MT-8554 for Reduction of Vasomotor Symptoms in Postmenopausal Women

This is a Phase II randomized, double-blind, placebo-controlled study for dose selection in
postmenopausal women with moderate to severe VMS, defined as follows:

- Moderate: sensation of heat with sweating, able to continue activity

- Severe: sensation of heat with sweating, causing cessation of activity This study is
comprised of a screening period, a run-in period and a 12-week double-blind treatment
period.

Inclusion Criteria:

Additional screening criteria check may apply for qualification:

- Provide written informed consent to participate in this study

- Spontaneous amenorrhea for ≥12 months; or spontaneous amenorrhea for at least 6 months
and with follicle stimulating hormone (FSH) levels >40 mIU/mL; or documented bilateral
salpingo oophorectomy ≥6 weeks, with or without hysterectomy

- 7 or more moderate to severe VMS per day, or 50 or more moderate to severe VMS per
week

- Have a consistent bedtime on at least 5 nights per week

- Mean VMS frequency during the Placebo Run in period does not drop by more than 50%
from the mean level reported for 2 weeks during the Screening period

- VMS diary compliance >50%

- In the Investigator's opinion, subject is able to understand the nature of the study
and any risk involved in participation, and is willing to cooperate and comply with
the protocol restrictions and requirements

Exclusion Criteria:

Additional screening criteria check may apply for qualification:

- History of any cancer within 5 years except for basal cell carcinoma

- History of undiagnosed abnormal vaginal bleeding

- History of Hepatitis B, Hepatitis C or HIV

- History of psychiatric illness, excessive alcohol intake or use of recreational drugs
who are unsuitable for study enrollment and compliance

- Presence or history of severe adverse reaction or allergy to any drug

- Peripheral vascular disease or disorders with associated vasculopathies

- Clinically significant conditions which could interfere with the objectives of the
study or the safety of the subject, as judged by the Investigator

- Endometrial thickness of >=5 mm as measured by transvaginal ultrasound

- Abnormal result from baseline endometrial biopsy (i.e., endometrial hyperplasia or
endometrial cancer)

- Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or total bilirubin
≥2.0 × upper limit of normal (ULN) above the reference range

- Subjects of childbearing potential