11 Androgenic AEs by Maximum Free T P hase II and Phase III % of patients Placebo N= 703 TTS Upper Decile N=58 Acne710.3 Alopecia2.73.5 Facial Hair55.2.

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11 Androgenic AEs by Maximum Free T P hase II and Phase III % of patients Placebo N= 703 TTS Upper Decile N=58 Acne710.3 Alopecia Facial Hair55.2 Voice Deepening 1.70 H20C

22 Effects of Testosterone in Rhesus Monkey Breast Tissue--Results Treatment (n)E (pg/mL)P (ng/mL)T (ng/mL)Ki67 (%) Control (5)< < E (4) < E/P (4) < E/T (5)  E/T was not different from control (p=0.07)  E/T was different from E (p =0.01) and E/P (p =0.005)  At roughly physiological levels, addition of testosterone reduced mammary tissue proliferation in OVX monkeys compared with estradiol alone; level is no different from control.  Flutamide administered to intact female monkeys for three months to suppress testosterone production doubled the proliferation rate. Dimitrakakis et al, Menopause 10 (4) (2003) S233

33 S Outcome by Age, y Coronary Heart Disease Stroke Venous Thromboembolism Invasive Breast Cancer Colorectal Cancer Hip Fracture Total Death Global Index CEE 16 (0.14) 87 (0.54) 74 (0.88) 19 (0.16) 79 (0.49) 60 (0.71) 18 (0.15) 49 (0.31) 34 (0.32) 25 (0.21) 42 (0.26) 27 (0.32) 8 (0.07) 26 (0.16) 27 (0.32) 5 (0.04) 6 (0.04) 27 (0.32) 34 (0.29) 127 (0.79) 130(1.54) 104 (0.89) 312 (1.95) 276 (3.28) Placebo 29 (0.24) 98 (0.59)) 72 (0.84) 19 (0.16) 50 (0.30) 49 (0.57) 15 (0.13) 39 (0.23) 24 (0.28) 35 (0.29) 60 (0.66) 29 (0.34) 14 (0.12) 31 (0.19) 13 (0.15) 1 (0.01) 19 (0.11) 44 (0.52) 47 (0.39) 131 (0.79) 111(1.30) 104 (0.89) 312 (1.95) 276 (3.28) 0.56 ( ) 0.92 ( )) 1.04 ( )) 1.08 ( ) 1.65 ( ) 1.25 ( ) 1.22 ( ) 1.31 ( ) 1.44 ( ) 0.72 ( ) 0.72 ( ) 0.94 ( ) 0.59 ( ) 0.88 ( ) 2.09 ( ) 5.04 ( ) 0.33 ( ) 0.62 ( ) 47 (0.39) 131 (0.79) 111(1.30) 104 (0.89) 312 (1.95) 276 (3.28) No. Cases Annualized (%) Hazard Ratio 95% CI) P-value for Interaction Favors CEE Favors Placebo Selected Clinical Outcomes by Participant Age and Randomization Assignment CEE=conjugated equine estrogen, CI=confidence interval

44 Multi-faceted Approach to Maximize Safe Use of Intrinsa Educational plans:  Package insert and patient information leaflet to promote safe use  Tools to help clinicians and patients diagnose/ recognize HSDD and identify appropriate patients  Web based education on the appropriate use of the product, prevalence and clinical implications of HSDD  CME programs supported by unrestricted grants W2C

55 Mean Change from Baseline in Efficacy Endpoints Satisfying Sexual Activity DesireDistress MCID>1>8.9< -20 Phase III TTS Patients Responders in Clinical Relevance Study C38

66 Sexuality After Hysterectomy with and without Oophorectomy Nathorst-Boos et al. J Psychosom Obstet Gynaecol 1993;14:283 * p<0.05 D7 ERT=Estrogen replacement therapy BSO w/ ERTBSO w/o ERTNo BSO Semi-structured Interview N=23N=25N=28 Libido same or better52%44%82%* Libido worse48%56%18%*

77 Power Considerations for Breast Cancer Assuming an event rate of 0.3%/year, alpha=0.05, one- sided test, with 15% disenrollment and 50% discontinuation, and 3 controls per Intrinsa user Year from launch RR Person years for Intrinsa Power % % % % % JAMA. 2004;291: LT3

88 Overlap of Free-T Between Low Libido and Normal Libido Women (SM Population Validation Studies) H36 Low LibidoNormal Libido Free Testosterone

99 Glucose (mg/dL) Change from Baseline SM 1 & SM 2 S49 PL (n=480) TTS (n=486) TTS 0-6 (n=855) TTS >6-12 (n=496) TTS >12-18 (n=132) Week 24 / Exit (a)Exposure to TTS (months) Change From Baseline

10 Insulin (  IU /mL) Change from Baseline SM 1 & SM 2 S50 Change From Baseline PL (n=469) TTS 0-6 (n=848) TTS >6-12 (n=354) Week 24 / Exit (a) TTS (n=481) Exposure to TTS (months)

11 Lipid Profile in NM 2 at 52 Weeks Excluding Patients Starting Antihyperlipidemics Post-Baseline* Triglycerides (mg/dL) Interim Data 1:2 Randomization LDL (mg/dL) HDL (mg/dL) Total Cholesterol (mg/dL) TTS N=234 PL N=108 Baseline/ Change from BL S108 * 7.7% Placebo vs 2.9% TTS

12 Carbohydrate Metabolism NM 1 & Placebo n=273 NM 1 TTS n=241 Placebo n=117 TTS n=276 Mean Baseline/  From Baseline Insulin (  IU/mL) HbA 1C (%) Glucose (mg/dL) NM 2 interim S120

13 Abuse is Impractical S19

14 Phase III Responders Compared to Women without HSDD Satisfying Sexual Activity/4 wks C32 Mean Score

15 Phase II Trial with Oral Estrogen  150 mcg/day testosterone not different from placebo  300 mcg/day testosterone safe and efficacious  450 mcg/day testosterone similar safety and no additional efficacy Sexual Desire Sexual Arousal Orgasm Sexual Pleasure Sexual Concerns Sexual Responsiveness Sexual Self Image Change from baseline Placebo 150mcg/d 300mcg/d 450mcg/d *p<0.05 * * E57 * Total Satisfying Activity

16 Time Course of Effect SM 1 & SM 2 E58 Week Sexual Desire Distress Total Satisfying Activity TTS Placebo * * * * * * * * * * * * * * p< 0.05

17 Insulin (  IU /mL) Change from Baseline SM 1 & SM 2 S50 Change From Baseline PL (n=469) TTS 0-6 (n=848) TTS >6-12 (n=354) Week 24 / Exit (a) TTS (n=481) Exposure to TTS (months)