Safety/Efficacy of Q-122 in Breast Cancer Patients Taking Tamoxifen or Aromatase Inhibitor

Vasomotor symptoms (VMS) are significant in postmenopausal women with the most effective
medications for relief being hormonal preparations. Non-hormonal medications have
demonstrated efficacy but at a far lower level than estrogen replacement therapy. For women
with a history of breast cancer, hormone replacement therapy is often contraindicated and is
not an option for women receiving endocrine therapy including tamoxifen (TAM) and aromatase
inhibitors (AI). Breast cancer survivors, and women receiving endocrine therapy in
particular, have a high rate of problematic hot flashes. In an open label Phase 1 study of
the safety and activity of Q-122 in breast cancer patients taking TAM or an AI, 8 of 9 women
who received at least 1 dose of 100 mg and 10 of 11 women who received at least 1 dose of 200
mg had a reduction in hot flashes of 2 or more per day, the FDA criteria for anti-VMS
activity. This study will define the effect of Q-122 versus placebo in a population of women
with a history of or current breast cancer who have an average of 50 or more moderate to
severe hot flashes per week.

Inclusion Criteria:

1. Be a female, aged between 18 - 70 years on the day of informed consent

2. Have a history of or current breast cancer and currently taking tamoxifen or an
aromatase inhibitor

3. On a stable dose of TAM or an AI for a minimum of 30 days before the Screening Visit
and no anticipated need to change the dose for the duration of the study

4. Experience an average of at least 50 moderate to severe hot flashes/week for the 2
weeks immediately preceding the Run-In Visit (i.e., during the Screening period).

5. If on thyroid medication, on a stable dose for a minimum of 30 days before the
Screening Visit and no anticipated need to change the dose for the duration of the
study

6. If taking an SSRI or SNRI, on a stable dose for a minimum of 30 days before the
Screening Visit and no anticipated need to change the dose for the duration of the
study

7. Willing and able to complete the daily participant diary, attend all study visits, and
participate in all study procedures

8. Able to provide informed consent

Exclusion Criteria:

1. Childbearing potential, pregnancy, or lactation. Non-childbearing potential is defined
as physiologically incapable of becoming pregnant by one of the following:

- Has had a partial or complete hysterectomy or

- Has had a bilateral oophorectomy or

- Has had a bilateral tubal ligation or fallopian tube inserts or

- Is post-menopausal (amenorrhea > 1 year in women over 55) confirmed by levels of
follicle stimulating hormone (FSH)

2. Currently experiencing undiagnosed vaginal bleeding

3. Women with advanced breast cancer (Stage 4)

4. Greater than 60% reduction in the frequency of hot flashes during the 1-week single
blind Run-In period or inability to correctly record hot flashes and/or drug dosing in
the participant diary

5. Participation in another clinical or surgical trial within 30 days prior to screening
or during the study without the prior written consent of the Medical Monitor

6. Gastrointestinal, liver, kidney or other conditions which could interfere with the
absorption, distribution, metabolism or excretion of Q-122

7. Untreated overt hyperthyroidism

8. Have any other medical condition, clinically important systemic disease or significant
co-morbidities or any finding during Screening that in the judgment of the
investigator puts the participant at increased risk by participation in this study, or
that may affect the reliability of participant diary entries

9. Known inability to complete all study visits and study assessments for scheduling or
other reasons

10. BMI > 40 kg/m2; Participants with a BMI greater than 40 kg/m2 may be enrolled on a
case-by-case basis if approved by the Medical Monitor and if the participant is not
deemed at increased risk of adverse effects based on body habitus and cardiovascular
health

11. Women with a history of, or current evidence of, abuse of alcohol or any drug
substance, or who regularly drink more than 3 standard drinks per day

12. Uncontrolled systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥95 mmHg
confirmed following 3 individual readings

13. Abnormal laboratory findings:

1. Hemoglobin < 9.5 gm/dL (g/L); or any abnormal values that are deemed clinically
significant by the investigator

2. Fasting ALT, AST, GGT, or bilirubin greater than twice the upper limit of normal
that is confirmed on a second sample.

3. <60 eGFR mL/min/1.73 m2

14. Any other reason which in the investigator's opinion makes the participant unsuitable
for a clinical trial.