A Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study of Intravenous ATYR1923 in Patients With Pulmonary Sarcoidosis
Phase: PHASE1
Conditions: Pulmonary Sarcoidosis
Sponsor: aTyr Pharma, Inc.

aTyr Pharma, Inc. 
Clinical Study Protocol Number ATYR1923-C-002 
25 September 2020 
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aTyr Pharma, Inc.
A Randomized, Double-Blind, Placebo-Controlled Multiple Ascending Dose Study of 
Intravenous ATYR1923 in Patients with Pulmonary Sarcoidosis 
Protocol Number: ATYR1923-C-002 
This study will be conducted according to the protocol and in compliance with  
Good Clinical Practice, the ethical principles stated in the Declaration of Helsinki, 
and other applicable regulatory requirements. 
Study Sponsor: 
aTyr Pharma, Inc. 
3545 John Hopkins Court, Suite #250 
San Diego, CA 92121 
USA 
IND Number: 
133692 
EudraCT Number: 
2018-004244-33 
Contract Research Organization: 
Axiom Real-Time Metrics 
1 City View Drive 
Toronto, Ontario 
M9W1J1 
Canada 
Document Date (Version): 
25 September 2020 (Version 3.0; Amendment 2) 
Previous Version: 
13 June 2019 (Version 2.0; Amendment 1) 
15 October 2018 (Version 1.0; Original) 
NCT #: NCT03824392

aTyr Pharma, Inc. 
Clinical Study Protocol Number ATYR1923-C-002 
25 September 2020 
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SPONSOR SIGNATORY 
aTyr Pharma, Inc. 
Date 
25 September 2020

aTyr Pharma, Inc. 
Clinical Study Protocol Number ATYR1923-C-002 
25 September 2020 
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INVESTIGATOR STATEMENT 
I understand that all documentation provided to me by aTyr Pharma, Inc. (aTyr), or its 
designated representative(s) concerning this study that has not been published previously 
will be kept in the strictest confidence. This documentation includes the study protocol, 
investigator brochure, case report forms, and other scientific data. 
This study will not commence without the prior written approval of a properly constituted 
Institutional Review Board (IRB)/Independent Ethics Committee (IEC). No changes will 
be made to the study protocol without the prior written approval of aTyr and the IRB/IEC, 
except where necessary to eliminate an immediate hazard to a patient. 
I have read, understood, and agree to abide by all the conditions and instructions contained 
in this protocol. 
Investigator Signature 
Date 
Printed Name 

aTyr Pharma, Inc. 
Clinical Study Protocol Number ATYR1923-C-002 
25 September 2020 
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CLINICAL STUDY SYNOPSIS 
Protocol Title: 
A Randomized, Double-Blind, Placebo-Controlled Multiple Ascending 
Dose Study of Intravenous ATYR1923 in Patients with Pulmonary 
Sarcoidosis 
Protocol Number: 
ATYR1923-C-002 
Study Phase: 
1b/2a 
Investigators / 
Study Centers: 
This multicenter study will be conducted at approximately 18 study 
centers globally. 
Study Objectives:  
Primary 
• 
To evaluate the safety and tolerability of multiple ascending 
intravenous (IV) doses of ATYR1923 in patients with 
pulmonary sarcoidosis. 
Secondary 
• 
To assess the potential steroid-sparing effect of multiple 
ascending doses of ATYR1923 in patients with pulmonary 
sarcoidosis. 
• 
To assess the potential immunogenicity of multiple ascending 
IV doses of ATYR1923 in patients with pulmonary 
sarcoidosis. 
• 
To characterize the pharmacokinetics (PK) of multiple 
ascending IV doses of ATYR1923 in patients with pulmonary 
sarcoidosis. 
Exploratory 
• 
To explore the preliminary efficacy of multiple ascending IV 
doses of ATYR1923 in patients with pulmonary sarcoidosis by 
evaluating changes over time in: 
- Disease activity (pulmonary parenchymal inflammation), 
assessed by 18F-fluorodeoxyglucose positron-emission 
tomography combined with computed tomography 
(18F-FDG-PET/CT) (optional). 
- Lung function, assessed by percent predicted forced vital 
capacity (FVC%) and diffusing capacity of the lungs for 
carbon monoxide (DLCO). 
- Serum biomarkers, including angiotensin converting 
enzyme (ACE), soluble IL-2 receptor (sIL-2R), 
extracellular histidyl-tRNA-synthetase, neuropilin 2 
(NRP2), and vascular endothelial growth factor C 
(VEGFC). 

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25 September 2020 
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- State of immune cell anergy in peripheral blood 
mononuclear cells (PBMCs) 
- Health-related quality of life scales, including the 
Sarcoidosis Assessment Tool (SAT), King’s Sarcoidosis 
Questionnaire (KSQ), Leicester Cough Questionnaire 
(LCQ), Fatigue Assessment Scale (FAS), and the self-
administered computerized Baseline/Transitional Dyspnea 
Indices (SAC BDI-TDI). 
- Skin lesions, for patients with cutaneous disease 
involvement at baseline, as assessed by Skin Physician 
Global Assessment (SPGA), body surface area (BSA) 
assessment, and the Sarcoidosis Activity and Severity 
Index (SASI; on a target lesion), as well as serial biopsies 
of non-target lesion(s) (optional at select sites). 
Study Design: 
This randomized, double-blind, placebo-controlled, study will evaluate 
the safety, tolerability, immunogenicity, PK, and preliminary efficacy 
of multiple ascending doses of IV ATYR1923 in patients with 
pulmonary sarcoidosis undergoing a protocol-guided oral corticosteroid 
(OCS) tapering regimen.  
This study will consist of 3 staggered multiple dose cohorts. Each 
eligible patient will participate in only one cohort during the study. 
Within each cohort, 12 patients will be randomized 2:1 (block size of 
6) to ATYR1923 (N=8) or placebo (N=4). Study drug will be 
administered via IV infusion every 4 weeks for a total of 6 doses 
(20 weeks of treatment). The follow-up study visit is scheduled for 
4 weeks after the last infusion. The ATYR1923 doses levels to be 
evaluated are 1.0 mg/kg, 3.0 mg/kg, and 5.0 mg/kg. 
Day 1 is the calendar day of first infusion.  
Starting on Day 15, patients will begin a taper (reduction) in OCS (per 
the ATYR1923-C-002 Oral Corticosteroid Taper Guidelines) from 
their starting dose of 10-25 mg/day of prednisone (or equivalent) to a 
target dose of 5 mg/day, to be completed on or before Day 50. The 
OCS dose will be tapered by 5.0 mg/day every 1 to 2 weeks, depending 
on the starting dose. Smaller incremental titrations to the target dose of 
5 mg/day by Day 50 may be implemented per Investigator judgement. 
Patients will be maintained at the target dose of 5.0 mg/day (or 
equivalent) through Week 24/End-of-Study (EOS). Optionally, further 
titrations in the OCS dose to below 5 mg/day may be attempted after 
the Week 16 visit, if determined by the Investigator to be feasible. 
Patients who develop an acute worsening of symptoms or are unable to 
adhere to the protocol-defined OCS tapering regimen may receive 
‘rescue’ treatment with higher OCS doses as clinically indicated. Upon 
resolution of symptoms, the Investigator may choose to reinstitute a 
taper back down to the target maintenance dose of 5 mg/day. Patients 

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who require rescue treatment following two attempts at tapering to 
5 mg/day may remain on a higher stable dose of OCS as determined by 
the Investigator. Patients who require an increase in OCS dose at any 
time in the study should continue to receive blinded study drug and 
followed through to the end of the study. It is planned that 36 patients 
with pulmonary sarcoidosis will be randomized into one of 3 sequential 
cohorts, each comprising 12 patients allocated 2:1 (block size of 6) to 
ATYR1923:Placebo. 
 
Planned Dose Cohorts 
The planned dose cohorts are as follows: 
Cohort 
Dose 
(mg/kg) 
# of 
Doses 
Dosing Frequency 
N 
Ratio 
ATYR1923: 
Placebo 
1 
1.0 
6 
Every 4 weeks 
12 
2:1 
2 
3.0  
6 
Every 4 weeks 
12 
2:1 
3 
5.0 
6 
Every 4 weeks 
12 
2:1 
 
Safety Monitoring 
Ongoing review of blinded safety and tolerability data will be 
performed by the Medical Monitor and aTyr Pharma personnel. 
An independent Data Safety Monitoring Board (DSMB) will perform 
interim reviews of unblinded safety, tolerability, and immunogenicity 
data to review and approve dose escalation to the next highest dose 
cohort (see Dose Escalation) and ad hoc as per Sponsor request if a 
pattern of unexpected, clinically significant trends or changes in other 
safety assessments is identified through blinded safety data reviews. 
Dose Escalation 
Cohorts 1 through 3 will be enrolled sequentially in a staggered 
manner. After at least 6 patients of a given cohort have received at least 
3 infusions of study drug (ATYR1923 or placebo), cumulative 
unblinded safety data (including but not limited to any reported adverse 
events (AEs), electrocardiogram (ECG) recordings, clinical laboratory 
values and vital signs) will be reviewed by the DSMB. Enrollment in 
the next scheduled (higher dose) cohort may commence after this 
review is completed, dose escalation is approved, and the remaining 6 
patients have been randomized in the previous cohort. Dose escalation 
will continue in this manner until the highest planned dose level of 
ATYR1923 is reached, or the criteria for pausing enrollment have been 
met.  
Criteria for Pausing Enrollment 
In the event that a serious unexpected suspected adverse reaction 
(SUSAR) has occurred, the enrollment and initiation of study drug 

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administration to new patients will be paused and the Sponsor will 
request an unblinded review by the DSMB, who will provide its 
recommendation to aTyr Pharma. Such recommendation may include, 
but is not limited to, stopping an ongoing cohort, stopping further dose 
escalation, continuing the study as planned, or continuing the study 
with modifications, such as evaluation of a lower or intermediate dose 
in the next cohort(s) to gain more information on safety and 
tolerability. 
In addition, if unexpected, clinically significant trends or changes in 
other safety assessments are identified during routine blinded safety 
reviews the Sponsor may request the DSMB to similarly perform an 
unblinded review and provide recommendations.  
Number of Patients 
Planned: 
It is planned that 36 adult patients with pulmonary sarcoidosis will be 
randomized into one of 3 sequential cohort. Patients who withdraw for 
reasons other than treatment-related AEs may be replaced at the 
discretion of the Sponsor. 
Diagnosis and Main 
Criteria for 
Inclusion: 
Inclusion Criteria 
The following inclusion criteria must be met for a patient to be eligible 
for inclusion in the study: 
1. Male or female patients aged ≥18 to ≤75 years inclusive at time 
of informed consent  
2. Diagnosis of pulmonary sarcoidosis for ≥6 months (cutaneous 
and ocular involvement allowed), defined as: 
• 
Histologically proven diagnosis of sarcoidosis by 
bronchoscopy, biopsy (any organ) or bronchioalveolar 
lavage. 
• 
Evidence of parenchymal lung involvement by historical 
radiological evidence (eg, computed tomography [CT], 
magnetic resonance imaging [MRI], 18F-FDG PET/CT or 
chest X-ray) or on the Screening 18F-FDG PET/CT. 
3. Must have symptomatic and/or active pulmonary sarcoidosis as 
evidence by: 
• 
Clinical findings of dyspnea, as indicated by a Modified 
Medical Research Council (MRC) Dyspnea Scale grade of 
at least 1; and 
• 
FVC% predicted ≥50%. 
4. Must be receiving treatment with 10 to 25 mg/day of oral 
prednisone (or oral equivalent; eg, methylprednisolone), at a 
stable dose for ≥4 weeks prior to Day 1, and be determined by 
the Investigator to be capable of undergoing the protocol-
specified steroid taper regimen. 

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• 
Treatment with one oral immunomodulatory therapy 
(eg, methotrexate, azathioprine, hydroxychloroquine) at a 
stable dose for ≥1 month prior to Day 1 is allowed but not 
required. The dose of this therapy should remain constant 
throughout the study. 
5. Body weight ≥45 kg and <160 kg. 
6. Female patients may be of childbearing potential or of non-
childbearing potential (either surgically sterilized or at least 
1 year postmenopausal (confirmed by amenorrhea duration of 
at least 12 months and serum follicle-stimulating hormone 
[FSH] ≥30 mIU/mL).  
• 
Female patients of childbearing potential must be non-
pregnant and non-lactating, and have a negative pregnancy 
test at Screening (serum) and at Day 1 (urine) prior to first 
study drug infusion.  
• 
Additionally, female patients of childbearing potential 
must be willing to use highly-effective contraception (see 
Section 7.1.6.4) from Screening until 90 days after the last 
follow-up visit.  
7. Male patients, if not infertile or surgically sterilized, must 
agree to use highly-effective contraception (see Section 
7.1.6.4) and not donate sperm from Screening until 90 days 
after the last follow-up visit. 
8. Provision of written informed consent. 
9. Be able to communicate well with the Investigator and site 
personnel, and agree to comply with all study procedures and 
requirements. 
Exclusion Criteria: 
A patient who meets any of the following exclusion criteria will not be 
eligible for inclusion in the study: 
1. Current disease presentation consistent with Lofgren’s 
syndrome (ie, presence of the triad of erythema nodosum, 
bilateral hilar lymphadenopathy on chest X-ray, and joint pain). 
2. History of severe allergic or anaphylactic reactions to 
therapeutic proteins, or known sensitivity to ATYR1923 or to 
its inactive components (L-histidine, sodium chloride, sucrose, 
L-methionine, and polysorbate-20). 
3. Treatment (within 4 months of Day 1) with biological 
immunomodulators such as tumor necrosis factor-alpha (TNF-
α) inhibitors (eg, infliximab, adalimumab). 
4. Current evidence of clinically significant cardiovascular, 
hepatic, renal, hematological, metabolic, or gastrointestinal 
disease, or has a condition that requires other treatment, may 

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not allow safe participation, or which in the opinion of the 
Investigator should preclude the patient’s participation in the 
clinical study.  
5. Clinically significant pulmonary hypertension requiring 
vasodilator treatment.  
6. Any history of tuberculosis, or evidence of active systemic 
non-tuberculous fungal or mycobacterial infection within 1 
year of Screening. 
7. History of clinically significant cardiac, neurological, 
gastrointestinal, and/or renal manifestations of their 
sarcoidosis. 
8. Active or history of malignancy within the last 5 years, with 
the exception of resected basal cell carcinoma, squamous cell 
carcinoma of the skin, or effectively managed cervical 
carcinoma. 
9. Major surgery within 3 months prior to Day 1 or anticipated 
surgery during the study. 
10. Any condition that necessitated hospitalization within the 
3 months prior to Day 1 or is likely to require so during the 
study. 
11. Participation in another clinical study of an investigational 
agent or device within 3 months (small molecules) / 6 months 
(biologics) or 5 half-lives (if known) of the agent, whichever is 
longer. 
12. History of or positive results of screening for hepatitis B 
(hepatitis B surface antigen [HBsAg]), hepatitis C (anti-
hepatitis C virus [HCV] antibodies [Ab]) or human 
immunodeficiency virus (HIV) (HIV Ab type 1 and 2). 
13. Is an active, heavy smoker of tobacco/nicotine-containing 
products (defined as >20 cigarettes/day or e-cigarette 
equivalent). 
14. Active substance abuse (drugs or alcohol) or history of 
substance abuse within the 12 months prior to Screening. 
15. Clinically significant abnormalities in the Screening physical 
examination, vital signs, ECG, or clinical laboratory test results 
that, in the opinion of the Investigator and Medical Monitor 
should preclude the patient’s participation in the clinical study.  
16. Patient has received a live vaccination within 8 weeks before 
Day 1 or inoculation with a live vaccine is planned during 
study participation. 
17. Jo-1 Ab levels >7 U/mL at Screening, or past history of Jo-1 
Ab positivity. 

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25 September 2020 
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18. Any other condition or circumstance that, in the opinion of the 
investigator, would be likely to prevent adequate compliance 
with the study protocol. 
19. Significant and/or acute illness (eg, change in pulmonary 
status, infection requiring antibiotics) within 5 days prior to 
(the first) drug administration that may impact safety 
assessments, in the opinion of the Investigator. 
Test Products, 
Doses, and Mode of 
Administration: 
ATYR1923 (or matching Placebo) will be provided in vials of 
25 mg/mL strength. Placebo infusion will be identical in appearance to 
the active drug to maintain blinding.  
All investigational product will be administered via an IV infusion over 
a 60-minute duration.  
For the preparation of the ATYR1923 dose levels the weight of the 
patients at Screening will be used.  
Duration of 
Screening, 
Treatment and 
Follow-up: 
The duration of patient participation is up to 28 weeks, including: 
• 
A Screening period for up to 4 weeks in duration. 
• 
A 20-week treatment period with six (6) study drug infusions 
administered every 4 weeks. 
• 
An EOS visit, 4 weeks after last study drug infusion. 
Note that patients with elevated confirmed positive Jo-1 antibody titers 
or who have ongoing study drug-related treatment-emergent adverse 
events (TEAEs) at Week 24/EOS will continue to be followed until 
resolution or determined by the Investigator to be stable (eg, by 
telephone contact or unscheduled visit). 
Duration of Study: 
Approximately 2 years. 
Study Endpoints: 
 
Primary: 
Safety 
Safety and tolerability of multiple IV doses of ATYR1923 in patients 
with pulmonary sarcoidosis based on the following analyses: 
• 
Incidence of TEAEs and serious adverse events (SAEs). 
Secondary: 
Potential to Decrease Background Oral Corticosteroid Dose 
• 
Total cumulative steroid dose administered over the primary 
study period (Day 1 through Week 24). 
• 
Number of patients who achieve the targeted tapered dose of 
prednisone 5 mg/day (or equivalent) and maintain it through 
Week 24. 

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• 
Exposure response analysis comparing steroid dose area under 
the curve (AUC) with ATYR1923 PK parameters through 
Week 24. 
Immunogenicity 
Immunogenicity of multiple IV doses of ATYR1923 in patients with 
pulmonary sarcoidosis based on the following endpoints: 
• 
Incidence and titer of positive anti-drug antibody (ADA) (anti-
ATYR1923) and anti-Jo-1 Ab. 
Exploratory: 
Change from baseline in clinical measures, including: 
• 
FVC% 
• 
DLco 
• 
SUVmax as measured by 18F-FDG-PET/CT 
• 
Health-Related Quality of Life, as assessed by the SAT, KSQ, 
LCQ, FAS, and SAC BDI-TDI. 
• 
Skin lesions in patients with cutaneous involvement utilizing 
SPGA, body surface area assessment, and the SASI. 
Change from baseline in serum and tissue biomarkers, including but 
not limited to: 
• 
ACE, and sIL2R (disease serum biomarkers). 
• 
Extracellular histidyl-tRNA synthetase (HARS), NRP2, and 
VEGFC (pathway serum biomarkers). 
• 
State of immune cell anergy in peripheral blood mononuclear 
cells (PBMCs). 
• 
Histopathology (skin biopsy). 
Pharmacokinetics 
ATYR1923 serum concentrations following multiple IV doses of 
ATYR1923 in all patients with pulmonary sarcoidosis. 
In addition, if available, the following ATYR1923 PK parameters will 
be calculated: 
• 
Time-to-steady-state PK assessment (based on comparison of 
mean trough levels at Weeks 4, 8, 12, 16, 20, and 24). 
• 
Individual patient serum PK parameters: maximum 
concentration (Cmax), time to maximum concentration (Tmax), 
and area under the curve (AUC0-wk4). When possible, AUCwk20-
wk24, half-life (t1/2), clearance (CL), volume of distribution (Vz), 
and volume of distribution at steady state (Vss) will be 
estimated. All parameters will be summarized by treatment 
group. 

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• 
Individual patient serum PK accumulation index assessment 
[based on ratio of 1hr (just prior to end-of-infusion [EOI]) 
concentrations at Week 20 versus Day 1; as well as ratio of 
trough concentrations at Week 24 versus Week 4). 
Sample Size 
Considerations: 
No formal sample size calculation was performed. 
It is anticipated that 36 patients will be randomized in this study; the 
actual number of patients will depend on the number of cohorts 
initiated. 
Statistical Methods: Statistical analyses of all data will be primarily descriptive in nature. 
Continuous variables will be summarized using descriptive statistics (n, 
mean, standard deviation, median, minimum, and maximum). 
Categorical variables will be summarized showing the number and 
percentage (n, %) of patients within each classification. 
Schedule of 
Assessments: 
The Schedule of Assessments is presented in Table 1. 
 

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Table 1: 
Schedule of Assessments  
Study Period 
Screen 
Treatment 
EOS 
Visit 
1 
1a 
2 
2a 
3 
3a, 
3b, 3c 
4 
4a 
5 
5a 
6 
6a 
7 
Study Day 
-28 to - 1 
D1 
W1/ 
D8 
W2/ 
D15 
W3/ 
D22 
W4/ 
D29 
W5, 
6, 7 
W8/ 
D57 
W10/ 
D71 
W12/ 
D85 
W14/ 
D99 
W16/ 
D113 
W18/ 
D127 
W20/ 
D141 
WK24/
D169 
Visit Window (Days) 
- 
- 
- 
±2 
±3 
±3 
±2 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Written informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Telephone Contact 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
 
Eligibility check 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height & weight1 
X 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Modified MRC Dyspnea Scale 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination2 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
Vital signs3 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Pulse oximetry4 
X 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
12-lead ECG5 
X 
X5 
 
 
 
X 
 
X 
 
X5 
 
X 
 
X5 
X 
Pulmonary Function Tests6 
X 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
DLCO7 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
Pregnancy test (females only)8 
X 
(serum) 
X 
 
 
 
 
 
X 
 
 
 
X 
 
 
X 
(serum) 
Serum FSH9 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rheumatoid factor 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Jo-1 antibody (serum) 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
ADA sampling (serum) for anti-
ATYR1923 antibodies17 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Safety laboratory testing 
(hematology, clinical chemistry) 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Urinalysis10 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Coagulation laboratory testing (PT, 
INR, PTT) 
X 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Serology (HBsAg, anti-HCV, and 
anti-HIV 1/2 tests) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Period 
Screen 
Treatment 
EOS 
Visit 
1 
1a 
2 
2a 
3 
3a, 
3b, 3c 
4 
4a 
5 
5a 
6 
6a 
7 
Study Day 
-28 to - 1 
D1 
W1/ 
D8 
W2/ 
D15 
W3/ 
D22 
W4/ 
D29 
W5, 
6, 7 
W8/ 
D57 
W10/ 
D71 
W12/ 
D85 
W14/ 
D99 
W16/ 
D113 
W18/ 
D127 
W20/ 
D141 
WK24/
D169 
Visit Window (Days) 
- 
- 
- 
±2 
±3 
±3 
±2 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
±3 
Serum complement, serum tryptase, 
and IgE11 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Plasma complement11 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
18F-FDG-PET/CT (optional)12 
X 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
Skin lesion visual assessments 
(if applicable)13 
X 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Skin lesion biopsy 
(optional for patients at select sites)14 
X 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
AE assessment/Concomitant 
medications 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization15 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
King’s Sarcoidosis Questionnaire 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Leicester Cough Questionnaire 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Baseline/Transitional Dyspnea 
Indices 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Fatigue Assessment Scale 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Sarcoidosis Assessment Tool 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Blood sampling (serum) for 
ATYR1923 PK16 
 
X16 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X16 
X 
PBMC collection18 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
 
X 
Serum biomarkers19 
 
X 
 
 
 
 
 
 
 
X 
 
 
 
X 
X 
Infusion site examination20 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
Study drug administration 
 
X 
 
 
 
X 
 
X 
 
X 
 
X 
 
X 
 
OCS Taper21 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
ADA = anti-drug antibodies; AE = adverse event; BMI = body mass index; D = Day; ECG = electrocardiogram; EOI = end of infusion; EOS = End-of-Study; ET= Early Termination; 
FSH = follicle stimulating hormone; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; HIV = human immunodeficiency virus; HRCT = high-resolution computed 
tomography; INR = international normalized ratio; OCS = Oral Corticosteroid; PBMC = peripheral blood mononuclear cell; PD = pharmacodynamics; PET = positron emission 
tomography; PK = pharmacokinetics; PT = prothrombin time; PTT = partial thromboplastin time; SOI=start of infusion; W = week(s).  
On dosing days, all assessments will be performed pre-dose unless otherwise specified. 
1. 
Height only at Screening. 
2. 
Physical examination. Full physical examinations are to be obtained at Screening, Week 12 and 24, abbreviated symptom-directed physical examination may be completed 
at other visits if needed. 

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3. 
Vital signs are to be obtained at every visit. On study drug administration days, vital signs are to be measured pre-infusion and at 15 and 30 minutes (±5 minutes) and at 1, 2, 
and 4 hours (±15 minutes) after the start of infusion (SOI). Vital signs are to be measured before blood sample collection. Vital signs will include blood pressure (systolic and 
diastolic, recorded after lying supine for 5 min), heart rate, respiratory rate. Temperature is to be obtained at Screening and on dosing days at pre-dose, 60 minutes (±15 minutes) 
after the SOI, and again at 4 hours (±15 minutes) after the SOI. 
4. 
Pulse oximetry: continuous pulse oximetry is to be measured on dosing days from 5 minutes pre-dose until EOI, and recorded at the same time points as vital signs. On non-
dosing days pulse oximetry is to be obtained with vital sign assessments.  
5. 
12-lead ECG is to be obtained at Screening, within 1-hour pre-dose on dosing days. At Day 1 and Weeks 12 and 20, an ECG is to be obtained at 4 hours (±30 minutes) after 
SOI. The ECG is to be obtained after patients have been lying supine for 5 minutes.  
6. 
Pulmonary Function Testing is to be performed using the same spirometer throughout the study. Parameters include forced vital capacity (FVC), forced expiratory volume 
in 1 second (FEV1), FEV1/FVC ratio at all specified visits. A minimum of 3 efforts should be obtained that meet the acceptance criteria of the American Thoracic Society or 
European Respiratory Society.  
7. 
DLCO measurements should be obtained after patients have been sitting quietly for 5 minutes. 
8. 
Pregnancy serum tests are to be performed on all females at Screening and at Week 24/EOS. A urine pregnancy test is to be performed at other time points indicated.  
9. 
FSH only required for all female patients. 
10. 
Urinalysis (semi-quantitative by dipstick): microscopy is to be performed if indicated by an abnormal and clinically significant result. 
11. 
Serum Complement, Tryptase/Plasma Complement, and IgE are to be collected at Day 1 pre-dose and again if an infusion related reaction (IRR) occurs. 
12. 
18F-FDG-PET/CT scans are optional; patients who elect to participate agree to have imaging performed within 4 weeks prior to Day 1,  and within ±5 days of Week 16 or if 
early termination prior to Week 16. 
13. 
Skin lesion evaluation: To be completed for patients with skin lesions present. Skin lesions will be evaluated by: Skin Physician Global Assessment (SPGA), body surface 
Area assessment, the Sarcoidosis Activity and Severity Index (SASI). 
14. 
Skin lesion biopsy: Optional for patients with skin lesions present. A non-target lesion (ie, a lesion that is not being assessed by SASI over time) is to be selected by the 
Investigator for biopsy during Screening and confirmed by the patient that it had been identified by his or her private dermatologist as cutaneous sarcoidosis. Skin lesion biopsy 
may be obtained within 4 weeks prior to Day 1 for patients who are otherwise deemed eligible for the study and within ±5 days of Week 12 or if early termination prior to 
Week 12. 
15. 
Randomization is to be performed within 0-3 days prior to Day 1 or on the day of dosing. 
16. 
ATYR1923 serum PK samples are to be collected pre-dose on dosing days. On Day 1 and Week 20 visits, PK samples are also collected post start of infusion at: 1 hr (just 
prior to [i.e., within 0-10 minutes] EOI), and at any single time point between 4-6 hours.  
17. 
ADA samples are to be collected pre-dose when obtained on dosing days. 
18. 
Blood for PBMC assessments will be collected pre-dose when obtained on dosing days.  
19. 
Serum for biomarkers are to be collected pre-dose when obtained on dosing days. 
20. 
Infusion site examination: the IV infusion site should be examined at 0.5 and 1.5 hours (+10 minutes) after the end of infusion. 
21. 
OCS Taper: OCS taper to start at Day 15 (Week 2) and continue through Day 50 (Week 7) per the ATYR1923-C-002 OCS Taper Guideline. 
 

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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
18F-FDG-PET/CT 
18F-fluorodeoxyglucose positron-emission tomography combined 
with computed tomography 
Ab 
Antibody 
ACE 
Angiotensin converting enzyme 
ADA 
Anti-drug antibody 
ALT 
Alanine aminotransferase 
APCs 
Antigen-presenting cells 
AST 
Aspartate aminotransferase 
AUC0-168h 
Area under the curve from time zero to 168 hours  
AUC0-336h 
Area under the curve from time zero to 336 hours 
AUC0-t 
Area under the curve from time zero to the last quantifiable time 
point  
BSA 
Body surface area 
CHP 
Chronic hypersensitivity pneumonitis 
Cmax 
Maximum concentration 
COVID-19 
Coronavirus disease-2019 
CRO 
Contract Research Organization 
CSR 
Clinical Study Report 
CT 
Computed tomography 
DLCO 
Diffusing capacity of the lungs for carbon monoxide 
DSMB 
Data Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EOS 
End-of-Study 
FAS 
Fatigue Assessment Scale 
FEV1 
Forced expiratory volume in 1 second 

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Abbreviation 
Definition 
FSH 
Follicle-stimulating hormone 
FVC% 
Percent predicted forced vital capacity 
Gamma-GT 
Gamma glutamyl transferase  
GCP 
Good Clinical Practice 
HARS 
Histidyl-tRNA synthetase 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
HIV 
Human immunodeficiency virus 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IFN-γ 
Interferon gamma 
IgE 
Immunoglobulin E 
IgG1 
Immunoglobulin G1 
ILD 
Interstitial lung disease 
iMod 
Human 59 amino acid protein 
IND 
Investigational New Drug Application 
IRB 
Institutional Review Board 
IRR 
Infusion-related reaction 
ITT 
Intent to Treat 
IV 
Intravenous 
IWRS 
Interactive web response system 
KSQ 
King’s Sarcoidosis Questionnaire 
LCQ 
Leicester Cough Questionnaire 
LDH 
Lactate dehydrogenase 
MCID 
Minimal clinically important difference 
MedDRA 
Medical Dictionary for Regulatory Activities 

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Abbreviation 
Definition 
MRC 
Medical Research Council 
MRI 
Magnetic resonance imaging 
NCI CTCAE 
National Cancer Institute Common Terminology Criteria for 
Adverse Events 
NHP 
Non-human primate 
NOAEL 
No-observed adverse effect level 
NRP2 
Neuropilin 2 
OCS 
Oral corticosteroids 
PAD 
Pharmacologically active dose 
PBMC 
Peripheral blood mononuclear cell 
PFT 
Pulmonary function test 
PK 
Pharmacokinetic 
PM/DM-ILD 
Polymyositis/dermatomyositis interstitial lung disease 
QM 
Once monthly 
RF 
Rheumatoid factor 
SAC BDI-TDI 
Self-administered computerized Baseline/Transitional Dyspnea 
Indices 
SAE 
Serious adverse events 
SAP 
Statistical Analysis Plan 
SASI 
Sarcoidosis Activity and Severity Index 
SAT 
Sarcoidosis Assessment Tool  
sIL-2R 
Soluble IL-2 receptor 
SOI 
Start of infusion 
SOP 
Standard operating procedure 
SPGA 
Skin Physician Global Assessment 
SUSAR 
Serious unexpected suspected adverse reaction 
SUV 
Standardized uptake value 
SUVmax 
Maximum standardized uptake value 

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Abbreviation 
Definition 
t1/2 
Half-life 
TEAE 
Treatment-emergent adverse event 
TNF-α 
Tumor necrosis factor-alpha 
USP 
United States Pharmacopeia 
VEGFC 
Vascular endothelial growth factor C 
 

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TABLE OF CONTENTS 
Sponsor Signatory ..............................................................................................................2 
INVESTIGATOR STATEMENT ....................................................................................3 
CLINICAL STUDY SYNOPSIS ......................................................................................4 
LIST OF ABBREVIATIONS .........................................................................................16 
TABLE OF CONTENTS ................................................................................................20 
LIST OF TABLES IN THE TEXT ................................................................................24 
1. 
Study Personnel and Administrative Structure ................................................25 
2. 
Introduction ..........................................................................................................26 
2.1. 
Pulmonary Sarcoidosis ............................................................................26 
2.2. 
ATYR1923 ................................................................................................27 
2.3. 
Rationale for Current Study ...................................................................29 
3. 
Study Objectives...................................................................................................30 
3.1. 
Primary .....................................................................................................30 
3.2. 
Secondary..................................................................................................30 
3.3. 
Exploratory ...............................................................................................30 
4. 
Investigational Plan .............................................................................................32 
4.1. 
Overall Study Design and Plan ...............................................................32 
4.1.1. 
Screening Period .........................................................................33 
4.1.2. 
Treatment Period.........................................................................33 
4.1.3. 
Follow-up ....................................................................................33 
4.1.4. 
Study Completion .......................................................................34 
4.2. 
Discussion of Study Design ......................................................................34 
5. 
Study Population ..................................................................................................36 
5.1.1. 
Inclusion Criteria ........................................................................36 
5.1.2. 
Exclusion Criteria .......................................................................37 
5.2. 
Source of Patients .....................................................................................38 
6. 
Study Conduct ......................................................................................................39 
6.1. 
Patient Identification, Enrollment, and Randomization ......................39 
6.2. 
Patient Management ................................................................................39 
6.3. 
Patient Adherence ....................................................................................39 
6.3.1. 
Study Conduct During the COVID-19 Public Health 
Emergency ..................................................................................40 

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6.4. 
Withdrawal and Replacement of Patients .............................................40 
6.4.1. 
Study Drug Discontinuation Criteria ..........................................40 
6.4.2. 
Study Withdrawal Criteria ..........................................................41 
6.4.3. 
Replacement of Patients..............................................................41 
6.5. 
Study Completion.....................................................................................41 
6.6. 
Study Termination ...................................................................................42 
6.7. 
Investigator Compliance .........................................................................42 
6.8. 
Data Safety Monitoring Board ...............................................................42 
7. 
Study Drug ............................................................................................................43 
7.1. 
Study Drug Dose and Administration ....................................................43 
7.1.1. 
Treatments Administered ............................................................43 
7.1.2. 
Identity of Investigational Products ............................................43 
7.1.3. 
Method of Assigning Patients to Treatment Cohorts .................44 
7.1.4. 
Selection of Doses in the Study ..................................................44 
7.1.5. 
Blinding ......................................................................................46 
7.1.6. 
Concomitant Medication and Other Restrictions During the 
Study ...........................................................................................46 
7.1.7. 
Treatment Compliance ................................................................49 
8. 
Study Visits and Assessments .............................................................................50 
8.1. 
Schedule of Assessments ..........................................................................50 
8.2. 
Screening and Baseline Measurements ..................................................50 
8.2.1. 
Informed Consent .......................................................................50 
8.2.2. 
Demographics .............................................................................50 
8.2.3. 
Medical History ..........................................................................50 
8.2.4. 
Serology ......................................................................................50 
8.2.5. 
Quality of Life Measures ............................................................51 
8.3. 
Pharmacokinetic Measurements and Variables ...................................52 
8.4. 
Pharmacodynamic/Exploratory Measurements and Variables ..........52 
8.4.1. 
Blood for Peripheral Blood Mononuclear Cells and Serum 
Biomarkers ..................................................................................52 
8.4.2. 
Pulmonary Function Tests ..........................................................53 

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8.4.3. 
Diffusion Capacity ......................................................................53 
8.4.4. 
Cutaneous Disease Assessment (for Patients with Cutaneous 
Disease) .......................................................................................53 
8.4.5. 
Cutaneous Lesion Biopsy (Optional at Selected Sites for Patients 
with Cutaneous Disease) .............................................................54 
8.4.6. 
Whole Body 18F-FDG-PET/CT ..................................................54 
8.5. 
Safety and Tolerability Measurements ..................................................55 
8.5.1. 
Physical Examination and Infusion Site Examination ................55 
8.5.2. 
Vital Signs and Temperature ......................................................56 
8.5.3. 
Electrocardiogram .......................................................................56 
8.5.4. 
Pulse Oximetry ...........................................................................56 
8.5.5. 
Height and Weight ......................................................................56 
8.5.6. 
Immunogenicity Measurements ..................................................57 
8.5.7. 
Adverse Events ...........................................................................57 
8.5.8. 
Concomitant Medications ...........................................................58 
8.5.9. 
Safety Laboratory Tests ..............................................................58 
8.5.10. 
Pregnancy Testing and Follicle Stimulating Hormone ...............59 
8.5.11. 
Appropriateness of Measurements..............................................59 
9. 
Adverse Events .....................................................................................................60 
9.1. 
Definitions .................................................................................................60 
9.1.1. 
Adverse Event .............................................................................60 
9.1.2. 
Suspected Adverse Reaction .......................................................60 
9.1.3. 
Serious Adverse Event ................................................................60 
9.1.4. 
Unexpected Adverse Event .........................................................61 
9.1.5. 
Serious and Unexpected Suspected Adverse Reaction ...............61 
9.2. 
Adverse Event Assessment ......................................................................61 
9.3. 
Recording Adverse Events ......................................................................64 
9.4. 
Reporting Serious Adverse Events .........................................................64 
9.5. 
Follow-Up of Adverse Events ..................................................................65 
9.6. 
Reporting Safety Information .................................................................65 

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9.7. 
Protocol Deviations Due to an Emergency or Adverse Event..............66 
9.8. 
Pregnancy .................................................................................................66 
9.9. 
Management of Potential Infusion Related Reactions, Including 
Anaphylaxis ..............................................................................................66 
9.9.1. 
Anaphylaxis ................................................................................68 
10. 
Statistical Analyses...............................................................................................70 
10.1. Statistical Procedures and Determination of Sample Size ...................70 
10.1.1. 
Analysis Sets ...............................................................................70 
10.1.2. 
Statistical and Analytical Plan for Pharmacokinetic, 
Pharmacodynamic, Safety and Exploratory Evaluation .............71 
10.1.3. 
Determination of Sample Size ....................................................72 
10.2. Data Quality Assurance ...........................................................................72 
10.2.1. 
Interim Analyses .........................................................................73 
10.3. Changes to the Planned Statistical Methods .........................................73 
11. 
Ethical, Legal, and Administrative Considerations ..........................................74 
11.1. Good Clinical Practice .............................................................................74 
11.2. Informed Consent ....................................................................................74 
11.3. Institutional Review Board/Independent Ethics Committee ...............74 
11.4. Amending the Protocol ............................................................................75 
11.5. Confidentiality/Data Protection ..............................................................75 
11.6. Publication Policy.....................................................................................75 
12. 
Study Management ..............................................................................................77 
12.1. Data Quality Assurance ...........................................................................77 
12.2. Case Report Forms and Source Documentation ...................................77 
12.3. Monitoring ................................................................................................77 
12.4. Inspections ................................................................................................78 
12.5. Financial Disclosure Reporting Obligations ..........................................78 
12.6. Archiving Study Records ........................................................................78 
13. 
REFERENCES .....................................................................................................79 
 

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LIST OF TABLES IN THE TEXT 
Table 1: 
Schedule of Assessments...................................................................................... 13 
Table 2: 
Planned Dose Cohorts .......................................................................................... 32 
Table 3: 
Criteria for Determination of Adverse Event Relationship to Study Drug .......... 62 
Table 4: 
Criteria for Determination of Adverse Event Intensity ........................................ 63 
Table 5: 
Criteria for Determination of Adverse Event Outcome........................................ 63 
Table 6: 
Study Drug Action Taken as a Result of Adverse Events .................................... 64 
 
 

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1. 
STUDY PERSONNEL AND ADMINISTRATIVE 
STRUCTURE 
Study Sponsor: 
aTyr Pharma, Inc. 
3545 John Hopkins Court, Suite #250 
San Diego, CA 92121 
USA 
Primary Sponsor Contact: 
 
ATYR1923 
 
aTyr Pharma, Inc. 
Telephone: 
 
E-mail: 
 
Sponsor Signatory: 
 
ATYR1923 
 
Medical Monitor: 
 
Axiom Real-Time Metrics 
Telephone: 
 
E-mail: 
 

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2. 
INTRODUCTION 
2.1. 
Pulmonary Sarcoidosis 
Pulmonary sarcoidosis is a form of interstitial lung disease (ILD) in which immune cells 
play a predominant role. Chronic hypersensitivity pneumonitis (CHP), 
polymyositis/dermatomyositis ILD (PM/DM-ILD), and connective tissue disease 
associated ILD (rheumatoid arthritis ILD; systemic sclerosis-associated ILD) are 
examples of other immune-mediate ILDs. These lung conditions are recognized as having 
a measurable immune component involving both innate and adaptive immune 
mechanisms that contribute to pathogenesis at several cellular and non-cellular levels 
(Kolahian et al, 2016; Meyer et al, 2014). 
Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that is 
characterized pathologically by the presence of non-caseating granulomas (Hunninghake 
et al, 1999). Sarcoidosis frequently presents with bilateral hilar lymphadenopathy, 
pulmonary infiltration, and ocular and skin lesions. This disease affects people of all 
ages, but typically presents before the age of 50 years, with the incidence peaking at 20-
39 years (Iannuzzi et al, 2007). The lungs are affected in more than 90% of patients with 
sarcoidosis (Baughman et al, 2011). Although spontaneous remissions occur, chronic or 
progressive disease is seen in 10–30% and the disease is fatal in 15% of patients, 
typically due to progressive respiratory insufficiency, central nervous system, or 
myocardial involvement. The liver, spleen, lymph nodes, salivary glands, heart, nervous 
system, muscles, bones, and other organs may also be involved. While sarcoidosis most 
frequently involves the lungs and thoracic lymph nodes, up to 30 percent of patients 
present with extrathoracic manifestations of sarcoidosis. 
In the lung, granulomas are most commonly found in the alveolar septa, the walls of 
bronchi, the pulmonary arteries and veins. The sarcoid granuloma is characterized by a 
core of monocyte-derived epithelioid histiocytes and multinucleate giant cells with 
interspersed CD4+ T lymphocytes (Baughman et al, 2011). A minority of cells in or near 
the granuloma are CD8+ lymphocytes, fibroblasts, regulatory T-cells, and B 
lymphocytes. 
For patients with pulmonary sarcoidosis, the primary goal of treatment is to improve the 
patient’s quality of life, while secondarily managing the inflammation that could lead to 
the development of more permanent fibrosis and impairment of pulmonary function. 
Currently, the only available therapy, H.P. Acthar® Gel, (Mallinckrodt Pharmaceuticals, 
2018) for the treatment of sarcoidosis, which was approved in 1952, is not widely used 
by physicians due to toxicity and cost issues (Baughman et al, 2016). The consensus 
standard of care is oral corticosteroids (OCS) that act mainly by suppressing 
inflammatory genes including interferon gamma (IFN-γ) and tumor necrosis factor-alpha 
(TNF-α), which are important to sarcoid granuloma development (Schutt et al, 
2010, Judson et al, 2012). OCS therapy has been shown to stabilize or improve the 

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disease, although relapse commonly occurs once OCS therapy is tapered or discontinued 
(Iannuzzi et al, 2007). Current consensus recommends initiating treatment at a daily 
prednisone equivalent dose of 20 - 40 mg/day for 1 to 3 months, followed by a taper to 
5 to 10 mg/day maintenance dose for 1 year (Hunninghake et al, 1999). For patients who 
subsequently relapse after taper or discontinuation of OCS therapy, the cycle of dosing is 
repeated. 
Long-term corticosteroid use is associated with significant side effects, including 
substantial weight gain, development of insulin resistance, osteoporosis, and risk of 
infection. As well, a cohort of sarcoidosis experts published a consensus that a 
maintenance dose of greater than 10 mg/day for pulmonary sarcoidosis was to be 
avoided, when possible (Hunninghake et al, 1999), forming the need for steroid-sparing 
treatments. Yet, unremitting inflammation may progress into pulmonary fibrosis and 
death. Alternatives, such as immunosuppressive and cytotoxic agents (eg, methotrexate 
and TNF-α inhibitors) have been used; however, these therapies can also have significant 
side effects and toxicities. (Judson et al, 2012). Most published data on the use of these 
therapies is anecdotal and based on small numbers of patients and results have been 
variable. Infliximab (TNF-α inhibitor) was shown to improve lung function in those with 
chronic pulmonary sarcoidosis; however, the treatment effect was modest (Baughman et 
al, 2006). 
Given the known toxicities of long-term corticosteroids, immunosuppressives and 
cytotoxic therapeutic regimens, treatment of patients with sarcoidosis is limited to those 
who are symptomatic and whose disease is considered ‘active’. The presence of 
granulomas from sarcoidosis define the disease as active (Beegle et al, 2013), and 
granulomatous inflammation is the major cause of fibrosis in pulmonary sarcoidosis. 
Studies to date have not clearly demonstrated that corticosteroids or other immuno-
suppressive therapy prevents disease progression or formation of fibrosis (Baughman et 
al, 2011). Therefore, there exists a substantial need for safer and more effective therapies 
for sarcoidosis. 
2.2. 
ATYR1923 
The immunopathogenesis of sarcoidosis is not yet well understood. A leading hypothesis 
is that granuloma formation involves the interplay between antigen, human leukocyte 
antigen class II molecules, and T-cell receptors (Moller et al, 2002): a presumptive 
sarcoid ‘antigen’ is engulfed by circulating antigen-presenting cells (APCs; macrophages, 
dendritic cells) and the subsequent interplay between APCs and CD4+ T cells initiates 
granuloma formation (Baughman et al, 2011). T lymphocyte activation subsequently 
plays a crucial role in sarcoidosis pathogenesis. The T-cell response is biased towards a 
Th-1 phenotype, with important roles for interferon-gamma (IFN-γ) and IL-12 
(Baughman et al, 2011). A variety of cytokines and chemokines have been associated 
with the granulomatous response in sarcoidosis, including TNF-α. Recently, TH17 

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effector CD4+ cells have been implicated in sarcoidosis granuloma formation (Facco et 
al, 2011). 
ATYR1923 is a novel molecular entity that acts as an extracellular immunomodulator. 
ATYR1923 comprises a human 59 amino acid protein (iMod) fused to the Fc region of 
human immunoglobulin G1 (IgG1). The amino acid sequence of the 59 amino acid iMod 
domain in ATYR1923 corresponds identically to the extracellularly active iMod domain 
of histidyl-tRNA synthetase (HARS) amino acids 2 to 60 (HARS 2-60). In solution, the 
ATYR1923 molecule forms a homodimer, similar to other Fc fusion proteins. 
ATYR1923 development builds upon aTyr’s (Sponsor’s) understanding of the biology of 
the extracellular activity of HARS, which we refer to as the neuropilin 2 (NRP2) 
pathway. Antibody blockade of the NRP2 pathway has been associated with disruption of 
immune, respiratory, and muscle homeostasis both in animals (Fernandez et al, 
2013; Katsumata et al, 2007; Sciorati et al, 2014; Sciorati et al, 2015; Hervier et al, 2016) 
and in humans. In humans, the rare disease, anti-synthetase syndrome is associated with 
loss of immune tolerance to HARS, with resultant Jo-1 antibody (Ab) that recognizes 
HARS (Mathews and Berstein, 1983; Bernstein et al, 1984; Yoshida et al, 1983; Yang et 
al, 1984; Stone et al, 2007; Tillie-Leblond et al, 2008; Richards et al, 2009). These 
patients commonly manifest with myositis and ILD, and the Sponsor has determined that 
all Jo-1 Ab-positive patients tested have antibodies that bind to the iMod domain.  
ATYR1923 may provide a naturally occurring human immunomodulatory function to 
therapeutically control or balance the human immune system. The mechanism of action 
of ATYR1923 in T-cells overlaps with the cellular pathology observed in lung 
sarcoidosis. In nonclinical studies, ATYR1923 has been shown to inhibit cytokines 
involved in regulation of inflammatory and immune responses and attenuate T-cell 
activation (Mertsching et al, 2018). As NRP2 was recently discovered to bind 
ATYR1923, and innate immune cells such as dendritic cells and macrophages are known 
to express NRP2 (Roy et al, 2017; Schellenburg et al, 2017), further research into the 
interaction between ATYR1923 and NRP2 on these cells could potentially elucidate 
additional mechanism through which ATYR1923 modulates the immune system. Finally, 
ATYR1923 has been shown to significantly reduce lung fibrosis and inflammation in 
bleomycin-induced animal models of ILD (Nangle et al, 2017; Ogilvie et al, 2018). 
To date, 25 healthy adult subjects have been exposed to ATYR1923 at doses ranging 
from 0.03 to 5.0 mg/kg in a first-in-human clinical study, ATYR1923-C-001. Data from 
this study demonstrated single doses of ATYR1923 over the dosing range of 0.03 to 
5 mg/kg to be well-tolerated in healthy volunteers No severe treatment-emergent adverse 
events (TEAEs), serious adverse events (SAEs), or TEAEs leading to study drug 
modification (dose reduction or discontinuation) were reported. No apparent dose 
relationship was seen across the range of doses studies with regard to the incidence of 
TEAEs. Adverse reactions reported to date include headache, dizziness, and back pain. 

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No ATYR1923-treated subject experienced a definitive infusion-related reaction (IRR). 
However, the occurrence of an IRR could not be ruled out for 1 subject, who experienced 
mild, transient symptoms of dizziness, abdominal pain, and “feeling cold” followed by 
back pain after ATYR1923 infusion. No subject was positive for anti-drug antibodies 
(ADA) or Jo-1 Ab after ATYR1923 exposure. 
ATYR1923 pharmacokinetics (PK) were dose-proportional over the range of 0.03 mg/kg 
to 5.0 mg/kg, and the mean half-life (t1/2) was consistent at doses of 0.1 mg/kg and above, 
with mean values ranging from 167 to 242 hours (7 to 10 days), supporting the potential 
for convenient dosing on a monthly basis. 
This study represents the first clinical investigation of ATYR1923 in patients with 
pulmonary sarcoidosis. 
2.3. 
Rationale for Current Study 
A large unmet need exists for a new therapy that can safely and effectively treat 
pulmonary sarcoidosis, a condition for which there exists a substantial need for safer and 
more effective therapies. The first-in-human clinical study of ATYR1923 demonstrated 
ATYR1923 to be well tolerated among healthy volunteers, with no significant safety 
concerns identified. Furthermore, PK data support convenient once monthly (QM) 
dosing. Accordingly, the current study is being conducted to determine the safety and 
tolerability, potential steroid-sparing effect, potential immunogenicity, and PK of 
ATYR1923 in this target patient population. The potential efficacy of ATYR1923 will 
also be preliminarily explored in this study. 

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3. 
STUDY OBJECTIVES  
3.1. 
Primary 
The primary objective is: 
• To evaluate the safety and tolerability of multiple ascending intravenous (IV) doses of 
ATYR1923 in patients with pulmonary sarcoidosis. 
3.2. 
Secondary 
Secondary objectives are: 
• To assess the potential steroid-sparing effect of multiple ascending doses of 
ATYR1923 in patients with pulmonary sarcoidosis. 
• To assess the potential immunogenicity of multiple ascending IV doses of 
ATYR1923 in patients with pulmonary sarcoidosis. 
• To characterize the PK of multiple ascending IV doses of ATYR1923 in patients with 
pulmonary sarcoidosis. 
3.3. 
Exploratory 
The exploratory objective is: 
• To explore the preliminary efficacy of multiple ascending IV doses of ATYR1923 in 
patients with pulmonary sarcoidosis by evaluating changes over time in: 
− Disease activity (pulmonary parenchymal inflammation), assessed by 18F-
fluorodeoxyglucose positron-emission tomography combined with computed 
tomography (18F-FDG-PET/CT) (optional). 
− Lung function, assessed by percent predicted forced vital capacity (FVC%) and 
diffusing capacity of the lungs for carbon monoxide (DLCO). 
− Serum biomarkers, including angiotensin converting enzyme (ACE), soluble IL-2 
receptor (sIL-2R), extracellular HARS, NRP2, and vascular endothelial growth 
factor C (VEGFC). 
− State of immune cell anergy in peripheral blood mononuclear cells (PBMCs) 
− Health-related quality of life scales, including the Sarcoidosis Assessment Tool 
(SAT), King’s Sarcoidosis Questionnaire (KSQ), Leicester Cough Questionnaire 
(LCQ), Fatigue Assessment Scale (FAS), and the self-administered computerized 
Baseline/Transitional Dyspnea Indices (SAC BDI-TDI). 
− Skin lesions, for patients with cutaneous disease involvement at baseline, as 
assessed by Skin Physician Global Assessment (SPGA), body surface area (BSA) 

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assessment, and the Sarcoidosis Activity and Severity Index (SASI; on a target 
lesion), as well as serial biopsies of non-target lesion(s) (optional at select sites). 

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4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design and Plan 
This randomized, double-blind, placebo-controlled, study will evaluate the safety, 
tolerability, immunogenicity, PK, and preliminary efficacy of multiple ascending doses 
of IV ATYR1923 in patients with pulmonary sarcoidosis undergoing a protocol-guided 
OCS tapering regimen.  
This study will consist of 3 staggered multiple dose cohorts, as shown in Table 2. 
Table 2: 
Planned Dose Cohorts 
Cohort 
Dose 
(mg/kg) 
# of Doses 
Dosing 
Frequency 
N 
Ratio ATYR1923: Placebo 
1 
1.0 
6 
Every 4 weeks 
12 
2:1 
2 
3.0 
6 
Every 4 weeks 
12 
2:1 
3 
5.0 
6 
Every 4 weeks 
12 
2:1 
 
Each eligible patient will participate in only one cohort during the study. Within each 
cohort, 12 patients will be randomized 2:1 (block size of 6) to ATYR1923 (N=8) or 
placebo (N=4). Study drug will be administered via IV infusion every 4 weeks for a total 
of 6 doses (20 weeks of treatment). The follow-up study visit is scheduled for 4 weeks 
after the last infusion. The ATYR1923 doses levels to be evaluated are 1.0 mg/kg, 
3.0 mg/kg, and 5.0 mg/kg. In total, approximately 36 patients with pulmonary sarcoidosis 
are planned to be randomized. The dose-escalation procedure is described in Section 
7.1.3.1. 
Day 1 is the calendar day of first infusion.  
Starting on Day 15, patients will begin a taper (reduction) in OCS (per the ATYR1923-C-
002 Oral Corticosteroid Taper Guidelines) from their starting dose of 10-25 mg/day of 
prednisone (or equivalent) to a target dose of 5 mg/day, to be completed on or before 
Day 50. The OCS dose will be tapered by 5.0 mg/day every 1 to 2 weeks, depending on 
the starting dose. Smaller incremental titrations to the target dose of 5 mg/day by Day 50 
may be implemented per Investigator judgement. Patients will be maintained at the target 
dose of 5.0 mg/day (or equivalent) through Week 24/End-of-Study (EOS). Optionally, 
further titrations in the OCS dose to below 5 mg/day may be attempted after the Week 16 
visit, if determined by the Investigator to be feasible. 
Patients who develop an acute worsening of symptoms or are unable to adhere to the 
protocol-defined OCS tapering regimen may receive ‘rescue’ treatment with higher OCS 
doses as clinically indicated. Upon resolution of symptoms, the Investigator may choose 
to reinstitute a taper back down to the target maintenance dose of 5 mg/day. Patients who 
require rescue treatment following 2 attempts at tapering to 5 mg/day may remain on a 

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higher stable dose of OCS, as determined by the Investigator. Patients who require an 
increase in OCS dose at any time in the study should continue to receive blinded study 
drug and followed through to the end of the study. 
Ongoing review of blinded safety and tolerability data will be performed by the Medical 
Monitor and aTyr Pharma personnel. 
An independent Data Safety Monitoring Board (DSMB) will perform interim reviews of 
unblinded safety, tolerability, and immunogenicity data from each cohort and ad hoc as 
per Sponsor’s request if a pattern of unexpected, clinically significant trends or changes 
in other safety assessments is identified through blinded safety data reviews. 
4.1.1. 
Screening Period 
Patients will report to the study center for the eligibility screening (see Section 5) for 
inclusion and exclusion criteria) within 28 days prior to (the first) drug administration.  
Patients will sign the study-specific informed consent form (ICF) prior to any 
study-specific screening procedures being performed. The written informed consent will 
be obtained for all patients, regardless of their eligibility for the study, and a copy will be 
provided to the patient.  
Eligibility screening will consist of the assessments as presented in the Schedule of 
Assessments (Table 1). 
4.1.2. 
Treatment Period 
The treatment period consists of 6 administrations of study drug via IV infusion every 
4 weeks for a total of 20 weeks of treatment (at Day 1 and Weeks 4, 8, 12, 16, and 20). 
Study drug will be administered by qualified study center personnel at scheduled study 
visits. 
Between scheduled study visits, patients will be contacted by study center personnel via 
telephone at Weeks 1, 3, 5-7, 10, 14, and 18. 
Assessments during the treatment period will be performed as presented in the Schedule 
of Assessments (Table 1). 
4.1.3. 
Follow-up 
All patients are to attend an End-of-Study (EOS) visit at Week 24, ie, 1 month after the 
last study drug dose. Note that patients with elevated confirmed positive Jo-1 antibody 
titers or who have ongoing study drug-related TEAEs at Week 24/EOS will continue to 
be followed until resolution or determined by the Investigator to be stable (eg, by 
telephone contact or unscheduled visit). 
Assessments during follow-up will be performed as presented in the Schedule of 
Assessments (Table 1). 

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4.1.4. 
Study Completion 
The study will be considered complete when the last patient completes the EOS visit and 
any necessary follow-up for Jo-1 Ab positivity or ongoing study drug-related TEAEs has 
been completed. 
4.2. 
Discussion of Study Design 
Single doses of ATYR1923 were found to be safe and well tolerated in a first-in-human 
clinical study, ATYR1923-C-001, in healthy volunteers. No significant immunogenic 
responses (induction of ADAs or Jo-1 Ab positivity) were observed following the 
administration of single doses of ATYR1923. The PK of ATYR1923 was well 
characterized and demonstrated dose-proportional exposures over the range of doses from 
0.03 to 5 mg/kg following IV drug administration. Terminal elimination phases were 
parallel, and the mean t1/2 was consistent from the 0.1 mg/kg (Cohort 2) onwards, with 
mean values ranging from 167 to 242 hours, supporting the potential for dosing every 
4 weeks.  
These data support the continued clinical evaluation of ATYR1923, including evaluations 
of the safety, tolerability, PK, immunogenicity, and potential efficacy of multiple doses 
of ATYR1923. ATYR1923 is being developed for pulmonary sarcoidosis, a condition 
with a significant unmet medical need. Given the significant unmet medical need for this 
condition, advancing safe and efficacious therapies to patients as rapidly as possible is 
warranted.  
Several design features have been employed in the current study in an effort to minimize 
bias, including a double-blind design. Within each cohort, patients will be randomized, 
on a 2:1 basis, to receive either ATYR1923 or placebo. Random assignment of patients 
avoids bias and helps ensure that both known and unknown risk factors are distributed 
evenly between treatment groups. The use of placebo control permits prospective 
comparison between the ATYR1923 groups and the control group.  
This study will be conducted at multiple-study centers. This multi-center design is needed 
not only for efficient enrollment of the required number of patients, allowing for a more 
efficient evaluation of ATYR1923, but it provides a better basis for the subsequent 
generalization of study findings (ICH E9, Statistical Principals for Clinical Trials, 1998). 
The current study is specifically designed, with the inclusion of detailed safety measures, 
to evaluate these parameters in patients with pulmonary sarcoidosis.  
Patients will be evaluated routinely during the treatment as well as 4 weeks after the last 
study drug dose.  
The development of humoral immune responses (formation of Ab) to exogenously 
administered proteins occurs commonly. ATYR1923 is a protein-based therapeutic; 
specifically, it is a human 59-amino acid protein (ie, iMod) directly fused to the C-

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terminus Fc region of human IgG1, and exists as an Fc fusion dimer. The 
immunogenicity assessments in the single-dose healthy subject study included 
assessment of both ADA and Jo-1 Ab, the Ab that recognizes HARS, with loss of 
immune tolerance to HARS being associated with anti-synthetase syndrome. In the 
single-dose healthy volunteer study, neither Jo-1 Ab or ADA were detected. However, 
ADA have occurred infrequently in nonclinical studies with ATYR1923 in the rat and 
non-human primate (NHP). ADA did not affect the PK of the drug. Thus, ADAs may be 
observed in the current clinical study. Accordingly, the study design includes ADA and 
Jo-1 Ab testing, detailed clinical monitoring for adverse immunological events, extended 
safety follow-up if indicated to follow-up on serological findings, and a specific plan to 
assist Investigators in the clinical management of patients in whom immunogenicity 
occurs (see Section 9.9).  
The Investigator will take all the usual medical safety precautions necessary for studies at 
an early stage in the development of a new drug and has full discretion to stop study drug 
infusion at any time, if clinically warranted, or otherwise in the patient’s best interest 
(Section 6.4). 

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5. 
STUDY POPULATION 
A total of 36 patients with pulmonary sarcoidosis (24 randomized to ATYR1923 and 
12 to placebo) are planned to be randomized in the study. 
5.1.1. 
Inclusion Criteria 
The following inclusion criteria must be met for a patient to be eligible for inclusion in 
the study: 
1. Male or female patients aged ≥18 to ≤75 years inclusive at time of informed 
consent  
2. Diagnosis of pulmonary sarcoidosis for ≥6 months (cutaneous and ocular 
involvement allowed), defined as: 
• Histologically proven diagnosis of sarcoidosis by bronchoscopy, biopsy (any 
organ), or bronchioalveolar lavage. 
• Evidence of parenchymal lung involvement by historical radiological 
evidence (eg, computed tomography [CT], magnetic resonance imaging 
[MRI], 18F-FDG-PET/CT or chest X-ray) or on the Screening 18F-FDG 
PET/CT. 
3. Must have symptomatic and/or active pulmonary sarcoidosis as evidence by: 
• Clinical findings of dyspnea, as indicated by a Modified Medical Research 
Council (MRC) Dyspnea Scale grade of at least 1; and 
• FVC% predicted ≥50%. 
4. Must be receiving treatment with 10 to 25 mg/day of oral prednisone (or oral 
equivalent; eg, methylprednisolone), at a stable dose for ≥4 weeks prior to Day 1, 
and be determined by the Investigator to be capable of undergoing the protocol-
specified steroid taper regimen. 
• Treatment with one oral immunomodulatory therapy (eg, methotrexate, 
azathioprine, hydroxychloroquine) at a stable dose for ≥1 month prior to 
Day 1 is allowed but not required. The dose of this therapy should remain 
constant throughout the study. 
5. Body weight ≥45 kg and <160 kg. 
6. Female patients may be of childbearing potential or of non-childbearing potential 
(either surgically sterilized or at least 1 year postmenopausal (confirmed by 
amenorrhea duration of at least 12 months and serum follicle-stimulating hormone 
[FSH] ≥30 mIU/mL).  

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• Female patients of childbearing potential must be non-pregnant and non-
lactating, and have a negative pregnancy test at Screening (serum) and at 
Day 1 (urine) prior to first study drug infusion.  
• Additionally, female patients of childbearing potential must be willing to use 
highly-effective contraception (see Section 7.1.6.4) from Screening until 
90 days after the last follow-up visit.  
7. Male patients, if not infertile or surgically sterilized, must agree to use highly-
effective contraception (see Section 7.1.6.4) and not donate sperm from Screening 
until 90 days after the last follow-up visit. 
8. Provision of written informed consent. 
9. Be able to communicate well with the Investigator and site personnel, and agree 
to comply with all study procedures and requirements. 
5.1.2. 
Exclusion Criteria 
A patient who meets any of the following exclusion criteria will not be eligible for 
inclusion in the study: 
1. Current disease presentation consistent with Lofgren’s syndrome (ie, presence of 
the triad of erythema nodosum, bilateral hilar lymphadenopathy on chest X-ray, 
and joint pain) 
2. History of severe allergic or anaphylactic reactions to therapeutic proteins, or 
known sensitivity to ATYR1923 or to its inactive components (L-histidine, 
sodium chloride, sucrose, L-methionine, and polysorbate-20). 
3. Treatment (within 4 months of Day 1) with biological immunomodulators such as 
TNF-α inhibitors (eg, infliximab, adalimumab).  
4. Current evidence of clinically significant cardiovascular, hepatic, renal, 
hematological, metabolic, or gastrointestinal disease, or has a condition that 
requires other treatment, may not allow safe participation, or which in the opinion 
of the Investigator should preclude the patient’s participation in the clinical study.  
5. Clinically significant pulmonary hypertension requiring vasodilator treatment. 
6. Any history of tuberculosis, or evidence of active systemic non-tuberculous 
fungal or mycobacterial infection within 1 year of Screening. 
7. History of clinically significant cardiac, neurological, gastrointestinal, and/or 
renal manifestations of their sarcoidosis. 
8. Active or history of malignancy within the last 5 years, with the exception of 
resected basal cell carcinoma, squamous cell carcinoma of the skin, or effectively 
managed cervical carcinoma. 

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9. Major surgery within 3 months prior to Day 1 or anticipated surgery during the 
study. 
10. Any condition that necessitated hospitalization within the 3 months prior to Day 1 
or is likely to require so during the study. 
11. Participation in another clinical study of an investigational agent or device within 
3 months (small molecules) / 6 months (biologics) or 5 half-lives (if known) of 
the agent, whichever is longer. 
12. History of or positive results of Screening for hepatitis B (hepatitis B surface 
antigen [HBsAg]), hepatitis C (anti-hepatitis C virus [HCV] Ab) or human 
immunodeficiency virus (HIV) (HIV Ab type 1 and 2). 
13. Is an active, heavy smoker of tobacco/nicotine-containing products (defined as 
>20 cigarettes/day or e-cigarette equivalent). 
14. Active substance abuse (drugs or alcohol) or history of substance abuse within the 
12 months prior to Screening. 
15. Clinically significant abnormalities in the Screening physical examination, vital 
signs, electrocardiogram (ECG), or clinical laboratory test results that, in the 
opinion of the Investigator and Medical Monitor should preclude the patient’s 
participation in the clinical study. 
16. Patient has received a live vaccination within 8 weeks before Day 1 or inoculation 
with a live vaccine is planned during study participation. 
17. Jo-1 Ab levels >7 U/mL at Screening, or past history of Jo-1 Ab positivity. 
18. Any other condition or circumstance that, in the opinion of the investigator, would 
be likely to prevent adequate compliance with the study protocol. 
19. Significant and/or acute illness (eg, change in pulmonary status, infection 
requiring antibiotics) within 5 days prior to (the first) drug administration that 
may impact safety assessments, in the opinion of the Investigator. 
5.2. 
Source of Patients 
This will be a multi-center study conducted globally. Each study center is required to 
obtain local Institutional Review Board (IRB)/Independent Ethics Committee (IEC) and 
regulatory approval to conduct the study before enrollment of patients may commence. 
Patients meeting the study entry criteria will be eligible for enrollment. 

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6. 
STUDY CONDUCT 
6.1. 
Patient Identification, Enrollment, and Randomization 
After obtaining informed consent, patients will be screened according to the inclusion 
and exclusion criteria. Patients will be assigned to a cohort based on their availability. 
Patients who have met all eligibility criteria will receive a unique screening number 
according to the screening order. Then, prior to dosing, each patient will be allocated a 
randomization number according to their chronological order of inclusion in the study. 
This number will correspond to a treatment (ATYR1923 or placebo) as specified on the 
pre-determined randomization schedule.  
The master randomization schedule will be made of randomly permuted blocks of 
appropriate sizes, as determined by the unblinded study team member producing the 
schedule. The schedule will be generated electronically. 
For patients who are replaced, the replacements should take the same treatment 
assignment as the original patient to ensure that the treatment groups stay balanced. 
The randomization code will be produced within the interactive web response system 
(IWRS). The study center pharmacist or designated unblinded study team member will be 
provided access to the randomization code within the IWRS. The laboratory where the 
PK samples are to be analyzed will also be provided access to distinguish between 
samples of patients dosed with ATYR1923 versus placebo. 
Patients who withdraw for any reason without completing all screening evaluations 
successfully, will be considered “screen failures”. Such patients will have a limited 
number of electronic case report forms (eCRFs) completed.  
6.2. 
Patient Management 
All patients must provide written informed consent before the performance of any study-
related procedure. Patients eligible for the study will be randomized into the study 0-
3 days prior to Day 1 and will receive a total of 6 IV infusions of study drug (either 
ATYR1923 or placebo) administered once every 4-weeks, according to their treatment 
assignment on a double-blind basis. Patients will attend a post-treatment follow-up visit 
4 weeks after completion of dosing. 
6.3. 
Patient Adherence 
All patients are required to adhere to the protocol-specified dosing and visit schedules. If 
a patient misses a scheduled visit, attempts should be made to reschedule the visit within 
the visit windows specified in Table 1. Failure to attend scheduled study visits may result 
in discontinuation from the study. 

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6.3.1. 
Study Conduct During the COVID-19 Public Health Emergency 
Note that due to the coronavirus disease-2019 (COVID-19) public health emergency, it is 
understood that some flexibility may be required around the timing of scheduled study 
visits beyond the visit windows specified in the Schedule of Assessments (Table 1). In 
particular, the 4-week Screening period may be extended to 6 weeks, laboratory or 
clinical tests may be performed locally, and telephone contacts may be utilized to follow 
patients with delayed or missed study visits.  
Patients missing 2 consecutive study drug doses are to have study drug permanently 
discontinued, complete the EOS visit, and be withdrawn from the study. (Patients who 
withdraw from the study due to COVID-19-related issues may be replaced; see Section 
6.4.3.) 
Note that COVID-19 screening is not required per protocol; however, each study center is 
to follow standard institutional practice regarding COVID-19. 
All deviations due to COVID-19 are to be documented. 
6.4. 
Withdrawal and Replacement of Patients 
6.4.1. 
Study Drug Discontinuation Criteria 
Study drug must be discontinued if any of the following events occur: 
• A serious adverse event (SAE) during or within 60 minutes of IV infusion that 
includes cardiac and/or respiratory observations, that has a reasonable possibility of a 
causal relationship with the study drug, including a severe IRR. 
• Pregnancy. 
• Patient request to discontinue study drug dosing for any reason. 
• Other findings that, at the discretion of the Investigator and/or Sponsor, indicate that 
study drug administration should be discontinued. 
• Missing 2 consecutive study drug doses. 
The Investigator has full discretion to stop study drug infusion at any time, if clinically 
warranted or in the patient’s best interest. 
All patients who have been dosed with any amount of study drug will continue to be 
followed for safety. Patients who discontinue study drug dosing at any time during the 
treatment period should return to the study center for the EOS visit and as clinically 
indicated. Patients who have skin lesions that are being followed and withdraw from the 
study prior to Week 12 will be asked to have a skin biopsy at the EOS Visit. If applicable, 
patients who withdraw from the study prior to Week 16 will be asked to have a 18F-FDG-
PET/CT at the EOS Visit. 

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Patients who decide not to receive any further study drug will be offered all follow-up 
safety assessments, including the EOS visit after their last infusion.  
If a patient fails to attend scheduled study assessments, the Investigator must determine 
and document the reasons and the circumstances as completely and accurately as 
possible. 
6.4.2. 
Study Withdrawal Criteria 
Patients will be informed that they have the right to discontinue from the study and 
withdraw consent at any time for any reason, without prejudice to their medical care. The 
Investigator also has the right to withdraw patients from the study for any of the 
following reasons: 
• Patient non-adherence to study drug or protocol requirements. 
• Patient unwillingness to continue in the study. 
• Any other reason, based upon the medical judgment of the Investigator. 
The reason for study withdrawal is to be documented in the patient’s source documents 
and eCRF. 
At the time of discontinuation from the study, patients are to have all the assessments 
planned for the final follow-up visit performed after the last study drug dose, if feasible.  
6.4.3. 
Replacement of Patients 
If a patient is withdrawn from the study for any reason, whether related to the study drug 
or not, or if a patient voluntarily withdraws before or after receiving the study drug, such 
patient will be considered an early-termination patient.  
Investigator will make every effort to ensure that early-termination patients who have 
received study drug complete the safety follow up assessments. 
Patients who withdraw for reasons other than treatment-related AEs may be replaced at 
the discretion of the Sponsor. The decision regarding the replacement of patients will be 
documented. 
6.5. 
Study Completion 
A patient is considered to have completed the study if they received at least 5 of 
6 scheduled study drug doses and completed all follow-up visits. 

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6.6. 
Study Termination 
If the Sponsor or Investigator discovers conditions arising during the study that suggest 
the study should be halted, then this can happen only after appropriate consultation 
between the Sponsor and Investigator. Conditions that may warrant study termination 
include, but are not limited to: 
• The discovery of any unexpected, significant, or unacceptable risk to the patients 
enrolled in the study. 
• Insufficient adherence to the protocol requirements. 
• A decision on the part of the Sponsor to discontinue the Study 
• A decision on the part of the Sponsor to suspend or discontinue development of 
ATYR1923. 
6.7. 
Investigator Compliance 
If the study center deviates significantly from the protocol without prior approval from 
the Sponsor and regulatory authorities, the center may be discontinued from the study. 
The Investigator is responsible for ensuring the accuracy and completeness of all research 
records, the accountability of Study Drug, and the conduct of clinical and laboratory 
evaluations as outlined in the protocol. The Investigator is responsible for ensuring that 
the clinical study is performed in accordance with the Declaration of Helsinki and the 
International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidance 
documents. 
6.8. 
Data Safety Monitoring Board 
Ongoing review of blinded safety and tolerability data will be performed by the Medical 
Monitor and aTyr Pharma personnel. 
In addition, an independent DSMB will perform interim reviews of unblinded safety, 
tolerability, and immunogenicity data from each cohort and hoc per Sponsor request if a 
pattern of unexpected, clinically significant trends or changes in other safety assessments 
is identified through blinded safety data reviews. 
The DSMB will provide its recommendation to aTyr Pharma. Such recommendation may 
include, but is not limited to: stopping an ongoing cohort, stopping further dose 
escalation, continuation of the study as planned, or continuation of the study with 
modifications, such as evaluation of a lower or intermediate dose in the next cohort(s) to 
gain more information on safety and tolerability. 

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7. 
STUDY DRUG 
7.1. 
Study Drug Dose and Administration 
7.1.1. 
Treatments Administered 
The planned study cohorts are identified in Table 2. In all study cohorts, it is planned that 
study drug will be administered as an IV infusion over approximately 60 minutes every 
4 weeks for a total of 6 doses (20 weeks of treatment). Within each cohort, patients will 
be assigned to ATYR1923 or placebo according to the computer-generated 
randomization list (see Section 7.1.3). 
Although this is an escalating dose study, if safety or tolerability issues are experienced, 
or the actual ATYR1923 PK appears to be substantially different from what is predicted, 
a different dose or interval may be administered in the next cohort. Further, an 
intermediate dose may be tested to gain more information on safety, tolerability and/or 
PK.  
For the preparation of the ATYR1923 dose levels, the patient’s weight at Screening will 
be used. 
7.1.2. 
Identity of Investigational Products 
7.1.2.1. 
AYTR1923 
The ATYR1923 Drug Product is a sterile, clear to slightly opalescent, colorless to 
slightly yellow, preservative-free liquid concentrate for IV administration. ATYR1923 
Drug Product (3.8 mL fill volume) is supplied in a single-use borosilicate glass vial, 
stoppered with bromobutyl rubber stopper (with FluroTec coating), and sealed with 
aluminum Flip-off® seal. The formulation of ATYR1923 Drug Product contains 
25 mg/mL ATYR1923, 20 mM L-histidine, 125 mM sodium chloride, 3% sucrose, 
10 mM L-methionine, and 0.02% polysorbate 20 at pH 6.9.  
ATYR1923 will be administered to patients by IV infusion after appropriate dilution in 
0.9% sterile sodium chloride solution, United States Pharmacopeia (USP) as outlined in 
the study Pharmacy Manual. 
7.1.2.2. 
Placebo 
Placebo will be supplied as the formulation buffer in vials that are similar in appearance 
to ATYR1923.  

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Placebo will be administered to patients by IV infusion after appropriate dilution in 0.9% 
sterile sodium chloride solution, USP, as outlined in the study Pharmacy Manual. 
7.1.3. 
Method of Assigning Patients to Treatment Cohorts 
After obtaining informed consent, patients will be screened according to the inclusion 
and exclusion criteria and will be assigned to a cohort based on their availability. Within 
each cohort, 12 patients will be randomized 2:1 (block size of 6) in a blinded fashion to 
ATYR1923 (N=8) or placebo (N=4).  
7.1.3.1. 
Dose Escalation Procedure 
Cohorts 1 through 3 will be enrolled sequentially in a staggered manner. After at least 
6 patients of a given cohort have received at least 3 infusions of study drug (ATYR1923 
or placebo), cumulative unblinded safety data (including but not limited to any reported 
AEs, ECG recordings, clinical laboratory tests, and vital signs) will be reviewed by the 
DSMB. Enrollment in the next scheduled cohort may commence after this review is 
completed, dose escalation is approved, and the remaining 6 patients have been 
randomized in the previous cohort. Dose escalation will continue in this manner until the 
highest planned dose level of ATYR1923 is reached, or the criteria for pausing 
enrollment have been met (see Section 7.1.3.2). 
7.1.3.2. 
Criteria for Pausing Enrollment 
In the event that a serious unexpected suspected adverse reaction (SUSAR) has occurred, 
the enrollment and initiation of study drug administration to new patients will be paused 
and the Sponsor will request an unblinded review by the DSMB, who will provide its 
recommendation to aTyr Pharma. Such recommendation may include, but is not limited 
to, stopping an ongoing cohort, stopping further dose escalation, continuing the study as 
planned, or continuing the study with modifications, such as evaluation of a lower or 
intermediate dose in the next cohort(s) to gain more information on safety and 
tolerability. 
In addition, if unexpected, clinically significant trends or changes in other safety 
assessments are identified during routine blinded safety reviews the Sponsor may request 
the DSMB to similarly perform an unblinded review and provide recommendations.  
7.1.4. 
Selection of Doses in the Study 
7.1.4.1. 
First-in-Human Study ATYR1923-C-001  
The first in human study ATYR1923-C-001 evaluated single ascending dose 
administration of ATYR1923 at doses of 0.03, 0.1, 0.3, 1, 3.0 and 5.0 mg/kg.  
The ATYR1923 starting dose of 0.03 mg/kg was based on: 1) the no-observed adverse 
effect level (NOAEL) from non-clinical Good Laboratory Practice toxicity studies; 

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2) estimation of the human minimum pharmacologically active dose (PAD) level range 
(0.035 to 0.1 mg/kg) based on total body weight; and 3) estimation of human PAD based 
on predicted ATYR1923 human serum PK parameters, determined from single species 
(NHP) allometric scaling to humans. These approaches supported a human starting dose 
level for ATYR1923 of 0.03 mg/kg, which was just below the lower end of the human 
PAD calculation range (0.035–1.0 mg/kg) and well below the maximum recommended 
starting dose (0.97 mg/kg). The highest single dose (5.0 mg/kg) planned in the first-in-
human Phase 1 study was anticipated to produce mean serum exposure levels that 
remained at least 2-fold below those seen in animal toxicity testing at the NOAEL. 
7.1.4.2. 
Current Study in Patients with Pulmonary Sarcoidosis 
The proposed doses in the current study in patients with pulmonary sarcoidosis are 
1.0 mg/kg (Cohort 1), 3.0 mg/kg (Cohort 2), and 5.0 mg/kg (Cohort 3). Cohorts will be 
enrolled sequentially in a staggered manner. 
Selection of the proposed doses is primarily informed by clinical and pharmacological 
findings from ATYR1923-C-001, in which single doses of ATYR1923 were well 
tolerated across the broad dose range from 0.03 up to 5.0 mg/kg, with no clear dose-
relationship with regard to the incidence of TEAEs, or changes in clinical laboratory 
parameters or other safety measures. No SAEs or severe AEs were reported at any dose, 
indicating that the starting dose of 1.0 mg/kg dose in this study should be acceptable.  
Repeat administration of ATYR1923 once monthly is expected to result in little or no 
accumulation of peak (ie, maximum concentration [Cmax]) and total (ie, area under the 
curve [AUC]) serum exposure measures at steady-state when compared to single dosing. 
For example, Cmax and area under the curve from time zero to 168 hours (AUC[0-168h]) 
after the 6th monthly dose of ATYR1923 at 5 mg/kg is predicted to be 109,618 ng/mL 
and 3,577,275 ng⋅h/mL, respectively; estimates that are highly similar to the values 
observed after a single dose of ATYR1923 at 5 mg/kg in ATYR1923-C-001 
(109,250 ng/mL and 3,417,001 ng⋅h/mL, respectively). 
In a Good Laboratory Practice-compliant 6-month duration toxicology study in NHPs, 
the NOAEL was 60 mg/kg by IV injection once weekly, the highest dose administered. 
The mean serum exposures (AUC[0-168h]) measured at the NOAEL in this study ranged 
from 27,900,000 ng⋅h/mL (Day 1) to 44,400,000 ng⋅h/mL (Day 176). Comparison of the 
mean serum exposures observed in NHPs with those predicted in subjects after the 6th 
monthly dose of ATYR1923 at the 5 mg/kg dose (3,577,275 ng⋅h/mL) estimates a safety 
margin of 8-12-fold. Safety margins based on comparison of mean maximal 
concentrations (mean C0 ranged from 1,880,000-2,080,000 ng/mL in NHPs versus the 
mean predicted Cmax of 109,618 ng/mL in humans) are higher at 17-19-fold. Therefore, 
repeat-dose administration of ATYR1923 to patients over a 6-month duration at doses up 
to 5 mg/kg is expected to produce mean serum exposures that remain well below those 
seen in animal toxicity testing for up to 6 months. 

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7.1.5. 
Blinding 
The following controls will be employed to maintain the double-blind status of the study: 
• The infusion solution containing active drug and placebo will be indistinguishable 
in appearance. 
• The study center pharmacist or designated unblinded study team member will 
have access to random treatment assignments via IWRS for dispensing purposes; 
treatment assignments will be accessible only to the pharmacist or designated 
unblinded study team member and will be maintained in a blinded fashion. 
• PK results for the interim analyses will be presented in a blinded fashion. 
To manage the patient’s condition in case of a medical emergency, the Investigator (or 
delegate) is allowed to break the code in order to identify whether a patient received 
ATYR1923 or placebo. If the blind is broken for an individual patient, the name of the 
person who broke the blind and the date and time of and the reason for breaking the blind 
must be documented. The Sponsor will be informed in case of unblinding. There are no 
specific antidotes for ATYR1923. Knowledge of whether the patient received 
ATYR1923 or placebo, may not necessarily help in the care of an individual patient. The 
need to break the blind must therefore be carefully considered. 
The laboratory where the PK samples are to be analyzed will also be provided access to 
the randomization code within the IWRS to distinguish between samples of patients 
dosed with ATYR1923 versus placebo. 
7.1.6. 
Concomitant Medication and Other Restrictions During the Study 
7.1.6.1. 
Prohibited or Restricted Concomitant Medications and Substances 
The following treatments and procedures are prohibited prior to and/or during study 
participation, as indicated below: 
• Immunomodulatory agents, such as TNF-α inhibitors (eg, infliximab, adalimumab), 
are prohibited from 4 months of Day 1 and through the duration of study drug 
treatment. 
• Live vaccination within 8 weeks before Day 1 and during study participation is 
prohibited. 
• All investigational agents or devices (other than ATYR1923) within 3 months for 
small molecules and 6 months for biologics, or 5 half-lives (if known) of the agent, 
whichever is longer, before the first study drug dose and through the duration of study 
drug treatment. 
• Major surgeries are prohibited from 3 months before the first study drug dose through 
the duration of study drug treatment. 

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• Heavy smoking/inhalation of tobacco/nicotine-containing products >20 cigarettes/day 
or e-cigarette equivalent. 
• Topical treatment of any lesion identified by the Investigator for cutaneous assessments 
(eg, biopsy). 
All other concomitant medications and procedures are allowed.  
Concomitant medications are to be recorded in the source documents and in the eCRF. 
7.1.6.2. 
Oral Corticosteroid Taper 
Starting on Day 15, patients will begin a taper (reduction) in OCS (per the ATYR1923-C-
002 Oral Corticosteroid Taper Guidelines) from their starting dose of 10-25 mg/day of 
prednisone (or equivalent) to a target dose of 5 mg/day, to be completed on or before 
Day 50. The OCS dose will be tapered by 5.0 mg/day every 1 to 2 weeks, depending on 
the starting dose. Smaller incremental titrations to the target dose of 5 mg /day by Day 50 
may be implemented per Investigator judgement. Patients will be maintained at the target 
dose of 5.0 mg/day (or equivalent) through Week 24/EOS. Optionally, further titrations 
in the OCS dose to below 5 mg/day may be attempted after the Week 16 visit, if 
determined by the Investigator to be feasible. 
Patient will document OCS doses in a diary, which will be reviewed at relevant 
scheduled telephone contacts and study visits. 
7.1.6.3. 
Rescue Treatment with Oral Corticosteroids 
Patients who develop an acute worsening of symptoms or are unable to adhere to the 
protocol-defined OCS tapering regimen may receive ‘rescue’ treatment with higher OCS 
doses as clinically indicated. 
The following criteria should be met prior to providing rescue OCS treatment: 
1a) Worsening cough, documented by a decrease of ≥1 point on the LCQ, 
OR 
1b) Worsening dyspnea, documented by an increase of ≥1 point on the TDI, 
AND 
2) The Investigator’s clinical judgement that rescue therapy is warranted. 
Rescue therapy is not mandated in the event of worsening cough or worsening dyspnea if 
the Investigator determines that an increase in steroid dose is not clinically indicated. 
Upon resolution of symptoms, the Investigator may choose to reinstitute a taper back 
down to the target maintenance dose of 5 mg/day.  
Patients who require rescue treatment following 2 attempts at tapering to 5 mg/day may 
remain on a higher stable dose of OCS as determined by the Investigator.  

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Patients who require an increase in OCS dose at any time in the study should continue to 
receive blinded study drug and followed through to the end of the study.  
Patient will document OCS doses in a diary, which will be reviewed at relevant 
scheduled telephone contacts and study visits. 
7.1.6.4. 
Contraception 
For this study, male patients will be considered to be of non-childbearing potential if they 
have azoospermia (whether due to having had a vasectomy or due to an underlying 
medical condition).  
Female patients will be considered of non-childbearing potential if they are either 
surgically sterilized (eg, hysterectomy and/or bilateral oophorectomy, bilateral 
salpingectomy or bilateral tubal ligation/occlusion) or at least 1 year postmenopausal 
(confirmed by amenorrhea duration of at least 12 months and serum FSH ≥30 mIU/mL). 
Female patients of childbearing potential must be non-pregnant and non-lactating, and 
have a negative pregnancy test at Screening (serum) and at Day 1 (urine) prior to first 
study drug infusion. A urine pregnancy tests must be repeated at Weeks 8 and 16 and a 
serum pregnancy test must be repeated at Week 24. 
Female and male patients of childbearing potential must agree to avoid becoming 
pregnant or impregnating a partner, respectively, while receiving study drug and for 
90 days after the last dose of study drug by complying with one of the following:   
• Practice abstinence1 from heterosexual activity. (If a patient who was initially 
abstinent decides to be sexually active during study participation, the patient must 
agree to use highly-effective contraception, as outlined below.) 
OR  
• Use (or have their partner use) highly-effective contraception during heterosexual 
activity. Examples of highly-effective methods of contraception include: 
Single method (one of the following is acceptable): 
- Intrauterine device. 
- Vasectomy of a female patient’s exclusive male partner. 
                                                     
1 
Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is 
consistently employed as the patient’s preferred and usual lifestyle and if considered acceptable by 
local regulatory agencies and IRB/IEC. Periodic abstinence (eg, calendar, ovulation, sympto-
thermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. 

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- Contraceptive rod implanted into the skin. 
Combination method (requires use of two of the following): 
- Diaphragm with spermicide (cannot be used in conjunction with cervical 
cap/spermicide). 
- Cervical cap with spermicide (nulliparous women only). 
- Contraceptive sponge (nulliparous women only). 
- Male condom or female condom (cannot be used together). 
- Hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or 
progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or 
subcutaneous contraceptive injection. 
Refer to the Clinical Trials Facilitation Group guidelines (available 
at:  https://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf) for 
additional details regarding highly effective birth control methods (i.e., methods that can 
achieve a failure rate of less than 1% per year when used consistently and correctly).  
If a highly effective contraceptive method is restricted by local regulations/guidelines, 
then it does not qualify as an acceptable method of contraception for patients 
participating at sites in that location. 
7.1.7. 
Treatment Compliance 
Study drug will be administered at the study center. To ensure treatment compliance, 
administration of the study drug will be supervised by the Investigator or authorized 
designee. Compliance will be further confirmed by bioanalytical assessment of 
ATYR1923 in serum samples (see Section 8.2.5). 
The exact times of study drug infusion start and completion and number of milligrams 
and total volume administered will be recorded in the eCRF.  

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8. 
STUDY VISITS AND ASSESSMENTS 
8.1. 
Schedule of Assessments 
The Schedule of Assessments is presented in Table 1. 
8.2. 
Screening and Baseline Measurements 
8.2.1. 
Informed Consent 
All patients must provide written informed consent, based on local age of majority, 
before any samples are collected or evaluations performed in this study that are not part 
of standard patient care.  
8.2.2. 
Demographics 
Patient demographics, including age, sex, and race, are to be documented during 
Screening. 
8.2.3. 
Medical History 
A complete medical history, including history of pulmonary sarcoidosis and prior 
treatments thereof, is to be documented during Screening.  
8.2.4. 
Serology 
A blood sample for serology, including HIV1 and 2, HBsAg, and anti-HCV, is to be 
collected during Screening. Patients with positive results are not eligible for study 
participation.  
Rheumatoid Factor (RF) will also be tested at Day 1. ATYR1923 is an FC-fusion protein 
and as such, the presence and binding of RF to the FC region of ATYR1923 could 
confound the detection of ADA. Rheumatoid factor positivity status will be used to 
facilitate the interpretation of ADA assay results and in the modification of the ADA 
assay to detect only antibodies directed against the therapeutic part of the molecule. 
RF positivity will not exclude the patient from the study. 
8.2.4.1. 
Modified MRC Dyspnea Scale 
The Modified MRC Dyspnea Scale is a five-level rating scale based on the patient’s 
perception of dyspnea in daily activities, ranging from none (Grade 0) to very severe 
dyspnea (Grade 4). The score is the number that best fits the patient’s level of activity. 
All the questions relate to everyday activities and are generally easily understood by 
patients. A score can usually be obtained in a few seconds.  
The Modified MRC Dyspnea Scale is to be administered during Screening.  

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8.2.5. 
Quality of Life Measures 
All quality of life assessments are to be performed before other study procedures at each 
designated visit and are to be completed in the same order at each designated visit.  
8.2.5.1. 
Sarcoidosis Assessment Tool 
The SAT is a sarcoidosis-specific patient-reported outcome developed for use in 
sarcoidosis clinical studies to measure the patient’s assessment of impact of disease and 
response to therapy. The SAT requires approximately 5–10 minutes for completion 
(Judson et al, 2015).  
The SAT Tool is to be administered at the time points designated in Table 1. 
8.2.5.2. 
The Self-Administered Computerized Baseline and Transitional Dyspnea 
Indices (SAC BDI-TDI) 
The BDI measures the severity of dyspnea at the baseline (or the beginning of a clinical 
study), and the TDI measures changes from this baseline (transition period) at subsequent 
visits. The BDI and TDI each contain 24 items, with items on the BDI rated in 5 grades 
from 0 (very severe) to 4 (no impairment), and items on the TDI rated by 13 grades 
ranging from -6 (major deterioration) to +6 (major improvement). The lower the score on 
the BDI, the worse the severity of dyspnea at baseline and the lower the score on the TDI, 
the more deterioration in the severity of dyspnea. The minimal clinically important 
difference of the TDI is a total score of 1 (Witek and Mahler, 2003). The SAC BDI-TDI 
takes approximately 5-10 minutes to complete. 
The SAC BDI-TDI indices are to be administered at the time points designated in 
Table 1. 
8.2.5.3. 
King’s Sarcoidosis Questionnaire  
The KSQ is an online 29-item questionnaire to be completed by sarcoidosis patients 
(Patel et al. 2012). The KSQ is split into 5 sections; general health status, lungs, 
medication, skin, and eyes. Results are given as a number between 1-100 with higher 
numbers indicating better health. The questionnaire takes approximately 10 minutes to 
complete. 
The KSQ is to be administered at the time points designated in Table 1. 
8.2.5.4. 
Leicester Cough Questionnaire 
The LCQ is a 19-item self-completed quality of life measure of chronic cough which is 
responsive to change (Birring et al, 2003). Items on the scale are divided into 3 domains, 
physical, psychological, and social. Items are scored on a 7-point Likert scale. A total 
score (range 3 to 21) is also calculated by adding the domain scores together, with higher 
scores indicating better quality of life. The questionnaire takes 5 to 10 minutes to 

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complete (Ward, 2016). The minimal clinically important difference (MCID) for chronic 
cough is 1.3 (Raj et al, 2009). 
The LCQ is to be administered at the time points designated in Table 1. 
8.2.5.5. 
Fatigue Assessment Scale 
The FAS contains 10 specific fatigue questions that have been validated in sarcoidosis 
patients (De Vries et al, 2004). On each question, one of 5 answer categories can be 
chosen, from never to always: 1=never; 2=sometimes (about monthly or less); 
3=regularly (about a few times a month); 4=often (about weekly); 5=always (about every 
day). An answer to each question has to be given, even if the person does not have any 
complaints at the moment. Scores on questions 4 and 10 should be recoded (1=5, 2=4, 
3=3, 4=2, 5=1). Subsequently, the total FAS score can be calculated by summing the 
scores on all questions (the recoded scores for question 4 and 10). The sum of questions 
3 and 6–9 indicates mental fatigue, and the sum of the questions 1, 2, 4, 5 and 10 
indicates physical fatigue. The minimal score is 10, and the maximal score is 50. Scores 
of ≥22 are considered to represent substantial fatigue. A change in the FAS score of 
4 points is considered to be the MCID (de Kleijn et al, 2011). The FAS takes 
approximately 5-10 minutes to complete. 
The Fatigue Assessment Scale is to be administered at the time points designated in 
Table 1.  
8.3. 
Pharmacokinetic Measurements and Variables 
At the time points defined in the Schedule of Assessments (Table 1), blood samples will 
be taken for the PK analysis of ATYR1923 in serum samples. The blood samples will be 
taken via an indwelling IV catheter or by direct venipuncture into plain serum tubes. The 
exact times of blood sampling will be recorded in the eCRF.  
Details on sample collection, handling, storage and shipping of blood samples for PK 
analysis of ATYR1923 will be described in the Laboratory Manual. 
8.4. 
Pharmacodynamic/Exploratory Measurements and Variables 
8.4.1. 
Blood for Peripheral Blood Mononuclear Cells and Serum Biomarkers 
Blood samples for the analysis of PBMCs and biomarkers in serum will be taken at the 
time points designated in Table 1. The blood samples will be taken via an indwelling IV 
catheter in tubes containing anticoagulants or by direct venipuncture into plain serum 
tubes. The exact times of blood sampling will be recorded in the eCRF.  
The state of immune cell anergy in PBMCs will be measured by flow cytometry and 
cytokine secretion, at baseline and after activation with T-cell receptor-dependent 
and -independent stimuli. Immunophenotyping may also be performed. 

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Serum biomarkers to be measured will include, but will not be limited to, ACE, sIL-2R, 
extracellular HARS, NRP2, and VEGFC. 
Details on sample collection, handling, storage and shipping of blood samples for 
analysis will be described in the study Laboratory Manual prepared by Sponsor and study 
center. 
8.4.2. 
Pulmonary Function Tests 
Pulmonary function tests (PFTs), including FVC, forced expiratory volume in 1 second 
(FEV1), and FEV1/FVC ratio, are to be determined by spirometry at the time points 
designated in Table 1.  
Spirometry testing will be performed according to the American Thoracic 
Society/European Respiratory Society guidelines (Miller et al, 2005). The spirometry 
equipment will be supplied to each site for the study. The same spirometry equipment 
should be used for all assessments performed for a patient. A limited number of staff, as 
designated by the investigator, will evaluate all patients at all visits throughout the entire 
trial. Where possible the same technician should perform all maneuvers for an individual 
patient. All staff conducting the spirometry tests must have received appropriate training 
which must be documented. Information on the procedure can be found in the 
Instructions for Use Manual. 
Spirometry ideally is to be performed with the patient in a seated position for at least 
2 minutes and wearing nose-clips; the patient is to remain seated throughout the test 
procedure. It is recommended that the test be performed at least 1 hour after a light meal, 
with the patient having refrained from recent exercise. Spirometry is to be performed in 
the same manner across all assessment time points. 
If the patient cannot tolerate nose-clips and/or cannot perform the maneuver in a seated 
position, then spirometry may be performed without nose-clips and/or in a standing 
position; however, all subsequent assessments are to be performed in the same manner. 
8.4.3. 
Diffusion Capacity 
DLCO is to be measured using the single-breath technique at the time points designated in 
Table 1. DLCO measurements should be obtained after patients have been sitting quietly 
for 5 minutes. 
DLCO is to be corrected for hemoglobin. 
8.4.4. 
Cutaneous Disease Assessment (for Patients with Cutaneous Disease) 
For patients with cutaneous disease at baseline, cutaneous disease will be assessed by the 
Investigator using the SPGA, BSA assessment, and SASI. 

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The patient’s overall skin health will be assessed by the Investigator during Screening 
and at the time points designated in Table 1 using the SPGA, a visual analog scale 
ranging from 0 (perfect health) to 10 (worst skin condition imaginable).  
The handprint method, with 1 handprint equaling ~1% BSA, will be used to determine 
the percentage of the body surface is affected by cutaneous disease. 
The SASI is an instrument that will be used to evaluate a lesion prospectively identified 
as the ‘target’ lesion, located anywhere on the body. The Investigator will score the 
extent of erythema and induration of this lesion, each on a scale ranging from 0 (none) to 
4 (very severe) (Baughman et al, 2012; Drake et al, 2013; Judson et al, 2014).  
Topical treatment of target lesion selected for the SASI assessment should be avoided. 
8.4.5. 
Cutaneous Lesion Biopsy (Optional at Selected Sites for Patients with 
Cutaneous Disease) 
For patients with cutaneous disease, a non-target lesion (ie, a lesion that is not being 
assessed by the SASI over time) is to be selected during Screening by the Investigator 
and confirmed by the patient that it had been identified by his or her private 
dermatologist as cutaneous sarcoidosis. The lesion is to be biopsied (skin punch) during 
Screening and again at Week 12 (±5 days), or at early termination if occurring prior to 
Week 12. Skin punch biopsy is to be performed according to standard institutional 
practice with regard to antiseptic preparation technique and local anesthesia.  
8.4.6. 
Whole Body 18F-FDG-PET/CT 
In this study, patients who elect to do so will undergo whole-body head to mid-thigh 18F-
FDG imaging on a PET/CT scanner with a reconstructed resolution of ≤5 mm. Whole 
body 18F-FDG is to be performed within 4 weeks prior to Day 1, within ±5 days of Week 
16, or at early termination if occurring prior to Week 16. Patients with glucose levels 
above 11 mmol/L (200 mg/dL) should have their scan delayed or be rescheduled as 
appropriate. The blood glucose level measured prior to the radiotracer administration 
should be recorded in an image transmittal form. Patients are to fast for a minimum of 
4 hours prior to the injection of 18F-FDG. During the uptake phase, patients are to rest 
quietly and to refrain from talking, walking, and any other muscular activity to prevent 
non-specific FDG uptake in the skeletal muscles. The radiotracer will be administered 
through an IV line, after which the patient will be positioned comfortably in a supine 
position to rest for 60 to 90 minutes while the radiotracer distributes through the body. 
Patients will be asked to void their bladder prior to the scanning procedure.  
A whole body low-dose attenuation correction CT will be acquired with a whole body 
effective dose of 1.5 mSv. The maximum injected radioactivity dose of 555 MBq 
of 18F-FDG will result in a maximum whole body effective dose per PET/CT timepoint of 
≤8.5 mSv, dependent upon patient habitus and calculated injected activity. As a weight-

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based dose approach is allowed and is dependent upon subject weight, it is possible that 
in large or obese patients, a higher 18F-FDG activity may be required to ensure sufficient 
imaging quality; however in such cases, the injected activity will not exceed 555 MBq. 
The baseline and follow-up 18F-FDG uptake PET scan will be assessed centrally by a 
qualified nuclear medicine physician visually and quantitatively using standardized 
uptake values (SUVs) and results will be compared with baseline scan. SUV is taken as 
an index of disease activity. Total injected activity and body weight will be recorded and 
used to compute SUV values. PET response will be determined by the nuclear medicine 
physician according to the European Organization for Research and Treatment of Cancer 
criteria.  
The total dose for all PET scanning in this protocol will be maximally 17 mSv in larger 
or obese patients who have received a higher 18F-FDG injected dose. 
Detailed information will be provided in a separate 18F-FDG-PET/CT Imaging Manual.  
8.5. 
Safety and Tolerability Measurements 
Safety and tolerability assessments will consist of physical examinations, vital signs and 
temperature, 12-lead ECGs, pulse oximetry, weight, immunogenicity, AEs, and clinical 
laboratory tests. Concomitant medications also will be documented. Assessments will be 
performed in accordance with the Schedule of Assessments. 
8.5.1. 
Physical Examination and Infusion Site Examination 
A complete physical examination is to be performed during Screening and at Week 12 
and Week 24/EOS. The complete physical examination is to include measurement of 
height during Screening.  
Complete physical examinations also will include a review of the following body 
systems: 
• General appearance. 
• Head, eyes, ears, nose, and throat. 
• Respiratory. 
• Cardiovascular. 
• Abdomen. 
• Neurologic. 
• Extremities. 
• Dermatologic. 
Abbreviated symptom-directed physical examinations are to be performed at the other 
study visits, as indicated. 

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The findings of each examination are to be documented in the eCRF. 
The IV infusion site will be examined at 0.5 and 1.5 hours (+10 minutes) after the end of 
each study drug infusion. Any clinically significant findings will be recorded as AEs. 
8.5.2. 
Vital Signs and Temperature 
Vital signs, including blood pressure, heart rate, and respiration rate, are to be measured 
at the time points designated in Table 1.  
At each clinic visit, vital signs are to be measured before blood sample collection that 
day. Heart rate and blood pressure determinations will be measured after the patient has 
been lying supine for at least 5 minutes. 
On study drug administration days, vital signs are to be measured pre-infusion and at 
15 and 30 minutes (±5 minutes) and at 1, 2, and 4 hours (±15 minutes) after the start of 
infusion (SOI). Vital signs are to be measured before blood sample collection.  
Temperature is to be measured at the time points designated in Table 1. On study drug 
administration days, temperature is to be measured pre-dose, 60 minutes (±15 minutes) 
after the SOI, and again at 4 hours (±15 minutes) after the SOI. Temperature is to be 
measured at the same time as vital signs. 
8.5.3. 
Electrocardiogram 
A 12-lead ECG is to be performed at the time points designated in Table 1 after the 
patient has been lying supine for at least 5 minutes. On all study drug dosing days, the 
ECG is to be performed within 1 hour pre-dose. At Day 1 and Weeks 12 and 20, an ECG 
also is to be performed at 4 hours (±30 minutes) after the SOI.  
The ECG will be recorded using an ECG machine equipped with computer based interval 
measurements The following ECG parameters will be recorded: heart rate, PR-interval, 
QRS-duration, QT-interval, QTc-interval (Fridericia's) and the interpretation of the ECG 
profile by the Investigator. 
8.5.4. 
Pulse Oximetry 
Continuous pulse oximetry is to be performed at the time points designated in Table 1. 
On study drug administration days, continuous pulse oximetry is to be performed from 
5 minutes pre-dose until the end of study drug infusion, and also obtained and recorded at 
the same time points as vital signs. On non-study drug administration days, pulse 
oximetry is to be obtained with vital sign assessments (see Section 8.5.2). 
8.5.5. 
Height and Weight 
Height will be measured at Screening only. Weight is to be measured at the time points 
designated in Table 1. 
The patient’s Screening weight is to be used to calculate the study drug dose. If the 
patient has experienced a notable change in weight (±10%), the patient’s study drug dose 

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will be recalculated. Any change in study drug dose is to be documented in the source 
documents and in the eCRF. 
8.5.6. 
Immunogenicity Measurements 
Blood samples for determination of Jo-1 Ab levels in serum will be collected at the time 
points designated in Table 1. Those with a level considered equivocal or positive (ie, 
>7 U/mL) for the assay will not receive study drug. Any patients who develops positive 
Jo-1 antibodies will also be monitored clinically for signs/symptoms of anti-synthetase 
syndrome. 
In addition, blood samples for determination of ADAs against ATYR1923 in serum will 
be collected at the time points designated in Table 1. ADA blood samples collected 
during Screening from patients who subsequently are determined to be screen failures 
will be used towards additional modification and validation of the ADA assay.  
Blood samples will be processed as described in the Laboratory Manual and evaluated for 
the presence of ADAs. The exact times of blood sampling will be recorded in the eCRF. 
8.5.7. 
Adverse Events 
AEs will be recorded from the time of written informed consent through the last visit for 
a patient. Any clinically significant observations in results of clinical laboratory, 12-lead 
ECGs, vital signs, pulse oximetry, or physical examinations are to be recorded as part of 
the patient’s medical history if occurring prior to start of dosing and as an AE if occurring 
after the start of study drug administration at Day 1, where the finding represents a 
change from Baseline. 
A TEAE is defined as any event not present prior to (the first) administration of the study 
drug or any event already present that worsens in either intensity or frequency following 
exposure to the study drug.  
An AE which occurs prior to (the first) administration of the study drug will be 
considered a pre-treatment AE. 
AEs that occur during or within 24 hours after study drug injection should be captured as 
individual signs and symptoms (eg, dyspnea, rash, flushing) rather than a diagnosis of 
allergic reaction or IRR.  
At study visits, patients will be asked non-leading questions to determine the occurrence 
of AEs. Patients will be asked in general terms about any AEs at regular intervals during 
the study. In addition, all AEs reported spontaneously during the course of the study will 
be recorded. 
The intensity of each AE will be rated by the Investigator using the National Cancer 
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0 
(available 

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at:  https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v
5_Quick_Reference_8.5x11.pdf).  
AEs not listed on the NCI CTCAE are to be rated by the Investigator as “mild (Grade 1)”, 
“moderate (Grade 2)”, “severe” (Grade 3), “life-threatening”(Grade 4), or “fatal” 
(Grade 5).  
The relationship between the AEs and the study drug will be indicated as “not related”, 
“unlikely related”, “possibly related”, or “related”. AEs assessed as “possibly related” or 
“related” will be considered to be related to the study drug whereas AEs assessed as “not 
related” or “unlikely related” will be considered not to be related to the study drug.  
Details on the rating of the severity of the AEs and relationship to the study treatment are 
given in Section 9.2. 
8.5.8. 
Concomitant Medications 
All medications and supplements the patient receives during the course of the study are to 
be documented in the source documents and in the eCRF. 
8.5.9. 
Safety Laboratory Tests 
Blood and urine samples for clinical laboratory assessments will be collected according 
to the Laboratory Manual and study center standard operating procedures (SOPs). 
The following parameters will be measured: 
• Clinical chemistry (serum quantitatively): 
- 
Total bilirubin, alkaline phosphatase, gamma glutamyl transferase 
(gamma-GT), aspartate aminotransferase (AST), alanine aminotransferase 
(ALT), lactate dehydrogenase (LDH), creatine phosphokinase, albumin, 
creatinine, blood urea nitrogen, total protein, glucose, inorganic phosphate, 
sodium, potassium, calcium and chloride, complete lipid panel. 
• Hematology (blood quantitatively): 
- 
Leukocytes, erythrocytes, hemoglobin, hematocrit, thrombocytes, partial 
automated differentiation (lymphocytes, monocytes, eosinophils, basophils, 
neutrophils), mean corpuscular volume, mean corpuscular hemoglobin, mean 
corpuscular hemoglobin concentration 
• Coagulation (blood quantitatively): 
- 
Prothrombin time (reported in seconds and as international normalized ratio) 
and partial thromboplastin time 
• Urinalysis (semi-quantitative by dipstick): 
- 
Hemoglobin, urobilinogen, ketones, glucose, protein 

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- 
Microscopy is to be performed if indicated by an abnormal and clinically 
significant result 
• Serum Complement, Tryptase/Plasma Complement and immunoglobulin E (IgE): 
- Blood samples for serum complement, tryptase/plasma complement and IgE 
are to be collected at Day 1. Such test are to be repeated if a patient 
experiences an IRR (see Section 9.9). 
In case of unexplained or unexpected clinical laboratory test values, the tests will be 
repeated as soon as possible and followed up until the results have returned to the normal 
range, baseline level and/or an adequate explanation for the abnormality is found. The 
clinical laboratory will clearly mark all laboratory test values that are outside the normal 
range and the Investigator will indicate which of these deviations are clinically 
significant. These clinically significant deviating laboratory results will then be recorded 
as AEs and the relationship to the treatment will be indicated (see also Section 9.2).  
The procedures for the collection, handling, and shipping of laboratory samples are 
specified in the Laboratory Manual provided to the study site. 
8.5.10. 
Pregnancy Testing and Follicle Stimulating Hormone 
FSH will be measured in all female patients during Screening. Female patients of 
childbearing potential must have a serum pregnancy test performed during Screening and 
a urine pregnancy test performed at Day 1 prior to first study drug infusion. Any patient 
with a positive pregnancy test result is not eligible for study participation.  
Additional pregnancy testing is to be performed during the study at the time points 
indicated in Table 1. Pregnancy test results are to be obtained and confirmed to be 
negative prior to randomization and study drug infusions. 
All serum samples will be analyzed by the central laboratory, and urine samples will be 
analyzed locally. Any patient determined to be pregnant during study participation must 
have study drug permanently discontinued immediately (see Section 6.4.1 and Section 
9.8). 
8.5.10.1. 
Total of Blood Volume 
The total volume of blood to be collected over the duration of the study is approximately 
450 mL (ranging from 30 mL to 75 mL per visit). 
8.5.11. 
Appropriateness of Measurements 
The assessments, which will be made in this study are standard, and generally recognized 
as reliable, accurate and relevant. Assessments will be performed according to the study 
site.  

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9. 
ADVERSE EVENTS 
9.1. 
Definitions 
9.1.1. 
Adverse Event 
An AE is defined in the ICH Guideline for GCP as “any untoward medical occurrence in 
a patient or clinical investigation subject administered a pharmaceutical product and that 
does not necessarily have a causal relationship with this treatment” (ICH E6:1.2). 
Worsening of a pre-existing medical condition, (ie, diabetes, migraine headaches, gout) is 
to be considered an AE if there is either an increase in severity, frequency, or duration of 
the condition or an association with significantly worse outcomes. 
Interventions for pretreatment conditions (ie, elective cosmetic surgery) or medical 
procedures that were planned before study enrollment are not considered AEs. 
In the case of death, only record “Fatal” for the event causing death. AEs that are ongoing 
at the end of the study or time of death are to be noted as “continuing.”  
The Investigator is responsible for reviewing laboratory test results and determining 
whether an abnormal value in an individual patient represents a significant change from 
baseline. In general, abnormal laboratory findings without clinical significance (based on 
the Investigator’s judgment) should not be recorded as AEs; however, laboratory value 
changes requiring therapy or adjustment in prior therapy are considered AEs. 
9.1.2. 
Suspected Adverse Reaction 
A suspected adverse reaction is any AE for which there is a reasonable possibility that the 
drug caused the AE. For the purposes of Investigational New Drug Application (IND) 
safety reporting, “reasonable possibility” and/or at least possibly related means there is 
evidence to suggest a causal relationship between the drug and the AE. A ‘suspected 
adverse reaction’ implies a lesser degree of certainty about causality than ‘adverse 
reaction’, which means any AE caused by a drug. 
9.1.3. 
Serious Adverse Event 
An AE or suspected adverse reaction is considered “serious” if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes:  
• is fatal 
• is life-threatening (ie, places the patient at immediate risk of death) 
• requires in-patient hospitalization (overnight stay) or prolongation of existing 
hospitalization 
• results in persistent or significant disability/incapacity 
• is a congenital anomaly/birth defect 

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• is an important medical event; an important medical event is an event that may 
not result in death, be life-threatening, or require hospitalization but may be 
considered an SAE when, based upon appropriate medical judgment, it may 
jeopardize the patient and may require medical or surgical intervention to prevent 
one of the outcomes listed in the definitions for SAEs. Examples of such medical 
events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
A hospitalization meeting the regulatory definition for “serious” is any inpatient hospital 
admission that includes a minimum of an overnight (≥24 hours) stay in a health care 
facility. Any AE that does not meet one of the definitions of serious (ie, emergency room 
visit, out-patient surgery, or requires urgent investigation) may be considered by the 
Investigator to meet the “important medical event” criterion for classification as an SAE. 
9.1.4. 
Unexpected Adverse Event 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the 
Investigator’s Brochure or is not listed at the specificity or intensity that has been 
previously observed; or, if an Investigator’s Brochure is not required or available, is not 
consistent with the risk information described in the General Investigational Plan or 
elsewhere in the current application, as amended.  
9.1.5. 
Serious and Unexpected Suspected Adverse Reaction 
A SUSAR is any event that meets all 3 of the following definitions: 
1) suspected adverse reaction (Section 9.1.2); 
2) serious (Section 9.1.3); and  
3) unexpected (Section 9.1.4). 
9.2. 
Adverse Event Assessment 
All AEs will be collected and recorded in this study from the time of written informed 
consent through the last visit for a patient. This includes AEs the patient reports 
spontaneously, those observed by the Investigator, and those elicited by the Investigator 
in response to open-ended questions during scheduled study visits. 
AEs that occur during or within 24 hours after study drug infusion are to be captured as 
individual signs and symptoms rather than a diagnosis of allergic reaction or IRR. 

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Each AE is to be assessed by the Investigator with regard to the following categories. 
Serious/Non-Serious 
AEs that meet the criteria specified in Section 9.1.3 are to be considered serious. 
Relationship to Study Drug 
This determination is based on the Investigator’s clinical judgment regarding the 
likelihood that the study drug caused the AE and may include consideration of some or 
all of the following factors:  
• Alternative possible causes of the AE, including the patient’s underlying disease 
or co-morbid conditions, other drugs, other host and environmental factors; 
• The chronological relationship between the exposure to study drug and the AE;  
• Whether the clinical or laboratory manifestations of the AE are consistent with 
known actions or toxicity of the study drug;  
• Whether the AE resolved or improved with decreasing the dose or stopping the 
study drug (i.e., dechallenge);  
Whether the AE recurred or worsened with re-exposure to the drug (i.e., rechallenge).  
The relationship between the study drug and the AE will be described using one of the 
following categories Table 3. 
Table 3: 
Criteria for Determination of Adverse Event Relationship to Study 
Drug 
Relationship 
Definition 
Related  
The study drug is more likely the cause of the AE than other factors 
Possibly Related 
There is a reasonable possibility that the study drug is the cause of the 
AE, including that the study drug and another factor(s) are equally 
likely as causes of the AE 
Unlikely Related  
Another factor is considered more likely the cause of the AE than the 
study drug 
Not related  
Another factor is considered to be the cause of the AE 
 
Intensity 
The intensity of each AE is to be assessed by the Investigator using the NCI CTCAE, 
version 5.0 (available 
at:  https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v
5_Quick_Reference_8.5x11.pdf ).  

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AEs not listed on the NCI CTCAE are to be rated by the Investigator according to the 
categories in Table 4. 
Table 4: 
Criteria for Determination of Adverse Event Intensity 
Intensity 
Definition 
Mild (Grade 1):  
Asymptomatic or mild symptoms: clinical or diagnostic observations 
only; intervention not indicated. 
Moderate (Grade 2) 
Minimal, local, or non-invasive intervention indicated; limiting age-
appropriate instrumental activities of daily living. 
Severe (Grade 3):  
Severe or medically significant but not immediately life threatening: 
hospitalization or prolongation of hospitalization indicated; disabling; 
limiting self-care activities of daily living; incapacitating with inability 
to work or perform normal daily activity. 
Life-threatening (Grade 4):  
Consequences: urgent intervention indicated. 
Fatal (Grade 5) 
AE resulted in death 
 
Outcome 
The outcome of each AE will be described using the categories in Table 5. 
Table 5: 
Criteria for Determination of Adverse Event Outcome 
Outcome 
Definition 
Resolved without sequelae: 
The event resolved and patient returned to baseline 
Resolved with sequelae: 
The event resolved but the patient is left with residual problems (e.g., 
functional deficits, pain) 
Resolving 
At the last observation, the event was improving 
Not Resolved 
At the last observation, the event was unchanged 
Death (Fatal) 
To be used for the one AE which, in the judgment of the Investigator, 
was the primary cause of death 
Unknown 
There were no observations after the onset (initial observation or report) 
of the event 
 

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Study Drug Action 
For each AE, the Investigator will indicate the action taken regarding the administration 
of study drug per the categories in Table 6. 
Table 6: 
Study Drug Action Taken as a Result of Adverse Events 
Action 
Definition 
Discontinued (withdrawn) 
Study drug was stopped permanently due to the AE 
Dosing Interrupted 
Study drug regimen was modified by being temporarily halted, ie, one 
or more doses were not administered, but drug was not stopped 
permanently 
Dose Decreased 
Study drug regimen was modified by subtraction, ie, by decreasing the 
frequency, strength or amount 
Dose Increased 
Study drug regimen was modified by addition, ie, by increasing the 
frequency, strength or amount 
None 
No change in the administration of study drug 
 
9.3. 
Recording Adverse Events 
All AEs occurring from the time of written informed consent through the last follow-up 
visit, or after the end of the study, if thought to be related to study drug, are to be 
recorded in the source documents and in the eCRF. All AE reports are to contain the 
following details regarding the AE:  a brief description, onset date and time, resolution 
date and time, intensity, treatment required, relationship to study drug, action taken with 
study drug, outcome, and whether the event is classified as serious. 
AEs that occur during or within 24 hours after study drug injection should be captured as 
individual signs and symptoms (eg, dyspnea, rash, flushing) rather than a diagnosis of 
allergic reaction or IRR.  
9.4. 
Reporting Serious Adverse Events 
SAEs will be collected and recorded throughout the study period, beginning with the 
signing of the ICF through the last follow-up visit, or after the end of the study if thought 
to be related to study drug. 
The Investigator must report all SAEs within 24 hours of discovery to the Contract 
Research Organization (CRO) Safety Team. 
SAE reporting, including supporting materials, will be performed by the study center 
personnel using a system approved by the Sponsor. Detailed training will be provided by 
the CRO. Contact information for guidance and assistance with SAE reporting is 
provided in the Study Reference Manual. A completed SAE report is to be entered into 
the system approved by the Sponsor within 24 hours of discovering the event. Upon entry 

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into the system, the responsible parties (including Medical Monitor and Safety Reporting 
Specialist) will be immediately notified. 
The Study Reference Manual will include an emergency back-up paper based reporting 
system, to be used if needed. 
The CRO Safety Team will immediately (within one business day of receipt) forward the 
SAE report to the Sponsor. The initial report should include at least the following 
information:  
• Patient’s ID number; 
• Description and date of the event; 
• Criterion for serious; and 
• Preliminary assignment of causality to study drug.  
The Medical Monitor may contact the Investigator via telephone for urgent follow-up 
information regarding the SAE, as appropriate. 
The Investigator, or designated party, should notify the appropriate IRB/IEC of SAEs 
occurring at the study center and other AE reports received from aTyr, in accordance 
with local procedures and statutes. 
SAEs that are considered as possibly or definitely related to the investigational product, 
and as unexpected (ie, SUSARs), will be reported to the National Regulatory 
Authority(ies) and IRB/IEC by the Sponsor or Sponsor’s designee as required by 
applicable local regulations. Per regulation, any fatal or life-threatening SUSAR will be 
reported to the National Regulatory Authority(ies)/IRB/IEC within 7 calendar days, and 
additional information within an additional 8 calendar days. The Sponsor or Sponsor¹s 
designee is required to submit any other SUSAR to the National Regulatory 
Authority(ies)/IRB/IEC within 15 calendar days of notification. The Sponsor or its 
designee is also responsible for notifying the investigational sites of all expedited SAEs, 
in accordance with local requirements. The Investigator must keep copies of all expedited 
SAE information including correspondence with the Sponsor on file.  
9.5. 
Follow-Up of Adverse Events 
The Investigator must continue to follow all study drug-related TEAEs either until 
resolution or the Investigator assesses them as chronic or stable. This follow-up may 
extend after the end of the study and may be conducted by telephone contact or 
unscheduled visit. 
9.6. 
Reporting Safety Information 
The Investigator must promptly report to his or her IRB/IEC all unanticipated problems 
involving risks to patients, in accordance with local requirements. This may include death 

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from any cause and all SAEs reasonably or possibly associated with the use of study drug 
according to the IRB/IEC’s procedures.  
9.7. 
Protocol Deviations Due to an Emergency or Adverse Event 
Departures from the protocol will be determined as allowable on a case-by-case basis and 
only in the event of an emergency (e.g., COVID-19 public health emergency). The 
Investigator or other physician in attendance in such an emergency must contact the 
Medical Monitor as soon as possible to discuss the circumstances of the emergency. 
The Medical Monitor, in conjunction with the Investigator, will decide whether the 
patient should continue to participate in the study. All protocol deviations and reasons for 
such deviations must be noted in the eCRF. Deviations specifically due to COVID-19 are 
to be documented as such. 
9.8. 
Pregnancy 
Pregnancies occurring while the patient is receiving study drug or within 30 days after the 
patient’s last dose of ATYR1923 will not be considered serious, but are to be reported 
using the same procedures as for SAEs described in Section 9.4. 
In the event of a pregnancy, the patient should be referred to an obstetrician/gynecologist 
experienced in reproductive toxicity for further evaluation and counseling. 
The Investigator will follow the patient until completion of the pregnancy, and must 
notify the Medical Monitor of the outcome within 5 days. The Investigator will provide 
this information as a follow-up to the initial report. 
If the outcome of the pregnancy meets the criteria for immediate classification as an SAE 
(ie, spontaneous abortion [any congenital anomaly detected in an aborted fetus is to be 
documented], stillbirth, neonatal death, or congenital anomaly), then the Investigator 
should report it as such. Furthermore, all neonatal deaths that occur within 30 days of 
birth are to be reported, without regard to causality, as SAEs. In addition, any infant 
death after 30 days that the Investigator suspects is related to the in utero exposure to the 
study drug should also be reported. 
9.9. 
Management of Potential Infusion Related Reactions, 
Including Anaphylaxis 
ATYR1923 is a biologic and as with all biologics there is a risk for IRRs. These reactions 
typically occur in close temporal relationship with the infusion. They may be related to 
cytokine release or immune mediated.  
A generalized IRR could be occurring when any symptoms begin during the study drug 
infusion or during the post-infusion observation period. While these symptoms may be 
self-limiting, such symptoms may signal the possibility of a severe reaction that could 
escalate into a life-threatening situation.  

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Should a patient develop an IRR the subsequent management will depend on the nature 
of the IRR. Where the IRR symptoms are not cardiorespiratory in nature i.e. they 
comprise cutaneous rash, flushing, burning sensation etc. and are mild to moderate in 
intensity – the patient may complete the infusion and receive subsequent doses. The 
patient will need to be observed until all symptoms resolve or for 6 hours after the end of 
the infusion. Subsequent dosing should continue to occur in a facility where the patient 
can be monitored closely. The Investigator, in consultation with the Medical Monitor, 
may opt to adjust the infusion duration and/or administer pre-medication (antihistamines, 
non-steroidal anti-inflammatories and anti-emetics) if clinically indicated, although this is 
not mandatory.  
If the IRR symptoms constitute a cardiorespiratory risk (hypotension, dyspnea, hypoxia 
etc.) or any severe AE then all further dosing should be stopped for the patient. If 
necessary, the patient should be transferred to an acute care facility.  
Once the patient is stabilized, additional blood samples are to be collected and procedures 
performed as outlined below: 
• Vital signs, pulse oximetry, infusion site examination, and ECGs are to be 
performed to gather clinical information as soon as possible after the onset of 
clinical symptoms of a generalized IRR (for instance, immediately after cessation 
of the study drug infusion if such a reaction is seen). Vital signs are to be 
monitored as medically indicated and pulse oximetry is to be monitored 
continuously for at least 2 hours or until the patient has recovered, whichever is 
longer. ECGs should be repeated as medically indicated. 
Once medical treatment of the IRR has begun, blood samples are to be obtained for 
assessment of: 
• Plasma complement factors (C3a, C4a, C5a, Bb, SC5b-9). 
• Serum complement (CH50, C3, and C4) and tryptase. 
• ATYR1923 serum concentrations. 
• Jo-1 and ADA. 
Additionally, the following tests and procedures are to be performed 1 to 2 hours after the 
onset of symptoms:  
• Samples for assessment of: 
- Complete safety laboratory panel, including urine analysis and urine microscopy. 
- IgE. 
- Plasma complement factors (C3a, C4a, C5a, Bb, SC5b-9). 
- Serum complement (CH50, C3, and C4) and serum tryptase. 

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- Serum biomarkers/cytokines. 
The Investigator must inform the study Medical Monitor promptly regarding any patient 
who experiences a generalized IRR for additional instruction. 
Patients who experience generalized IRRs will continue to be monitored / have repeat 
assessments performed at a schedule determined by the Investigator in consultation with 
the Medical Monitor and Sponsor. Appropriate follow up for the patient must occur to 
ensure that there are no late-occurring sequelae. 
Note that in the eCRF, AEs that occur during or within 24 hours after study drug 
injection should be captured as individual signs and symptoms rather than a diagnosis of 
allergic reaction or IRR.  
9.9.1. 
Anaphylaxis 
IRRs meeting the definition of anaphylaxis are to be reported in the eCRF as such 
(Sampson et al. 2006):   
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-
tongue-uvula). 
And at least one of the following: 
a. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, 
reduced peak expiratory flow, hypoxemia). 
b. Reduced blood pressure or associated symptoms of end-organ dysfunction 
(eg, hypotonia [collapse], syncope, incontinence). 
2. Two or more of the following that occur rapidly after exposure to a likely allergen 
for that patient (minutes to several hours): 
a. Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, 
swollen lips-tongue-uvula). 
b. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, 
reduced peak expiratory flow, hypoxemia). 
c. Reduced blood pressure or associated symptoms (eg, hypotonia [collapse], 
syncope, incontinence). 
d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting). 
3. Reduced blood pressure after exposure to known allergen for that patient (minutes 
to several hours): 
a. Infants and children: low systolic blood pressure (age specific) or greater than 
30% decrease in systolic blood pressure*. 

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b. Adults: systolic blood pressure of less than 90 mm Hg or greater than 30% 
decrease from that person’s baseline. 
Patients who experience anaphylaxis are to be managed as described in Section 9.9. 

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10. 
STATISTICAL ANALYSES 
10.1. 
Statistical Procedures and Determination of Sample Size 
10.1.1. 
Analysis Sets 
10.1.1.1. 
Intent to Treat Set 
The Intent to Treat (ITT) Set will comprise all randomized patients and will be based on 
the randomized cohort and treatment, regardless of which treatment the patient actually 
received. 
10.1.1.2. 
Safety Set 
The Safety Set will comprise all patients who receive any amount of study drug and will 
be based on the actual treatment received, if this differs from that to which the patient 
was randomized. 
10.1.1.3. 
Pharmacokinetic Concentration Set 
The PK Concentration Set will comprise all patients who receive any amount of study 
drug, who have at least 1 quantifiable PK concentration and will be based on the actual 
treatment received, if this differs from that to which the patient was randomized to. A 
quantifiable PK concentration will be determined at the discretion of the 
pharmacokineticist. Patients who receive only placebo will be excluded from the PK 
Concentration Set. 
10.1.1.4. 
Pharmacokinetic Parameters Set 
The PK Parameters Set will comprise all patients who receive any amount of study drug, 
who have at least 1 evaluable PK parameter and will be based on the actual treatment 
received, if this differs from that to which the patient was randomized. An evaluable PK 
profile allows the determination of 1 or more PK parameters and will be determined at 
the discretion of the pharmacokineticist. Patients with dosing deviations that could 
potentially affect the PK profile will be excluded from the PK Parameters Set, at the 
discretion of the pharmacokineticist. Patients who receive only placebo will be excluded 
from the PK Parameters Set. 
10.1.1.5. 
Efficacy Set 
The Efficacy Set will comprise all randomized patients who receive any amount of study 
drug and who have at least 1 post-baseline efficacy assessment and will be based on the 
actual treatment received, if this differs from that to which the patient was randomized.  

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10.1.1.6. 
Oral Corticosteroid Evaluation 
The oral corticosteroid evaluation parameters and their statistical evaluation will be 
included in the Clinical Study Report (CSR) for this study. 
All data will be summarized using descriptive statistics and will be listed and 
summarized in tabular and/or graphical form. Further details on how data from patients 
who discontinued prematurely will be handled and the types of exposure response 
analyses that will be performed will be provided in the Statistical Analysis Plan (SAP). 
10.1.2. 
Statistical and Analytical Plan for Pharmacokinetic, Pharmacodynamic, 
Safety and Exploratory Evaluation 
A SAP will be generated by the CRO Biostatistics Department; the SAP will be finalized 
prior to database lock or interim analysis if applicable and subsequent unblinding of 
study treatment codes. Full details of the analysis to be performed will be included in the 
SAP. 
Any deviation from the SAP will be reported in the section “Changes in Planned 
Analysis” in the CSR. 
10.1.2.1. 
Pharmacokinetic Evaluation 
The PK parameters and their statistical evaluation will be included in the CSR of this 
study. 
All data will be summarized using descriptive statistics and will be listed and 
summarized in tabular and/or graphical form. Any additional analyses will be specified in 
the SAP. 
10.1.2.2. 
Efficacy Evaluation 
The efficacy parameters and their statistical evaluation will be included in the CSR of this 
study. 
All data will be summarized using descriptive statistics and will be listed and 
summarized in tabular and/or graphical form. 
10.1.2.3. 
Evaluation of Safety and Tolerability 
Safety and tolerability will be assessed through AEs, clinical laboratory, vital signs, 
ECGs and physical examination findings, and any other parameter that is relevant for 
safety assessment. 
10.1.2.3.1. Adverse Events 
A listing of all individual AEs will be provided. Summary tables of TEAEs will be 
presented by system organ class based on the Medical Dictionary for Regulatory 

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Activities (MedDRA) terminology list (preferred terms): 1 containing the number of 
TEAEs (frequency of occurrence, number of patients experiencing the event) by 
treatment and 1 containing the number of drug-related TEAEs (frequency of occurrence, 
number of patients experiencing the event) per treatment. Additional tables of total 
counts by treatment and relationship and by treatment and intensity will be given. 
10.1.2.3.2. Clinical Laboratory 
Clinical laboratory data will be listed, and will also be flagged if the parameter is outside 
the reference range. A summary of all data outside the reference range of the clinical 
laboratory will be provided. Clinical laboratory data will be presented descriptively, 
where applicable. 
10.1.2.3.3. Vital Signs, Pulse Oximetry and Electrocardiograms 
Vital signs, pulse oximetry and ECG parameters will be listed and they will be presented 
descriptively, where applicable. 
10.1.2.3.4. Immunogenicity 
The presence of ADAs and Jo-1 antibodies in serum will be listed and presented 
descriptively, where applicable. 
10.1.2.4. 
Evaluation of Exploratory Variables 
Exploratory variables will be listed and presented descriptively, where applicable. 
10.1.3. 
Determination of Sample Size 
For this study, no prospective calculations of statistical power have been made. The 
sample size has been selected to provide information on safety, tolerability, PK and 
efficacy following single doses of ATYR1923. Any p-values to be calculated according 
to the SAP will be interpreted in the perspective of the explorative character of this study. 
10.2. 
Data Quality Assurance 
The study may be audited to assess adherence to the clinical study protocol and Quality 
System. During the conduct of the study, process-related audits may be performed. An 
audit certificate will be provided in the appendices of the final CSR outlining any audits 
and other related activities performed.  
The clinical research site will be monitored by the study monitor to ensure correct 
performance of the study procedures and assure that the study will be conducted 
according to the relevant regulatory requirements. The eCRF entries will be verified with 
the source documentation, if applicable (in some cases there are no source pages, 
therefore verification is not necessary). 

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Regulatory authorities, the IRB/IEC and/or the Sponsor’s clinical quality assurance group 
may request access to all source documents, eCRFs, and other study documentation for 
on-site audit or inspection. Direct access to these documents must be guaranteed by the 
Investigator, who must provide support at all times for these activities. 
Quality control principles will be applied throughout the performance of this study. 
Review procedures will be followed by the Sponsor and designees for all documents that 
are generated in relation with the study. Essential study activities of personnel will be 
checked by colleagues during execution, and each of them will sign off the 
documentation for execution or checking of the activities. 
An explanation will be given for all missing, unused and spurious data in the relevant 
sections of the CSR. 
10.2.1. 
Interim Analyses 
Details of any interim analyses will be provided in the SAP. 
10.3. 
Changes to the Planned Statistical Methods 
Changes to the planned statistical methods will be documented in the CSR. 

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11. 
ETHICAL, LEGAL, AND ADMINISTRATIVE 
CONSIDERATIONS 
11.1. 
Good Clinical Practice 
This study will be conducted according to the protocol and in compliance with ICH GCP, 
the ethical principles stated in the Declaration of Helsinki, and other applicable 
regulatory requirements. 
The Investigator confirms this by signing the protocol. 
11.2. 
Informed Consent 
Written informed consent, based on age of majority, in compliance with 21 Code of 
Federal Regulations § 50 and/or ICH regulations will be obtained from each patient prior 
to undergoing any protocol-specific tests or procedures that are not part of routine care. 
The Sponsor or designee will provide an ICF template to the Investigator for use in 
developing a study center-specific consent documents. Prior to submission of the study 
center-specific ICF form to the IRB/IEC, these documents must be reviewed and 
approved by the Sponsor or designee. Any changes requested by the IRB/IEC must also 
be approved by the Sponsor or designee. The final IRB/IEC-approved ICF must be 
provided to the Sponsor or designee. Revisions to the ICF required during the study must 
be approved by the Sponsor or designee, and a copy of the revised ICF provided to the 
Sponsor or designee. 
Before recruitment and enrollment, each prospective patient will be given a full 
explanation of the study and be allowed to read the ICF in a language they understand. 
After the Investigator or designee is assured that the patient understands the commitments 
of participating in the study, the patient will be asked to sign and date the ICF, as 
appropriate.  
A copy of the fully signed and dated ICF will be given to the patient. The original will be 
maintained in the patient’s medical record at the study center. All active patients will sign 
an updated ICF if revisions are made to the ICF during the course of the study. 
11.3. 
Institutional Review Board/Independent Ethics Committee 
Federal regulations and ICH require that approval be obtained from an IRB/IEC prior to 
participation of patients in research studies. Prior to the study onset, the protocol, any 
protocol amendments, ICFs, advertisements to be used for patient recruitment and any 
other written information regarding this study to be provided to a patient must be 
approved by the IRB/IEC. 
All IRB/IEC approvals must be dated and signed by the IRB/IEC Chairperson or 
designee and must identify the IRB/IEC by name and address, the clinical protocol by 
title and/or protocol number, and the date approval or favorable opinion was granted for 
the clinical research. 

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No drug will be released to the site to dose a patient until written IRB/IEC authorization 
has been received by the Sponsor or designee. 
The Investigator is responsible for obtaining continuing review of the clinical research at 
least annually or more often if specified by the IRB/IEC. The Investigator must supply 
the Sponsor or designee with written documentation of the approval of the continued 
clinical research. 
The Investigator, sponsor, or designee as applicable, will make all attempts to ensure that 
the IRB/IEC is constituted and operates in accordance with Federal and ICH GCP and 
any local regulations. 
11.4. 
Amending the Protocol 
Any changes in this research activity, except those to remove an apparent immediate 
hazard to the patient, must be reviewed and approved by the Sponsor or designee and the 
IRB/IEC that approved the study. Amendments to the protocol must be submitted in 
writing to the Investigator’s IRB/IEC for approval prior to patients being enrolled into the 
amended protocol. 
The Sponsor may make administrative changes (ie, changes that do not significantly 
affect patient safety or the study’s scope or scientific quality) without any further 
approvals.  
All amendments will be distributed to all protocol recipients. 
11.5. 
Confidentiality/Data Protection 
All study findings and documents will be regarded as confidential. The Investigator and 
other study personnel must not disclose such information without prior written approval 
from the Sponsor. 
Patients will be assigned a unique identifier by the Sponsor. Any participant records or 
datasets that are transferred to the Sponsor will contain the identifier only; patient names 
or any information which would make the participant identifiable will not be transferred. 
The patient must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also 
be explained to the patient. 
The patient must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
11.6. 
Publication Policy 
It is anticipated that the results of this study will be presented at scientific meetings 
and/or published in a peer reviewed scientific or medical journal. The initial planned 
publication will be a multi-center report of the study outcome. Additional publications 

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from a given center can only occur after the publication of the multi-center results. A 
prepublication manuscript is to be provided to the Sponsor at least 30 days prior to the 
submission of the manuscript to a publisher. Similarly, the Sponsor will provide any 
company-prepared manuscript to the Investigators for review at least 30 days prior to 
submission to a publisher. 

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12. 
STUDY MANAGEMENT 
12.1. 
Data Quality Assurance 
The Sponsor or its designated representative will conduct telephone or a study visit to 
verify the qualifications of each Investigator, review/inspect study center facilities, and 
inform the Investigator of responsibilities and procedures for ensuring adequate and 
correct study documentation. 
12.2. 
Case Report Forms and Source Documentation 
The Investigator and designees agree to maintain accurate eCRFs and source 
documentation as part of case histories. Source documents are the originals of any 
documents used by the Investigator or subinvestigator or hospital/institution that allow 
verification of the existence of the patient and substantiate the integrity of the data 
collected during the study. 
 The Sponsor or designee will provide eCRF access to the study center. eCRFs will be 
completed for each patient. It is the Investigator’s responsibility to ensure the accuracy, 
completeness, and timeliness of the data reported in the patient’s eCRF. Source 
documentation supporting the eCRF data should indicate the patient’s participation in the 
study and should document the dates and details of informed consent, study procedures, 
AEs, and patient status.  
The Investigator, or designated representative, should complete the eCRF as soon as 
possible after information is collected / data are available, preferably on the same day that 
a patient is seen for an examination, treatment, or any other study procedure. Any 
outstanding entries must be completed immediately after the final examination. An 
explanation should be given for all missing data. 
The Investigator must sign and date the Investigator’s Statement at the end of the eCRF 
to endorse the recorded data.  
12.3. 
Monitoring 
A clinical research associate (CRA) or other representative of the Sponsor or designee 
will conduct remote or study visits to verify the qualifications of each Investigator, 
review/inspect study center facilities, and inform the Investigator of responsibilities and 
procedures for ensuring adequate and correct study documentation. 
During the course of the study, the CRA will conduct remote monitoring or study visits to 
review protocol compliance, compare eCRFs and individual patient medical records, 
assess drug accountability, and ensure that the study is being conducted according to 
pertinent regulatory requirements in respect to GCP. eCRFs will be verified with source 
documentation. The review of medical records will be performed in a manner to ensure 
that patient confidentiality is maintained. 

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12.4. 
Inspections 
Regulatory authorities and/or quality assurance personnel from the Sponsor or its 
designated representative may wish to carry out such source data checks and/or in-center 
audit inspections. The Investigator assures the Sponsor of the necessary support at all 
times. In the event of an audit, the Investigator agrees to allow the Sponsor’s 
representatives and any regulatory agencies access to all study records. 
12.5. 
Financial Disclosure Reporting Obligations 
Investigators and subinvestigators are required to provide financial disclosure 
information to the sponsor to permit the sponsor to fulfill its regulatory obligation. 
Investigators and subinvestigators must commit to promptly updating the information if 
any relevant changes occur during the study and for a period of one year after the 
completion of the study. 
12.6. 
Archiving Study Records 
Essential documents should be retained for a minimum of 2 years after the last approval 
of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region or at least 2 years have elapsed 
since the formal discontinuation of clinical development of the investigational product. 
However, these documents should be retained for a longer period if required by the 
applicable local requirements. 
ICH requires that patient identification codes be retained for at least 15 years after the 
completion or discontinuation of the study. 
 

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