Study of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD)

Key Inclusion Criteria:

1. Age ≥ 18 years

2. Genetically confirmed Facioscapulohumeral muscular dystrophy type 1 (FSHD1) or FSHD2
(or a first-degree relative with genetically confirmed FSHD1 or FSHD2) and clinical
findings meeting FSHD criteria

3. Part 1 TA cohorts:

1. 6-minute walk distance (6MWD) ≥ 150 meters (without a brace)

2. Mild to moderate weakness in left and/or right ankle dorsiflexion

Part 1 BB cohorts:

a. Mild to moderate weakness in left and/or right elbow flexion

Part 2 TA cohorts:

1. 6MWD ≥ 150 and ≤ 500 meters (without a brace)

2. Mild to moderate weakness in left and right ankle dorsiflexion

Part 2 BB cohorts:

a. Mild to moderate weakness in left and/or right elbow flexion

4. Females of childbearing potential must have negative urine pregnancy test prior to
enrollment and use highly effective birth control methods during study
participation. Hormonal birth control use must be stable for at least 14 days prior
to Day 1. Males must agree to use a condom during any sexual contact with females of
childbearing potential while participating in the study even if he has undergone a
successful vasectomy.

Key Exclusion Criteria:

1. Current/ active malignancy (e.g., remission less than 5 years duration), with the
exception of fully excised or treated basal cell carcinoma, cervical carcinoma
in-situ, or ≤ 2 squamous cell carcinomas of the skin

2. Symptomatic cardiopulmonary disease, significant functional impairment, or other co
morbidities that in the opinion of the investigator would limit a patient's ability
to complete strength and/or functional assessments on study

3. Renal impairment (serum creatinine ≥ 2 times the upper limit of normal,(ULN))

4. Aspartate transaminase (AST) and/or alanine transaminase (ALT) ≥ 3 times ULN

5. Increased risk of bleeding (i.e., due to hemophilia, platelet disorders, or use of
any anti-coagulation/platelet modifying therapies up to 2 weeks prior to Study Day
1; low dose aspirin [≤ 100 mg daily] is permitted)

6. Major surgery within 4 weeks prior to Study Day 1

7. Chronic systemic corticosteroids (≥ 2 weeks) within 4 weeks before Study Day 1 and
for duration of study; intra-articular/topical/inhaled therapeutic or physiologic
doses of corticosteroids are permitted

8. Androgens or growth hormone within 6 months before Study Day 1 and for duration of
study; topical physiologic androgen replacement is permitted

9. Any condition that would prevent MRI scanning or compromise the ability to obtain a
clear and interpretable scan of the TA or BB muscles, as applicable (e.g.,
pacemaker, knee/hip replacement, or metallic implants)