Intranasal PH80 Spray for Acute Management of the Symptoms of Premenstrual Dysphoric Disorder

Premenstrual disorders are characterized by negative mood, behavioral, and physical symptoms
that occur consistently for several days to two weeks before menses, that can disrupt normal
functioning, and that subside during the postmenstrual phase of the cycle. Marked
irritability, marked depressed mood, marked anxiety, overeating of specific food cravings,
mood swings, lack of energy, and pain are among the most common symptoms of moderate to
severe premenstrual disorders.

It is estimated that 75% women of reproductive age (menarche to perimenopause) experience
physical and behavioral symptoms premenstrually and in 40% women symptoms are intense
(moderate to severe) and require medical attention. For 3-8 % women premenstrual symptoms
are severe enough to interfere with work and interpersonal relationships. Premenstrual
Dysphoric Disorder (PMDD) as defined by the Diagnostic and Statistical Manual of Mental
Disorders, fourth edition (DSM-IV) research criteria, represents the more severe and
disabling end of the premenstrual disorders spectrum. For women with severe premenstrual
symptoms or PMDD, these symptoms are bothersome enough to produce an impact on psychological
and/or occupational functioning, and professional attention is required.

Selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertaline and paroxetine have
been approved by the United States Food and Drug Administration (FDA) as a chronic treatment
for PMDD, however the use of SSRIs significantly increases the risk of suicide in
adolescents and young adults. Antidepressants are also associated with significant relapse
during short and long term treatment of PMDD. Contraceptives are also prescribed to treat
moderate and severe premenstrual symptoms, but besides the severe adverse effects
(drospirenone and ethinyl estradiol) they re not the treatment choice for women willing to
become pregnant.

Pherin Pharmaceuticals synthesized a number of pherines and screened them for biologic
activity in vitro. PH80 is a pherine shown to bind to a subset of peripheral receptors in
nasal chemosensory neurons. Pherines such as PH80 are thought to exert their activity by
rapid stimulation of the hypothalamus, which does not require systemic uptake and
distribution. PH80 is being investigated as a potential treatment in women that suffer the
cycle related symptoms of Premenstrual Dysphoric Disorder.

Each single administration of PH80 to be tested in this study will deliver a similar amount
of PH80 (800 nanogram) to the nasal passages as was found in previous investigations (Pherin
Clinical Study #PH80 CL003, #PH80 CL015 and #PH80 CL016) to improve premenstrual symptoms in
PMDD patients when administered intranasally on an acute basis.

Inclusion Criteria:

- Female, age 18 to 43 years, with regular menstrual cycles between 22 - 35 days in
length inclusive.

- Women of childbearing potential may participate if they are not pregnant or breast
feeding, and if they agree to use one of the following methods of contraception
throughout the study: abstinence, intrauterine device, condom and foam, diaphragm and
spermicide, vasectomy and spermicide, tubal ligation and spermicide, oral
contraceptives and barrier method. Women using oral contraceptives must have been on
a stable dosing regimen for at least 6 months prior to study entry and must agree to
continue on that same dosing regimen throughout all phases of the study.

- Patients who reported at least a 1-year history of regularly experiencing PMDD.

- Patients who are able to read and understand the Informed Consent document; are
willing and able to comply with the protocol; and who had read, understood, and
voluntarily signed the written Informed Consent prior to the performance of any
study-specific procedures.

Exclusion Criteria:

- Patients who fail to meet the study criteria for PMDD

- Patients with active diabetes mellitus, neurological, cardiac, renal, hepatic, or
pulmonary disease, or with any other significant medical or gynecological abnormality
or condition, as determined by physical examinations and/or clinical laboratory
tests.

- Patients diagnosed with Major Depressive Disorder or Bipolar Depression.

- Patients with an acute or chronic condition that at the judgment of the clinical
Investigator could harm the patient and/or alter the outcome of the study. Additional
clinical examinations and symptom assessment will be performed at this time to
determine continuing eligibility for study participation.

- Patients who used any intranasal medication other than study drug within 14 days
prior to study entry and/or during the Run-In and/or Treatment Phases of the study.

- Patients with other clinical conditions or diseases, or those who were taking
concomitant medications, which in the clinical judgment of the Investigator could
place the patient at undue risk, interfere with study participation, or confound the
results of the study.

- Patients with current or last 2 years history of substance abuse.

- Patients who had a positive urine drug screen for any of the following: amphetamines,
barbiturates, cocaine metabolites, opiates, benzodiazepines, and/or cannabinoids.

- Patients who had been treated previously with PH80.

- Patients who had participated in another research study or received another
investigational drug within 30 days prior to study entry or during the study.

- Patients who used any other exclusionary prescription and/or nonprescription
medications as specified in the study protocol (described in this report) within 14
days prior to study entry and/or during the Run-In and/or Treatment Phases of the
study.