SPIRIT 1: Efficacy and Safety Study of Relugolix in Women With Endometriosis-Associated Pain

This study is an international phase 3 randomized, double-blind, placebo-controlled efficacy
and safety study to evaluate 24 weeks of oral, once-daily relugolix (40 mg) co-administered
with either 12 or 24 weeks of low-dose estradiol (1.0 mg) and norethindrone acetate (0.5 mg),
compared with placebo.

Approximately 600 women with endometriosis-associated pain will be enrolled and randomized
1:1:1 to Group A - relugolix plus low-dose hormonal add-back therapy, Group B - relugolix
monotherapy for 12 weeks followed by co-administration with low-dose hormonal add-back
therapy, or Group C - placebo (N = 200 per group).

Once eligibility has been confirmed, patients will be randomized on Baseline Day 1 to
Treatment Group A, B or C, and will begin double-blinded study drug treatment on Day 1.
Between the Baseline Day 1 and Week 24 visits, patients will attend visits every 4 weeks, and
will take the blinded study treatment (1 tablet and 1 capsule) orally once daily for 24
weeks. The last dose of study drug will be taken on the day prior to the Week 24 visit.

Eligible patients, including women randomized to placebo, will be offered the opportunity to
enroll in a 28-week open label extension study where patients will receive relugolix
co-administered with low-dose estradiol and norethindrone acetate. Patients who do not enroll
into the extension study will have a Follow-Up visit approximately 30 days after the
patient's last dose of study drug.

Key Inclusion Criteria:

1. Is a premenopausal female aged 18 to 50 years old (inclusive) on the day of signing of
the informed consent form.

2. Has agreed to use only study-specified analgesic medications during the study and is
not known to be intolerant to these.

3. Has a diagnosis of endometriosis with surgical visualization of endometriosis via
laparoscopy or laparotomy performed within 10 years prior to signing the informed
consent form.

4. During the Run-In Period has a dysmenorrhea NRS score ≥ 4.0 on at least 2 days AND

- Mean NMPP NRS score ≥ 2.5, OR

- Mean NMPP NRS score ≥ 1.25 AND NMPP NRS score ≥ 5.0 on ≥ 4 days.

Key Exclusion Criteria:

1. Has a history of chronic pelvic pain that is not caused by endometriosis.

2. Has any chronic pain or frequently recurring pain condition, other than endometriosis
that is treated with opioids or requires analgesics for ≥ 7 days per month.

3. Has had gynecological surgery or other surgical procedures for treatment of
endometriosis within the 3 months prior to the Screening visit.

4. Has a history of or currently has osteoporosis or other metabolic bone disease.

5. Has a clinically significant gynecologic condition identified during Screening or
Run-In period transvaginal ultrasound or endometrial biopsy.