Safety, Tolerability, Pharmacokinetics, and Biological Activity of ATYR1940 in Adult Patients With Muscular Dystrophy

Study ATYR1940-C-002 is a multi-national, multi-center, double-blind, randomized,
placebo-controlled, ascending dose study designed to evaluate the safety, tolerability, PK,
immunogenicity, and pharmacodynamic effects of ATYR1940 in patients with FSHD. Up to 44
patients are planned to be enrolled at multiple study centers in the U.S. and Europe; the
actual number of patients enrolled will depend on the number of cohorts initiated.

Patients will be screened for study eligibility during the Screening period within 3 weeks
before Baseline (i.e., Day 1, the first day of Study Drug administration). Eligible patients,
based on Screening assessments, will be randomly assigned to treatment with ATYR1940 or
placebo. Patients who are randomized are considered to be enrolled in the study.

After enrollment, patients will enter the 1-week single-blind placebo period during which all
patients will receive a single 30-minute IV infusion of placebo. Thereafter, patients will
enter the double-blind treatment period and will receive 30-minute IV infusions of Study Drug
(ATYR1940 or placebo) according to their random treatment assignment.

Inclusion Criteria:

- Patient is a male or female aged 18 to 65 years, inclusive.

- Patient has an established, genetically-confirmed, diagnosis of facioscapulohumeral
dystrophy with clinical findings meeting existing criteria.

- Patient has provided written informed consent after the nature of the study has been
explained and prior to the performance of any research-related procedures.

- Patient is, in the Investigator's opinion, willing and able to comply with all study
procedures.

- Cohorts ≥2 only: Patient has imaging findings meeting defined criteria for muscle
inflammation in at least 1 skeletal muscle

Exclusion Criteria:

- Patient is currently receiving treatment with an immunomodulatory agent or has a
history of such treatment, including targeted biological therapies (e.g., etanercept,
omalizumab) within the 3 months before Baseline; corticosteroids within 4 weeks before
Baseline; or high-dose non-steroidal anti-inflammatory agents (NSAIDs) within 2 weeks
before Baseline.

- Patient is currently receiving curcumin or albuterol or requires such treatment during
study participation.

- Patient has evidence of an alternative diagnosis other than FSHD, based on prior
muscle biopsy or genetic test findings.

- Patient has a presumptive diagnosis of FSHD, based on clinical assessment, but does
not yet have genetic confirmation of the diagnosis.

- Patient has a severe retinopathy.

- Patient has a history of obstructive or restrictive lung disease (including
interstitial lung disease, pulmonary fibrosis, or asthma), or evidence for
interstitial lung disease on Screening chest radiograph.

- Patient has a history of anti-synthetase syndrome, prior Jo-1 antibody
(Ab)-positivity, or has a positive or equivocally positive Jo-1 Ab test result during
Screening.

- Patient has acute or clinically relevant Epstein-Barr virus or cytomegalovirus
infection or re-activation.

- Patient has a chronic infection such as hepatitis B virus, hepatitis C virus, or human
immunodeficiency virus or a history of tuberculosis.

- Patient has received a vaccination within 8 weeks before Baseline or vaccination is
planned during study participation.

- Patient has symptomatic cardiomyopathy or severe cardiac arrhythmia that may, in the
Investigator's opinion, limit the patient's ability to complete the study protocol.

- Patient has anemia (as defined for patient's age and gender by local laboratory
range).

- Patient has gamma-glutamyl transferase (GGT) or serum creatinine levels >2 × the upper
limit of normal (ULN).

- Patient has abnormal baseline findings, medical condition(s), or laboratory findings
that, in the Investigator's opinion, might jeopardize patient's safety or decrease the
chance of obtaining satisfactory data needed to achieve the objectives of the study.

- Patient has evidence of clinically significant cardiovascular, pulmonary, hepatic,
renal, hematological, metabolic, dermatological, or gastrointestinal disease, or has a
condition that requires immediate surgical intervention or other treatment or may not
allow safe participation.

- Patient has used any investigational product or device (other than a mobility
assistance device) within 30 days before Baseline.

- Patient has received a product intended to enhance muscle growth within 30 days before
Baseline.

- Patient underwent muscle biopsy within 30 days before Baseline.

- Patient initiated treatment with a statin or had a significant adjustment to their
statin regimen within 3 months before Baseline. (Stable, chronic statin use is
permissible.)

- Patient has received a product that putatively enhances muscle growth (e.g.,
insulin-like growth factor, growth hormone) or activity (e.g., Coenzyme A) on a
chronic basis within 4 weeks before Baseline.

- Patient is unwilling to abstain from strenuous physical activity for 24 hours prior to
each study center visit.

- Patient previously received ATYR1940.

- If female and of childbearing potential (premenopausal and not surgically sterile),
patient has a positive pregnancy test at Screening or is unwilling to use
contraception from the time of Screening through 1 -month after the last Study Drug
dose. Acceptable methods of birth control include abstinence, barrier methods,
hormones, or intra-uterine device.

- If male, patient is unwilling to use a condom plus spermicide during sexual
intercourse from the time of Screening through 1 -month after the last Study Drug
dose.

- Cohorts ≥2 only: Patient has a known contraindication for MRI assessments (e.g., metal
prosthesis or pacemaker) as per local site MRI protocol