Phase IIb One Year Efficacy and Safety Study of S-2367 in Obese Subjects With Reduced Calorie Diet

Inclusion Criteria:

- Males and females between 18 and 65 years of age and body mass index between 30.0 to
45.0 kg/m2, inclusive, and a weight that has not fluctuated by more than 3% for the
last 3 months

- Medically stable for 3 months prior to Visit 1 and in otherwise good health, with no
clinically significant findings from medical history, physical examination, 12-lead
electrocardiograms (ECG), and vital signs

- Clinical laboratory evaluations (including clinical chemistry [fasted at least 8
hours], complete blood count, urinalysis, including creatine phosphokinase, amylase,
lipase, lipid profile, insulin, Homeostatic Model Assessment of Insulin Sensitivity
Index, hemoglobin A1c, thyroid stimulating hormone, free thyroxine, cortisol, iron,
and ferritin) within the reference range for the test laboratory, unless deemed not
clinically significant by the investigator

- Males will be sterile or agree to use an approved method of contraception. Some of the
approved methods of contraception for males includes a surgically sterile (for at
least 3 months prior to Visit 1) female sexual partner; a postmenopausal (for at least
1 year since last menstrual cycle) female sexual partner; a female sexual partner who
uses (for at least previous 3 months prior to Visit 1 and during study) oral,
implantable, transdermal, or injectable oral contraceptives; or use of the following
double-barrier method: male condom with spermicide

- Females will be non-pregnant, non-lactating, and either postmenopausal for at least 1
year since last menstrual period, surgically sterile for at least 3 months prior to
Visit 1, or agree to use an approved method of contraception. Some of the approved
methods of contraception for females include a sterile (for at least 3 months prior to
Visit 1) male sexual partner; use of oral, implantable, transdermal, or injectable
oral contraceptives; or use of one of the following double-barrier methods:
intrauterine device with spermicide, diaphragm with spermicide, cervical cap with
spermicide, female condom with spermicide, or a male condom with spermicide by the
male sexual partner

- Able to understand and willing to sign an informed consent form and comply with all
study procedures

Exclusion Criteria:

- History or clinical manifestations of significant metabolic, hepatic, immunological
(e.g., human immunodeficiency virus/ acquired immunodeficiency syndrome), renal,
hematological, pulmonary, cardiovascular, gastrointestinal (GI), urological,
neurological, or psychiatric disorders

- History or presence of an abnormal ECG, which in the investigator's opinion, is
clinically significant

- History or evidence of a psychological disorder, other than stable or controlled
anxiety or depression, including but not limited to the schizophrenias. Treatment with
an antidepressant or anxiolytic drug(s) will be permitted if the dose and form has
remained stable for at least the previous 3 months and the medication is not
precluded/ excluded by this protocol because of potential effects on body weight and
is not expected to change during the remainder of this clinical protocol

- History or evidence of an eating disorder with a compensatory behavior such as
"purging bulimia nervosa" or "non-purging bulimia nervosa"

- History of obesity of endocrine origin

- History of type 1 or type 2 diabetes mellitus

- Clinically significant hypertension defined as blood pressure > 160/90 mm Hg for
either the systolic or diastolic values in either the untreated or treated state

- Clinically significant GI history or surgery. NOTE: Appendectomy and cholecystectomy
will be allowed

- Gastric bypass surgery, stomach banding surgery, or any other surgical procedure(s)
that attempt to promote/aid weight loss

- History of polycystic ovarian syndrome

- History of fenfluramine or dexfenfluramine or "fen-phen" administration with abnormal
findings on echocardiograms at the time of "fen-phen" discontinuation

- History of participation in any weight loss program within 3 months prior to Visit 1

- History of body weight loss or gain greater than 3% within 3 months prior to Visit 1

- History of alcoholism or drug addiction/ substance abuse within 1 year prior to Visit
1

- History of any tobacco-containing or nicotine-containing product use (including
cigarette, pipe, cigar, chewing, nicotine patch, or nicotine gum) within 1 year prior
to Visit 1

- Participation in any other investigational study drug trial in which receipt of
investigational study drug occurred within 3 months prior to Visit 1

- Previous use or participation in a study of S-2367 or any other neuropeptide Y5
agonist or antagonist

- Participation in any weight loss medication/product study in which receipt of weight
loss medication/product occurred within 3 months prior to Visit 1

- Use of any prescription or non-prescription over-the-counter (OTC) medication/product
or herbal/phytotherapeutic/plant-derived medications/products within 3 months prior to
Visit 1 that is intended to induce weight loss, appetite suppression, weight control,
or treat obesity, including, but not limited to, phentermine, sibutramine, orlistat,
ephedra, rimonabant and other anorexogenics and/or stimulants, as well as topiramate

- Use of chronic medications/products within 3 months prior to Visit 1 or during the
study that are known to cause weight gain. The list includes but is not limited to
amitriptyline (Elavil), paroxetine (Paxil), setraline (Zoloft), and mirtazepine
(Remeron)

- Use of any prescription or non-prescription OTC medications/products within 1 month
prior to Visit 1, unless deemed acceptable by the investigator. Some examples of
allowed medications are stable use (over the 3-month period prior to Visit 1) of the
following will be allowed: hormone replacement therapy (e.g., for postmenopausal
women); antihypertensive agents (e.g., for hypertensive subjects); statins (e.g., for
hyperlilidaemia); thyroid replacement therapy (e.g., for thyroid subjects and provided
thyroid replacement therapy has been stable for 3 months and no clinically significant
changes in thyroid stimulating hormone and/or free thyroxine occur[s] during the
study); oral, implantable, transdermal, or injectable contraceptive(s), etc.
Anticholinergics (if used acutely), centrally acting antihistamines, and
anti-inflammatories will be also allowed. Continued, stable, moderate use (over 3
month period prior to Visit 1) of vitamins and minerals is allowed and additional use
of multivitamin-mineral supplements (non-herbal) may be allowed by the investigator
(or designee) as part of the study diet program

- Donation of blood or blood products 3 months prior to Visit 1 or during the entire
study

- Any acute or chronic condition that, in the opinion of the investigator, would limit
the subject's ability to complete and/ or participate in this clinical study