rights               North American rights paying mid to upper single digit royalties


                     Method of use patent expires Feb 2018; approx. 16 months HW extension
Market and Data
                     Topical GI product; systemic levels do not predict activity
Exclusivity
                     Extended release formulations (BID) under development to extend exclusivity




21
Expected Milestones

               H1 2012                                                     H2 2012

                                             VEN 309
                                                        FDA meeting
  PH 3 enrollment completion
                                                        Recurrence data read-outs from
  Results from PH 3 trial (expected June)               1st pivotal
  Clinical pharmacology results                        Launch second pivotal and
  Publication of preclinical pharmacology               recurrence trial
                                                        Data publication/presentation
                                                        Patent office action


                                             VEN 307
  Data read-out from first pivotal PH 3                FDA meeting
   trial (expected in May)
                                                        Launch of second pivotal
  Go/no go decision and selection of                   Results of new formulation
   extended release formulation                         Data publication/presentation



22
Financials

 Nasdaq (IPO 2011):                                                                               VTUS
 Cash balance
        Cash and cash equivalents at Sept 30, 2011                                                $ 53.3 Mil
        Cash and cash equivalents YE 2011 end guidance *                                         $ 34-$ 36 Mil

 Stock data
        Fully diluted shares outstanding                                                          15.3 Mil
        Shares outstanding                                                                        12.4 Mil




         * Includes payment for rights to Amer: estimates - our operations expenditures could change

23
Conclusion

 Development risk stratified across three late-stage products
   NCE and 505(b)2 registration pathways
   Two pivotal Phase III read-outs for two separate products expected in 2Q 2012
       Possible validation of two lead programs
       Range of co-promotion/partnership opportunities could follow data

 Products address large, underserved, and untapped markets
   3 of the top 10 GI disorders
   Significant market potentials in specialty pharma and primary care

 Well funded through key milestones
        Cash and cash equivalents of $ 53.3 Mil (Sept. 30, 2011)
        $20 mm IPO (with overallocation) in Dec 2010; $50 mm follow-on in July 2011




24
Russell H. Ellison, MD, MSc
Chief Executive Officer and Chairman of the Board

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VTUS Cowen Final March 2012

  • 1. Russell H. Ellison, MD, MSc Chief Executive Officer and Chairman of the Board
  • 2. Forward Looking Statements This material contains estimates and forward-looking statements. The words “believe,” “may,” “might,” “will,” “aim,” “estimate,” “continue,” “would,” “anticipate, ”“intend,” “expect,” “plan” and similar words are intended to identify estimates and forward-looking statements. Our estimates and forward-looking statements are mainly based on our current expectations and estimates of future events and trends, which affect or might affect our businesses and operations. Although we believe that these estimates and forward-looking statements are based upon reasonable assumptions, they are subject to many risks and uncertainties and are made in light of information currently available to us. Our estimates and forward-looking statements may be influenced by the following factors, among others: risks related to the costs, timing, regulatory review and results of our studies and clinical trials; our ability to obtain FDA approval of our product candidates; differences between historical studies on which we have based our planned clinical trials and actual results from our trials; our anticipated capital expenditures, our estimates regarding our capital requirements, and our need for future capital; our liquidity and working capital requirements; our expectations regarding our revenues, expenses and other results of operations; the unpredictability of the size of the markets for, and market acceptance of, any of our products, including VEN 309; our ability to sell any approved products and the price we are able realize; our need to obtain additional funding to develop our products, and our ability to obtain future funding on acceptable terms; our ability to retain and hire necessary employees and to staff our operations appropriately; our ability to compete in our industry and innovation by our competitors; our ability to stay abreast of and comply with new or modified laws and regulations that currently apply or become applicable to our business; estimates and estimate methodologies used in preparing our financial statements; the future trading prices of our common stock and the impact of securities analysts’ reports on these prices; and the risks set out in our filings with the SEC, including our Annual Report on Form 10-K. Estimates and forward- looking statements involve risks and uncertainties and are not guarantees of future performance. As a result of known and unknown risks and uncertainties, including those described above, the estimates and forward-looking statements discussed in this material might not occur and our future results and our performance might differ materially from those expressed in these forward-looking statements due to, including, but not limited to, the factors mentioned above. Estimates and forward-looking statements speak only as of the date they were made, and, except to the extent required by law, we undertake no obligation to update or to review any estimate and/or forward-looking statement because of new information, future events or other factors. 1
  • 3. Company Overview  A Phase III biopharmaceutical company focused exclusively on gastroenterology; specifically, anal disorders - a neglected area of drug development  Development risk stratified across three late-stage products  NCE and 505(b)2 registration pathways  Two pivotal Phase III read-outs for two separate products expected in 2Q 2012  Possible validation of two lead programs  Range of co-promotion/partnership opportunities could follow data  Products address large, underserved, and untapped markets  3 of the top 10 GI disorders  Significant market potentials in specialty pharma and primary care  Well funded through key milestones  Cash and cash equivalents of $ 53.3 Mil (Sept. 30, 2011)  $20 mm IPO (with overallocation) in Dec 2010; $50 mm follow-on in July 2011 2
  • 4. Pipeline Late Stage Pipeline with Two Pivotal Phase III Read-outs Expected in 2Q 2012 for Validation of Two Lead Programs Program Clinical Phase Potential Commercial Indication (Pathway) I II III NDA Filing Rights VEN 309 World Wide, Hemorrhoids 2014 Iferanserin (NCE) Unpartnered VEN 307 North Diltiazem Anal Fissures 2013 America, (505(b)2) Unpartnered North VEN 308 Fecal 2015 America, (505(b)2) Incontinence Unpartnered 3
  • 5. VEN 309: Iferanserin NCE for Hemorrhoids
  • 6. Hemorrhoids: A Large, Underserved Market  10,000 consumer surveyed, 1,125 report suffering from hemorrhoids1:  Past two years 11.0% 25.8 million2  Past year 9.3% 21.7 million2  Day of survey 2.9% 6.7 million2  Current treatment options:  Invasive procedures: banding, sclerosing agents, surgery for prolapsed hemorrhoids  Rx: No FDA approved Rx drugs  4+ million prescriptions of non-approved and non-DESI intra-anal steroids3  Minimal to no reimbursement; No other known drugs in dev. in US, EU* or Japan  OTC: 20-22 million3,4 OTC units sold annually in US (e.g., Preparation H®) 85% reported using OTC or Rx treatment at least once (86% OTC/14% Rx)^ 10% of all patients reported having an invasive procedure (61% surgery) with 75% reporting recurrence of symptoms after surgery^ 1. Princeton Brand Econometrics Survey 2011. 2: calculated from the 2010 US Adult population – 234,564,000 (2010 US census) 3. IMS 2003 4. IMS 2009 * Oral Daflon has a hemorrhoid indication in France ^ PBE survey of 10,202 consumers 2011 5
  • 7. Physiology of Hemorrhoids Primary Symptoms: Increased intra-pelvic Bleeding, Itching & Pain pressure Efferent venous Dilatation of the constriction & hemorrhoidal plexus, platelet increased pressure, aggregation swelling 5HT2a receptor Local serotonin activation External hemorrhoid (5HT) release Internal hemorrhoid VEN 309 6 
  • 8. VEN 309 (iferanserin) Summary Topical rectal ointment applied intra-anally BID x 2 weeks (with proprietary single-use applicator)  Selective 5HT2a antagonist Mechanism  Does not cross the blood brain barrier except at doses much higher than to be of Action used therapeutically  Systemic exposure is < 10% Preclinical Safety  Therapeutic ratio is > 17x Clinical  Metabolized by CYP2D6 in liver Pharmacology  No accumulation of the drug on twice daily dosing  Seven clinical trials in 359 subjects (220 exposures)  No SAEs, limited AEs (mainly GI), similar AE profile vs. placebo Clinical Data  Significant improvements in symptoms related to hemorrhoids including bleeding, pain and itching 7
  • 9. Efficacy Phase IIb (German study1) Primary endpoint BLEEDING (n=111 patients)  121 patients randomized to VEN 309 (iferanserin) BID vs. placebo ointment x 14 days P < 0.05  Weekly visits for 2 week treatment; follow-up at 45 Mean (Bleed) days p<0.0001 p < 0.0075  Symptoms recorded in daily diaries (scale of 1-10; 1 = no symptoms)  Statistically significant improvement in symptoms: bleeding, itching, pain 1. Herold A, Dietrich J, Aitchison R. Intra-anal iferanserin 10 mg BID for hemorrhoid disease: VEN 309 PLACEBO a prospective, randomized, double-blind, placebo-controlled trial. Clin Ther. 2012;34(2):329-340. 8
  • 10. Efficacy Phase IIb (German study1) Secondary endpoints: rapid, sustained effect ITCHING (n=60 patients) PAIN (n=40 patients) DAY 7 P < 0.0008; DAY 14 P < 0.02 * = P < 0.05 Mean (Pain) Mean (Itch) P < 0.05 * * 1. Herold A, Dietrich J, Aitchison R. Intra-anal iferanserin 10 mg BID for hemorrhoid disease: VEN 309 PLACEBO a prospective, randomized, double-blind, placebo-controlled trial. Clin Ther. 2012;34(2):329-340. 9
  • 11. Modeling of Phase IIb1 Data for Phase III Endpoints* Absence of symptom Day 7 through Day 14 PRIMARY ENDPOINT: No Bleeding from Day 7 to Day 14 (2nd week of Treatment) 60% 57%  Secondary Endpoints 50% P = ≤ 0.0001  Itching:  59% vs. 32% 40%  p<0.034 Response 30%  Pain:  50% vs. 18% 20% 20%  p<0.032 10% 0% Iferanserin Placebo Majority of responders in the treatment arm respond by Day 3 1. Herold A, Dietrich J, Aitchison R. Intra-anal iferanserin 10 mg BID for hemorrhoid disease: a prospective, randomized, double-blind, placebo-controlled trial. Clin Ther. 2012;34(2):329-340. *Post hoc 10
  • 12. Robust, Disciplined Phase III Trial Endpoints Meaningful improvement (proposed by FDA) • Primary endpoint: cessation of bleeding day 7 – 14 (>99% powered) • Secondary endpoints: cessation of pain, itching day 7 – 14 (>95% powered) Design Three arms: • 7 day / 14 day / placebo • 200 pts per arm • Open label extension to 1 year to treat recurrence Sites 70 US sites Inclusion Meaningful symptoms (bleeding, itching, pain for 2 days) to clearly criteria demonstrate therapeutic effect Progress • Discussion with FDA on all major elements of the protocol • Enrolling correct patients • Continuous data review (blind) • Minimal loss of key outcome data • Reporting of top line results expected June 2012 11
  • 13. Development Plan: Next Steps Chronic repeated use product (FDA definition, may not apply in Japan/EU)  1,500 subjects needed for complete safety profile (US and possibly EU)  7 clinical trials in 359 subjects (220 exposures)  600 patients in Phase III study designed to provide program validation  Second pivotal Phase III trial planned (double blind Phase III recurrence trial to determine safety/efficacy and treatment for recurrence for the US)  Clinical pharmacology program including: DDI, PK in poor metabolizers (results expected Q2), QT and special populations  Preclinical: Chronic Tox and Carcinogenicity studies (two species for 2 yrs)  Carcinogenicity is critical path for NDA, clinical trials can be done serially 12
  • 14. Patient/Prescriber Response to VEN 3091  Strong willingness to ask their doctor for VEN 309 at the next visit  For patients who are having symptoms now, (estimated at 6.7 mm)  80% would* request a prescription  In the whole sample:  66% receiving a prescription would fill the Rx at a $35 out-of-pocket co-pay*  78% with household income above $50k/year would fill the Rx at a $35 copay*  Health care providers showed high willingness to prescribe and minimal co-pay price sensitivity  Probability of HCPs to grant a patient Rx request ranged from .88 - .92* 1. Princeton Brand Econometrics Survey 2011. * PBE factored 13
  • 15. VEN 307: Diltiazem Cream Novel Treatment for Anal Fissures
  • 16. Anal Fissures: Cause and Management Cause Treatment options Increased sphincter Control constipation, tone topical steroids Reduce sphincter tone Local ischemia Compounded Topical drugs: Tear (fissure) in • GTN* anal canal • diltiazem Sphincters Anal (muscles) fistula Anal fissure Botox Surgery Severe pain on 1.1 mm office visits/year defecation *Rectiv (topical GTN) recently approved by FDA but not yet launched 15
  • 17. VEN 307 (diltiazem) Summary 2% topical diltiazem cream applied peri-anally TID Mechanism  Calcium channel blocker of Action  Relaxes the internal anal sphincter, reducing pain and increasing tissue blood flow Preclinical Safety  Preclinical topical safety with 2% diltiazem twice daily for ninety days  Topical has < 10% systemic exposure as oral dose but significantly greater effect Clinical on sphincter tone – i.e., blood levels do not predict activity. Low exposure = Pharmacology better tolerability than oral diltiazem  Ten clinical trials in 453 individuals Clinical Data  Infrequent mild AEs reported  Similar or better reduction in pain, significantly better tolerability than GTN 16
  • 18. Pivotal Phase III Trial  FDA (analgesia division) pre-IND meeting conducted in August 2007  Achieved clarity on primary endpoint: reduction in pain  Confirmed safety database and tox requirement  NDA filing possible 2013  Phase III trial conducted by SLA (Ex-NA licensor)  3 arms, 155 pts per arm: 2% 4% diltiazem TID, and placebo in 31 sites in Europe  Primary endpoint: reduction in pain on defecation using a validated scale (Likert, NRS)  Ventrus review of blinded data and study operations 10/2011: Correct patients enrolled, data compliance and GCRP are good, data are being reviewed continuously  Enrollment completed; data readout expected in May 2012  Planned Second Phase III trial(s):  Developing 4 possible extended release formulations: may test some or all in human manometry trial in 2012. Next phase could be 2 PH III trials with extended release formulation if one is acceptable, or 1 with original formulation 17
  • 19. Competitive Treatments for Anal Fissure Rectiv™ 0.4% GTN Approved in the US for moderate and severe pain of chronic anal fissure, launched ointment BID March 2012 (Topical Priced at $730 WAC per 8 week course Nitroglycerine) Extensive literature reporting improved pain but difficult side effect profile: high rate of headaches (64% of patients, often severe), flushing, nausea and dizziness Medical associations’ guidelines have consistently directed physicians to topical diltiazem over GTN as 1st line therapy1, 2 Calcium Channel Compounded nifedipine is used to a lesser extent than diltiazem Blockers Less literature available Botox Out of pocket cost for patients Surgery Forcible dilatation and sphincterotomy Most often curative, but fecal incontinence is a problem Diltiazem is the recommended first-line treatment for anal fissures among GIs and CRS The launch of Rectiv™ could allow cost effective targeting of prescribers and increase AF awareness With our AE advantage, VEN 307 could rapidly establish market dominance once launched 1 Cross, KLR., et al., (2008) The Management of Anal Fissure: ACPGBI Position Statement. Colorectal Disease, 10 (Suppl. 3), 1-7. 2 Madoff, RD., & Fleshman, JW. (2003) AGA Technical Review on the Diagnosis and Care of Patients With Anal Fissure. Gastroenterology, 124, 235–245 18
  • 21. Target Markets Provide Optimal Strategic Flexibility  Specialty sales force and DTC can be highly effective  Diltiazem is the recommended first-line treatment in focused market of specialists  50% of current hemorrhoid scripts (4 million) are concentrated in 21,000 prescribers  No data to support the use of intra anal steroids as effective treatment; not approved  Direct To Consumer (DTC) advertising could be highly impactful for VEN 3091  Partnerships  We intend to seek a marketing partner for VEN 309 for ex-US territories  Co-promotion opportunities exist for broader PCP coverage of VEN 309  Pricing and Reimbursement  VEN 309: No other drugs in class or indication: Medicare Part D and managed care implications  VEN 307: Parity pricing to Rectiv® ($730 two month supply) is possible; Expect major share of existing compounded Rx, new Rectiv™ patients, plus additional patients 1:Princeton Brand Econometrics forecast model 2012 20
  • 22. Rights and Exclusivity VEN 309 Rights  Ventrus has all rights and title, World-wide, paying royalties between 1% and 4%  New concentration range patent filed with USPTO & PTC (August 2010)  Composition of matter expires August 2015 Market and Data  5 years and 10 years of data exclusivity in the US under Hatch-Waxman Act and Exclusivity EU, respectively  Topical GI Product with low bioavailability VEN 307 Rights  North American rights paying mid to upper single digit royalties  Method of use patent expires Feb 2018; approx. 16 months HW extension Market and Data  Topical GI product; systemic levels do not predict activity Exclusivity  Extended release formulations (BID) under development to extend exclusivity 21
  • 23. Expected Milestones H1 2012 H2 2012 VEN 309  FDA meeting  PH 3 enrollment completion  Recurrence data read-outs from  Results from PH 3 trial (expected June) 1st pivotal  Clinical pharmacology results  Launch second pivotal and  Publication of preclinical pharmacology recurrence trial  Data publication/presentation  Patent office action VEN 307  Data read-out from first pivotal PH 3  FDA meeting trial (expected in May)  Launch of second pivotal  Go/no go decision and selection of  Results of new formulation extended release formulation  Data publication/presentation 22
  • 24. Financials  Nasdaq (IPO 2011): VTUS  Cash balance  Cash and cash equivalents at Sept 30, 2011 $ 53.3 Mil  Cash and cash equivalents YE 2011 end guidance * $ 34-$ 36 Mil  Stock data  Fully diluted shares outstanding 15.3 Mil  Shares outstanding 12.4 Mil * Includes payment for rights to Amer: estimates - our operations expenditures could change 23
  • 25. Conclusion  Development risk stratified across three late-stage products  NCE and 505(b)2 registration pathways  Two pivotal Phase III read-outs for two separate products expected in 2Q 2012  Possible validation of two lead programs  Range of co-promotion/partnership opportunities could follow data  Products address large, underserved, and untapped markets  3 of the top 10 GI disorders  Significant market potentials in specialty pharma and primary care  Well funded through key milestones  Cash and cash equivalents of $ 53.3 Mil (Sept. 30, 2011)  $20 mm IPO (with overallocation) in Dec 2010; $50 mm follow-on in July 2011 24
  • 26. Russell H. Ellison, MD, MSc Chief Executive Officer and Chairman of the Board