1. Vaccines and Related Biological Products Advisory Committee Meeting Male Indication for GARDASIL® [Human Papillomavirus Quadrivalent (Types 6, 11, 16, and 18) Vaccine, Recombinant] Jeff Roberts, M.D. FDA/CBER/OVRR/DVRPA September 9, 2009

10. Demographics Total (N = 4,065) n % Region Africa 538 13.2 Asia-Pacific 361 8.9 Europe 496 12.2 Latin America 1,575 38.7 North America 1,095 26.9 Race/Ethnicity Asian 406 10.0 Black 805 19.8 Hispanic American 835 20.5 Native American 3 0.1 White 1,431 35.2 Other 585 14.4

11. Subject Characteristics, HPV Status at Enrollment N = Number of subjects randomized. m = Number of subjects in the respective category. n = Number of subjects with non-missing data *14 HPV types were tested for by PCR (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) Characteristic Total (N = 4,065) m/n (%) Age (mean in years) 20.5 Age at first sexual intercourse (mean in years) 16.8 Sexual orientation HM 3458 / 4059 (85%) MSM 601 / 4059 (15%) PCR status at Day 1 Pos(+) for 6, 11, 16, 18 456 / 3736 (12%) Pos(+) for any HPV tested* 948 / 3723 (26%) Serostatus on Day 1 Pos (+) for 6, 11, 16, or 18 306 / 4042 (8%) Pos (+) by serology or PCR to 6, 11, 16, or 18 647 / 3737 (17%)

13. Efficacy Against HPV 6/11/16/18-Related EGL in the PPE Population, by HPV Type N = Number of subjects randomized to the respective vaccination group. n = Number of subjects in the PPE population eligible for the respective analysis EGL = External genital lesions with a diagnosis of condyloma, PIN, or Penile/Perianal/Perineal Cancer; PIN = Penile/Perianal/Perineal intraepithelial neoplasia Endpoint Gardasil (N=2025) AAHS control (N=2030) Efficacy % (95%CI) n # of cases n # of cases HPV 6/11/16/18-Related EGL 1397 3 1408 31 90.4% (69.2, 98.1) HPV 6-Related EGL 1245 3 1244 19 84.3% (46.5, 97.0) HPV 11-Related EGL 1245 1 1244 11 90.9% (37.7, 99.8) HPV 16-Related EGL 1295 0 1271 2 100% (-420.8, 100) HPV 18-Related EGL 1335 0 1354 1 100% (-3804.6, 100)

14. Efficacy Against HPV 6/11/16/18-Related EGL in the PPE Population, by Disease Endpoint N = Number of subjects randomized to the respective vaccination group. n = Number of subjects in the PPE population eligible for the respective analysis EGL = External genital lesions with a diagnosis of condyloma, PIN, or Penile/Perianal/Perineal Cancer; PIN = Penile/Perianal/Perineal intraepithelial neoplasia Endpoint Gardasil (N=2025) AAHS control (N=2030) Efficacy % (95%CI) n # of cases n # of cases Condyloma 1397 3 1408 28 89.4% (65.5, 97.9) PIN1 1397 0 1408 2 100% (-431.1, 100) PIN1 or worse 1397 0 1408 3 100% (-141.2, 100) PIN2/3 or worse 1397 0 1408 1 100% (-3788.2, 100) Penile/Perianal/Perineal Cancer 1397 0 1408 0 N/A

15. Efficacy Against Condyloma in Different Analysis Populations n = Number of subjects in the relevant population eligible for the respective analysis PPE = Per Protocol Efficacy population GHN = Generally HPV Naïve (received at least 1 dose of vaccine or placebo; seronegative to 6, 11, 16, and 18 AND PCR negative to all 14 types tested (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59); cases counted starting at Day 1) FAS = Full Analysis Set CI = Confidence interval Analysis Population Gardasil AAHS control Efficacy % (95%CI) n # of cases n # of cases PPE (HPV 6/11-related) 1245 3 1244 28 89% (66, 98) GHN (any HPV type-related) 1275 5 1270 33 85% (62, 96) FAS (HPV 6/11-related) 1943 24 1937 71 67% (47, 80) FAS (any HPV type-related) 1943 32 1937 83 62% (42, 76)

16. Efficacy Against Any HPV Type Related Condyloma Stratified by Subject Characteristics ( FAS Population) N = Number of subjects randomized to the respective vaccination group. n = Number of subjects in the FAS population eligible for the respective analysis *Any HPV Type Tested = PCR (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59); serology (6, 11, 16, and 18) Subject Characteristic Gardasil (N=2025) AAHS control (N=2030) Efficacy % (95%CI) n # of cases n # of cases Any HPV Type Related Condyloma 1943 32 1937 83 62% (42, 76) 15-20 years old 966 17 1004 49 64% (36, 81) 21-27 years old 977 15 933 34 59% (23, 79) Sexual Orientation – HM 1653 22 1648 61 65% (42, 79) Sexual Orientation – MSM 290 10 289 22 55% (0, 81) Circumcised 743 11 699 24 56% (7, 81) Not Circumcised 1200 21 1238 59 65% (41, 80) PCR(+) and/or sero(+) for 6 and/or 11 at Day 1 186 19 178 22 21% (-53, 60)

17. Immunogenicity Bridging to Males 9-15 Years of Age: Month 7 anti-HPV GMTs ( in mMU* ) † 9-15 year-old male subjects from Protocols 016 and 018. ‡ 16-26 year-old male subjects from Protocol 020 χ For the null hypothesis that GMTBoys/GMTMen <=0.5 (2-fold decrease), a p-value <0.025 supports a conclusion that the specific type anti-HPV response in Boys is non-inferior to the response in Men. N = Number of subjects randomized in the respective group who received at least 1 injection. n = Number of subjects in the indicated immunogenicity population. *mMu = Milli Merck units (units for reporting titer by Merck’s competitive luminex immunoassay (cLIA) Group A ( 9-15yo’s ) † (N=1073) Group B ( 16-26yo’s ) ‡ (N=2025) Fold Difference Group A/Group B (95%CI) χ n GMT n GMT Anti-HPV 6 885 1036.9 1093 447.0 2.32 (2.10, 2.56) Anti-HPV 11 886 1386.3 1093 624.2 2.22 (2.03, 2.43) Anti-HPV1 6 883 6047.1 1136 2402.5 2.52 (2.27, 2.79) Anti-HPV 18 888 1356.9 1175 402.2 3.37 (3.02, 3.76)

18. Immunogenicity Stratified by Age and Gender: Month 7 anti-HPV GMTs(in mMU) † 9-15 year-old subjects from Protocols 018. ‡ 16-26 year-old female subjects from Protocols 007, 013, 015 (consistency lot substudy), 016 and 019. ║ 16-26 year-old male subjects from Protocol 020 N = Number of subjects randomized in the respective group who received at least 1 injection. n = Number of subjects contributing to the analysis. CI = Confidence interval; GMT = Geometric mean titer Females ( 9-15yo’s ) † (N=615) Males ( 9-15yo’s ) † (N=564) Females ( 16-26yo’s ) ‡ (N=9885) Males ( 16-26yo’s ) ║ (N=2025) n GMT (95%CI) n GMT (95%CI) n GMT (95%CI) n GMT (95%CI) Anti-HPV 6 501 884 (813, 962) 471 968 (885, 1,058) 3333 545 (528, 563) 1093 447 (423, 473) Anti-HPV 11 501 1,336 (1,225, 1,457) 471 1,383 (1,264, 1,514) 3357 749 (726, 773) 1093 624 (590, 660) Anti-HPV 16 502 5,007 (4,501, 5,570) 471 6,193 (5,540, 6,923) 3253 2,411 (2,312, 2,515) 1136 2,403 (2,238, 2,580) Anti-HPV 18 503 1,128 (1,017, 1,251) 474 1,475 (1,318, 1,650) 3571 476 (458, 494) 1175 402 (377, 429)

21. Summary of AEs, Days 1-15 Following Any Vaccination, V501-020 N = number of subjects in the ASaT analysis set in the respective vaccination group who had follow-up data n = number of cases *Causality determined by clinical investigator **Deaths in the entire study period: Gardasil: 3 (2 MVAs and 1 gunshot wound); Control: 10 Gardasil (N=1945) AAHS control (N=1950) n % n % With one or more AEs 1345 69.2 1244 63.8 Injection-site AEs 1169 60.1 1047 53.7 Systemic AEs 615 31.6 613 31.4 With vaccine-related AEs* 1242 63.9 1134 58.2 Vaccine-related injection-site AEs 1169 60.1 1046 53.6 Vaccine-related systemic AEs 274 14.1 284 14.6 With SAEs 5 0.3 1 0.1 Who died** 0 0.0 0 0.0 Discontinued due to an AE 2 0.1 4 0.2 Discontinued due to an SAE 0 0.0 0 0.0

23. Injection Site AEs, Days 1-5 Following Vaccination, V501-020 N = number of subjects in the ASaT analysis set in the respective vaccination group who had follow-up data n = number of subjects with the indicated characteristic Injection Site Reaction Gardasil (N=1945) AAHS control (N=1950) n % n % One or more injection-site AEs 1166 59.9 1046 53.6 One or more severe injection-site AEs 25 1.3 20 1.0 Injection-site pain 1113 57.2 991 50.8 Injection-site erythema 304 15.6 275 14.1 Injection-site pruritis 22 1.1 24 1.2 Injection-site swelling 219 11.3 187 9.6

25. SAEs, Days 1 to 15 Following Vaccination, Pooled Safety Population *There were a total of 7 subjects who received a mixed vaccine/placebo regimen that are not counted in the safety tables. SAE Gardasil* (N=3092) AAHS control* (N=2303) n % n % With Serious AEs 9 0.3 1 0.0 abdominal pain 1 0.0 0 0.0 acute renal failure 1 0.0 0 0.0 new onset type 1 diabetes mellitus 1 0.0 0 0.0 localized infection and pain (lower extremity) 1 0.0 0 0.0 appendicitis 1 0.0 0 0.0 cellulitis (lower extremity) 1 0.0 0 0.0 chest pain 1 0.0 0 0.0 peanut allergy 1 0.0 0 0.0 varicella infection with seizure 1 0.0 0 0.0 contusion 0 0.0 1 0.0

26. Injection Site Reactions in Boys Compared with Men † 9-15 year-old male subjects from Protocols 016 and 018. ‡ 16-26 year-old male subjects from Protocol 020 N = Number of subjects randomized in the respective group who received at least 1 injection. n = Number of subjects in the indicated immunogenicity population. Males ( 9-15yo’s ) † (N=506) Males ( 16-26yo’s ) ‡ (N=2025) n % n % One or more injection-site AEs 403 80.4 1046 53.6 One or more severe injection-site AEs 22 4.4 20 1.0 Injection-site erythema 101 20.2 275 14.1 Injection-site pain 398 79.4 991 50.8 Injection-site pruritis 13 2.6 24 1.2 Injection-site swelling 127 25.3 187 9.6

35. Autoimmune-Associated Events, Pooled Safety Dataset N = Number of individuals who received at least one dose of either vaccine or placebo n = Number of individuals with specific new Medical Conditions Conditions GARDASIL (N = 3092) AAHS Control or Saline Placebo (N = 2303) n (%) n (%) Alopecia Areata Ankylosing Spondylitis Arthralgia/Arthritis/Reactive Arthritis Autoimmune Thrombocytopenia Diabetes Mellitus Type 1 Hyperthyroidism Hypothyroidism Inflammatory Bowel Disease Myocarditis Proteinuria Psoriasis Vitiligo 1 (0.0) 1 (0.0) 30 (1.0) 1 (0.0) 3 (0.1) 0 (0.0) 3 (0.1) 0 (0.0) 1 (0.0) 1 (0.0) 0 (0.0) 2 (0.1) 0 (0.0) 2 (0.1) 17 (0.7) 0 (0.0) 2 (0.1) 1 (0.0) 0 (0.0) 2 (0.1) 1 (0.0) 0 (0.0) 2 (0.1) 5 (0.2) All Conditions 43 (1.4) 32 (1.4)