1. Uprima ® E001451 Primary 1 2/21/2016 Summary of Efficacy

2. E001451 Primary 2 2/21/2016 Uprima ® Efficacy Erection Erection Intercourse Intercourse Timing/onset of action Timing/onset of action Couple/physician choice Couple/physician choice Clinical Considerations in ED Efficacy Assessment

3. E001451 Primary 3 2/21/2016 Uprima ® Efficacy No standard physical measurement No standard physical measurement No accepted means of determining etiologies in most cases No accepted means of determining etiologies in most cases Duplex ultra sound, pharmacotesting and Nocturnal Penile Tumescense (NPT) are not used routinely Duplex ultra sound, pharmacotesting and Nocturnal Penile Tumescense (NPT) are not used routinely The International Index of Erectile Function (IIEF*) and Brief Sexual Function Inventory (BSFI**) are validated clinical trial instruments The International Index of Erectile Function (IIEF*) and Brief Sexual Function Inventory (BSFI**) are validated clinical trial instruments Measurements of ED in Clinical Trials *Rosen et al. Urology 49:822-830, 1997. **O’Leary et al. Urology 46:697-706, 1995. Efficacy Assessment

4. E001451 Primary 4 2/21/2016 Uprima ® Efficacy Determined after each dose administration (every attempt) from the home-use questionnaire Determined after each dose administration (every attempt) from the home-use questionnaire –Erection firm enough for intercourse based on patient response –Erection firm enough for intercourse based on partner response –Intercourse rates based on patient/partner responses Efficacy Assessment Uprima ® Endpoints

5. E001451 Primary 5 2/21/2016 Uprima ® Advantages of Home-Use Questionnaire vs. Retrospective Questionnaire (e.g., IIEF) Direct assessment of efficacy at each dosing attempt Direct assessment of efficacy at each dosing attempt Does not require patient to: Does not require patient to: –Recall attempts after a 4-week period –Create an estimate of average erectile function during that 4-week period Efficacy Assessment Efficacy

6. Uprima ® E001451 Primary 6 2/21/2016 Representative ED Patient Population

7. E001451 Primary 7 2/21/2016 Uprima ® Patient Population Heterosexual males, ages 18 – 70 Heterosexual males, ages 18 – 70 Partner consent Partner consent Confirmed presence of ED (inability to attain and maintain erection firm enough for intercourse  50% of attempts  3 months prior to study) Confirmed presence of ED (inability to attain and maintain erection firm enough for intercourse  50% of attempts  3 months prior to study) Physically able to obtain an erection documented by: Physically able to obtain an erection documented by: –Ability to attain and maintain an erection sufficient for intercourse on some occasion during 3 months prior to study i.e., nocturnal/morning erections or masturbation –Nocturnal Penile Tumescence (NPT) testing with 55% or greater base rigidity for at least 10 minutes on at least 1 of 2 nights of NPT testing Phase III Studies (M96-470, M97-658, M98-941, M97-763) Patient Population

8. E001451 Primary 8 2/21/2016 Uprima ® Patient Population (cont.) No uncontrolled disease No uncontrolled disease Clinically acceptable pre-study laboratory values, including normal testosterone and prolactin Clinically acceptable pre-study laboratory values, including normal testosterone and prolactin Diabetic patients: fasting glucose values <250 mg/dL, no episode of ketoacidosis within 3 months prior to study Diabetic patients: fasting glucose values <250 mg/dL, no episode of ketoacidosis within 3 months prior to study Hypertensive patients: Systolic Blood Pressure (SBP) <180 mm Hg and Diastolic Blood Pressure (DBP) <100 mm Hg Hypertensive patients: Systolic Blood Pressure (SBP) <180 mm Hg and Diastolic Blood Pressure (DBP) <100 mm Hg Smokers:  1/2 pack per day Smokers:  1/2 pack per day Patients were excluded with a history of allergic reaction to morphine (or other opiates) or a history of pharmacotherapy for ED (within 3 months prior to study) Patients were excluded with a history of allergic reaction to morphine (or other opiates) or a history of pharmacotherapy for ED (within 3 months prior to study) Phase III Studies (M96-470, M97-658, M98-941, M97-763) Patient Population

9. E001451 Primary 9 2/21/2016 Uprima ® Definition of “No Major Organic Component” This term was used to exclude: This term was used to exclude: –Prostatectomy –Spinal cord injury –Parkinson’s disease –Multiple sclerosis –Penile prosthesis, penile deformity –End-stage and unstable disease Patient Population

10. E001451 Primary 10 2/21/2016 Uprima ® Patient Demographics Age (yrs)55.121 - 762379 Weight (lbs)199.9112 - 3552376 Duration of Erectile Dysfunction4.8 yrs3 mo. - 47 yrs1771 Race Caucasian 88.6%2107 Caucasian 88.6%2107 Black6.3% 150 Black6.3% 150 Hispanic3.6% 85 Hispanic3.6% 85 Asian/Pacific Islander0.8% 20 Asian/Pacific Islander0.8% 20 Other0.7% 17 Other0.7% 17 RangeN Mean Phase II/III Studies Patient Population

11. E001451 Primary 11 2/21/2016 Uprima ® Representative ED Patient Population Subgroups with organic disease Subgroups with organic disease Baseline ED severity based on IIEF criteria Baseline ED severity based on IIEF criteria RigiScan values compared with established norms RigiScan values compared with established norms Duration of ED Duration of ED Patient Population

12. E001451 Primary 12 2/21/2016 Uprima ® Major Subgroups Hypertension31% Hypertension31% Diabetes16% Diabetes16% Coronary Artery Disease16% Coronary Artery Disease16% Benign Prostatic Hyperplasia16% Benign Prostatic Hyperplasia16% Alcohol Use63% Alcohol Use63% Smoking16% Smoking16% Phase II/III Studies Patient Population

13. E001451 Primary 13 2/21/2016 Uprima ® Baseline ED Severity Based on IIEF* Severe39.3% Severe39.3% Moderate35.4% Moderate35.4% Mild24.9% Mild24.9% No ED0.5% No ED0.5% Phase III Studies (M97-658, M97-763, M97-804, M98-941 and M98-876) * <10= Severe 11-16= Moderate 17-25= Mild >25= No ED >25= No ED Patient Population

14. E001451 Primary 14 2/21/2016 Uprima ® Duration of ED (mean)4.8 years5 years Medical Condition (%) Hypertension31%25%33% Coronary Artery Disease (CAD) 16%14% 16% Hyperlipidemia16%14% — Diabetes16%18%9% 1 Approval Package for Viagra ® (Sildenafil Citrate). FDA.GOV/CDER/CONSUMERINFO/VIAGRA/VIAGRA/HTM. Joint Clinical Review p. 14. April 1999. 2 Johannes et al. J. Urology 163: 460-463, 2000. Uprima ® StudiesViagra ® Studies 1 MMAS 2 ED Population Patient Population

15. E001451 Primary 15 2/21/2016 Uprima ® Comparison of Uprima ® NPT Values with Values for Normals Maximum Tip RAU Values Note:Data from Normals Extrapolated from Graph in Levine and Carroll, Journal of Urology, Vol. 152, 1103-1107, Oct. 1994. Maximum Tip Rigidity Activity Unit (RAU)  ® % Patient Population

16. E001451 Primary 16 2/21/2016 Uprima ® Comparison of Uprima ® NPT Values with Values for Normals Maximum Base RAU Values Note:Data from Normals Extrapolated from Graph in Levine and Carroll, Journal of Urology, Vol. 152, 1103-1107, Oct. 1994. Maximum Base RAU  ® % Patient Population

17. E001451 Primary 17 2/21/2016 Uprima ® Representative ED Patient Population Conclusion Reflective of the ED patient population as a whole including both organic and non-organic disease Reflective of the ED patient population as a whole including both organic and non-organic disease Clearly defined and relevant to clinical practice Clearly defined and relevant to clinical practice Consistent with the Viagra ® patient population Consistent with the Viagra ® patient population Consistent with MMAS Consistent with MMAS Included patients with mild, moderate and severe ED Included patients with mild, moderate and severe ED RigiScans abnormal RigiScans abnormal The patient population studied does support the proposed indication The patient population studied does support the proposed indication Patient Population

18. Uprima ® E001451 Primary 18 2/21/2016 Efficacy Endpoints

19. E001451 Primary 19 2/21/2016 Uprima ® Home-Use Questionnaire Completed After Every Attempt Efficacy Endpoints for Phase III Studies Primary Endpoint Primary Endpoint –Percent of patient “Yes” responses to the question: “Did you attain and maintain an erection firm enough for intercourse?” Secondary Endpoints Secondary Endpoints –Percent of partner “Yes” responses to the question: “Was the erection firm enough for intercourse?” –Percent of patient/partner “Yes” responses to the question: “Did you have intercourse with your partner?” –Time to erection Efficacy Endpoints

20. E001451 Primary 20 2/21/2016 Uprima ® Secondary (cont.) Efficacy Endpoints for Phase III Studies –Patient Brief Sexual Function Inventory (BSFI) data –Partner Brief Sexual Function Inventory data –Patient International Index of Erectile Function (IIEF) data Efficacy Endpoints

21. E001451 Primary 21 2/21/2016 Uprima ® Uprima ® -Efficacy Endpoints Consistent Consistent Clear Clear Relevant Relevant Rigorous Rigorous Efficacy Endpoints

22. E001451 Primary 22 2/21/2016 Uprima ® Efficacy Results are shown from the 3 crossover studies combined, but the results from the individual studies are consistent with the combined data Efficacy

23. E001451 Primary 23 2/21/2016 Uprima ® Open-Label Flexible Dose Long-Term Study Baseline 24-96 Hours Washout 2-4 Week Baseline 4 Week Treatment Period 1 4 Week Treatment Period 2 Washout Period Washout Period 2 mgPlacebo 2 mg Uprima ® Washout Period Washout Period Placebo4 mg Placebo4 mg Uprima ® Washout Period Washout Period Placebo6 mg Placebo6 mg Uprima ® Randomization Washout Period Washout Period Placebo5 mg Placebo5 mg Uprima ® Phase III M96-470, M97-658 & M98-941 Crossover Study Schematic Efficacy-Crossover Studies

24. E001451 Primary 24 2/21/2016 Uprima ® Crossover Studies Suggested by the FDA and provided a powerful design Suggested by the FDA and provided a powerful design Allows patients to be their own control Allows patients to be their own control All patients are exposed to study drug All patients are exposed to study drug Appropriate for stable chronic diseases Appropriate for stable chronic diseases Rationale for Crossover Study Design Efficacy-Crossover Studies

25. E001451 Primary 25 2/21/2016 Uprima ® p<.001 Patient Response (per attempt) “Erection Firm Enough for Intercourse” Phase III – Crossover M96-470, M97-658 & M98-941 p<.001 % “Yes” Combined Data – Phase III Crossover Studies ® Efficacy-Crossover

26. E001451 Primary 26 2/21/2016 Uprima ® Patient Response (per attempt) “Did Attempt Result in Intercourse” p<.001 % “Yes” p<.001 Phase III – Crossover M96-470, M97-658 & M98-941 ® Combined Data – Phase III Crossover Studies Efficacy-Crossover

27. E001451 Primary 27 2/21/2016 Uprima ® Intercourse Rates Comparison of Uprima ® to Viagra ® Uprima ® vs. Viagra ® Uprima ® Viagra ®1 % 1 Calculated from data provided in the Approval Package for Viagra ® (Sildenafil Citrate). FDA.GOV/CDER/CONSUMERINFO/VIAGRA/VIAGRA/HTM. Joint Clinical Review. April 1999. Phase III Crossover StudiesPhase III Studies Efficacy-Viagra

28. Uprima ® E001451 Primary 28 2/21/2016 Partner Responses

29. E001451 Primary 29 2/21/2016 Uprima ® Partner Involvement in Uprima ® Studies Partner responses were a unique factor for the Uprima ® clinical trials Partner responses were a unique factor for the Uprima ® clinical trials Partner BSFI was developed, utilized and validated Partner BSFI was developed, utilized and validated Partner consent and participation were required for all studies Partner consent and participation were required for all studies ED is a couple’s issue ED is a couple’s issue Efficacy-Crossover

30. E001451 Primary 30 2/21/2016 Uprima ® p<.001 Partner Response (per attempt) “Erection Firm Enough for Intercourse” Phase III – Crossover M96-470, M97-658 & M98-941 p<.001 % “Yes” Combined Data – Phase III Crossover Studies ® Efficacy-Crossover

31. E001451 Primary 31 2/21/2016 Uprima ® p<.001 Partner Response (per attempt) “Did Attempt Result in Intercourse” p<.001 % “Yes” Combined Data – Phase III Crossover Studies Phase III – Crossover M96-470, M97-658 & M98-941 ® Efficacy-Crossover

32. E001451 Primary 32 2/21/2016 Uprima ® Primary Endpoint Subgroup Analyses Organic Organic Non-organic Non-organic Hypertensive Patients Hypertensive Patients Diabetic Patients Diabetic Patients Coronary Artery Disease Coronary Artery Disease Benign Prostatic Hyperplasia Benign Prostatic Hyperplasia Alcohol Users Alcohol Users Smokers Smokers Age >65 Age >65 ED Severity ED Severity Efficacy-Crossover/Subgroups

33. E001451 Primary 33 2/21/2016 Uprima ® p<.001 Patient Response (per attempt) “Erection Firm Enough for Intercourse” Phase III – Crossover M96-470, M97-658 & M98-941 p<.001 % “Yes” Subgroup: Documented Organic Disease (Hypertension, CAD or Diabetes) ® p<.001 Efficacy - Subgroups

34. E001451 Primary 34 2/21/2016 Uprima ® p=.027p=.002 Patient Response (per attempt) “Erection Firm Enough for Intercourse” p<.001 Phase III – Crossover M96-470, M97-658 & M98-941 p<.001 % “Yes” Subgroup: Age >65 ® Efficacy - Subgroups

35. Uprima ® E001451 Primary 35 2/21/2016 ED Severity

36. E001451 Primary 36 2/21/2016 Uprima ® Assessment of Effect of ED Severity on Efficacy Analyses were performed in patients with: Analyses were performed in patients with: –mild, moderate and severe ED severity scores at baseline –no success during baseline –abnormal RigiScan scores at inclusion into study Efficacy - ED Severity

37. E001451 Primary 37 2/21/2016 Uprima ® Definition of ED Severity Based on IIEF ED severity was determined based on the sum of 6 questions from the IIEF (questions 1-5 and 15) ED severity was determined based on the sum of 6 questions from the IIEF (questions 1-5 and 15) Severe<10 Severe<10 Moderate11-16 Moderate11-16 Mild17-25 Mild17-25 No ED>25 No ED>25 Efficacy-ED Severity IIEF Scoring For Erectile Dysfunction

38. E001451 Primary 38 2/21/2016 Uprima ® p=.003p<.001 Patient Response (per attempt) “Erection Firm Enough for Intercourse” Phase III – Crossover M97-658 & M98-941 p<.001 % “Yes” Erectile Dysfunction: Severe* (39% of patients) ® * IIEF scores: no ED >25, mild ED 17-25, moderate ED 11-16, severe ED 25, mild ED 17-25, moderate ED 11-16, severe ED <10. Efficacy-ED Severity

39. E001451 Primary 39 2/21/2016 Uprima ® Patient Response (per attempt) “Erection Firm Enough for Intercourse” Phase III – Crossover M96-470, M97-658 & M98-941 p<.001 % “Yes” p<.001 For Patients (39%) With No Success During Baseline ® Efficacy-ED Severity

40. E001451 Primary 40 2/21/2016 Uprima ® Patient Response (per attempt) “Erection Firm Enough for Intercourse” p=.008p=.002p<.001 % “Yes” p=.001 ® Phase III – Crossover Patients with Maximum Tip RAU  9.5 Efficacy-ED Severity

41. E001451 Primary 41 2/21/2016 Uprima ® ED Severity Conclusion Uprima ® is effective in patients with severe ED as evaluated by: Uprima ® is effective in patients with severe ED as evaluated by: –Baseline IIEF ED severity –Baseline success rate –Abnormal NPT (Tip RAU  9.5) Uprima ® is also effective in patients with mild or moderate ED Uprima ® is also effective in patients with mild or moderate ED Efficacy-ED Severity

42. Uprima ® E001451 Primary 42 2/21/2016 Other Endpoints

43. E001451 Primary 43 2/21/2016 Uprima ® Other Endpoints Home-Use (per attempt) Endpoints Home-Use (per attempt) Endpoints –Timing of erections –Treatment Success (% achieving erections sufficient for intercourse in >50% of attempts) –Diary Satisfaction Scale (per attempt) Validated Questionnaires Validated Questionnaires –Partner Satisfaction Scale (PBSFI) –IIEF (4 point improvement in erectile function) Efficacy-Other Endpoints

44. E001451 Primary 44 2/21/2016 Uprima ® Dose (N placebo, Placebo Minutes Uprima ® Minutes N Uprima ® ) Median (IQR)Median (IQR) Median Time to Erection (Using Only Attempts When an Erection Was Achieved) Phase III – Crossover M96-470, M97-658 & M98-941 More erections occurred with Uprima ® than with placebo. IQR = interquartile range. Combined Data – Phase III Crossover Studies 2 mg (271, 309)16.3(10 – 25)17.5(10 – 25) 4 mg (271, 318)15.0(9 – 25)16.4(10 – 28) Efficacy-Other Endpoints  Erection firm enough for intercourse 33.8% on placebo and 54.4% on 4 mg  Natural time course (in context of clinical trial)  Not dose related

45. E001451 Primary 45 2/21/2016 Uprima ® Patient Assessment Percentage of Patients Deemed a Treatment Success % p<.001 Definition of Success:A treatment is deemed a “success” for a patient if at least 50% of all attempts while using the treatment resulted in erections firm enough for intercourse. p<.001 Phase III – Crossover M96-470, M97-658 & M98-941 ® Combined Data – Phase III Crossover Studies Efficacy-Other Endpoints

46. E001451 Primary 46 2/21/2016 Uprima ® Percent of Patients with Mean Intercourse Attempt Satisfaction 3 and an Improvement Over Baseline Percent of Patients with Mean Intercourse Attempt Satisfaction >3 and an Improvement Over Baseline Phase III – Crossover M96-470, M97-658 & M98-941 p<.001 ® Combined Data – Phase II/III Studies Scale: 1=Very dissatisfied 2=Mostly dissatisfied 3=Neutral or mixed (about equally satisfied and dissatisfied) 4=Mostly satisfied 5=Very satisfied Efficacy-Other Endpoints

47. E001451 Primary 47 2/21/2016 Uprima ® Percent of Partners with Mean Intercourse Attempt Satisfaction 3 and an Improvement Over Baseline Percent of Partners with Mean Intercourse Attempt Satisfaction >3 and an Improvement Over Baseline Phase III – Crossover M96-470, M97-658 & M98-941 p<.001 ® Combined Data – Phase II/III Studies Scale: 1=Very dissatisfied 2=Mostly dissatisfied 3=Neutral or mixed (about equally satisfied and dissatisfied) 4=Mostly satisfied 5=Very satisfied Efficacy - Other Endpoints

48. E001451 Primary 48 2/21/2016 Uprima ® p<.001 Percent of Patients with 4 Point Improvement in the Erectile Function Domain Index of the IIEF p<.001 Phase III – Crossover Studies M97-658 & M98-941 p<.001 % ® Combined Data – M97-658 & M98-941 Based on a scale of 1 to 30, with higher scores being better. Efficacy-Other Endpoints

49. E001451 Primary 49 2/21/2016 Uprima ® Phase III Crossover Studies Conclusion Clinical significance has been shown at all dose strengths and demonstrated in all subgroups (organic, non-organic, hypertensive, etc.) with these endpoints Clinical significance has been shown at all dose strengths and demonstrated in all subgroups (organic, non-organic, hypertensive, etc.) with these endpoints The robustness of the Uprima ® efficacy results has been demonstrated across a variety of home-use efficacy endpoints and is confirmed by the results of validated questionnaires The robustness of the Uprima ® efficacy results has been demonstrated across a variety of home-use efficacy endpoints and is confirmed by the results of validated questionnaires Efficacy-Crossover

50. E001451 Primary 50 2/21/2016 Uprima ® Phase III Crossover Studies Conclusion (cont.) Clinical Relevance of 2 mg Clinical Relevance of 2 mg –Statistically superior compared to placebo in all Phase III Crossover studies for the primary endpoint and virtually all secondary endpoints –Shows a 4-point improvement on IIEF in 45% of patients (compared to 27% of placebo) –Statistically significant compared to placebo in patients with moderate to severe ED as well as patients with a variety of organic diseases (hypertension, diabetes, CAD, etc.) –Intercourse rates increase from a placebo rate of 29% to 42% for Uprima ® 2 mg (13% increase) compared to 16% increase seen with Viagra ® 25 mg Efficacy-Crossover

51. E001451 Primary 51 2/21/2016 Uprima ® Efficacy Efficacy

52. E001451 Primary 52 2/21/2016 Uprima ® Efficacy in Diabetics

53. E001451 Primary 53 2/21/2016 Uprima ® Phase III 4 mg n (%) 5 mg n (%) Baseline IIEF Severity Rating* Severe6171.84250.010361.0 Moderate2023.52428.64426.0 Mild 44.71821.42213.0 Combined** n (%) Diabetes Study Baseline ED Severity M97-804 *Severity rating determined by Erectile Function total. Severity Score; Mild (17-25), Moderate (11-16), and Severe (<10). Note: No NPT required for enrollment. **Due to randomization imbalance, the 4 and 5 mg were combined to represent the overall diabetic population. Efficacy-Diabetes

54. E001451 Primary 54 2/21/2016 Uprima ® 5.1 12.2 8.1 14.5 27.2 20.4 24.6 34.1 28.9 0 10 20 30 40 50 4 mg (N=90)5 mg (N=86)Combined (N=176) Baseline Placebo Uprima ® Patient Response (per attempt) “Did You Achieve an Erection Firm Enough for Intercourse” Phase III – Diabetic p=.020p=.179 % “Yes” p=.009 M97-804 Efficacy-Diabetes

55. E001451 Primary 55 2/21/2016 Uprima ® p=.038p=.021 19.6 6.4 13.4 11.5 22.4 18.3 25.9 30.0 40.3 29.2 36.2 45.2 0 10 20 30 40 50 2 mg (N=30)4 mg (N=113)5 mg (N=111)6 mg (N=8) Baseline Uprima ® p=.004 % “Yes” p=.090 Patient Response (per attempt) “Erection Firm Enough for Intercourse” Phase III – Crossover M96-470, M97-658, M98-941 & M97-804 Diabetic Patients– Phase III Crossover Studies (M96-470, M97-658, M98-941 & M97-804) Efficacy-Diabetes Placebo

56. E001451 Primary 56 2/21/2016 Uprima ® Diabetes Efficacy Conclusion Similar to the results seen in the Viagra ® studies, efficacy in diabetic patients is lower than seen in the general population Similar to the results seen in the Viagra ® studies, efficacy in diabetic patients is lower than seen in the general population Although there was a randomization imbalance, statistically significant results were noted in the 4 mg arm and both dosing groups combined from the M97-804 Diabetes Study Although there was a randomization imbalance, statistically significant results were noted in the 4 mg arm and both dosing groups combined from the M97-804 Diabetes Study In diabetic patients enrolled in the Phase III Crossover studies, efficacy improved approximately 10-20% over placebo in all dose strengths In diabetic patients enrolled in the Phase III Crossover studies, efficacy improved approximately 10-20% over placebo in all dose strengths Efficacy-Diabetes

57. E001451 Primary 57 2/21/2016 Uprima ® Uprima ® Efficacy

58. E001451 Primary 58 2/21/2016 Uprima ® Open-Label Long-Term Extension Study Placebo 6 mg Baseline 2-4 Weeks Day 1 5 mg Informed ConsentRandomization Placebo 6 mg Fixed Dose VOLUNTARY TITRATION 5 mg Fixed Dose Week 1Week 2Week 3Week 4Week 8 2 mg4 mg5 mg6 mg Optimal Dose Parallel Study Schematic Design Phase III – Parallel M97-763 Efficacy-Parallel

59. E001451 Primary 59 2/21/2016 Uprima ® Average Percent p<.001 p<0.001 N=114N=112 N=114N=84N=82N=232N=230 N=232 2, 4, 5, 6 mg2, 4 mg p=.003 Phase III – Parallel M97-763 Patient Response (per attempt) “Erections Firm Enough for Intercourse” ® Based on last 8 attempts. M97-763 Efficacy-Parallel

60. E001451 Primary 60 2/21/2016 Uprima ® p<.001 p=.002 N=112 N=114N=112N=80N=84N=225N=228 N=224 2, 4, 5, 6 mg2, 4 mg p=.004 Phase III – Parallel M97-763 Partner Response (per attempt) “Erections Firm Enough for Intercourse” Based on last 8 attempts. M97-763 Average Percent ® Efficacy-Parallel

61. E001451 Primary 61 2/21/2016 Uprima ® p<.001 p=.003 N=114N=112 N=114N=84N=82N=232N=230 N=232 2, 4, 5, 6 mg2, 4 mg p=.005 Phase III – Parallel M97-763 Patient Response (per attempt) “Did Attempt Result in Intercourse” Based on last 8 attempts. M97-763 Average Percent ® Efficacy-Parallel

62. E001451 Primary 62 2/21/2016 Uprima ® Efficacy

63. E001451 Primary 63 2/21/2016 Discontinuations in Long-Term Studies

64. E001451 Primary 64 2/21/2016 Uprima ® Long-Term Studies The long-term studies were designed primarily to collect safety information The long-term studies were designed primarily to collect safety information A number of factors contributed to patient discontinuation in the long-term studies A number of factors contributed to patient discontinuation in the long-term studies –Lack of efficacy –Adverse events –Approval of new compounds (MUSE ®, Viagra ® ) –Length of studies and stringent patient requirements (office visits, diary completion after every attempt, etc.) –Competing investigational studies Efficacy-Long -Term

65. E001451 Primary 65 2/21/2016 Uprima ® Phase III – Long-Term Open-Label M96-471, M97-659, M97-682 & M98-936 Percentage of Erections Firm Enough for Intercourse N=1,008N=887N=728N=599N=492N=426 All Doses (2, 4, 5, and 6 mg) N=1,019 Efficacy-Long -Term

66. E001451 Primary 66 2/21/2016 Uprima ® Long-Term Studies Short-term studies show that treatment success is achieved in 50-60% of patients, yet approximately 80% of eligible patients enrolled into long-term studies Short-term studies show that treatment success is achieved in 50-60% of patients, yet approximately 80% of eligible patients enrolled into long-term studies Dropout rates of 20-30% are not unexpected based on the number of patients who enrolled from the short-term studies who had no efficacy Dropout rates of 20-30% are not unexpected based on the number of patients who enrolled from the short-term studies who had no efficacy Dropout rates were also influenced by adverse events, approval of Viagra ®, other competing ED trials and the burden of patient inconvenience associated with frequent visits, diary completion, etc. Dropout rates were also influenced by adverse events, approval of Viagra ®, other competing ED trials and the burden of patient inconvenience associated with frequent visits, diary completion, etc. Despite this, over 42% of patients reached the 6-month time point in the long-term studies and demonstrated sustained and reliable efficacy Despite this, over 42% of patients reached the 6-month time point in the long-term studies and demonstrated sustained and reliable efficacy Efficacy-Long -Term

67. E001451 Primary 67 2/21/2016 Uprima ® Phase III – Long-Term Open-Label M96-471, M97-659 & M97-682 Percentage of Erections Firm Enough for Intercourse N=417N=425N=422N=425N=426 All Doses (2, 4, 5, and 6 mg) Includes only patients who remained on drug for at least 6 months. N=426 Efficacy-Long -Term

68. E001451 Primary 68 2/21/2016 Uprima ® Phase III – Long-Term Open-Label M96-471, M97-659 & M97-682 Percentage of Erections Firm Enough for Intercourse N=126N=123N=117 N=125N=128 2 and 4 mg N=129 Includes only patients who remained on drug for at least 6 months. Efficacy-Long -Term

69. E001451 Primary 69 2/21/2016 Uprima ® Efficacy in Long-Term Studies Conclusion Patients remaining in long-term studies have sustained and reliable response with erections in more than 80% of attempts Patients remaining in long-term studies have sustained and reliable response with erections in more than 80% of attempts Patients obtaining efficacy in the long-term studies are similar to all Uprima ® patients as evidenced by their baseline success rates Patients obtaining efficacy in the long-term studies are similar to all Uprima ® patients as evidenced by their baseline success rates Efficacy - Long -Term

70. Uprima ® E001451 Primary 70 2/21/2016 Overall Efficacy Conclusions

71. E001451 Primary 71 2/21/2016 Uprima ® Overall Efficacy Conclusions Clinical trials included patients representative of the general ED population, similar to Viagra ® and MMAS Clinical trials included patients representative of the general ED population, similar to Viagra ® and MMAS Uprima ® 2 and 4 mg has been shown to be statistically and clinically significantly better than placebo in large scale controlled studies Uprima ® 2 and 4 mg has been shown to be statistically and clinically significantly better than placebo in large scale controlled studies Uprima ® 2 and 4 mg have demonstrated a clinically relevant improvement in the IIEF Erectile Function Domain (4-point) compared to placebo Uprima ® 2 and 4 mg have demonstrated a clinically relevant improvement in the IIEF Erectile Function Domain (4-point) compared to placebo Uprima ® partner efficacy data has been shown to be almost identical to Uprima ® patient efficacy data Uprima ® partner efficacy data has been shown to be almost identical to Uprima ® patient efficacy data Patients remaining in the long-term studies have substantial and reliable responses with erections in more than 80% of attempts Patients remaining in the long-term studies have substantial and reliable responses with erections in more than 80% of attempts Efficacy-Conclusions

72. E001451 Primary 72 2/21/2016 Uprima ® Overall Efficacy Conclusions (cont.) Uprima ® efficacy has been demonstrated in subsets of patients with: Uprima ® efficacy has been demonstrated in subsets of patients with: –organic disease - benign prostatic hyperplasia –hypertension - alcohol users –diabetes - smokers –coronary artery disease Uprima ® efficacy has been demonstrated in all severities of ED Uprima ® efficacy has been demonstrated in all severities of ED Uprima ® has been shown to have a rapid onset of erectile response Uprima ® has been shown to have a rapid onset of erectile response Uprima ® has demonstrated significance in all satisfaction and erectile function indices (BSFI, IIEF, Partner BSFI) Uprima ® has demonstrated significance in all satisfaction and erectile function indices (BSFI, IIEF, Partner BSFI) Efficacy-Conclusions