`CFAD V. UPENN
`PENN EX. 2045
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`1 of 15
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`Vice President, PPD Discovery
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`Gail McIntyre, PhD
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`Dapoxetine
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`2 of 15
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`•2003: PPD acquires from Lilly the patents for dapoxetine for
`•2000: PPD licenses dapoxetine to Alza
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`development in the field of genitourinary disorders
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`investigates drug as treatment for premature ejaculation
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`•1998-1999: PPD licenses dapoxetine from Lilly and
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`Program highlights
`Dapoxetine
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`3 of 15
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`•The premature ejaculation is not due exclusively to the direct
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`effects of a substance (e.g., withdrawal from opioids)
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`•The disturbance causes marked distress or interpersonal
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`difficulty
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`frequency of sexual activity
`age, novelty of the sexual Partner or situation, and recent
`factors that affect duration of the excitement phase, such as
`the person wishes it. The clinician must take into account
`stimulation before, on, or shortly after penetration and before
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`•Persistent or recurrent ejaculation with minimal sexual
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`DSM IV diagnostic criteria for Premature Ejaculation (302.75):
`Dapoxetine
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`4 of 15
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`1Laumann et al., JAMA 281: 537 (1999)
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`Prevalence of Premature Ejaculation (PE) v
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`Prevalence
`Dapoxetine
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`18
`11
`9
`7
`(5 million)
`ED
`[% within each age group]1
`Erectile Dysfunction (ED)
`
`31
`28
`32
`30
`(20 million)
`PE
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`50-59
`40-49
`30-39
`18-29
`(# Affected in US)
`Age
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`5 of 15
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`•McCabe, "Intimacy and Quality of Life Among Sexually Dysfunctional Men..”
`"Quality of Life"
`emotional, and sexual intimacy and various aspects of
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`•PE correlates with decreased levels of intellectual,
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`J. Sex Marital Ther. 23: 276 ('97)
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`•Rust et al., "Marital Problems and Sexual Dysfunction..." Br.J. Psychiatry
`marriage
`•PE correlates significantly with male perception of poor
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`152:629 ('88)
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`•Kockott et al., "Symptomatology and Psycholgical Aspects of Male Sexual
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`Inadequacy...." Archives Sex. Behav. 9:457 ('80)
`•Sexual avoidance, anxiety, inadequacy
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`Consequences of PE
`Dapoxetine
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`6 of 15
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`•Behavioral - clumsy, painful and poorly effective for long term
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`•Master's and Johnsons - pause-squeeze technique
`•Seman's - pause technique
`management
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`•Pharmacological - none approved
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`•Antidepressants
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`Current therapies
`Dapoxetine
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`7 of 15
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`and sexual intimacy and various aspects of "Quality of Life"
`•PE correlates with decreased levels of intellectual, emotional
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`•Drug action addresses important regulator of sexual function
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`•PE correlates significantly with male perception of poor
`•Sexual avoidance, anxiety, inadequacy
`•positive and negative regulation of sex
`•libido, arousal, orgasm
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`marriage
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`Rationale for use in PE
`Dapoxetine
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`8 of 15
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`Source: R&D Focus
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`*PoC study did not demonstrate delayed time to ejaculation; studies continue
`Pfizer
`VIVUS
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`II
`IIa*
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`PoC
`IIa
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`Phase
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`PDE5
`(Alprostadil cream/anesthetic)
`Topical: prostaglandin
`SSRI
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`NexMed
`Enhance/Barr
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`Class of Drug
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`Company
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`Competition
`Dapoxetine
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`9 of 15
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`•Dapoxetine has PK profile favorable for p.r.n. dosing
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`•Sex is intermittent and spontaneous, thus treatment should:
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`•Have rapid onset of action
`•Be conducive to “as needed” dosing
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`Competitive advantage
`Dapoxetine
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`10 of 15
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`•Secondary endpoints: global satisfaction and PE
`•Primary endpoint: ejaculation latency
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`questionnaire
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`HCl in the treatment of premature ejaculation
`cross-over study of the safety and efficacy of dapoxetine
`•Phase II, double-blind, randomized, placebo-controlled,
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`Proof-of-concept study
`Dapoxetine
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`11 of 15
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`Post-Treatment
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`PE Patients
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`Pre-Treatment
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`PE Patient
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`15% 15%
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`Increase
` 3 Fold
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`~~
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`41% 41%
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`0%
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`10%
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`20%
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`30%
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`40%
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`50%
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`Sexual Satisfaction Rating of “Good” or “Very Good”
`Sexual Satisfaction Rating of “Good” or “Very Good”
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`Percent of Patients Reporting
`Percent of Patients Reporting
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`Improves satisfaction rating
`Dapoxetine
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`12 of 15
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`•Dapoxetine appears to be generally well tolerated based on
`improvements in subjects with PE following p.r.n. dosing
`•Dapoxetine produces statistically and clinically significant
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`clinical and preclinical data available at this time
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`Conclusions from Phase IIa study
`Dapoxetine
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`13 of 15
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`•Safety profile remains the same
`•Program is on schedule
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`•Additional safety studies have been conducted
`•Involves 2,400 patients
`•Phase III studies are in progress
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`Program at ALZA
`Dapoxetine
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`14 of 15
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`•No products currently approved
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`•Competition weak
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`•Affects 25-35% of men ages 18-64 years
`•Large, unsatisfied patient population
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`Potential market
`Dapoxetine
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`IPR2015-01835
`CFAD V. UPENN
`PENN EX. 2045
`
`15 of 15
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`1Laumann et al., ('99); 2Reading and Weist ('84)
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`•60% of “Western men” (i.e., 55 million in US) “wish to
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`delay ejaculation”2
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`•21% incidence PE1- 20 million have clinical diagnosis of
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`•74% of our patients rated severity as "extreme"
`•5-fold greater recruitment rate than we expected
`PE
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`Treatable population: dapoxetine
`Dapoxetine