A Phase 2 Randomized, Double-blind, Placebo-controlled, Crossover Multicenter Study to Evaluate the Safety and Efficacy of KZR-616 in the Treatment of Patients With Active Polymyositis or Dermatomyositis
Phase: PHASE2
Conditions: Polymyositis, Dermatomyositis
Sponsor: Kezar Life Sciences, Inc.

 
KZR-616-003 
A PHASE 2 RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED, CROSSOVER 
MULTICENTER STUDY TO EVALUATE THE 
SAFETY AND EFFICACY OF KZR-616 IN THE 
TREATMENT OF PATIENTS WITH ACTIVE 
POLYMYOSITIS OR DERMATOMYOSITIS 
TITLE PAGE 
 
 
Clinicaltrials.gov Identifier 
NCT04033926 
Release date of report: 
01 March 2019 
 
 
 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
Confidential 
Page 1 of 95 
CLINICAL STUDY PROTOCOL 
Protocol Title: 
A Phase 2 Randomized, Double-blind, Placebo-controlled, 
Crossover Multicenter Study to Evaluate the Safety and Efficacy of 
KZR-616 in the Treatment of Patients with Active Polymyositis or 
Dermatomyositis 
Protocol Number: 
KZR-616-003 
Investigational Medicinal 
Product: 
KZR-616 
Indications: 
Polymyositis (PM) and Dermatomyositis (DM) 
Development Phase: 
2 
US IND Number: 
 
Sponsor: 
Kezar Life Sciences, Inc. 
4000 Shoreline Court, Suite 300 
South San Francisco, CA 94080 
Telephone: 
  
Original Protocol Date: 
01 March 2019 
Confidentiality Statement: 
The concepts and information contained herein are confidential and proprietary and shall not be 
disclosed in whole or part without the express written consent of the Sponsor. 
Compliance Statement: 
This study will be conducted in accordance with this protocol, the International Conference on 
Harmonisation (ICH), Guideline for Good Clinical Practice (GCP), and the applicable country and 
regional (local) regulatory requirements. 
 
 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
Confidential 
Page 3 of 95 
PROTOCOL ACCEPTANCE PAGE 
I have read and agree to the protocol, as detailed in this document. I am aware of my 
responsibilities as an Investigator under the International Conference on Harmonisation 
Guideline (ICH) for Good Clinical Practice (GCP), the Declaration of Helsinki, all local, 
regional, and national regulatory requirements (including the Code of Federal Regulations [CFR] 
Title 21 for US Investigators), requirements of the applicable Institutional Review 
Board/Independent Ethics Committee, and the clinical trial protocol. I agree to conduct the trial 
according to these regulations and guidelines, to appropriately direct and assist the staff under 
my control that will be involved in the trial, and ensure that all staff members are aware of their 
clinical trial responsibilities. 
 
Investigator’s Name: 
 
Name of Institution/Site: 
 
Signature: 
 
Date: 
 
 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
Confidential 
Page 4 of 95 
PROTOCOL SYNOPSIS 
INVESTIGATIONAL PRODUCT (IP) 
Name of IP 
KZR-616 
Name of Active Ingredient 
KZR-616 
CLINICAL CONDITION(S)/INDICATION(S) 
 
Polymyositis (PM)  
 
Dermatomyositis (DM) 
PROTOCOL ID 
KZR-616-003 
PROTOCOL TITLE 
A Phase 2 Randomized, Double-blind, Placebo-controlled, Crossover 
Multicenter Study to Evaluate the Safety and Efficacy of KZR-616 in the 
Treatment of Patients with Active Polymyositis or Dermatomyositis 
Short Title 
A Phase 2 Study of KZR-616 to Evaluate Safety and Efficacy in Patients 
with Active Polymyositis or Dermatomyositis 
STUDY PHASE 
Phase 2 
STUDY OBJECTIVES  
Primary Objective 
 
Evaluate efficacy of KZR-616 in patients with PM or DM. 
Secondary Objective(s)  
 
Evaluate safety and tolerability of KZR-616 in patients with PM or DM 
 
Evaluate pharmacokinetics (PK) of KZR-616 in patients with PM or DM. 
Exploratory Objectives 
 
Evaluate biomarkers related to efficacy and safety of KZR-616 in patients with PM or DM 
 
Evaluate the PK and pharmacodynamic (PD) relationship of KZR-616 in patients with PM or DM. 
STUDY DESIGN  
Study Type 
Interventional 
Allocation 
Randomized 
Intervention model  
Crossover 
Blinding/Masking 
Double-blind 
Primary Purpose 
Treatment 
Planned Duration of Patient 
Participation 
Up to 44 weeks: 4-week Screening Period, 32-week Treatment Period, and  
8-week Safety Follow-up (SFU) 
Study Design 
This is a Phase 2 randomized, double-blind, placebo-controlled, crossover, multicenter study to evaluate the 
safety, tolerability, efficacy, PK and PD of treatment with KZR-616 in patients with active PM or DM. Patients 
will be evaluated for eligibility during the Screening Period. Eligible patients will be randomized 1:1 to Arm A or 
Arm B of the study. Patients will be stratified by their diagnosis of PM or DM.  
During the 32-week treatment period, patients will receive study drug subcutaneously (SC) once weekly. The 
16 weeks of dosing during Treatment Period 1 begins at Week (W) 0 and continues through W15 (ie, ends 
immediately before dosing at Week 16 [approximately Day 113]); patients allocated to Arm A will receive  
KZR-616 and those in Arm B will receive placebo. The 16 weeks of dosing during Treatment Period 2 begins 
with administration of the first dose at W16 and continues through W31 (ie, ends immediately before Week 32); 
patients allocated to Arm A will receive placebo and those in Arm B will receive KZR-616.  
This study will be conducted on an outpatient basis. Study visits will occur at Screening, W0, W4, W8, W12, 
W16, W20, W24, W28, W32, W36, and W40. Day 1 of W0 will be defined as Baseline. The W36 and W40 visits 
will comprise the Safety Follow-up (SFU). 
Randomized patients who withdraw from the study prior to W32 will be requested to undergo the Early 
Termination Visit (ETV) procedures, and all patients who withdraw prematurely also will be requested to return 
for a SFU visit 9 weeks (W40 visit procedures) after receipt of their last dose of the study drug.  

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
Confidential 
Page 5 of 95 
Efficacy assessments will be performed for all patients, unless indicated otherwise, and will include: International 
Myositis Assessment and Clinical Studies Group (IMACS) core set Activity and Damage measures (Manual 
Muscle Testing-8 Muscle Groups [MMT-8]; Physician and Patient Global Assessments of Disease Activity 
[MDGA and PtGADA, respectively]; Health Assessment Questionnaire-Disability Index [(HAQ-DI]; muscle 
enzymes [clinical laboratory assessments]: creatine phosphokinase [CK], aldolase, lactate dehydrogenase [LDH], 
alanine aminotransferase [ALT], and aspartate aminotransferase [AST]; Myositis Disease Activity Assessment 
Tool [MDAAT, 2005 version]; Myositis Damage Index [MDI]; and the Patient Global Assessment of Disease 
Damage [PtGADD]), Functional Index-2 (FI-2; performed for the dominant side only), Functional Index-3 (FI-3; 
30-second chair stand test, timed up and go test, and 6-minute walk distance), Physician Global Impression of 
Change (MDGIC), and Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI; performed only 
for patients with DM). 
Additional patient reported outcome measures (PROMs) will be performed for all patients, unless indicated 
otherwise, and will include: Patient Reported Outcomes Measurement Information System 29-item Short Form 
Profile Version 2.1 (PROMIS-29), EuroQoL 5-dimension 5-level (EQ-5D-5L), Healthcare Resource Utilization 
(HRU), Treatment Satisfaction Questionnaire for Medication Version II (TSQM), Patient Global Impression of 
Change (PGIC), and the Peak Pruritus Numeric Rating Scale (NRS; performed only by patients with DM). 
Safety will be assessed throughout the study by monitoring vital signs (blood pressure, pulse rate, temperature, 
and respiration rate), physical examination, electrocardiograms (ECGs), clinical laboratory tests (hematology, 
chemistry, urinalysis, immunoglobulins), and by recording and analyzing all adverse events (AEs) and serious 
adverse events (SAEs). 
Biopsies will be collected from a subset of enrolled patients; skin biopsies will be performed only for selected 
patients with DM, and muscle biopsies will be performed for selected patients with PM or DM. For selected 
patients, biopsies will be collected from skin and/or muscle at Baseline, W16, and optionally at W32. The tissue 
samples may be used for exploratory investigations of treatment-related changes and regulation of inflammatory 
pathways. 
Efficacy Endpoints 
The primary efficacy endpoint is: 
 
Mean change from start to end of KZR-616 treatment in the Total Improvement Score (TIS), which 
ranges from 0 to 100. 
Secondary efficacy endpoints are: 
 
Proportion of patients with an increase ≥20 points on the TIS from start to end of KZR-616 treatment. 
The categories and ranges of scores for improvement are: 20-39 points being minimal improvement,  
40-59 points being moderate improvement, and ≥60 points being major improvement 
 
Proportion of patients from start to end of KZR-616 treatment meeting IMACS Definition of 
Improvement (DOI). The IMACS DOI is ≥20% improvement in at least 3 of 6 core set activity 
measures, with no more than 2 core set activity measures (CSAMs) worsening by ≥25% (the MMT-8 
cannot be a worsening measure) 
 
Absolute change and percent change from start to end of KZR-616 treatment in the IMACS individual 
CSAMs 
 
For patients with DM, the mean change from start to end of KZR-616 treatment in the CDASI 
 
For patients with DM, the mean change from start to end of KZR-616 treatment in the Peak Pruritus 
NRS. 
Exploratory efficacy endpoints are: 
 
Mean change over time from start to end of KZR-616 treatment in the TIS in all patients, patients 
with DM only, and in patients with PM only 
 
Proportion of patients over time with an increase of ≥20, ≥40, or ≥60 points on the TIS from start to 
end of KZR-616 treatment in all patients, in patients with DM only, and in patients with PM only 
 
For patients with an increase of ≥20 points on the TIS from Baseline to W16, the proportion of 
patients with no change or increase in their TIS at W32 for all patients, in patients with DM only, and 
in patients with PM only 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
Confidential 
Page 6 of 95 
 
Mean change and mean percent change over time from start to end of KZR-616 treatment in the 
IMACS individual CSAMs and core set damage measures (CSDMs) for all patients, in patients with 
DM only, and in patients with PM only 
 
Mean change from Baseline over time from start to end of KZR-616 treatment in the FI-2, the FI-3 
and the individual components of the FI-3 for all patients, in patients with DM only, and in patients 
with PM only 
 
For patients with DM, mean change over time from start to end of KZR-616 treatment in the CDASI 
 
For patients with DM, the proportion over time with ≥7 points improvement in the CDASI from start 
to end of KZR-616 treatment  
 
For patients with DM, the mean change over time from start to end of KZR-616 treatment in the Peak 
Pruritus NRS 
 
Mean change over time from start to end of KZR-616 treatment in the individual domains of the 
PROMIS-29 for all patients, in patients with DM only, and in patients with PM only 
 
Mean change over time in TSQM from start to end of KZR-616 treatment for all patients, in patients 
with DM only, and in patients with PM only 
 
The change in quality of life over time from start to end of KZR-616 treatment as measured by the  
EQ-5D-5L for all patients, in patients with DM only, and in patients with PM only 
 
The HRU over time from start to end of KZR-616 treatment for all patients, in patients with DM only, 
and in patients with PM only 
 
The MDGIC over time from start to end of KZR-616 treatment for all patients, in patients with DM 
only, and in patients with PM only 
 
The PGIC over time from start to end of KZR-616 treatment for all patients, in patients with DM 
only, and in patients with PM only. 
Note: The primary analysis period is from start to end of KZR-616 treatment for both sequence arms combined. 
A secondary analysis comparing KZR-616 to parallel placebo will be confined to the Baseline to Week 16 period. 
Lastly, the usual crossover analysis comparing placebo to KZR-616 will be carried out as an exploratory analysis 
approach. The rationale for this priority order is as follows. The usual crossover analysis for this design is 
prespecified as exploratory since it is unknown whether that analysis would be confounded by carryover effect. 
In order to maximize the precision for assessment of KZR-616 effect, it is assessed primarily via all patients’  
start to end of KZR-616 treatment, and secondarily by the Treatment Period 1 between-treatment comparison. 
Safety Endpoints 
 
Incidence, nature, and severity of AEs 
 
Incidence, nature, and severity of SAEs 
 
Incidence and severity of infection-related AEs and SAEs 
 
Incidence and severity of AEs with onset within 24 hours from the start of dosing with any study drug 
 
Incidence of AEs leading to study drug discontinuation 
 
Changes in standard laboratory parameters, vital signs, and ECGs. 
Pharmacokinetic and Pharmacodynamic Endpoints 
The secondary PK endpoint will: 
 
Evaluate the plasma PK parameters for KZR-616 and its metabolite KZR-59587. 
The exploratory PK/PD endpoints will: 
 
Evaluate the relationships between KZR-616 PK, clinical efficacy, clinical safety, and various PD 
endpoints including proteasome inhibition and changes in circulating cytokine and immune cell 
profiles 
 
Evaluate the relationships between KZR-616 PK, clinical efficacy, clinical safety, and various PD 
endpoints related to skin and muscle biopsy histology and gene expression profiles. 
INVESTIGATIONAL PRODUCT(S), DOSE AND MODE OF ADMINISTRATION 
Active Product 
Dosage form: KZR-616 Lyophile, 125 mg/vial, is supplied as a refrigerated 
lyophilized drug product containing 125 mg of KZR-616 (150 mg of KZR-616 
maleate) and 
 (inactive excipient) in single-use 3.0-mL 
borosilicate glass vial. 
Dose and dose frequency: 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
Confidential 
Page 7 of 95 
The study consists of 2 arms: 
Arm A:  
 
Treatment Period 1: KZR-616 30 mg SC weekly for 2 weeks  
(W0-W1), then 45 mg SC weekly for 14 weeks (W2-W15) 
 
Treatment Period 2: Placebo SC weekly for 16 weeks (W16-W31). 
 
Arm B:  
 
Treatment Period 1: Placebo SC weekly for 16 weeks (W0-W15) 
 
Treatment Period 2: KZR-616 30 mg SC weekly for 2 weeks  
(W16-W17), then 45 mg SC weekly for 14 weeks (W18-W31). 
Control/Comparator 
A placebo control will be used to maintain blinding and will be sterile water for 
injection (WFI). 
Dose and dose frequency: Refer to the dose and dose frequency of the active 
product, KZR-616. 
PATIENT SELECTION  
Targeted Accrual 
Approximately 24 enrolled patients; it is anticipated 40 patients will be screened 
to achieve 24 patients enrolled 
Number of Arms 
Two with approximately 12 patients in each arm 
Planned Number of Sites 
Up to approximately 18 sites 
Inclusion Criteria 
1. Adult patients at least 18 years of age at the time of signing informed consent at Screening 
2. Body Mass Index (BMI) of 18 to 40 kg/m2 
3. Diagnosis of probable or definite DM or PM by the 2017 European League Against Rheumatism 
(EULAR)/American College of Rheumatology (ACR) Classification Criteria 
4. Must have their data reviewed by an adjudication committee to confirm eligibility unless at least 1 of the 
following is present: 
a. 
Muscle biopsy with evidence of active myositis within the last 6 months prior to or at 
Screening 
b. Electromyography or magnetic resonance imaging (MRI) with evidence of active myositis 
within the last 6 months prior to Screening  
c. 
A CK ≥4 × upper limit of normal (ULN). 
5. Must have demonstrable muscle weakness as measured by the MMT-8 with a score ≥80/150 but 
≤136/150 units and any 2 of the following: 
a. 
MDGA visual analog scale (VAS) ≥2 cm 
b. PtGADA VAS ≥2 cm 
c. 
At least one muscle enzyme laboratory measurement (ie, CK, aldolase, LDH) ≥1.3 × ULN 
d. MDAAT Extramuscular Global Activity VAS ≥1 cm. 
6. Documented inadequate response to a 12-week trial of corticosteroids or at least 1 immunosuppressant 
(eg, methotrexate [MTX], mycophenolate mofetil [MMF], mycophenolate sodium [MPS], azathioprine 
[AZA], leflunomide [LEF], tacrolimus, cyclosporine [CyA]) OR have demonstrated significant 
documented toxicity or intolerance to such therapies  
7. Has had age-appropriate cancer screening that is up to date and negative for evidence of malignancy as 
per local standard of care (see Appendix A) 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
Confidential 
Page 8 of 95 
8. Female patients of childbearing potential must have a negative serum pregnancy test at Screening and a 
negative urine pregnancy test at Baseline and must agree to employ adequate birth control measures for 
the duration of the study. 
Women of childbearing potential (WOCBP) must use highly effective and medically acceptable 
methods of contraception to prevent pregnancy during Screening and must agree to continue to practice 
adequate contraception during the study and for 4 weeks after administration of the last dose of the study 
drug. 
For the purposes of this study, WOCBP are defined as: all postpubescent female patients, unless the 
patient is postmenopausal (defined by amenorrhea for at least 2 years or amenorrhea for at least 1 year 
with confirmatory follicle stimulating hormone [FSH] level in the postmenopausal range as documented 
historically or measured by the central laboratory at Screening and if patient is not on supplementary 
hormonal therapy) or if the patient is surgically sterile (ie, tubal ligation, hysterectomy, bilateral 
salpingoophorectomy). 
Highly effective contraception is defined as the use of 2 barrier methods (eg, female diaphragm and 
male condom), 1 barrier method with spermicide, intrauterine device, or hormonal contraceptives 
(eg, implant or oral). If using a hormonal form of contraception, it must have been stable for at least 
4 weeks prior to Screening, and if using concomitant mycophenolate, the patient must use another 
nonhormonal form of highly effective contraception. Abstinence will be acceptable only if it is in line 
with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, ovulation) and 
withdrawal are not acceptable methods of contraception 
9. Male patients must be either congenitally sterile or surgically sterile (vasectomy with documented 
confirmation of aspermia) or willing to use a condom in addition to having their female partner use 
another form of contraception (such as an intrauterine device, barrier method with spermicide, or 
hormonal contraceptive [eg, implant, injectable, patch, or oral]) from Screening until 12 weeks after the 
last dose of study drug, unless their partners are infertile or surgically sterile 
10. Willing and able to comply with the requirements of the protocol 
11. Provide written informed consent prior to any study-related procedure. 
Exclusion Criteria 
1. Has significant muscle damage (eg, severe muscle atrophy, end-stage disease, postmyopathic DM) per 
Investigator opinion or has a muscle damage VAS score ≥5 cm on the MDI  
2. Any other form of myositis or myopathy other than PM or DM (eg, metabolic or drug-induced 
myopathy, drug-induced myositis, juvenile PM or DM, inclusion body myositis, cancer-associated 
myositis [myositis diagnosed within 3 years, either before or after, of a diagnosis of any malignancy 
except for squamous or basal cell carcinoma of the skin or cervical carcinoma in situ], myositis in 
overlap with another connective disease [eg, systemic lupus erythematosus{SLE}, systemic sclerosis, 
rheumatoid arthritis {RA}], or muscular dystrophy); patients with secondary Sjogren’s syndrome, 
necrotizing myopathy, or antisynthetase syndrome are permitted to participate in this study 
3. Any condition (eg, severe arthritis with limited range of motion or severe calcinosis) that, in the 
Investigator’s opinion, precludes the ability to quantitate muscle strength  
4. Has severe interstitial lung disease per Investigator opinion or has a pulmonary damage VAS score ≥5 
cm on the MDI 
5. Presence of autoinflammatory disease (eg, psoriatic arthritis, axial spondyloarthropathy, inflammatory 
bowel disease) 
6. Has received treatment with any of the following: 
a. 
Oral prednisone (or prednisone equivalent) >20 mg/day at Screening or during the Screening 
Period, or initiation of oral prednisone during the Screening Period. If oral prednisone is being 
used at Screening, use should be stable during the 2 weeks prior to Baseline 
b. Use of nonsteroidal immunosuppressants other than oral MMF or MPS (≤3 g/day or 
2160 mg/day, respectively); oral, intramuscular (IM), or SC MTX (≤25 mg/week); AZA 
(≤2.5 mg/kg/day); LEF (≤20 mg/day); tacrolimus (≤3 g/day); or concurrent use of more than 1 
nonsteroidal immunosuppressant at Baseline. If a permitted nonsteroidal immunosuppressant is 
being used, it must have used for at least 12 weeks and must have been taken at a stable dose 
(including stable route of administration) for the last 4 weeks prior to Screening. If MMF, 
MPS, MTX, AZA, LEF, or tacrolimus is being discontinued, it must be discontinued at least 
4 weeks prior to Baseline 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
Confidential 
Page 9 of 95 
c. 
Antimalarials exceeding the recommended doses (hydroxychloroquine up to 400 mg/day or 
6.5 mg/kg/day, whichever is less; chloroquine up to 250 mg/day, or quinacrine up to 
100 mg/day are permitted) or taken at an unstable dose during the 12 weeks prior to Screening. 
If an antimalarial is being discontinued, it must be discontinued at least 4 weeks prior to 
Baseline. Antimalarials are considered distinct from corticosteroids in (a) and nonsteroidal 
immunosuppressants in (b) above 
d. Initiation of or use of an unstable dose of topical therapy (eg, corticosteroids, pimecrolimus) in 
the 4 weeks prior to Screening. If topical therapy is being discontinued, it must be discontinued 
at least 4 weeks prior to Baseline. 
7. Receipt of any of the following treatments within the following timeframes before Screening: 
a. 
Oral corticosteroids at doses ≥1 mg/kg/day prednisone or equivalent: 4 weeks 
b. Intravenous or IM corticosteroids: 4 weeks 
c. 
Intra-articular therapies, such as corticosteroids or hyaluronic acid preparations: 4 weeks 
d. Intravenous, SC, or IM Ig: 4 weeks 
e. 
Cyclophosphamide or chlorambucil: 24 weeks 
f. 
Prohibited nonbiologic nonsteroidal immunosuppressants or targeted therapies including, but 
not limited to, CyA, dapsone, tofacitinib, baricitinib: 8 weeks 
g. Cytokine or integrin antagonists or selective costimulation modulators including, but not 
limited to, interleukin (IL)-1, IL-6, IL-17, IL-12/23, IL-23, interferon (IFN), integrin, and 
tumor necrosis factor (TNF)α antagonists or abatacept: 12 weeks 
h. B cell-depleting or -modulating therapies (eg, rituximab, ofatumumab, obinutuzumab, 
ocrelizumab, belimumab, atacicept): 24 weeks 
For those patients who have used an anti-cluster of differentiation (CD) 20 drug at ≥24 weeks 
and <48 weeks before Screening, they must have levels of circulating CD19+ B cells ≥the 
lower limit of normal (LLN). A CD19 count is not required for patients with prior use of an 
anti-CD20 drug ≥48 weeks prior to Screening 
i. 
Previous treatment with the following cell-depleting therapies, including investigational agents 
or approved therapies: alemtuzumab, anti-CD4, anti-CD5, or anti-CD3: at any time 
j. 
Other biologics or investigational drugs: 8 weeks or 5 half-lives, whichever is longer 
k. Transfusion with blood, packed red blood cells, or platelets or treatment with plasmapheresis or 
plasma exchange: 6 weeks 
l. 
Creatine dietary supplements: 4 weeks. 
8. Initiation of an exercise program (including physical therapy or occupational therapy) for muscle 
strengthening within 4 weeks of Screening or initiation planned during the study. Any exercise program 
or regimen that was initiated >4 weeks prior to Screening must be continued in a stable manner during 
Screening and the study  
9. Patient has had recent serious or ongoing infection, or risk for serious infection, including: 
a. 
Acute or chronic infection defined as any infection requiring systemic antibiotic, antifungal, or 
antiviral (antimicrobial) therapy within 2 weeks of Baseline 
b. Hospitalization or receipt of a course of IV antimicrobial therapy within 24 weeks prior to 
Screening or during the Screening Period 
c. 
Symptomatic herpes zoster or herpes simplex infection (HSV) (not including simple oral HSV 
lesions) within 12 weeks prior to Screening or during the Screening Period  
d. History of severe and/or disseminated viral infections, and/or opportunistic infections 
e. 
Known seropositivity for or active infection by human immunodeficiency virus (HIV) 
f. 
Active, chronic, or resolved hepatitis B or hepatitis C infection (hepatitis B core antibody or 
surface antigen positive, or hepatitis C antibody positive at Screening) 
g. History of progressive multifocal leukoencephalopathy 
h. Active or untreated latent tuberculosis (TB), as suggested by chest radiograph performed within 
the 12 weeks prior to or at Screening (see Section 7.2.6.3) or positive (or 2 indeterminate or 
borderline) results of an approved TB test at Screening (see Section 7.2.6.1). Patients with a 
history of latent TB with documented completed treatment per Centers for Disease Control and 
Prevention guidelines and no known exposures post treatment are allowed to participate 
i. 
Receipt of a live-attenuated vaccine within 4 weeks of Screening 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
Confidential 
Page 10 of 95 
j. 
Primary immunodeficiency (unless otherwise considered, in the opinion of the Investigator or 
the Sponsor, to confer a clinically insignificant infection risk, such as deficiency in 
immunoglobulin A [IgA], C1q, C2, or C4 without a history of recurrent infections [3 or more 
infections in 1 year that required antimicrobial therapy]) 
k. History of recurrent infections [3 or more infections in 1 year that required antimicrobial 
therapy] in the 12 months prior to Baseline 
l. 
Prior hematopoietic cell or solid organ transplant. 
10. History of any concurrent illness (eg, asthma) that has required treatment with oral or parenteral 
corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to Screening 
11. Any of the following laboratory values at Screening: 
a. 
Estimated glomerular filtration rate <45 mL/min by CKD-EPI (Chronic Kidney Disease 
Epidemiology Collaboration) equation 
b. Hemoglobin <10 g/dL 
c. 
White blood cell (WBC) count <3.0 × 109/L 
d. Absolute neutrophil count (ANC) <1.5 × 109/L (1500/mm3) 
e. 
Platelet count <100 × 109/L 
f. 
Serum AST or serum ALT >2.5 × ULN (unless considered consistent with muscle origin) 
g. Serum alkaline phosphatase >2.5 × ULN 
h. Total bilirubin >1.5 × ULN (3 × ULN for patients with documented Gilbert’s syndrome) 
i. 
Thyroid stimulating hormone outside of the central laboratory normal range 
j. 
Immunoglobulin G (IgG) <500 mg/dL. 
12. Presence of New York Heart Association Class III or IV heart failure, or uncontrolled blood pressure 
(systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg at rest), or QT interval 
with Fredericia’s correction (QTcF) or Bazett’s correction (QTcB) >480 msec on ECG 
13. Major surgery within 12 weeks before Screening, major surgery planned during the study period, or any 
surgery planned during the study period that would require an alteration of concomitant 
immunosuppressant or corticosteroid therapy or additional corticosteroid therapy 
14. Clinical evidence of significant unstable or uncontrolled diseases (eg, cardiac [including congestive 
heart failure, hypertension, angina, or recent {<6 months prior to Screening} myocardial infarction], 
pulmonary [including chronic obstructive pulmonary disease, asthma requiring systemic corticosteroid 
therapy, pulmonary hypertension, or interstitial lung disease], hematologic, gastrointestinal, 
endocrinologic [eg, hypothyroidism, diabetes], hepatic, renal, neurological, or infectious) that, in the 
opinion of the Investigator or Sponsor, could confound the results of the study, put the patient at undue 
risk, or interfere with protocol adherence 
15. Evidence of current or previous clinically significant disease, medical condition (including abnormal 
laboratory values), or finding in the medical examination that in the Investigator's or Sponsor’s opinion 
would compromise the safety of the patient or the ability to interpret the data 
16. Any active or suspected malignancy, including myeloproliferative or lymphoproliferative disorder, or 
history of documented malignancy within the last 5 years before Screening or within 3 years of 
diagnosis of myositis, except appropriately excised and cured cervical carcinoma in situ or basal or 
squamous cell carcinoma of the skin; patients with a history of basal or squamous cell carcinomas of the 
skin must have had 3 or fewer in their lifetime to be eligible 
17. Alcohol abuse or drug abuse in the last 1 year prior to Screening in the opinion of the Investigator 
18. Women who are pregnant, lactating, or discontinued lactation less than 12 weeks prior to Screening, or 
who plan to become pregnant or initiate lactation during the study 
19. Patients unable to comply with the protocol in the Investigator's or Sponsor’s opinion. 
STATISTICAL ANALYSIS 
Planned Statistical Analysis 
The Safety Analysis Set consists of all patients who receive at least one dose of study drug. The Full Analysis Set 
(FAS) consists of all patients who received at least one dose of study drug and have a Baseline and post-Baseline 
observation. This is the primary efficacy analysis set for the study. The Per Protocol Analysis Set consists of all 
patients who received at least one dose of KZR-616 and for whom the PK data are considered sufficient. Since 
this is a Phase 2 study, all analyses and summaries will be based on the actual test treatment the respective 
patients received. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
Confidential 
Page 11 of 95 
Efficacy Analysis 
The primary endpoint is mean change from start to end of KZR-616 treatment in TIS.2 For the continuous 
efficacy parameters, within patient changes will be analyzed as follows: 
 
(1: primary) by comparing the Baseline and post-Baseline observations within patients for the KZR-616 
treatment periods combined, ie, W16 versus W0 for patients allocated to the randomized treatment 
sequence KZR-616 followed by placebo and W32 versus W16 for patients allocated to the randomized 
treatment sequence placebo followed by KZR-616, combined; 
 
(2: secondary) by comparing the change from Baseline in Treatment Period 1 between treatments, ie, 
change from W0 to W16 for patients allocated to the randomized treatment sequence KZR-616 followed 
by placebo versus change from W0 to W16 for patients allocated to the randomized treatment sequence 
placebo followed by KZR-616; and 
 
(3: exploratory) by comparing the last response on test treatment between treatments via a crossover 
design analysis, ie, W16 for patients allocated to the randomized treatment sequence KZR-616 followed 
by placebo and W32 for patients allocated to the randomized treatment sequence placebo followed by  
KZR-616, combined, versus W16 for patients allocated to the randomized treatment sequence placebo 
followed by KZR-616 and W32 for patients allocated to the randomized treatment sequence KZR-616 
followed by placebo, combined.  
The rationale for this priority order is as follows. The usual crossover analysis for this design is prespecified as 
exploratory since it is unknown whether that analysis would be confounded by carryover effect. In order to 
maximize the precision for assessment of KZR-616 effect, it is assessed primarily via all patients’ Baseline 
versus post-Baseline KZR-616 assessment and secondarily by the Treatment Period 1 between-treatment 
comparison. Summary statistics, including 95% confidence intervals, will be provided for each treatment for each 
of the 3 types of analysis. Within-patient changes will be analyzed via paired t-tests and corroborated by signed 
rank tests. Between-patient differences will be analyzed via analysis of covariance, with Baseline as a covariate. 
The crossover analysis will be via a mixed model repeated measures analysis. Normality will be assessed 
graphically and via the Shapiro-Wilk statistic. If substantial departure from normality is observed, transformations, 
eg, natural log and rank, will be explored. P values will be 2-sided with the type 1 error level at 0.05. 
Binary endpoints will be summarized by counts and percent and 95% confidence intervals via Clopper-Pearson 
method. Additional analyses will be specified in the Statistical Analysis Plan (SAP). 
Safety Analysis 
The safety analysis set will be used for all presentations of safety endpoints. No statistical testing will be used to 
compare treatment arms for different safety endpoints. Safety data will be summarized descriptively for each test 
treatment. All AEs will be coded using the current version of the Medical Dictionary for Regulatory Activities 
(MedDRA). Treatment emergent AEs will be presented within summary presentations by MedDRA system organ 
class and preferred term, cohort, and treatment arm.  
Pharmacokinetic and Pharmacodynamic Analyses 
Blood samples for assay of KZR-616 plasma concentrations will be collected periodically. The plasma 
concentrations of KZR-616 and its metabolite KZR-59587, and PK parameters will be listed and summarized by 
appropriate summary statistics (eg, geometric means, natural log-scale standard deviation [SD], medians, 
quartiles). Whole blood samples for determination of proteasome activity will be collected periodically and 
processed to washed whole blood and isolated peripheral blood mononuclear cell (PBMC) pellets. 
Chymotrypsin-like (CT-L) activity and proteasome subunit active site occupancy in each compartment will be 
assessed and presented as absolute and predose normalized values. Pharmacodynamic data will be listed for each 
individual and summarized by nominal sampling time point and treatment group with descriptive statistics 
(eg, sample size, arithmetic mean, SD, median, minimum, maximum). 
Sample Size Calculation 
Prior summary statistics on change from Baseline in TIS score are not available. Hence, statistical power is 
quantified via standardized effect size (mean difference divided by pooled SD). A sample size of 24 patients has 
80% power to yield a statistically significant (alpha=0.05 2-sided) improvement from Baseline if the true 
underlying effect size is 0.6 (90% power if true effect size is 0.7). The minimum observed effect size that would 
yield statistical significance is 0.42. This level of statistical precision is thought to be adequate for this initial trial 
of KZR-616 in PM and DM. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 12 of 95 
TABLE OF CONTENTS  
PROTOCOL APPROVAL PAGE .............................................................................................2 
PROTOCOL ACCEPTANCE PAGE ........................................................................................3 
PROTOCOL SYNOPSIS ..........................................................................................................4 
TABLE OF CONTENTS .........................................................................................................12 
LIST OF ABBREVIATIONS ..................................................................................................17 
1. 
BACKGROUND .......................................................................................................22 
1.1. 
Study Diseases and Description of the Population under Study ........................22 
1.1.1. 
Polymyositis .................................................................................................22 
1.1.2. 
Dermatomyositis ..........................................................................................22 
1.2. 
26S Proteasome ..................................................................................................23 
1.3. 
KZR-616 .............................................................................................................23 
1.4. 
Rationale for Use in the Proposed Study Populations ........................................25 
1.5. 
Risk/Benefit Assessment ....................................................................................26 
2. 
STUDY OBJECTIVES AND ENDPOINTS ............................................................28 
2.1. 
Study Objectives ................................................................................................28 
2.1.1. 
Primary Objective ........................................................................................28 
2.1.2. 
Secondary Objectives ...................................................................................28 
2.1.3. 
Exploratory Objectives .................................................................................28 
2.2. 
Study Endpoints .................................................................................................28 
2.2.1. 
Efficacy Endpoints .......................................................................................28 
2.2.2. 
Safety Endpoints ..........................................................................................30 
2.2.3. 
Pharmacokinetic and Pharmacodynamic Endpoints ....................................30 
3. 
STUDY DESIGN ......................................................................................................31 
3.1. 
Type and Design of Study ..................................................................................31 
3.1.1. 
Sequence and Duration of Study Periods .....................................................34 
3.1.2. 
Dose and Regimen Rationale .......................................................................34 
3.1.3. 
Study Design Rationale ................................................................................34 
3.2. 
Minimization of Bias ..........................................................................................34 
3.2.1. 
Randomization .............................................................................................34 
3.2.2. 
Blinding ........................................................................................................35 
3.2.3. 
Breaking the Blind .......................................................................................35 
3.3. 
Number of Sites ..................................................................................................35 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 13 of 95 
4. 
PATIENT SELECTION AND ENROLLMENT ......................................................36 
4.1. 
Number of Patients .............................................................................................36 
4.1.1. 
Patient Screening ..........................................................................................36 
4.2. 
Inclusion Criteria ................................................................................................36 
4.3. 
Exclusion Criteria ...............................................................................................37 
5. 
STUDY DRUG INFORMATION ............................................................................42 
5.1. 
Physical Description of the Study Drugs ...........................................................42 
5.2. 
Packaging and Labeling .....................................................................................42 
5.3. 
Supply, Dispensing, Storage, and Investigational Product Accountability ........42 
6. 
DOSAGE AND STUDY DRUG ADMINISTRATION ...........................................44 
6.1. 
Study Drug Administration ................................................................................44 
6.1.1. 
Dosing Criteria .............................................................................................44 
6.1.2. 
Administrative Site .......................................................................................45 
6.1.3. 
Monitoring of Dose Administration .............................................................45 
6.1.4. 
Dose Modification Guidelines for KZR-616 ...............................................46 
6.1.4.1. 
Dose Reduction ......................................................................................46 
6.1.4.2. 
Missed Doses ..........................................................................................46 
6.2. 
Prior and Concomitant Treatments ....................................................................47 
6.2.1. 
Permitted Concomitant Medications ............................................................47 
6.2.1.1. 
Myositis Disease-related Concomitant Medications ..............................47 
6.2.1.2. 
Other Concomitant Medications ............................................................48 
6.2.1.3. 
Vaccinations ...........................................................................................48 
6.2.2. 
Rescue Therapy ............................................................................................48 
6.2.2.1. 
Nonpharmacologic Therapies.................................................................49 
6.2.3. 
Restricted or Prohibited Therapies ...............................................................49 
6.2.4. 
Other Restrictions and Prohibitions .............................................................50 
7. 
STUDY EVALUATIONS .........................................................................................51 
7.1. 
Schedules of Assessments ..................................................................................51 
7.1.1. 
Unscheduled Visits .......................................................................................51 
7.2. 
Study Procedures and Assessments ....................................................................59 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 14 of 95 
7.2.1. 
Demographic Data ........................................................................................59 
7.2.2. 
PM/DM Classification ..................................................................................59 
7.2.3. 
Medical History ............................................................................................59 
7.2.4. 
Efficacy Assessments ...................................................................................59 
7.2.4.1. 
Total Improvement Score .......................................................................59 
7.2.4.2. 
Manual Muscle Testing-8 Muscle Groups (MMT-8).............................60 
7.2.4.3. 
Myositis Disease Activity Assessment Tool (MDAAT) ........................60 
7.2.4.4. 
Physician Global Assessments of Disease Activity (MDGA) ...............61 
7.2.4.5. 
Physician Global Impression of Change (MDGIC) ...............................61 
7.2.4.6. 
Functional Index-2 (FI-2) .......................................................................61 
7.2.4.7. 
Functional Index-3 (FI-3) .......................................................................62 
7.2.4.8. 
Myositis Damage Index (MDI) ..............................................................62 
7.2.4.9. 
Cutaneous Dermatomyositis Disease Area and Severity Index 
(CDASI) .................................................................................................62 
7.2.4.10. 
Muscle Enzymes ....................................................................................63 
7.2.5. 
Patient Reported Outcome Assessments ......................................................63 
7.2.5.1. 
Patient Global Assessment of Disease Activity (PtGADA) ...................63 
7.2.5.2. 
Health Assessment Questionnaire-Disability Index (HAQ-DI) .............63 
7.2.5.3. 
Patient Global Impression of Change (PGIC) ........................................64 
7.2.5.4. 
Patient Reported Outcomes Measurement Information System 
29-item Short Form Profile Version 2.1 (PROMIS-29) .........................64 
7.2.5.5. 
EuroQoL 5-dimension 5-level (EQ-5D-5L) ...........................................64 
7.2.5.6. 
Healthcare Resource Utilization (HRU) ................................................65 
7.2.5.7. 
Patient Global Assessment of Disease Damage (PtGADD) ..................65 
7.2.5.8. 
Peak Pruritus Numeric Rating Scale ......................................................65 
7.2.5.9. 
Treatment Satisfaction Questionnaire for Medication Version II 
(TSQM) ..................................................................................................66 
7.2.6. 
Safety Assessments ......................................................................................66 
7.2.6.1. 
Tuberculosis ...........................................................................................66 
7.2.6.2. 
Viral Serology ........................................................................................67 
7.2.6.3. 
Chest Radiograph ...................................................................................67 
7.2.6.4. 
Follicle Stimulating Hormone and Pregnancy .......................................67 
7.2.6.5. 
Coagulation, Thyroid, and Antiphospholipid Antibodies ......................67 
7.2.6.6. 
Physical Examination .............................................................................67 
7.2.6.7. 
Vital Sign Measurements .......................................................................68 
7.2.6.8. 
Weight and Height .................................................................................68 
7.2.6.9. 
Electrocardiogram ..................................................................................68 
7.2.6.10. 
Clinical Laboratory Tests .......................................................................68 
7.2.6.11. 
Hematology and Erythrocyte Sedimentation Rate .................................69 
7.2.6.12. 
Clinical Chemistry, C-Reactive Protein, and Aldolase ..........................69 
7.2.6.13. 
Urinalysis ...............................................................................................70 
7.2.6.14. 
Immunoglobulins ...................................................................................70 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 15 of 95 
7.2.6.15. 
CD19 Count ............................................................................................70 
7.2.7. 
Pharmacokinetic Assessments ......................................................................71 
7.2.8. 
Pharmacodynamic Assessments ...................................................................71 
7.2.9. 
Exploratory Biomarkers ...............................................................................71 
7.2.9.1. 
Cytokines, Proteomics, and Leukocyte Subsets .....................................71 
7.2.9.2. 
Autoantibodies .......................................................................................71 
7.2.9.3. 
Pharmacogenomics/Gene Expression ....................................................72 
7.2.9.4. 
Biopsy .....................................................................................................72 
8. 
STUDY DISCONTINUATION ................................................................................73 
8.1. 
Individual and Study Stopping Rules for Safety ................................................73 
8.1.1. 
Study Stopping Rules ...................................................................................73 
8.1.2. 
Individual Patient Stopping Rules ................................................................73 
8.2. 
Early Withdrawal of Patients from the Study ....................................................73 
8.3. 
Termination or Suspension of the Study ............................................................74 
9. 
ADVERSE EVENTS ................................................................................................75 
9.1. 
Adverse Event Reporting ...................................................................................75 
9.1.1. 
Definition of an Adverse Event ....................................................................75 
9.1.2. 
Assessment of Severity ................................................................................75 
9.1.3. 
Assessment of Causality ...............................................................................75 
9.1.4. 
Action Taken ................................................................................................76 
9.1.5. 
Follow-up on Adverse Events ......................................................................76 
9.1.6. 
Documentation and Reporting of Adverse Events .......................................76 
9.2. 
Serious Adverse Events ......................................................................................77 
9.2.1. 
Serious Adverse Event Definition ................................................................77 
9.2.2. 
Serious Adverse Event Reporting and Documentation Requirements .........77 
9.3. 
Pregnancy Reporting ..........................................................................................78 
9.4. 
New or Worsening Disease Manifestations .......................................................79 
9.5. 
Adverse Events of Special Interest .....................................................................79 
9.5.1. 
Systemic Injection Reactions .......................................................................79 
9.5.2. 
Thrombotic Microangiopathy ......................................................................79 
9.6. 
Unexpected Adverse Reactions ..........................................................................79 
9.6.1. 
Unexpected Adverse Reaction Definition ....................................................79 
9.7. 
Data Monitoring Committee ..............................................................................80 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 16 of 95 
10. 
STATISTICAL ANALYSES ....................................................................................81 
10.1. 
Sample Size Calculation .....................................................................................81 
10.2. 
Analysis Populations ..........................................................................................81 
10.3. 
Efficacy Analysis ...............................................................................................81 
10.4. 
Safety Analysis ...................................................................................................82 
10.5. 
Pharmacokinetic and Pharmacodynamic Analyses ............................................82 
11. 
ETHICAL AND ADMINISTRATIVE CONSIDERATIONS .................................84 
11.1. 
Compliance Statement ........................................................................................84 
11.2. 
Institutional Review Board or Independent Ethics Committee ..........................84 
11.3. 
Informed Consent and Human Patient Protection ..............................................84 
11.4. 
Direct Access to Source Data, Source Documents, and Study Reports .............85 
11.5. 
Data Collection and Handling ............................................................................85 
11.6. 
Confidentiality ....................................................................................................85 
11.7. 
Financing and Insurance .....................................................................................86 
11.8. 
Audit and Inspection ..........................................................................................86 
11.9. 
Monitoring ..........................................................................................................86 
11.10. 
Data Management and Coding ...........................................................................86 
11.11. 
Reporting and Publication, Including Archiving ...............................................87 
12. 
REFERENCES ..........................................................................................................88 
13. 
APPENDICES ...........................................................................................................93 
Appendix A: Recommended Cancer Screenings .....................................................................93 
Appendix B: Potentially Clinically Significantly Abnormal Laboratory Values ....................95 
 
LIST OF TABLES 
Table 1 
Study Drug Administration ..............................................................................44 
Table 2 
Schedule of Assessments for Screening and Treatment Period 1 ....................52 
Table 3 
Schedule of Assessments for the Study Drug Administration Visits 
during Treatment Period 1 ...............................................................................55 
Table 4 
Schedule of Assessments for Treatment Period 2 and Safety Follow-up ........56 
Table 5 
Schedule of Assessments for the Study Drug Administration Visits 
during Treatment Period 2 ...............................................................................58 
Table 6 
Hematology Tests ............................................................................................69 
Table 7 
Clinical Chemistry, Aldolase, and C-Reactive Protein Tests ..........................70 
 
LIST OF FIGURES 
Figure 1 
Study Design Schema ......................................................................................33 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 18 of 95 
ELISA 
enzyme-linked immunosorbent assay 
EMG 
electromyography 
EQ-5D-5L 
EuroQoL 5-dimension 5-level 
ESR 
erythrocyte sedimentation rate 
ETV 
Early Termination Visit 
EULAR 
European League Against Rheumatism 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
FI 
Functional Index 
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
gamma glutamyltransferase 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
HAQ-DI 
Health Assessment Questionnaire-Disability Index 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen 
HMG-CoA 
3-hydroxy-3-methylglutaryl-coenzyme A 
HRU 
Healthcare Resource Utilization 
HSV 
herpes simplex virus 
HUS 
hemolytic uremic syndrome 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IFN 
interferon 
Ig 
immunoglobulin 
IL 
interleukin 
IM 
intramuscular 
IMACS 
International Myositis Assessment and Clinical Studies Group 
IND 
Investigational New Drug 
IRB 
Institutional Review Board 
ISR 
injection site reaction 
IV 
intravenous 
IVIg 
intravenous immunoglobulin 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 19 of 95 
LDH 
lactate dehydrogenase 
LEF 
leflunomide 
LLN 
lower limit of normal 
LMP 
low-molecular mass polypeptide 
MCH 
mean cell hemoglobin 
MCHC 
mean cell hemoglobin concentration 
MCV 
mean cell volume 
MDAAT 
Myositis Disease Activity Assessment Tool 
MDGA 
Physician Global Assessment 
MDGIC 
Physician Global Impression of Change 
MDI 
Myositis Damage Index 
MECL-1 
multicatalytic endopeptidase complex-like 1 
MedDRA 
Medical Dictionary for Regulatory Activities 
Mg 
magnesium 
MHC 
major histocompatibility complex 
MITAX 
Myositis Intention to Treat Activity Index 
MMF 
mycophenolate mofetil 
MMT-8 
Manual Muscle Testing-8 Muscle Groups 
MPS 
mycophenolate sodium 
MRI 
magnetic resonance imaging 
MTX 
methotrexate 
N 
sample size 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NOAEL 
no observed adverse effect level 
NSAID 
nonsteroidal anti-inflammatory drug 
NRS 
Numeric Rating Scale 
PBMC 
peripheral blood mononuclear cell 
PD 
pharmacodynamic 
PGIC 
Patient Global Impression of Change 
P-gp 
P-glycoprotein 
PK 
pharmacokinetic 
PM 
polymyositis 
ProCISE 
proteasome constitutive/immunoproteasome subunit ELISA 
PROM 
patient reported outcome measures 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 20 of 95 
PROMIS-29 
Patient Reported Outcomes Measurement Information System 29-item Short 
Form Profile Version 2.1 
PtGADA 
Patient Global Assessments of Disease Activity 
PtGADD 
Patient Global Assessment of Disease Damage 
QTcB 
QT interval with Bazett’s correction 
QTcF 
QT interval with Fredericia’s correction 
RA 
rheumatoid arthritis 
RBC 
red blood cell 
RNA 
ribonucleic acid 
RTSM 
Randomization and Trial Supply Management system 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SC 
subcutaneous 
SD 
standard deviation 
SFU 
Safety Follow-up 
SLE 
systemic lupus erythematosus 
STS 
sit-to-stand 
SUSAR 
suspected unexpected serious adverse reactions 
TB 
tuberculosis 
TEAE 
treatment emergent adverse event 
Th 
T helper cell 
TIS 
Total Improvement Score 
TMA 
thrombotic microangiopathy 
Tmax 
time to maximum concentration 
TNFα 
tumor necrosis factor alpha 
Treg 
regulatory T cell 
TSQM 
Treatment Satisfaction Questionnaire for Medication Version II 
TTP 
thrombotic thrombocytopenic purpura 
TUG 
timed up and go 
ULN 
upper limit of normal 
US 
United States 
VAS 
visual analog scale 
W 
Week 
WBC 
white blood cell 
WFI 
water for injection 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 21 of 95 
WHO 
World Health Organization 
WOCBP 
women of childbearing potential 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 22 of 95 
1. BACKGROUND 
1.1. 
Study Diseases and Description of the Population under Study 
1.1.1. 
Polymyositis 
Polymyositis (PM) is an inflammatory autoimmune myopathy that affects striated muscle 
with a subacute onset of a few weeks to months15 and affects adults over 18 years of age. The 
estimated incidence of PM in the United States (US) ranges from 2.5 to 3.8 cases per 100,000 
person-years, with the peak incidence occurring in those 65 years of age and over.19,46 It 
presents with symmetrical weakness of the proximal muscles, sparing the facial and eye 
muscles. Muscle weakness manifests as difficulty in climbing steps, rising from a chair, 
lifting objects, and combing hair.12,16 The diagnosis of PM is based on history and physical 
examinations, which are confirmed by laboratory examination. Laboratory findings include 
elevated serum levels of muscle associated enzymes (eg, creatine kinase [CK], aldolase, 
lactate dehydrogenase [LDH]), electromyography (EMG) consistent with myopathy,16,34 and 
muscle biopsy demonstrating primary inflammation with the presence of cluster of 
differentiation (CD)8+ lymphocytes invading muscle fibers expressing major 
histocompatibility complex (MHC) class I antigens and the absence of vacuoles. Myositis 
specific and myositis associated antibodies, eg, anti-Jo-1 or anti-SSA, present in about 60% 
of patients, may help to confirm the diagnosis.14 
Although the exact etiology of PM is not yet fully understood, several risk factors have been 
associated with disease pathogenesis. Genetic risk factors include human leukocyte antigen 
(HLA) alleles found on chromosome 6 (HLA-DQA1*0501 and HLA-DRB1*0301) and 
polymorphisms in tumor necrosis factor alpha (TNFα). Environmental risk factors that have 
been implicated comprise infectious agents including vaccinations, medications 
(eg, penicillamine, 3-hydroxy-3-methylglutaryl-coenzyme A [HMG-CoA] reductase 
inhibitors), and occupational exposures (eg, silica).12 
The aim of treatment for PM is to suppress inflammation, increase muscle strength, and 
prevent long-term damage to muscles and extramuscular organs.12 Initial treatment includes 
high doses of systemic corticosteroids such as prednisone; intravenous (IV) 
methylprednisolone may be required in severe cases. With improvement, the dose can be 
tapered to reach an adequate maintenance dose. Immunosuppressive agents such as 
methotrexate (MTX) and azathioprine (AZA) alone or in combination may be added to the 
drug regimen when there is poor response to corticosteroids. Other drugs that may be 
considered include mycophenolate mofetil (MMF), cyclophosphamide (CYC), rituximab, or 
IV immunoglobulin (Ig).12 Physical therapy is recommended to maintain a full range of joint 
movement. Scoring systems may be used to assess improvement, stability or deterioration in 
symptoms and can help guide therapeutic choices.12 
1.1.2. 
Dermatomyositis 
Dermatomyositis (DM) is a multifactorial, chronic autoimmune disorder distinguished by 
inflammation involving the muscle and the skin. Dermatomyositis affects both children 
(juvenile DM) and adults. Although some overlap between disease characteristics exist, adult 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 23 of 95 
and juvenile DM are separate entities with variable features. Adult DM is most often 
observed over age 40 years.43 The estimated incidence of adult DM in the US is 
approximately 1.5 cases per 100,000 person-years.19,46  
Proximal symmetrical skeletal muscle weakness is the most common feature of DM. Skin 
involvement may present concurrently with, precede, or postdate myositis, and a small 
percentage of patients never develop myositis. Other organ systems may be involved 
including blood vessels, joints, esophagus, lungs, and heart.43 Up to 40% of patients may 
develop interstitial lung disease, which may be associated with rapidly progressive 
pulmonary failure and death.43 Several factors have been implicated in the disease 
pathogenesis, including genetic, environmental, and immune mediated factors.43 A small 
percentage of patients with DM have been reported to have a concomitant diagnosis of 
another connective tissue disorder, particularly scleroderma.16,49 
Treating DM is difficult because it affects multiple organ systems and has a variable clinical 
presentation. Systemic corticosteroids, particularly prednisone, are considered first-line 
therapy. However, since long-term corticosteroid therapy can be associated with several 
adverse effects, an immunosuppressive agent (eg, MTX, cyclosporine [CyA], AZA, or 
MMF) is often introduced early during disease management. Antimalarials such as 
hydroxychloroquine and chloroquine may be effective but carry a cumulative risk of ocular 
toxicity with prolonged use and are associated with exacerbation of cutaneous symptoms in 
about one-third of patients. High-dose IV Ig (IVIg) has proved beneficial for refractory cases 
in the short term. Rituximab has been shown to improve muscle strength but has mixed 
results in controlling skin disease. Other therapies for skin disease include avoiding sun 
exposure and use of topical corticosteroids.9,43 
1.2. 
26S Proteasome 
The 26S proteasome is a ubiquitously expressed protein complex responsible for the 
homeostatic control of protein turnover and regulated degradation of proteins involved in 
most cellular functions.11,13,51 The proteasome exists in 2 forms, the constitutive proteasome 
and the immunoproteasome. The immunoproteasome is expressed primarily in hematopoietic 
cells (eg, lymphocytes and monocytes) and is induced in cytokine-exposed  
nonhematopoietic cells.21,35,37 In the immunoproteasome, low-molecular mass polypeptide 7 
(LMP7), LMP2, and multicatalytic endopeptidase complex-like 1 (MECL-1) replace β5, β1, 
and β2, respectively. The LMP7 subunit has a similar substrate preference as β5 and is, thus, 
referred to as the chymotrypsin-like (CT-L) subunit of the immunoproteasome. 
The proteasome has been validated as a therapeutic drug target through regulatory approval 
of the 3 nonselective proteasome inhibitors, bortezomib (VELCADE®), carfilzomib 
(KYPROLIS®), and ixazomib (NINLARO®), for use in the treatment of the plasma cell 
neoplasm, multiple myeloma. 
1.3. 
KZR-616 
KZR-616 is a tripeptide ketoepoxide-based selective inhibitor of the immunoproteasome. 
The nonselective proteasome inhibitors, such as bortezomib, carfilzomib, and ixazomib, are 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 24 of 95 
cytotoxic and equipotent inhibitors of the 2 forms of proteasomes found in cells, namely the 
constitutive proteasome and the immunoproteasome.30,31 Selective inhibitors of the 
immunoproteasome such as KZR-616 have no cytotoxic potential.39 
In vitro, KZR-616 demonstrates potent and selective inhibition of the LMP7 subunit of the 
immunoproteasome and can target multiple subunits of the immunoproteasome. Inhibition of 
immunoproteasome active site subunits by KZR-616 occurs through an irreversible 
mechanism, similar to that for carfilzomib 7,26. Peptide ketoepoxides show no off-target 
activity,5,31 and KZR-616 has been found to exhibit no activity in a broad diversity panel of 
biochemical assays that included 110 receptor/ligand and enzyme assays. 
The safety of KZR-616 has been demonstrated in Good Laboratory Practice (GLP)-
compliant toxicity studies in rats, rabbits, and monkeys. In repeat dose studies, KZR-616 was 
administered by subcutaneous (SC) injection once weekly for 13 consecutive weeks in rats 
and monkeys and for 26 consecutive weeks in rats. For both species, KZR-616 was well 
tolerated at doses expected to result in potent and selective inhibition of the 
immunoproteasome. In rats, the target organs identified at the no observed adverse effect 
level (NOAEL) were mostly similar between animals dosed for 13 or 26 weeks. Injection site 
reactions (ISRs) were noted in both species at the NOAEL. Lymphoid depletion in lymph 
nodes, thymus, and spleen were noted in rats only; however, none of these findings were 
considered adverse due to the low magnitude and severity. In rats, higher doses of KZR-616, 
including those that resulted in mortality, induced potent inhibition of both proteasome types, 
a profile equivalent to carfilzomib. It should be noted that in rats, administration of 
carfilzomib and bortezomib induced mortality in rats at doses ~20% and 30% below the 
labeled dose and administration for each compound respectively.17,38 This suggests that rats 
are significantly more sensitive to dual proteasome inhibition than humans.  
The safety, pharmacokinetics (PK), and proteasome inhibition level of KZR-616 has been 
studied in healthy volunteers in a Phase 1 trial, KZR-616-001. Subcutaneous administration 
of KZR-616 was well tolerated at doses of 30 mg and 45 mg, which resulted in potent and 
selective inhibition of the immunoproteasome. Adverse events (AEs) were generally mild 
and transient and were predominantly ISRs. Following 4 weeks of treatment with KZR-616, 
there were no clinically significant laboratory abnormalities that are commonly seen with the 
dual-targeting proteasome inhibitors. Subcutaneous administration of KZR-616 resulted in 
consistent, dose-proportional PK and pharmacodynamics (PD). At all dose levels, KZR-616 
was rapidly absorbed and cleared with no accumulation following weekly repeat doses with 
dose-dependent inhibition of peripheral blood mononuclear cell (PBMC) CT-L activity 
(predominantly immunoproteasome). At doses of ≥30 mg, mean inhibition of PBMC CT-L 
activity 4 hours postdose exceeded 80% with significant but not complete recovery within 
6 days of dosing. Mean inhibition of whole blood CT-L activity (predominantly constitutive 
proteasome) was less than 43% for all doses. No difference in the level of 
immunoproteasome inhibition was seen after the fourth weekly dose relative to the first dose 
suggesting that there is no accumulation of proteasome inhibition. From a PK and PD 
perspective, weekly SC administration of KZR-616 is tantamount to serial episodic dosing. 
Ongoing studies include KZR-616-002, “A Phase 1b/2 Study of KZR-616 in Patients with 
Systemic Lupus Erythematosus (SLE) with and without Nephritis.”; and Study  

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 25 of 95 
KZR-616-004, “A Phase 1, Randomized, Double-Blind, Placebo Controlled, Single and 
Multiple Ascending Dose Study to Evaluate the Safety, Tolerability and Pharmacokinetics of 
KZR-616 in Healthy Female Subjects”. No reportable data are yet available for Study 
KZR-616-004. In Study KZR-616-002, as of 31 January 2019, weekly administration of 
KZR-616 up to 45 mg (Cohort 1) for 13 weeks was well tolerated in patients with active 
SLE. For this cohort, treatment emergent AEs (TEAEs) predominantly consisted of ISRs that 
were mild. There were no moderate or severe AEs or serious adverse events (SAEs) reported 
for the cohort. All 3 patients who discontinued the study were due to withdrawal of consent. 
In patients who received an initial dose of 60 mg of KZR-616, all 5 patients who were 
enrolled reported some combination of Grade 1 or Grade 2 AEs of nausea, vomiting, 
dizziness, or chills that started approximately 8 to 24 hours after receiving their first 
injection. One patient who received a second dose of 60 mg had recurrent nausea and 
vomiting starting at approximately 8 hours and resolved by approximately 24 hours. These 
AEs were similar to those encompassed by the preferred term of adverse drug reaction 
reported for the 60 mg dose in the KZR-616-001 study. Preliminary analysis of the 
laboratory data, vital signs, and ECG data for both cohorts demonstrated no concerning 
trends. To see if 60 mg is a dose at which KZR-616 could be administered routinely, a third 
cohort (Cohort 2a) is being enrolled to receive a step up dosing regimen of KZR-616 (30 mg, 
then 45 mg, then 60 mg) to potentially tolerize patients to receiving higher doses of 
KZR-616.  
In Study KZR-616-002, 2 SAEs have been reported to date in the open-label Phase 1b 
portion of the study: 1 event of thrombotic microangiopathy (TMA) (Cohort 2, 60 mg) and 
1 event of shingles (localized herpes zoster) (Cohort 2a, post receipt of 2 doses of 30 mg and 
1 dose of 45 mg). While both events may have been related to the patient’s underlying 
condition of SLE or other risk factors present, causality cannot be ruled out, especially as 
these events have also been reported to occur with the nonspecific proteasome inhibitors.  
Please refer to the Investigator’s Brochure (IB) for further information on KZR-616. 
1.4. 
Rationale for Use in the Proposed Study Populations 
Idiopathic inflammatory myopathies such as PM are characterized by inflammatory 
infiltrates in the skeletal muscle. Innate and adaptive immune mechanisms (eg, macrophages, 
autoreactive lymphocytes, autoantibodies, pro-inflammatory cytokine production) as well as 
intrinsic defects in skeletal muscle contribute to muscle weakness and damage in myositis. 
For example, regulatory T cells (Treg) are considered instrumental for healing via 
interactions with muscle stem cells, whereas accumulation of CD4+ and CD8+ 
T lymphocytes are associated with further immune-mediated injury as occurs in 
inflammatory myositis and some muscular dystrophies.44 The immunoproteasome has also 
been shown to be upregulated in the muscle of patients with PM and DM and the skin in 
patients with DM.8,20 Further, increased levels of circulating proteasomes, likely reflecting 
immunoproteasomes, have been observed in patients with inflammatory myositis and appear 
to be associated with disease markers such as CK and myoglobin levels.18  
In vitro, KZR-616 and other immunoproteasome inhibitors block cytokine production across 
multiple immune cell types, reduce the activity of inflammatory T helper (Th) cell subsets, 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 26 of 95 
increase the number of Tregs, and block plasma cell formation and autoantibody 
production.27,28,36 KZR-616 does not induce cytotoxicity in vitro, has demonstrated promising 
therapeutic activity in animal models of rheumatoid arthritis (RA) and SLE/lupus nephritis, 
and has a favorable safety profile in healthy volunteers. Because of these characteristics, 
KZR-616 represents a new agent with a novel mechanism of action that may have broad 
therapeutic potential across autoimmune conditions, including PM and DM. As patients exist 
who have an inadequate response to currently available treatments, unmet medical need 
remains for new therapies for the treatment of PM and DM. 
1.5. 
Risk/Benefit Assessment 
The safety profile of KZR-616, a selective and irreversible inhibitor of the 
immunoproteasome, is distinct from dual proteasome inhibitors, such as carfilzomib and 
bortezomib, which induce thrombocytopenia, anemia, and neutropenia within 1 month of 
dosing10,25 and are associated with constitutional toxicities such as prolonged fatigue, 
myalgia, and gastrointestinal toxicities. 
Adverse events most often associated with KZR-616 treatment at doses of 30 mg and 45 mg 
are ISRs that are transient, generally mild, and do not appear to increase in severity or 
frequency with repeat dosing. All healthy volunteers and most patients who received repeat 
doses of ≥30 mg experienced ISRs. At higher doses (ie, 60 mg), AEs included transient rash 
and an event with the preferred term adverse drug reaction in healthy volunteers and nausea, 
vomiting, chills, headache and dizziness in patients with SLE. These AEs were similar to the 
dermatomyositsequelae of events associated with infusion reactions seen with carfilzomib. In 
healthy volunteers in cohorts evaluating doses of 30 mg and/or 45 mg, which utilized 
prophylactic antihistamine and corticosteroids and/or intrasubject dose escalation, and that 
achieved similar levels of exposure and target inhibition, AEs of adverse drug reaction were 
not reported. Similarly, transient AEs of nausea, vomiting, headache, chills, and dizziness 
each were seen in 25% or less of the patients with active SLE receiving 45 mg. 
Aside from the 2 SAEs reported with preferred term of adverse drug reaction in healthy 
volunteers in Study KZR-616-001, there have been 2 related SAEs, each in 1 patient, 
reported in ongoing Study KZR-616-002 of KZR-616 in patients with active SLE. The SAEs 
of TMA and shingles, while both potentially attributable to the patients’ underlying condition 
of SLE and other risk factors that were present, have also been described in the prescribing 
information of 1 or more of the nonselective proteasome inhibitors. 
Thorough monitoring and assessment of all AEs will be performed in this study, and safety 
assessments according to the protocol will include physical examination, vital sign 
measurements, electrocardiograms (ECGs), and clinical laboratory tests. Guidance is 
provided to monitor for TMA, and occurrence of such an event will be reported as an AE of 
special interest (AESI) and trigger a prompt review of safety data by the Data Monitoring 
Committee (DMC). In addition, related to herpes zoster, patients who have had a recent 
episode of herpes zoster will be excluded, and vaccinations are recommended to be up to 
date. Patients who discontinue KZR-616, whether or not prematurely, will be monitored for 
worsening of disease and may receive rescue therapy as clinically appropriate. Generally, 
safety data will be reviewed and recommendations regarding protocol conduct will be made 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 27 of 95 
by a DMC comprising a participating Investigator, a Medical Monitor, and a Kezar 
representative or designee. Supportive measures, such as IV or oral hydration, diuresis, 
transfusions, growth factor support, and/or prophylactic antimicrobials will be recommended 
to be considered when clinically appropriate.  
Based on nonclinical studies with KZR-616 and the safety of KZR-616 at 45 mg in healthy 
volunteers, the potential benefit from anti-inflammatory activity induced by 
immunoproteasome inhibition may include an improvement in patients with PM and DM. 
These benefits are anticipated to outweigh the known risks of associated with KZR-616 
administration to date.  
Refer to the IB for further guidance regarding the risks and potential toxicities of KZR-616, 
which are based on current clinical trial data, nonclinical toxicology studies conducted in 
rodents and monkeys, as well as known safety risks of currently marketed proteasome 
inhibitors. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 28 of 95 
2. STUDY OBJECTIVES AND ENDPOINTS  
2.1. 
Study Objectives 
2.1.1. 
Primary Objective 
 Evaluate the efficacy of KZR-616 in patients with PM or DM. 
2.1.2. 
Secondary Objectives 
 Evaluate the safety and tolerability of KZR-616 in patients with PM or DM 
 Evaluate the PK of KZR-616 in patients with PM or DM. 
2.1.3. 
Exploratory Objectives 
 Evaluate biomarkers related to efficacy and safety of KZR-616 in patients with PM or 
DM 
 Evaluate the PK and PD relationship of KZR-616 in patients with PM or DM. 
2.2. 
Study Endpoints 
2.2.1. 
Efficacy Endpoints 
The primary efficacy endpoint is: 
 Mean change from start to end of KZR-616 treatment in the Total Improvement Score 
(TIS), which ranges from 0 to 100. 
Secondary efficacy endpoints are: 
 Proportion of patients with an increase ≥20 points on the TIS from start to end of  
KZR-616 treatment. The categories and ranges of scores for improvement are:  
20-39 points being minimal improvement, 40-59 points being moderate improvement, 
and ≥60 points being major improvement 
 Proportion of patients from start to end of KZR-616 treatment meeting International 
Myositis Assessment and Clinical Studies Group (IMACS) Definition of Improvement 
(DOI). The IMACS DOI is ≥20% improvement in at least 3 of 6 core set activity 
measures, with no more than 2 core set activity measures (CSAMs) worsening by 
≥25% (the Manual Muscle Testing-8 Muscle Groups [MMT-8] cannot be a worsening 
measure) 
 Absolute change and percent change from start to end of KZR-616 treatment in the 
IMACS individual CSAMs 
 For patients with DM, the mean change from start to end of KZR-616 treatment in the 
Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) 
 For patients with DM, the mean change from start to end of KZR-616 treatment in the 
Peak Pruritus Numeric Rating Scale (NRS). 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 29 of 95 
Exploratory efficacy endpoints are: 
 Mean change over time from start to end of KZR-616 treatment in the TIS in all patients, 
patients with DM only, and in patients with PM only 
 Proportion of patients over time with an increase of ≥20, ≥40, or ≥60 points on the TIS 
from start to end of KZR-616 treatment in all patients, in patients with DM only, and in 
patients with PM only 
 For patients with an increase of ≥20 points on the TIS from Baseline to W16, the 
proportion of patients with no change or increase in their TIS at W32 for all patients, in 
patients with DM only, and in patients with PM only 
 Mean change and mean percent change over time from start to end of KZR-616 treatment 
in the IMACS individual CSAMs and core set damage measures (CSDMs) for all 
patients, in patients with DM only, and in patients with PM only 
 Mean change from Baseline over time from start to end of KZR-616 treatment in the  
FI-2, the FI-3 and the individual components of the FI-3 for all patients, in patients with 
DM only, and in patients with PM only 
 For patients with DM, mean change over time from start to end of KZR-616 treatment in 
the CDASI 
 For patients with DM, the proportion over time with ≥7 points improvement in the 
CDASI from start to end of KZR-616 treatment 
 For patients with DM, the mean change over time from start to end of KZR-616 treatment 
in the Peak Pruritus NRS 
 Mean change over time from start to end of KZR-616 treatment in the individual domains 
of the Patient Reported Outcomes Measurement Information System 29-item Short Form 
Profile Version 2.1 (PROMIS-29) for all patients, in patients with DM only, and in 
patients with PM only 
 Mean change over time in Treatment Satisfaction Questionnaire for Medication 
Version II (TSQM) from start to end of KZR-616 treatment for all patients, in patients 
with DM only, and in patients with PM only 
 The change in quality of life over time from start to end of KZR-616 treatment as 
measured by the EuroQoL 5-dimension 5-level (EQ-5D-5L) for all patients, in patients 
with DM only, and in patients with PM only 
 Healthcare Resource Utilization (HRU) over time from start to end of KZR-616 treatment 
for all patients, in patients with DM only, and in patients with PM only 
 Physician Global Impression of Change (MDGIC) over time from start to end of  
KZR-616 treatment for all patients, in patients with DM only, and in patients with PM 
only 
 Patient Global Impression of Change (PGIC) over time from start to end of KZR-616 
treatment for all patients, in patients with DM only, and in patients with PM only. 
Note: The primary analysis period is from start to end of KZR-616 treatment for both 
sequence arms combined. A secondary analysis comparing KZR-616 to parallel placebo will 
be confined to the Baseline to Week 16 period. Lastly, the usual crossover analysis 
comparing placebo to KZR-616 will be carried out as an exploratory analysis approach. The 
rationale for this priority order is as follows. The usual crossover analysis for this design is 
prespecified as exploratory since it is unknown whether that analysis would be confounded 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 30 of 95 
by carryover effect. In order to maximize the precision for assessment of KZR-616 effect, it 
is assessed primarily via all patients’ start to end of KZR-616 treatment, and secondarily by 
the Treatment Period 1 between-treatment comparison. 
2.2.2. 
Safety Endpoints 
Safety endpoints are: 
 Incidence, nature, and severity of AEs 
 Incidence, nature, and severity of SAEs 
 Incidence and severity of infection-related AEs and SAEs 
 Incidence and severity of AEs with onset within 24 hours from the start of dosing with 
any study drug 
 Incidence of AEs leading to study drug discontinuation 
 Changes in standard laboratory parameters, vital signs, and ECGs. 
2.2.3. 
Pharmacokinetic and Pharmacodynamic Endpoints 
The secondary PK endpoint will: 
 Evaluate the plasma PK parameters for KZR-616 and its metabolite KZR-59587. 
The exploratory PK/PD endpoints will: 
 Evaluate the relationships between KZR-616 PK, clinical efficacy, clinical safety, and 
various PD endpoints including proteasome inhibition and changes in circulating 
cytokine and immune cell profiles 
 Evaluate the relationships between KZR-616 PK, clinical efficacy, clinical safety, and 
various PD endpoints related to skin and muscle biopsy histology and gene expression 
profiles. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 31 of 95 
3. STUDY DESIGN  
3.1. 
Type and Design of Study 
This is a Phase 2 randomized, double-blind, placebo-controlled, crossover, multicenter study 
designed to evaluate the safety, tolerability, efficacy, PK, and PD of treatment with KZR-616 
in patients with active PM or DM.  
Patients will be evaluated for eligibility during the Screening Period. Eligible patients will be 
allocated in a 1:1 fashion to a randomized treatment arm (Arm A or Arm B). Patients will be 
stratified by their diagnosis of PM or DM.  
During the 32-week treatment period, patients will receive study drug SC once weekly. The 
16 weeks of dosing during Treatment Period 1 begins at Week (W) 0 and continues through 
W15 (ie, ends immediately before dosing at Week 16 [approximately Day 113]); patients 
allocated to Arm A will receive KZR-616 and those in Arm B will receive placebo. The 
16 weeks of dosing during Treatment Period 2 begins with administration of the first dose at 
W16 and continues through W31 (ie, ends immediately before Week 32); patients allocated 
to Arm A will receive placebo and those in Arm B will receive KZR-616.  
This study will be conducted on an outpatient basis. Study visits will occur at Screening, W0, 
W4, W8, W12, W16, W20, W24, W28, W32, W36, and W40. Day 1 of W0 will be defined as 
Baseline. The W36 and W40 visits will comprise the Safety Follow-up (SFU). 
Randomized patients who withdraw from the study prior to W32 will be requested to 
undergo the Early Termination Visit (ETV) procedures, and all patients who withdraw 
prematurely also will be requested to return for a SFU visit 9 weeks (W40 visit procedures) 
after receipt of their last dose of the study drug.  
Efficacy assessments will be performed for all patients, unless indicated otherwise, and will 
include:  
 IMACS core set Activity and Damage measures  
o MMT-8 
o Physician Global Assessment (MDGA) 
o Patient Global Assessments of Disease Activity (PtGADA) 
o Health Assessment Questionnaire-Disability Index (HAQ-DI) 
o Muscle enzymes (clinical laboratory assessments): CK, aldolase, LDH, alanine 
aminotransferase (ALT), and aspartate aminotransferase (AST) 
o Myositis Disease Activity Assessment Tool (MDAAT, 2005 version) 
o Myositis Damage Index (MDI) 
o Patient Global Assessment of Disease Damage (PtGADD). 
 Functional Index-2 (FI-2, performed for the dominant side only). 
 Functional Index-3 (FI-3) assessments: 
o 30-second chair stand test 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
Confidential 
Page 32 of 95 
o
Timed up and go test
o
6-minute walk distance.

MDGIC

CDASI, performed only for patients with DM.
Additional patient reported outcome measures (PROMs) will be performed by all patients, 
unless indicated otherwise, and will include: 

PROMIS-29

EQ-5D-5L

HRU

TSQM

PGIC

Peak Pruritus NRS, performed only by patients with DM.
Safety will be assessed throughout the study by monitoring of vital signs (blood pressure, 
pulse rate, temperature, and respiration rate), laboratory tests (hematology, chemistry, 
urinalysis, immunoglobulins), ECGs, and physical exams; and by recording and analyzing all 
AEs and SAEs.  
Biopsies will be collected from a subset of enrolled patients; skin biopsies will be performed 
only for selected patients with DM, and muscle biopsies will be performed for selected 
patients with PM or DM. For selected patients, biopsies will be collected from skin and/or 
muscle at Baseline, W16, and optionally at W32. The tissue samples will be used for 
exploratory investigations of treatment-related changes and regulation of inflammatory 
pathways. Complete instructions for the collection and processing of biopsy samples will be 
included in the Laboratory Manual. 
The study design schema is presented in Figure 1. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 33 of 95 
Figure 1 
Study Design Schema 
 
Screening 
Double-Blind Treatment Perioda 
Safety Follow-up 
Adult patients 
with active 
PM or DM 
Arm A (N = 12) 
Arm B (N = 12) 
KZR-616  
SC once weeklyb 
Treatment Period 1 
W0 to W16 
Treatment Period 2 
W16 to W32 
Days -28 to -1 
KZR-616  
SC once weeklyb 
Placebo 
SC once weekly  
Placebo 
SC once weekly  
W16 
Endpoint 
a 
Treatment Period 1 is from Day 1 of Week 0 and continues until immediately before dosing at Week 16 (approximately Day 113). Treatment Period 2 begins with administration of the first dose at 
Week 16 and continues through Week 32. 
b 
In Treatment Periods 1 and 2, KZR-616 30 mg will be administered for the first 2 doses of each treatment period followed by administration of KZR-616 45 mg for the remaining 14 doses of each 
Treatment Period. 
Day 1, W0 
Randomization 
(1:1) 
W32 
Endpoint 
W40 
End of Study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 34 of 95 
3.1.1. 
Sequence and Duration of Study Periods 
The study comprises a 4-week Screening Period, a 32-week Treatment Period divided into 
two 16-week periods, and an 8-week SFU.  
Individual patients will participate for approximately 44 weeks, inclusive of the Screening 
and SFU Periods. 
3.1.2. 
Dose and Regimen Rationale 
The planned doses of KZR-616 for administration in this study are 30 and 45 mg SC once 
weekly for 16 consecutive weeks; 30 mg doses will be administered the first 2 weeks (ie, the 
first 2 doses of the Treatment Period) followed by administration of 45 mg doses for the 
remaining 14 weeks of the Treatment Period.  
In a Phase 1 study in healthy volunteers and a Phase 1b study in SLE patients, weekly SC 
administration of 45 mg was determined to be tolerated and resulted in potent and selective 
inhibition of the immunoproteasome. Anticipated levels of exposure with KZR-616 45 mg 
SC once weekly are lower than those achieved at the NOAEL for rats and monkeys. The 
profile of immunoproteasome inhibition at this dose correlated with anti-inflammatory 
activity in nonclinical models at the minimally efficacious dose.  
The duration of dosing per treatment period will be 16 weeks. This is to allow adequate time 
to detect a change in muscle strength while minimizing the time patients spend on placebo. 
3.1.3. 
Study Design Rationale 
This placebo-controlled double-blind crossover study is designed to minimize bias in the 
evaluation of KZR-616 in patients with DM/PM and to maximize the opportunity for each 
patient to contribute data. All patients may still receive background treatment in the form of 
the allowed concomitant therapies as described in the study exclusion criteria (Section 4.3). 
A crossover design was selected for use in this study to: 
 Increase the power of the study because not only will there be the opportunity for 
evaluation of between-group comparisons, but the patients initially treated with placebo 
can serve as their own controls  
 Data for bortezomib allude to maintenance of effect of proteasome inhibition postdosing.3 
The Treatment and SFU Periods allow for evaluation of the treated population after drug 
discontinuation in terms of both safety and efficacy; these data are best obtained from 
those patients that start on KZR-616 first and then cross over to placebo. 
3.2. 
Minimization of Bias 
3.2.1. 
Randomization 
Patients will be allocated to a randomized treatment sequence (Arm A: KZR-616 followed by 
placebo; Arm B: placebo followed by KZR-616) in a 1:1 fashion. Patients will receive the 
first assigned study drug treatment in Treatment Period 1 (W0 through before dosing at W16) 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 35 of 95 
and cross over to receive the next study drug treatment beginning on the first day of 
Treatment Period 2 (administration of the first dose at W16 through W32). Patients will be 
stratified according to their diagnosis of PM or DM. Patients will be stratified by their 
diagnosis of DM or PM. 
3.2.2. 
Blinding 
This is a double-blind study. The Sponsor, Investigator, study personnel, and patients will not 
make any efforts to determine which study drug is being received. Unblinded pharmacy (or 
other qualified site) personnel will be utilized in this study to prepare the study drug, and 
unblinded study personnel (eg, Clinical Pharmacologist required for conducting any PK 
analyses and Statistician) may be utilized in this study. 
3.2.3. 
Breaking the Blind 
If the treatment allocation for a patient becomes known to the Investigator or other study staff 
involved in the management of study patients, the Sponsor must be notified immediately by 
the Investigator.   
Patients should not be routinely unblinded to treatment assignment. Only in the case of an 
emergency, when knowledge of the study drug is essential for the clinical management or 
welfare of a specific patient, may the Investigator unblind a patient’s treatment assignment. 
The unblinding of the patient’s treatment assignment can be completed through the use of the 
electronic data capture (EDC) Randomization and Trial Supply Management (RTSM) system 
to determine treatment and institute appropriate follow-up care. However, prior to any 
unblinding, the Investigator is strongly advised to discuss options with the Medical Monitor 
or appropriate Sponsor study personnel. As soon as possible and without revealing the 
patient’s study treatment assignment (unless important to the safety of patients remaining in 
the study), the Investigator must notify the Sponsor if the blind is broken for any reason. The 
Investigator will record in source documentation the date and reason for unblinding and the 
names and roles of personnel unblinded. The reason for unblinding will be captured directly 
within the EDC system prior to the unblinding as well. The EDC system will automatically 
store the date and time of the unblinding.   
All unblinding events (with the exception of those by pharmacovigilance for regulatory 
reporting purposes) must be reported to the Sponsor’s Medical Monitor and designee 
promptly. 
Patients who have been unblinded for pharmacovigilance reporting purposes only will not, 
based on the unblinding alone, be discontinued from further receipt of investigational 
product.  
3.3. 
Number of Sites 
Up to approximately 18 sites are planned to participate in this study. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 36 of 95 
4. PATIENT SELECTION AND ENROLLMENT 
4.1. 
Number of Patients 
Approximately 24 patients are planned for enrollment. It is anticipated that 40 patients will 
be screened to achieve 24 patients enrolled. 
4.1.1. 
Patient Screening 
Study participation begins once written informed consent is obtained (see Section 11.3 for 
details). The Investigator will ensure that the patient has provided written informed consent 
before performing any study-related assessments. 
Once informed consent is obtained, a sequential patient identification number will be 
assigned by the site, and the screening evaluations may begin to assess study eligibility 
(inclusion/exclusion) criteria. The patient identification number will be used to identify the 
patient during the screening process and throughout study participation, if applicable. 
Screening assessments (see the Schedule of Assessments [Table 2]) for this study should be 
performed between Day -28 and Day -1. The Screening Period can be extended to 35 days 
upon Sponsor or designee approval only. Patients who fail Screening or do not meet 
inclusion/exclusion criteria may be rescreened 1 time. 
Only individuals who fulfill all of the inclusion criteria and none of the exclusion criteria 
may be enrolled into the study. Data collected at Screening will be reviewed by the Sponsor, 
designee(s), or adjudication committee (as defined in the Study Manual) to confirm 
eligibility, of the patient to be enrolled. 
4.2. 
Inclusion Criteria 
1. Adult patients must be at least 18 years of age at the time of signing informed consent 
at Screening 
2. Body Mass Index (BMI) of 18 to 40 kg/m2 
3. Diagnosis of probable or definite DM or PM by the 2017 European League Against 
Rheumatism (EULAR)/American College of Rheumatology (ACR) Classification 
Criteria 
4. Must have their data reviewed by an adjudication committee to confirm eligibility 
unless at least 1 of the following is present: 
a. Muscle biopsy with evidence of active myositis within the last 6 months prior to 
or at Screening 
b. Electromyography or magnetic resonance imaging (MRI) with evidence of active 
myositis within the last 6 months prior to Screening 
c. A CK ≥4 × upper limit of normal (ULN). 
5. Must have demonstrable muscle weakness as measured by the MMT-8 with a score 
≥80/150 but ≤136/150 units and any 2 of the following: 
a. MDGA visual analog scale (VAS) ≥2 cm 
b. PtGADA VAS ≥2 cm 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 37 of 95 
c. At least one muscle enzyme laboratory measurement (ie, CK, aldolase, LDH) 
≥1.3 × ULN 
d. MDAAT Extramuscular Global Activity VAS ≥1 cm. 
6. Documented inadequate response to a 12-week trial of corticosteroids or at least 
1 immunosuppressant (eg, MTX, MMF, mycophenolate sodium [MPS], AZA, 
leflunomide [LEF], tacrolimus, CyA) OR have demonstrated significant documented 
toxicity or intolerance to such therapies 
7. Has had age-appropriate cancer screening that is up to date and negative for evidence 
of malignancy as per local standard of care (see Appendix A) 
8. Female patients of childbearing potential must have a negative serum pregnancy test 
at Screening and a negative urine pregnancy test at Baseline and must agree to 
employ adequate birth control measures for the duration of the study. 
Women of childbearing potential (WOCBP) must use highly effective and medically 
acceptable methods of contraception to prevent pregnancy during Screening and must 
agree to continue to practice adequate contraception during the study and for 4 weeks 
after administration of the last dose of the study drug. 
For the purposes of this study, WOCBP are defined as: all postpubescent female 
patients, unless the patient is postmenopausal (defined by amenorrhea for at least 
2 years or amenorrhea for at least 1 year with confirmatory follicle stimulating 
hormone [FSH] level in the postmenopausal range as documented historically or 
measured by the central laboratory at Screening and if patient is not on supplementary 
hormonal therapy) or if the patient is surgically sterile (ie, tubal ligation, 
hysterectomy, bilateral salpingoophorectomy). 
Highly effective contraception is defined as the use of 2 barrier methods (eg, female 
diaphragm and male condom), 1 barrier method with spermicide, intrauterine device, 
or hormonal contraceptives (eg, implant or oral). If using a hormonal form of 
contraception, use must have been stable for at least 4 weeks prior to Screening, and 
if using concomitant mycophenolate, the patient must use another nonhormonal form 
of highly effective contraception. Abstinence will be acceptable only if it is in line 
with the preferred and usual lifestyle of the patient. Periodic abstinence (eg, calendar, 
ovulation) and withdrawal are not acceptable methods of contraception 
9. Male patients must be either congenitally sterile surgically sterile (vasectomy with 
documented confirmation of aspermia) or willing to use a condom in addition to 
having their female partner use another form of contraception (such as an intrauterine 
device, barrier method with spermicide, or hormonal contraceptive [eg, implant, 
injectable, patch, or oral]) from Screening until 12 weeks after administration of the 
last dose of the study drug, unless their partners are infertile or surgically sterile 
10. Willing and able to comply with the requirements of the protocol 
11. Provide written informed consent prior to any study-related procedure. 
4.3. 
Exclusion Criteria 
1. Has significant muscle damage (eg, severe muscle atrophy, end-stage disease, 
postmyopathic DM) per Investigator opinion or has a muscle damage VAS score 
≥5 cm on the MDI 
2. Any other form of myositis or myopathy other than PM or DM (eg, metabolic or 
drug-induced myopathy, drug-induced myositis, juvenile PM or DM, inclusion body 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 38 of 95 
myositis, cancer-associated myositis [myositis diagnosed within 3 years, either before 
or after, of a diagnosis of any malignancy except for squamous or basal cell 
carcinoma of the skin or cervical carcinoma in situ], myositis in overlap with another 
connective disease [eg, SLE, systemic sclerosis, RA], or muscular dystrophy); 
patients with secondary Sjogren’s syndrome, necrotizing myopathy, or antisynthetase 
syndrome are permitted to participate in this study 
3. Any condition (eg, severe arthritis with limited range of motion or severe calcinosis) 
that, in the Investigator’s opinion, precludes the ability to quantitate muscle strength 
4. Has severe interstitial lung disease per Investigator opinion or has a pulmonary 
damage VAS score ≥5 cm on the MDI 
5. Presence of autoinflammatory disease (eg, psoriatic arthritis, axial 
spondyloarthropathy, inflammatory bowel disease) 
6. Has received treatment with any of the following: 
a. Oral prednisone (or prednisone equivalent) doses >20 mg/day at Screening or 
during the Screening Period, or initiation of oral prednisone during the Screening 
Period. If oral prednisone is being used at Screening, use should be stable during 
the 2 weeks prior to Baseline 
b. Use of nonsteroidal immunosuppressants other than oral MMF or MPS (≤3 g/day 
or 2160 mg/day, respectively); oral, intramuscular (IM), or SC MTX 
(≤25 mg/week); AZA (≤2.5 mg/kg/day); LEF (≤20 mg/day); tacrolimus 
(≤3 g/day); or concurrent use of more than 1 nonsteroidal immunosuppressant at 
Baseline. If a permitted nonsteroidal immunosuppressant is being used, it must 
have used for at least 12 weeks and must have been taken at a stable dose 
(including stable route of administration) for the last 4 weeks prior to Screening. 
If MMF, MPS, MTX, AZA, LEF, or tacrolimus is being discontinued, it must be 
discontinued at least 4 weeks prior to Baseline 
c. Antimalarials exceeding the recommended doses (hydroxychloroquine up to 
400 mg/day or 6.5mg/kg/day, whichever is less; chloroquine up to 250 mg/day, or 
quinacrine up to 100 mg/day are permitted) or taken at an unstable dose during 
the 12 weeks prior to Screening. If an antimalarial is being discontinued, it must 
be discontinued at least 4 weeks prior to Baseline. Antimalarials are considered 
distinct from corticosteroids in (a) and nonsteroidal immunosuppressants in (b) 
above 
d. Initiation of or use of an unstable dose of topical therapy (eg, corticosteroids, 
pimecrolimus) in the 4 weeks prior to Screening. If topical therapy is being 
discontinued, it must be discontinued at least 4 weeks prior to Baseline. 
7. Receipt of any of the following treatments within the following time frames before 
Screening: 
a. Oral corticosteroids at doses ≥1 mg/kg/day prednisone or equivalent: 4 weeks 
b. Intravenous or IM corticosteroids: 4 weeks 
c. Intra-articular therapies, such as corticosteroids or hyaluronic acid preparations: 
4 weeks 
d. Intravenous, SC, or IM Ig: 4 weeks 
e. Cyclophosphamide or chlorambucil: 24 weeks 
f. Prohibited nonbiologic nonsteroidal immunosuppressants or targeted therapies 
including, but not limited to, CyA, dapsone, tofacitinib, baricitinib: 8 weeks 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 39 of 95 
g. Cytokine or integrin antagonists or selective costimulation modulators including, 
but not limited to, interleukin (IL)-1, IL-6, IL-17, IL-12/23, IL-23, interferon 
(IFN), integrin, and tumor necrosis factor (TNF)α antagonists or abatacept: 
12 weeks 
h. B cell-depleting or modulating therapies (eg, rituximab, ofatumumab, 
obinutuzumab, ocrelizumab, belimumab, atacicept): 24 weeks  
For those patients who have used an anti-CD20 drug at ≥24 weeks and <48 weeks 
before Screening, they must have levels of circulating CD19+ B cells ≥the lower 
limit of normal (LLN). A CD19 count is not required for patients with prior use of 
an anti-CD20 drug ≥48 weeks prior to Screening 
i. Previous treatment with the following cell-depleting therapies, including 
investigational agents or approved therapies: alemtuzumab, anti-CD4, anti-CD5, 
or anti-CD3: at any time 
j. Other biologics or investigational drugs: 8 weeks or 5 half-lives, whichever is 
longer 
k. Transfusion with blood, packed red blood cells, or platelets or treatment with 
plasmapheresis or plasma exchange: 6 weeks 
l. Creatine dietary supplements: 4 weeks. 
8. Initiation of an exercise program (including physical therapy or occupational therapy) 
for muscle strengthening within 4 weeks of Screening or initiation planned during the 
study. Any exercise program or regimen that was initiated >4 weeks prior to 
Screening must be continued in a stable manner during Screening and the study 
9. Patient has had recent serious or ongoing infection, or risk for serious infection, 
including: 
a. Acute or chronic infection defined as any infection requiring systemic antibiotic, 
antifungal, or antiviral (antimicrobial) therapy within 2 weeks of Baseline 
b. Hospitalization or receipt of a course of IV antimicrobial therapy within 24 weeks 
prior to Screening or during the Screening Period 
c. Symptomatic herpes zoster or herpes simplex infection (HSV) (not including 
simple oral HSV lesions) within 12 weeks prior to Screening or during the 
Screening Period 
d. History of severe and/or disseminated viral infections, and/or opportunistic 
infections 
e. Known seropositivity for or active infection by human immunodeficiency virus 
(HIV) 
f. Active, chronic, or resolved hepatitis B or hepatitis C infection (hepatitis B core 
antibody or surface antigen positive, or hepatitis C antibody positive at Screening) 
g. History of progressive multifocal leukoencephalopathy 
h. Active or untreated latent tuberculosis (TB), as suggested by chest radiograph 
performed within the 12 weeks prior to or at Screening (see Section 7.2.6.3) or 
positive (or 2 indeterminate or borderline) results of an approved TB test at 
Screening (see Section 7.2.6.1). Patients with a history of latent TB with 
documented completed treatment per Centers for Disease Control and Prevention 
guidelines and no known exposures post treatment are allowed to participate 
i. Receipt of a live-attenuated vaccine within 4 weeks of Screening 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 40 of 95 
j. Primary immunodeficiency (unless otherwise considered, in the opinion of the 
Investigator or the Sponsor, to confer a clinically insignificant infection risk, such 
as deficiency in IgA, C1q, C2, or C4 without a history of recurrent infections [3 or 
more infections in 1 year that required antimicrobial therapy]) 
k. History of recurrent infections [3 or more infections in 1 year that required 
antimicrobial therapy] in the 12 months prior to Baseline 
l. Prior hematopoietic cell or solid organ transplant. 
10. History of any concurrent illness (eg, asthma) that has required treatment with oral or 
parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks 
prior to Screening 
11. Any of the following laboratory values at Screening: 
a. Estimated glomerular filtration rate <45 mL/min by CKD-EPI (Chronic Kidney 
Disease Epidemiology Collaboration) equation 
b. Hemoglobin <10 g/dL 
c. White blood cell (WBC) count <3.0 × 109/L 
d. Absolute neutrophil count (ANC) <1.5 × 109/L (1500/mm3) 
e. Platelet count <100 × 109/L 
f. Serum AST or serum ALT >2.5 × ULN (unless considered consistent with muscle 
origin) 
g. Serum alkaline phosphatase >2.5 × ULN 
h. Total bilirubin >1.5 × ULN (3 × ULN for patients with documented Gilbert’s 
syndrome) 
i. Thyroid stimulating hormone outside of the central laboratory normal range 
j. IgG <500 mg/dL. 
12. Presence of New York Heart Association Class III or IV heart failure, or uncontrolled 
blood pressure (systolic blood pressure ≥160 mm Hg or diastolic blood pressure 
≥100 mm Hg at rest), or QT interval with Fredericia’s correction (QTcF) or Bazett’s 
correction (QTcB) >480 msec on ECG 
13. Major surgery within 12 weeks before Screening, major surgery planned during the 
study period, or any surgery planned during the study period that would require an 
alteration of concomitant immunosuppressant or corticosteroid therapy or additional 
corticosteroid therapy 
14. Clinical evidence of significant unstable or uncontrolled diseases (eg, cardiac 
[including congestive heart failure, hypertension, angina, or recent {<6 months prior 
to Screening} myocardial infarction], pulmonary [including chronic obstructive 
pulmonary disease, asthma requiring systemic corticosteroid therapy, pulmonary 
hypertension, or interstitial lung disease], hematologic, gastrointestinal, 
endocrinologic [eg, hypothyroidism, diabetes], hepatic, renal, neurological, or 
infectious) that, in the opinion of the Investigator or Sponsor, could confound the 
results of the study, put the patient at undue risk, or interfere with protocol adherence 
15. Evidence of current or previous clinically significant disease, medical condition 
(including abnormal laboratory values), or finding in the medical examination that in 
the Investigator's or Sponsor’s opinion would compromise the safety of the patient or 
the ability to interpret the data 
16. Any active or suspected malignancy, including myeloproliferative or 
lymphoproliferative disorder, or history of documented malignancy within the last 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 41 of 95 
5 years before Screening or within 3 years of diagnosis of myositis, except 
appropriately excised and cured cervical carcinoma in situ or basal or squamous cell 
carcinoma of the skin; patients with a history of basal or squamous cell carcinomas of 
the skin must have had 3 or fewer in their lifetime to be eligible 
17. Alcohol abuse or drug abuse in the last 1 year prior to Screening in the opinion of the 
Investigator 
18. Women who are pregnant, lactating, or discontinued lactation less than 12 weeks 
prior to Screening, or women who plan to become pregnant or initiate lactation during 
the study 
19. Patients who are unable to comply with the protocol in the Investigator's or Sponsor’s 
opinion. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 42 of 95 
5. STUDY DRUG INFORMATION 
Instructions for the receipt, inspection, storage, preparation, administration, and disposal of 
KZR-616 are to be provided in a separate Pharmacy Manual at each clinical site. 
5.1. 
Physical Description of the Study Drugs 
KZR-616 Lyophile, 125 mg/vial, is supplied as a refrigerated lyophilized drug product 
containing 125 mg of KZR-616 (150 mg of KZR-616 maleate) and 
 
(inactive excipient) in single use 3.0-mL borosilicate glass vial. Each vial is reconstituted 
with sterile water for injection (WFI) prior to administration.  
Placebo will be sterile WFI and will be supplied by the individual clinical sites.  
5.2. 
Packaging and Labeling 
The lyophilized drug product will be supplied in 3-mL single-use vials packaged in multivial 
cartons. 
The Sponsor or its representatives will be responsible for labeling according to local 
regulatory requirements.  
All packaging and labeling operations will be performed according to Good Manufacturing 
Practice (GMP) for Medicinal Products and the relevant regulatory requirements. 
5.3. 
Supply, Dispensing, Storage, and Investigational Product Accountability  
The Sponsor or its representatives will supply KZR-616 Lyophile to the investigational site. 
The study drug supplies provided for this study will be manufactured under current GMP, 
will be subject to release, and will be suitable for human use. 
Only participants enrolled in the study may receive study drug and only authorized staff may 
supply or administer study drug.  
KZR-616 Lyophile must be stored in a refrigerator at 2°C to 8°C. Reconstituted study drug 
can be stored until use in a refrigerator (recommended) controlled at 2°C to 8°C for a 
maximum of 24 hours or at room temperature at 15°C to 30°C for a maximum of 4 hours, or 
until use, whichever occurs first. All study drug should be stored in an environmentally 
controlled and monitored (manual or automated) area in accordance with the labeled storage 
conditions. Access to study drug must be limited to the Investigator and authorized study 
personnel. 
Further information of the storage, preparation, and administration of study drug will be 
provided in a Pharmacy Manual. 
On receipt of the study drug, the Investigator (or designee) will conduct an inventory of the 
supplies and verify that study drug supplies are received intact and in the correct amounts. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 43 of 95 
The study monitor may check the study supplies at each study center at any time during the 
study. 
The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance (such 
as receipt, reconciliation and final disposition records).  
It is the responsibility of the study monitor to ensure that the Investigator (or designee) has 
correctly documented the amount of the study drug received, dispensed, and returned on the 
dispensing log that will be provided. A full drug accountability log will be maintained at the 
study center at all times. The study monitor will perform an inventory of study drug at the 
closeout visit to the study center. All discrepancies must be accounted for and documented. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 45 of 95 
6.1.2. 
Administrative Site 
A different SC injection site should be used for each administration. Injection sites should be 
rotated (eg, 4 abdominal quadrants, posterior upper arms, anterior thighs), and a minimum of 
4 weeks should separate injections to the same site. 
6.1.3. 
Monitoring of Dose Administration 
Systemic injection reactions have been observed with KZR-616 and other proteasome 
inhibitors; the following guidance is based on these known experiences45,23 and may be 
modified as clinical experience with KZR-616 evolves and matures. 
In KZR-616-001, 4 of 12 healthy volunteer subjects who received 60 mg KZR-616 SC 
experienced AEs with the preferred term of adverse drug reaction; consisting of hypotension, 
tachycardia, nausea, vomiting, rigors, and/or chills, associated with an acute phase-like 
response, including leukocytosis and elevated C-reactive protein (CRP), which occurred 
approximately 8 to 12 hours after dosing. These events are similar to the infusion-related 
reactions observed with the currently marketed proteasome inhibitor carfilzomib, which 
generally occur in the first cycle of dosing. 
Systemic injection reactions with other proteasome inhibitors include a number of signs and 
symptoms, including fever, chills, myalgia, facial swelling or flushing, vomiting, weakness, 
hypotension, chest tightness, and shortness of breath, as well as abnormalities in laboratory 
values (eg, creatinine, transaminases). However, the relative roles of the immunoproteasome 
versus constitutive proteasomes to these specific events are not known. The individual 
signs/symptoms of systemic injection reactions must be reported as AESIs within 24 hours 
using the AE electronic case report form (eCRF) (refer to Section 9.5.1). 
With other proteasome inhibitors, prophylactic measures such as predose hydration and  
low-dose dexamethasone (4 mg) reduce the incidence and severity of infusion-related 
reactions. Therefore, upon the development of signs and/or symptoms suggestive of a 
systemic drug reaction, the following interventions are suggested: 
 Supportive measures, including the administration of oral and/or IV fluids, 
antiemetics, acetaminophen, antihistamines and/or systemic corticosteroids 
(eg, prednisone 25 mg – equivalent to 4 mg of dexamethasone) 
 Collection of serum and/or plasma samples for analysis of potentially elevated levels 
of eg, cytokines, histamines 
 For patients who develop signs and/or symptoms that may be consistent with a 
cardiac etiology (eg, hypo- or hypertension, tachycardia, arrhythmia, or abnormal 
cardiac enzymes), the following should be obtained to rule out cardiac toxicity which 
has been described with proteasome inhibitors: 
o Serial ECGs, cardiac enzymes (eg, CK-MB, troponins, B-type natriuretic 
peptide [BNP]) to rule out myocardial infarction 
o Echocardiogram, unless heart failure can otherwise be ruled out by the 
preceding investigations. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
Confidential 
Page 46 of 95 

Prophylactic measures may be considered at the time of the first dose, or with
subsequent doses if signs and/or symptoms consistent with a systemic drug reaction
develop, including:
o
Fluid hydration, eg, 30 mL/kg orally at least 48 hours prior to dosing; and/or
250 to 500 mL IV after dosing if symptoms are present
o
Antiemetics, acetaminophen, and antihistamines
o
Systemic corticosteroids (eg, dexamethasone 4 mg or prednisone 25 mg) prior
to subsequent doses. Use of systemic corticosteroids for prophylaxis should be
discussed in advance with the Medical Monitor as their use could confound
efficacy assessments.
6.1.4. 
Dose Modification Guidelines for KZR-616 
6.1.4.1. 
Dose Reduction 
Patients who experience a KZR-616-related AE are permitted to undergo dose reduction of 
KZR-616 in a blinded manner for subsequent doses at the discretion of the Investigator or 
upon recommendation by the DMC as per Section 8.1.2; written Medical Monitor approval 
must be obtained in advance of implementing dose reduction. Any dose modifications should 
be documented in the eCRF as per Section 9.1.4. Patients must continue to fulfill the Dosing 
Criteria in Section 6.1.1 prior to each dose. After dose reduction is implemented, patients 
who are currently on treatment with KZR-616 will remain on 30 mg throughout the relevant 
Treatment Period if the dose reduction occurs at W1 (Treatment Period 1) or W17 (Treatment 
Period 2); they will have their dose reduced to 30 mg from 45 mg if the dose reduction 
occurs at or after W2 (Treatment Period 1) or W18 (Treatment Period 2). Once the dose has 
been reduced, it will remain at the reduced dose level only for the duration of the Period 
during which the dose was reduced. 
6.1.4.2. 
Missed Doses 
Doses should be administered within the visit windows as per the Schedules of Assessments 
(Section 7.1). Any doses administered outside of the visit window will be considered a 
protocol deviation, but if necessary to avoid missing a dose, doses can be administered up to 
3 days from the date of scheduled administration per Section 7.1 with a minimum of 4 days 
required between doses. 
Patients who do not fulfill Dosing Criteria (Section 6.1.1) or who meet Individual Patient 
Stopping Rules (Section 8.1.2) may miss up to 2 consecutive doses, or patients may miss up 
to 4 total doses for any reason (eg, AE, scheduling, emergency). Upon resumption of dosing, 
subsequent doses should be timed according to the original dosing schedule based on Day 1. 
If more than 2 consecutive doses or more than 4 total doses were missed, then the patient 
should be discussed with the Medical Monitor to evaluate if KZR-616 should be 
discontinued. Any dose modifications should be discussed with the Medical Monitor and 
documented in the eCRF as per Section 9.1.4. Patients who are discontinued for missed doses 
should have their discontinuation per Section 8.2 recorded in the eCRF based on the reason 
the doses were missed, eg, AE, protocol noncompliance. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 47 of 95 
If study medication is permanently discontinued due to an AE, the planned assessments 
(see Schedule of Assessments) should continue for the protocol specified time period. 
6.2. 
Prior and Concomitant Treatments 
Any concomitant therapies must be recorded on the eCRF. A concomitant therapy is any 
therapy that may be used, eg, transfusions, physical therapy, surgery, medication. A 
concomitant medication is any prescription or over-the-counter preparation, including 
vitamins and supplements. Except as described below, prior and concomitant medication use 
will be recorded for the 60 days prior to screening until the last follow-up visit. Details to be 
recorded include, but are not limited to, the concomitant medication generic name, dose, 
route, frequency of administration, and indication. Prior to study initiation, the Sponsor will 
specify which version of the drug dictionary is to be used. 
All prior DM/PM medications (eg, corticosteroids, immunosuppressants, antimalarials, 
biologics) regardless of time frame of use will be recorded.  
Background medication(s) will not be provided by the Sponsor unless required by local 
legislation. 
6.2.1. 
Permitted Concomitant Medications 
6.2.1.1. 
Myositis Disease-related Concomitant Medications 
Patients should continue all concomitant medications related to myositis therapy throughout 
the study, as outlined in the Inclusion/Exclusion Criteria (Section 4.2 and Section 4.3) at a 
stable dose, without modification throughout the study, unless there is documented toxicity, 
intolerability, or lack of availability. No new immunomodulatory therapies, including 
investigational agents, are permitted to be introduced during the study. If a concomitant 
treatment for myositis needs to be decreased or discontinued for safety reasons, the reason 
must be documented in the eCRF and should be discussed with the Medical Monitor (and 
discussed in advance where possible). 
The permitted medications for myositis include the use of the following:  
 Oral prednisone (or prednisone equivalent) dose ≤20 mg/day. If used, it must have been 
present at Screening, used at a stable dose for the 2 weeks prior to Baseline. 
 The use of a maximum of 1 of the following immunosuppressants is allowed:  
o Oral MMF or MPS (≤3 g/day or 2160 mg/day, respectively) 
o Oral, IM, or SC MTX (≤25 mg/week) 
o Oral AZA (≤2.5 mg/kg/day) 
o LEF (≤20 mg/day) 
o Tacrolimus (≤3 g/day). 
If a permitted immunosuppressant is being used, it must have used for at least 12 weeks and 
must have been taken at a stable dose (including stable route of administration) for the last 
4 weeks prior to Screening. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 48 of 95 
 The use of the following antimalarials is allowed if present at a stable dose for at least 
12 weeks prior to Screening: 
o Hydroxychloroquine up to 400 mg/day or 6.5 mg/kg/day, whichever is less 
o Chloroquine up to 250 mg/day 
o Quinacrine up to 100 mg/day. 
 Continued use of a stable dose of topical therapy (eg, corticosteroids, pimecrolimus) is 
allowed. 
6.2.1.2. 
Other Concomitant Medications 
Hormonal contraception is allowed; if used by a WOCBP, it should be used and have been 
stable as described in Section 4.2 and continued for the duration of the study. If hormonal 
contraception is discontinued for safety reasons, the Investigator should ensure that the 
patient is using another acceptable form of contraception. 
Other concomitant therapies for comorbid conditions, such as antihypertensives or lipid 
lowering agents, are permitted. The patient should be advised to maintain a stable dosage 
regimen for lipid lowering agents (such as statins) and nonsteroidal anti-inflammatory drugs 
(NSAIDs) unless dosage adjustment is clinically necessary.  
KZR-616 is a substrate of the P-glycoprotein (P-gp) transporter. Given the rapid clearance of 
the drug (half-life <2 hours), it is unlikely that inhibitors of P-gp will affect drug exposure. 
However, no formal interaction studies with P-gp inhibitors have been performed. Therefore, 
KZR-616 should be administered at least 4 hours after drugs that are known inhibitors of  
P-gp (eg, atorvastatin, azithromycin, colchicine, omeprazole).  
6.2.1.3. 
Vaccinations 
It is strongly recommended that patients be up-to-date on immunizations per the Centers for 
Disease control (https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html) or current 
2015 American College of Rheumatology guidelines for RA. Vaccinations received at any 
time documenting that the patient is up to date on vaccines should be recorded in the eCRF. 
Note: Patients who received a live-attenuated vaccine within 4 weeks of Screening will be 
excluded from participation in the study as per Section 4.3. 
6.2.2. Rescue Therapy 
Rescue therapy is defined as any modification to the background DM or PM treatment, 
including dose or frequency increases of concomitant medications or initiation of a new 
medication. Rescue medications may include, but are not limited to IVIg, topical calcineurin 
inhibitors, systemic corticosteroids, or nonsteroidal immunosuppressants. While 
rescue therapy is typically restricted or prohibited therapy per protocol (Section 6.2.3), 
patients may receive rescue therapy during the study at the discretion of the Investigator 
when deemed medically necessary for the safety of the patient, eg, hospitalization for 
worsening DM or PM.  

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 49 of 95 
If an Investigator determines that a patient needs rescue therapy, the Medical Monitor should 
be informed; where possible, a discussion should occur between the Investigator and Medical 
Monitor prior to implementation of the rescue therapy. 
Any rescue medications administered should be recorded in the eCRF under concomitant 
medications. Patients who receive rescue therapy may continue in the study upon Medical 
Monitor approval but will be considered nonresponders from the timepoint of receipt or 
rescue therapy forward (as per Section 6.2). 
6.2.2.1. 
Nonpharmacologic Therapies 
Patients who are receiving physical or occupational therapy or exercising should have had a 
stable treatment or exercise regimen for at least 4 weeks prior to Screening as per Section 4.3 
and remain on a stable regimen throughout the duration of the study. A regimen should not be 
initiated during the study. 
6.2.3. 
Restricted or Prohibited Therapies 
Use of the following is prohibited during the study and as described in Section 4.3: 
 Oral prednisone (or prednisone equivalent) doses >20 mg/day 
 Intravenous or IM corticosteroids 
 Initiation of IV, SC, or IM Ig 
 Immunosuppressants (other than as presented in Section 6.2.1) 
 Antimalarials at doses that exceed the recommended dose (see Section 6.2.1) 
 Topical therapy (other than as presented in Section 6.2.1) 
 Intra-articular therapy (eg, corticosteroids or hyaluronic acid preparations) 
 Cyclophosphamide or chlorambucil 
 Nonbiologic immunosuppressants or targeted therapies including, but not limited to, 
CyA, dapsone, tofacitinib, baricitinib 
 Cytokine or integrin antagonists or selective costimulation modulators including, but not 
limited to, IL-1, IL-6, IL-17, IL-12/23, IL-23, IFN, integrin, and TNFα antagonists or 
abatacept 
 B cell-depleting or modulating therapies (eg, rituximab, ofatumumab, obinutuzumab, 
ocrelizumab, belimumab, atacicept) 
 Cell-depleting therapies, including investigational agents or approved therapies, 
alemtuzumab, anti-CD4, anti-CD5, or anti-CD3 
 Any other biologics or investigational drug(s) 
 Transfusion with blood, packed red blood cells, or platelets or treatment with 
plasmapheresis or plasma exchange 
 Creatine dietary supplements 
 Live-attenuated vaccines 
 Major surgery during the study period, or any surgery planned during the study period 
that would require an alteration of concomitant immunosuppressant or corticosteroid 
therapy or additional corticosteroid therapy. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 50 of 95 
6.2.4. 
Other Restrictions and Prohibitions 
Participants should not donate blood or blood products during the study and continuing 
through 4 weeks after administration of the last dose of the study drug. Female participants 
should not donate eggs during the study and continuing through 4 weeks after administration 
of the last dose of the study drug. Male participants should not donate sperm during the study 
and continuing through 12 weeks after administration of the last dose of the study drug. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
Confidential 
Page 51 of 95 
7. STUDY EVALUATIONS
7.1. 
Schedules of Assessments 
The Schedule of Assessments for Screening and Treatment Period 1 is presented in Table 2 
and the Schedule of Assessments for the study drug administration visits during Treatment 
Period 1 is presented in Table 3. 
The Schedule of Assessments for Treatment Period 2, the ETV, and SFU is presented in 
Table 4 and the Schedule of Assessments for the study drug administration visits during 
Treatment Period 2 is presented in Table 5. 
Please refer to the Laboratory Manual for details regarding the specific blood draw 
requirements for each visit. 
For details regarding visit windows, refer to the Schedule of Assessments (Table 2, Table 3, 
Table 4, and Table 5). 
7.1.1. 
Unscheduled Visits 
All attempts should be made to keep patients on the study schedule. Unscheduled visits may 
be necessary to repeat testing following abnormal laboratory results, for follow-up of AEs, or 
for any other reason, as warranted. During an unscheduled visit, the following information 
will be required to be collected: 

Concomitant medications

AEs
Any of the other procedures listed for the W32 visit may also be performed at the 
Investigator’s discretion. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
Confidential 
Page 54 of 95 
j.
Vital signs and weight will be measured at all visits; height will be measured at Screening only. Blood pressure and pulse rate should be collected after the patient has had at 
least 5 minutes of rest in the seated position. If the blood pressure is elevated on the first measurement at Screening or Baseline, it should be repeated after an additional 5 
minutes of rest. It is recommended that blood pressure is measured using the same arm at each assessment.
k.
12-lead ECG should be performed after at least 5 minutes of rest in a supine position.
l.
Should be completed by qualified personnel, and it is recommended that the same individual performs the assessment at all visits.
m.
Should be performed only in those patients with DM.
n.
Patient reported outcome measures are recommended to be completed first at each visit where performed, ie, prior to any other procedures or assessments other than signing 
of informed consent.
o.
Hematology: hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, white 
blood cell count (total and differential), and platelet count.
Clinical chemistry: creatinine, creatine kinase, urea (or blood urea nitrogen), aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase, alkaline 
phosphatase, lactate dehydrogenase, total bilirubin, albumin, total protein, sodium, potassium, chloride, glucose, uric acid, total cholesterol, magnesium, calcium, 
phosphorus.
p.
Erythrocyte sedimentation rate should be performed locally.
q.
CD19 count is required to be performed only for those patients being evaluated for eligibility who had their last dose of rituximab ≥24 and <48 weeks before Screening.
r.
Urinalysis: color, appearance, specific gravity, pH, protein, glucose, ketones, bilirubin, blood, urobilinogen, nitrite, leukocyte esterase with reflex testing for microscopic 
parameters.
s.
Quantitative immunoglobulins: IgG, IgM, IgA.
t.
Autoantibodies could potentially include the following: myositis autoantibodies: anti-Jo-1, anti-PL-7, anti-PL12, anti-EJ, anti-OJ, anti-SRP, anti-Mi-2α, anti-Mi-2β,
anti-MDA-5, anti-TIF-1γ, anti-NXP-2, anti-HMGCR; other autoantibodies: anti-PM-Scl, anti-U1RNP, anti-SSA, anti-SSB, anti-Ku, anti-SAE, anticentromere, antinuclear.
u.
Pharmacokinetics will be performed as sparse sampling before dosing and at 0.5 (±5 minutes) and 4 hours (±10 minutes) after dosing in all patients at Week 0 and at Week 
16 (see Table 4). In addition, a PK sample will be obtained at 0.25 (±5 minutes), 1 (±10 minutes), or 2 hours (±10 minutes) after dosing at Weeks 0 and 16 (see Table 4) 
based on the random assignment of a patient via the Randomization and Trial Supply Management system to PK Cohort A, B, or C.
v.
Blood sampling for PD (proteasome inhibition) will be performed in all patients before dosing and at 4 hours after dosing at Week 0 and at Week 16 (see Table 4).
w.
Blood sampling will be performed before dosing to measure cytokines including IFNα, IFNβ, IFNγ, IL-2, IL-6, IL-12, IL-17A, IL-21, IL-23, CXCL10, BLyS, TNFα, TGFβ; 
and to profile immune cells including B cell subgroups (naïve, activated, memory), plasma cell subgroups (long, short-lived), T cell subgroups (CD4 [Th1, Th17, all, naïve, 
activated], CD8 [memory], Treg).
x.
Will be performed in patients who have provided the proper informed consent for genetic analyses.
y.
Patients who do not have a muscle biopsy will be permitted to get one during the Screening Period if needed to determine eligibility. Skin and/or muscle biopsies for 
histology and gene expression analysis will be performed in consenting patients at qualified centers. Patients who agree to participate in the biopsy substudy will have 
biopsies obtained at the time points as specified.
z.
Patients need to be monitored for 2 hours after dosing at Week 0 and at Week 16 (see Table 4). Patients will receive study drug weekly. Home health service will be 
arranged for patients who choose not to return to investigative site for study drug administration weekly according to Table 3.

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
Confidential 
Page 57 of 95 
MDGA=Physician Global Assessment; MDI=Myositis Damage Index; MMT-8=Manual Muscle Testing-8 Muscle Groups; NRS=numeric rating scale; PD=pharmacodynamics; 
PK=pharmacokinetics; PROMIS-29=Patient Reported Outcomes Measurement Information System 29-item Short Form Profile Version 2.1; PtGADA=Patient Global 
Assessment of Disease Activity; PtGADD=Patient Global Assessment of Disease Damage; PGIC=Patient Global Impression of Change; RNA=ribonucleic acid; SFU=Safety 
Follow-up; TSQM=Treatment Satisfaction Questionnaire for Medication Version II. 
Note: Chest radiograph and ECG (as well as other assessments approved by the Medical Monitor) may be performed as needed to confirm findings requiring confirmation on the 
MDAAT. 
a.
Patients withdrawing prior to Week 32 visit should complete all Early Termination Visit (Week 32) assessments for their early termination visit. It is requested that these
patients return for their Safety Follow-up Visit 9 weeks after administration of the last dose of the study drug.
b.
A urine pregnancy test will be performed.
c.
A complete physical examination should be performed at the W32/Early Termination Visit and End of Study Visit. Physical examinations at all other time points may be
limited in nature.
d.
Vital signs and weight will be measured at all visits. Blood pressure and pulse rate should be collected after the patient has had at least 5 minutes of rest in the seated
position. If the blood pressure is elevated on the first measurement at Screening or Baseline, it should be repeated after an additional 5 minutes of rest. It is recommended
that blood pressure is measured using the same arm at each assessment.
e.
12-lead ECG should be performed after at least 5 minutes of rest in a supine position.
f.
Should be completed by qualified personnel, and it is recommended that the same individual performs the assessment at all visits.
g.
Should be performed only in those patients with DM.
h.
Patient reported outcome measures are recommended to be completed first at each visit where performed, ie, prior to any other procedures or assessments other than
signing of informed consent.
i.
Hematology: hemoglobin, hematocrit, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, white
blood cell count (total and differential), and platelet count.
Clinical chemistry: creatinine, creatine kinase, urea (or blood urea nitrogen), aspartate aminotransferase, alanine aminotransferase, gamma glutamyltransferase, alkaline
phosphatase, lactate dehydrogenase, total bilirubin, albumin, total protein, sodium, potassium, chloride, glucose, uric acid, total cholesterol, magnesium, calcium, phosphorus.
j.
Erythrocyte sedimentation rate should be performed locally.
k.
Urinalysis: color, appearance, specific gravity, pH, protein, glucose, ketones, bilirubin, blood, urobilinogen, nitrite, leukocyte esterase with reflex testing for microscopic
parameters.
l.
Quantitative immunoglobulins: IgG, IgM, IgA.
m.
Autoantibodies could potentially include the following: myositis autoantibodies: anti-Jo-1, anti-PL-7, anti-PL12, anti-EJ, anti-OJ, anti-SRP, anti-Mi-2α, anti-Mi-2β,
anti-MDA-5, anti-TIF-1γ, anti-NXP-2, anti-HMGCR; other autoantibodies: anti-PM-Scl, anti-U1RNP, anti-SSA, anti-SSB, anti-Ku, anti-SAE, anticentromere,
antinuclear.
n.
Pharmacokinetics will be performed as sparse sampling before dosing and at 0.5 (±5 minutes) and 4 hours (±10 minutes) after dosing in all patients at Week 16. In
addition, a PK sample will be obtained at 0.25 (±5 minutes), 1 (±10 minutes), or 2 hours (±10 minutes) after dosing at Weeks 16 based on the random assignment of a
patient via the Randomization and Trial Supply Management system to PK Cohort A, B, or C.
o.
Blood sampling for PD (proteasome inhibition) will be performed in all patients before dosing and at 4 hours after dosing at Week 16 and at Week 32.
p.
Blood sampling will be performed before dosing at Weeks 16 and 20 and at Week 32 to measure cytokines including IFNα, IFNβ, IFNγ, IL-2, IL-6, IL-12, IL-17A, IL-
21, IL-23, CXCL10, BLyS, TNFα, TGFβ; and to profile immune cells including B cell subgroups (naïve, activated, memory), plasma cell subgroups (long, short-lived),
T cell subgroups (CD4 [Th1, Th17, all, naïve, activated], CD8 [memory], Treg).
q.
Will be performed patients who have provided the appropriate informed consent for genetic analyses.
r.
Skin and or muscle biopsies for histology and gene expression analysis will be performed in consenting patients at qualified centers. Patients who agree to participate in
the biopsy substudy will have biopsies obtained at the time points as specified. The collection at W32 will be optional.
s.
Patients need to be monitored for 2 hours after dosing at Week 16. Patients will receive study drug weekly. Home health service will be arranged for patients who choose
not to return to investigative site for study drug administration weekly according to Table 5.

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
Confidential 
Page 59 of 95 
7.2. 
Study Procedures and Assessments 
All patients must be provided a consent form describing the study with sufficient information 
for patients to make an informed decision regarding their participation as per Section 11.3. 
All study procedures and assessments will be performed according to the schedules presented 
in Table 2, Table 3, Table 4, and Table 5. 
7.2.1. 
Demographic Data 
Demographic data will be recorded at Screening and will include date of birth, age 
(calculated), sex, ethnicity, and race. 
7.2.2. 
PM/DM Classification 
Patients will be classified as having PM or DM based on the 2017 EULAR/ACR 
classification criteria34 and the web calculator located at: 
https://www.niehs.nih.gov/research/resources/imacs/classificationcriteria/index.cfm 
(Last accessed: 28 February 2019) 
7.2.3. 
Medical History 
Documentation of the patient’s medical history should contain the patient’s full medical 
history including past and concomitant illnesses/diseases, disease duration, prior medications, 
prior procedures, and social history (including tobacco use, drugs of abuse, and alcohol use).  
7.2.4. 
Efficacy Assessments 
Efficacy assessments will be performed for all patients, unless indicated otherwise, at the 
time points shown in the Schedule of Assessments (Table 2 and Table 4). As interrater 
reliability may result in increased variability of within-patient assessments, it is 
recommended that the same individual performs the assessments at all visits for an individual 
patient. 
7.2.4.1. 
Total Improvement Score 
The Myositis Response Criteria are recommended for use as primary endpoints in myositis 
therapeutic trials. The criteria use the 6 IMACS core set measures, combining the absolute 
percentage change in each with varying weights to obtain a TIS on a scale of 0-100. Different 
thresholds of improvement have been set for minimal, moderate, and major response. The 
TIS may be used as a continuous outcome measure or as a categorical outcome of 
improvement (minimal, moderate, or major improvement). The TIS can be calculated using 
the 2016 ACR/EULAR criteria2 using the web calculator located at: 
https://www.niehs.nih.gov/research/resources/imacs/response_criteria/adult.html 
The User’s Guide is located at: 
https://www.niehs.nih.gov/research/resources/imacs/response_criteria/users_guide_for_the_a

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 60 of 95 
dult_dermatomyositis_and_polymyositis_response_criteria_online_calculator_508.pdf  
(Last accessed: 28 February 2019) 
Investigators will not be required to make these calculations for the study. 
7.2.4.2. 
Manual Muscle Testing-8 Muscle Groups (MMT-8) 
This partially validated tool assesses muscle strength using manual muscle testing.  
A 0 to 10-point scale is proposed for use. An abbreviated group of 8 proximal, distal, and 
axial muscles (neck flexors, deltoids, biceps brachii, gluteus maximus, gluteus medius, 
quadriceps, wrist extensors, ankle dorsiflexors) performs similarly to a total of 24 muscle 
groups, and this abbreviated group is also proposed for use for research studies.41,42 This is 
one of the IMACS disease CSAMs. 
The MMT-8 should be completed by qualified personnel, and it is recommended that the 
same individual performs the assessment at all visits. 
The MMT-8 can be found at: 
https://www.niehs.nih.gov/research/resources/assets/docs/mmt8_grading_and_testing_proced
ures_for_the_abbreviated_8_muscle_groups_508.pdf 
(Last accessed: 28 February 2019)  
7.2.4.3. 
Myositis Disease Activity Assessment Tool (MDAAT) 
This validated tool measures the degree of disease activity of extramuscular organ systems 
and muscle. This is a combined tool that includes the Myositis Disease Activity Assessment 
Visual Analogue Scales (MYOACT), which is a series of physician's assessments of disease 
activity of various organ systems modified from the Vasculitis Activity Index,50 and the 
Myositis Intention to Treat Activity Index (MITAX), which is modified from the British Isles 
Lupus Assessment Group approach to assess disease activity in SLE.24 The MITAX is 
composed of a series of organ-specific questions relating to the presence or absence of the 
clinical feature and the degree of treatment needed for it (intention to treat).42,47  
The MDAAT should be completed by qualified personnel, and it is recommended that the 
same individual performs the assessment at all visits. This is one of the IMACS disease 
CSAMs. 
The MDAAT assessment tool and glossary, respectively, can be located at: 
https://www.niehs.nih.gov/research/resources/assets/docs/myositis_disease_activity_assessm
ent_tool_2009_pdf_format_508.pdf  
(Last accessed: 28 February 2019)  
https://www.niehs.nih.gov/research/resources/assets/docs/glossary_for_myositis_disease_acti
vity_assessment_tool_0_4_version_2_2005_pdf_format_508.pdf 
(Last accessed: 28 February 2019) 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 61 of 95 
7.2.4.4. 
Physician Global Assessments of Disease Activity (MDGA) 
This partially validated tool measures the global evaluation by the treating physician of the 
overall disease activity of the patient at the time of assessment using a 10 cm visual analog 
scale (VAS) and a 5-point Likert scale.42 This is one of the IMACS disease CSAMs. 
The MDGA is located at: 
https://www.niehs.nih.gov/research/resources/assets/docs/physician_global_activity_pdf_for
mat_508.pdf 
(Last accessed: 28 February 2019) 
The MDGA should be completed by qualified personnel, and it is recommended that the 
same individual performs the assessment at all visits. 
7.2.4.5. 
Physician Global Impression of Change (MDGIC) 
The MDGIC consists of 1 item taken from the Clinical Global Impressions scale (CGI), 
which was published in 1976 by the US National Institute of Mental Health. Answers are 
based on a 7-point Likert scale ranging from very much improved to very much worse, 
asking regarding the patient’s overall status.22 
The MDGIC should be completed by qualified personnel, and it is recommended that the 
same individual performs the assessment at all visits. 
7.2.4.6. 
Functional Index-2 (FI-2) 
The FI-2 is a functional outcome developed for patients with adult PM or DM assessing 
muscle endurance in 7 muscle groups. Each muscle group is scored as the number of 
correctly performed repetitions with 60 or 120 maximal number of repetitions depending on 
muscle group. The FI-2 is a further development of the original FI where redundant tasks 
were eliminated and the number of repetitions for each task were increased to avoid ceiling 
effects. It has been validated as to content and construct validity and intra- and interrater 
reliability. The FI-2 can be performed just on the dominant side, which takes approximately 
21 minutes.4,42 
This assessment tool is located at: 
https://www.niehs.nih.gov/research/resources/assets/docs/functional_index2_training_guide_
508.pdf 
(Last accessed: 28 February 2019)  
The FI-2 should be completed by qualified personnel, and it is recommended that the same 
individual performs the assessment at all visits. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 62 of 95 
7.2.4.7. 
Functional Index-3 (FI-3) 
The FI-3 is an efficient and valid method for assessment of muscle endurance in DM and PM 
patients.32 It comprises 3 assessments as follows: 
 Sit-to-stand (STS): The score is the number of times that the patient rises to a full stand 
from the seated position with arms folded across the chest within 30 seconds1 
 Timed up and go (TUG): The amount of time it takes the patient to stand from a seated 
position, walk 3 meters, turn, return to the chair, and then sit down. 
 6-minute walk distance (6MWD): Distance patient walks in 6 minutes. 
The FI-3 should be completed by qualified personnel, and it is recommended that the same 
individual performs the assessment at all visits. The sit-to-stand test may be performed alone 
in place of the full FI-3 as per the Schedule of Assessments (Table 2 and Table 4). 
7.2.4.8. 
Myositis Damage Index (MDI) 
This validated tool assesses the degree of disease damage of all organ systems. It is 
composed of a series of organ-specific questions relating to the presence or absence of a 
given sign or symptom or problem to measure the extent of damage, and an overall rating of 
the disease damage of each system using a 10 cm VAS to measure the severity of 
damage.42,48 
The MDI is located at:  
https://www.niehs.nih.gov/research/resources/assets/docs/myositis_damage_index_pdf_form
at_508.pdf  
(Last accessed: 28 February 2019) 
The MDI should be completed by qualified personnel, and it is recommended that the same 
individual performs the assessment at all visits. 
7.2.4.9. 
Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) 
The CDASI will be performed only for those patients with DM. 
The CDASI is a clinician-scored single-page instrument that separately measures activity and 
damage in the skin of DM patients for use in clinical practice or clinical/therapeutic studies. 
The modified CDASI (Version 2) is the one in current use. The modified CDASI has 3 
activity measures (erythema, scale, and erosion/ulceration) and 2 damage measures 
(poikiloderma and calcinosis) which are assessed over 15 body areas. In addition, Gottron’s 
papules on the hands are evaluated both for activity and damage. Lastly, the activity of 
periungual changes and alopecia is assessed.42,52 
The CDASI is located at: 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 63 of 95 
https://www.niehs.nih.gov/research/resources/imacs/othertools/cdasi_training_slide_set_508.
pdf 
(Last accessed: 28 February 2019) 
The CDASI should be completed by qualified personnel, and it is recommended that the 
same individual performs the assessment at all visits. 
7.2.4.10. 
Muscle Enzymes 
Muscle enzymes (aldolase, ALT, AST, CK, and LDH) will be measured to evaluate disease 
activity via laboratory testing per Section 7.2.6.10. Muscle enzyme measurements are one of 
the IMACS disease CSAMs. 
7.2.5. 
Patient Reported Outcome Assessments 
Several PROMs will be used in this study, including the PtGADA, HAQ-DI, PGIC, 
PROMIS-29, EQ-5D-5L, HRU, PtGADD, Peak Pruritus NRS (DM patients only), and 
TSQM. It is recommended that PROMs be completed before any other assessments or 
procedures are performed, at each visit where they are to be performed. 
7.2.5.1. 
Patient Global Assessment of Disease Activity (PtGADA) 
This partially validated tool measures the global evaluation of the patient's overall disease 
activity at the time of assessment using a 10 cm VAS.42 The PtGADA is a PROM and is one 
of the IMACS disease CSAMs. It is recommended that, at each visit where it is to be 
performed that PROMs are completed before any other assessments or procedures are 
performed. 
The PtGADA is located at:  
https://www.niehs.nih.gov/research/resources/assets/docs/patientparent_global_activity_pdf_
format_508.pdf  
(Last accessed: 28 February 2019) 
7.2.5.2. 
Health Assessment Questionnaire-Disability Index (HAQ-DI) 
The HAQ-DI is a partially validated tool to assess physical function in myositis.42 The  
HAQ-DI is a PROM and is one of the IMACS disease CSAMs. It is recommended that, at 
each visit where they are to be performed, that PROMs are completed before any other 
assessments or procedures are performed. 
The HAQ-DI is located at: 
https://www.niehs.nih.gov/research/resources/assets/docs/haq_instructions_508.pdf 
(Last accessed: 28 February 2019) 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
Confidential 
Page 64 of 95 
7.2.5.3. 
Patient Global Impression of Change (PGIC) 
The PGIC is the PROM counterpart to the CGI, which was published in 1976 by the US 
National Institute of Mental Health. It consists of one item taken from the CGI and adapted 
to the patient. Answers are based on a 7-point Likert scale ranging from very much improved 
to very much worse, asking regarding the patient’s overall status.22 
It is recommended that, at each visit where they are to be performed, that PROMs are 
completed before any other assessments or procedures are performed. 
7.2.5.4. 
Patient Reported Outcomes Measurement Information System 29-item 
Short Form Profile Version 2.1 (PROMIS-29) 
The Patient Reported Outcomes Measurement Information System® (PROMIS) is a flexible 
set of tools designed to measure self-reported physical, mental, and social health and 
wellbeing. The PROMIS has been constructed and validated rigorously, with more than 
50 research protocols and over 60,000 people contributing data. Development included a 
comprehensive literature review, focus group and psychometric testing, cognitive interviews, 
and expert review. The PROMIS-29 is a generic health related quality of life survey 
containing 4 items for the following 7 domains: depression; anxiety; physical function; pain 
interference; fatigue; sleep disturbance; and ability to participate in social roles and activities. 
The 7 domains cover the most relevant areas of self-reported health for the greatest majority 
of people with chronic illness. The questions are ranked on a 5-point Likert Scale. There is 
also one 11-point rating scale for pain intensity. More information is available at: 
http://www.healthmeasures.net/explore-measurement-systems/promis. 
(Last accessed: 28 February 2019) 
An overview of the PROMIS-29 is available at: 
https://www.aci.health.nsw.gov.au/__data/assets/pdf_file/0003/402087/Overview-of-the-
PROMIS-29_EH-140817.pdf  
(Last accessed: 28 February 2019) 
The PROMIS-29 is a PROM. It is recommended that, at each visit where they are to be 
performed, that PROMs are completed before any other assessments or procedures are 
performed. 
7.2.5.5. 
EuroQoL 5-dimension 5-level (EQ-5D-5L) 
The EQ-5D is a standardized instrument developed by the EuroQoL Group as a measure of 
health related quality of life that can be used in a wide range of health conditions and 
treatments. The EQ-5D consists of a descriptive system and the EQ-VAS. 
The descriptive system comprises 5 levels of severity for each of 5 dimensions: mobility, 
self-care, usual activities, pain/discomfort, and anxiety/depression. The EQ-VAS records the 
patient’s self-rated health on a vertical VAS. This can be used as a quantitative measure of 
health outcome that reflects the patient’s own judgment. The scores on these 5 dimensions 
can be presented as a health profile or can be converted to a single summary index number 
(utility) reflecting preferability compared to other health profiles. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 65 of 95 
The EQ-5D-5L is located at: 
https://euroqol.org/eq-5d-instruments/  
(Last accessed: 28 February 2019) 
The EQ-5D-5L is a PROM. It is recommended that, at each visit where they are to be 
performed, that PROMs are completed before any other assessments or procedures are 
performed. 
7.2.5.6. 
Healthcare Resource Utilization (HRU) 
The HRU questionnaire to be used in this study has been modified from one created for 
osteoarthritis.33,40 It covers aspects of work productivity as well as hospitalizations, specialist 
and nonspecialist care, ancillary health care, use of community services, and out of pocket 
costs. Self-reported questionnaires on resource utilization have been shown to have good 
agreement with administrative data, although visits to general practitioners, outpatient days, 
and nurse visits had poorer agreement.  
Data entered by the patient on the HRU form should be reviewed by the Investigator or 
designee for the potential occurrence of AEs or SAEs to be reported. 
The HRU is a PROM. It is recommended that, at each visit where they are to be performed, 
that PROMs are completed before any other assessments or procedures are performed. 
7.2.5.7. 
Patient Global Assessment of Disease Damage (PtGADD) 
This partially validated tool measures the global evaluation of the patient's overall disease 
damage at the time of assessment using a 10 cm VAS. The PtGADD is a PROM. It is 
recommended that, at each visit where they are to be performed, that PROMs are completed 
before any other assessments or procedures are performed. 
The PtGADD is located at: 
https://www.niehs.nih.gov/research/resources/assets/docs/patientparent_global_assessment_o
f_disease_damage_pdf_format_508.pdf  
(Last accessed: 28 February 2019) 
7.2.5.8. 
Peak Pruritus Numeric Rating Scale 
In a study of patients with DM, 50% reported moderate-to-severe itch, and itch was 
correlated with increased cutaneous severity.29 The Peak Pruritus NRS, used to evaluate itch 
in atopic dermatitis, will be utilized to evaluate the severity of itch in patients with DM. It 
ranges from a score of 0 to 10, with 0 representing no itch and 10 representing the worst itch 
imaginable during the worst moment within a 24-hour recall period.  
The Peak Pruritus NRS will be performed only in those patients with DM. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 66 of 95 
The Peak Pruritus NRS is a PROM. It is recommended that, at each visit where they are to be 
performed, that PROMs are completed before any other assessments or procedures are 
performed. 
7.2.5.9. 
Treatment Satisfaction Questionnaire for Medication Version II (TSQM)   
The TSQM is a generic measure of treatment satisfaction for medication. It was rigorously 
developed and has sound psychometric properties.6 The TSQM assesses 4 key dimensions of 
treatment satisfaction: effectiveness (2 questions); side effects (3 questions); convenience 
(3 questions); and global satisfaction (2 questions). It comprises 11 questions, with possible 
responses ranging from yes/no to 5- to 7-point Likert-type scales. Higher scores indicated 
more satisfaction with the treatment. 
The TSQM is located at: 
https://www.iqvia.com/landing/treatment-satisfaction-questionnaire-for-medication-tsqm 
(Last accessed: 28 February 2019) 
The TSQM is a PROM. It is recommended that, at each visit where they are to be performed, 
that PROMs are completed before any other assessments or procedures are performed. 
7.2.6. 
Safety Assessments 
Safety will be assessed throughout the study by monitoring of vital signs (blood pressure, 
pulse rate, temperature, and respiration rate), laboratory tests (hematology, chemistry, 
urinalysis, immunoglobulins), ECGs, and physical examinations; and by recording and 
analyzing all AEs and SAEs.  
7.2.6.1. 
Tuberculosis 
Evaluation of all patients by an interferon gamma release assay for TB will be performed by 
the central clinical laboratory or local laboratory at Screening. The following tests are 
permitted: 
 QuantiFERON®-TB Gold 
 QuantiFERON®-TB Gold Plus 
 T-SPOT® TB. 
History of active TB infection is excluded, regardless of treatment history. 
If the screening test is negative and there is no known history of recent exposure to 
individuals with active TB, and chest radiograph shows no evidence of active TB, the patient 
may be enrolled and/or randomized. If the screening test is positive at Screening and/or the 
patient is diagnosed with latent TB, they must have documentation confirming completion of 
appropriate treatment prior to being permitted to enroll or being randomized. 
A patient with an indeterminate or borderline TB test at Screening must have a repeat test 
performed at least 1 time by the central laboratory or local laboratory, and it must be repeated 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 67 of 95 
as soon as possible. If the result remains indeterminate or borderline or is positive, the patient 
is not eligible for enrollment into the study or randomization. 
7.2.6.2. 
Viral Serology 
Viral serology tests for human immunodeficiency viruses 1 and 2, hepatitis B virus core 
antibody and surface antigen, and hepatitis C virus antibody will be performed at Screening. 
Patients with positive tests for any of these assessments will be excluded, regardless of 
treatment history. 
7.2.6.3. 
Chest Radiograph 
A chest radiograph should be obtained at Screening (posteroanterior view) if findings from a 
radiograph taken within 12 weeks before Screening are not available. The chest radiograph 
should be read by a radiologist or pulmonologist, and documented results should be reviewed 
by the Investigator or designee to exclude patients with active TB infection. If necessary, 
additional chest radiographs may be performed to confirm findings required for the MDAAT. 
7.2.6.4. 
Follicle Stimulating Hormone and Pregnancy 
Samples for FSH testing may be collected at Screening to confirm postmenopausal status in 
female patients. 
For WOCBP, a serum pregnancy test will be performed at Screening and urine testing will be 
performed at all other time points shown in the Schedule of Assessments (Table 2 and 
Table 4). 
7.2.6.5. 
Coagulation, Thyroid, and Antiphospholipid Antibodies 
Samples for coagulation, thyroid, and antiphospholipid antibodies (APLA) will be collected 
and testing will be performed at the time points shown in the Schedule of Assessments 
(Table 2). Coagulation tests will include: prothrombin time, INR, aPTT, and lupus 
anticoagulant panel. Thyroid function tests will include: free T4, free T3, and thyroid 
stimulating hormone. The APLA testing will include: anti-β2 glycoprotein I and 
anticardiolipin (IgG and IgM for both). 
7.2.6.6. 
Physical Examination 
Complete physical examinations will be performed only at Screening, W16, the ETV, and the 
End of Study Visit. A complete physical examination should include at least assessments of 
these systems: general appearance, head, ears, eyes, nose and throat, neck, dermatological, 
respiratory, cardiovascular, abdomen, extremities, neurological, musculoskeletal. 
At all other specified time points, a limited physical examination will be performed as 
directed by the patient complaints and the clinical judgment of the Investigator. Medically 
significant changes from physical examination will be recorded as AEs. Muscle evaluation 
findings captured in the muscle assessment instruments will not be recorded unless they are 
classifiable as SAEs, as per Section 9.4. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 68 of 95 
7.2.6.7. 
Vital Sign Measurements 
Blood pressure, pulse rate, respiration rate, and temperature will be measured at the time 
points shown in the Schedule of Assessments (Table 2, Table 3, Table 4, and Table 5). Blood 
pressure and pulse rate should be collected after the patient has had at least 5 minutes of rest 
in the seated position. If the blood pressure is elevated on the first measurement at Screening 
and Baseline, it should be repeated after an additional 5 minutes of rest. It is recommended 
that blood pressure is measured using the same arm at each assessment. When the time of 
vital signs measurement coincides with a blood sample collection, the vital signs will be 
measured before blood sample collection. 
7.2.6.8. 
Weight and Height 
Body weight will be recorded at the time points shown in the Schedule of Assessments 
(Table 2 and Table 4). Body weight, with the patient wearing light clothing and the shoes and 
jacket or coat removed, will be measured and recorded in kilograms. 
Body height will be measured and recorded, in centimeters, at Screening only.  
7.2.6.9. 
Electrocardiogram 
A 12-lead ECG will be taken at the time points shown in the Schedule of Assessments 
(Table 2 and Table 4). The ECG should be performed after the patient has rested for at least 
5 minutes in a supine position. When scheduled at the same time point as vital sign 
measurements or a blood sample collection, the ECG should be performed first.  
The ECG measurements will include heart rate, PR interval, QT interval, RR interval, QRS 
complex, and rhythm. It is preferable that the machine used has a capacity to calculate the 
standard intervals automatically. Corrections to QT interval should be done by both QTcF 
and QTcB, if possible. 
The Investigator or qualified designee will review and indicate if the ECG is normal or 
abnormal, and whether clinically significant. Any medically significant changes from the 
screening ECG will be recorded as an AE. 
7.2.6.10. 
Clinical Laboratory Tests 
Clinical laboratory tests for safety (hematology, serum chemistries, urinalyses, coagulation 
tests, serum pregnancy) and other tests during scheduled visits will be performed at a central 
laboratory. Urine pregnancy tests and erythrocyte sedimentation rate (ESR) will be 
performed locally using an approved test; TB testing may be performed locally or centrally 
using a licensed test.  
Clinical laboratory results the Investigator deems clinically significantly abnormal should be 
repeated ideally within 48 to 72 hours from when the result became available. Guidance for 
laboratory values that could be considered clinically significantly abnormal is provided in 
Appendix B. Certain clinically significantly abnormal laboratory values may also influence 
continued dosing as per Section 6.1.1. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 71 of 95 
7.2.7. 
Pharmacokinetic Assessments 
Blood samples will be collected as outlined in the Schedule of Assessments (Table 2 and 
Table 4). All patients will have blood samples collected at predose and at 0.5 and 4 hours 
postdose. In addition, patients will be randomly assigned via RTSM to Cohort A (0.25 hour 
postdose PK sample), Cohort B (1 hour postdose PK sample), or Cohort C (2 hour postdose 
PK sample). Samples will be used to measure the plasma concentration of KZR-616 and its 
metabolite KZR-59587 (area under the time-concentration curve [AUC], maximum 
concentration [Cmax], time to maximum plasma concentration [Tmax]), and other PK 
calculations). At the visits and times specified, blood samples of approximately 4 mL will be 
collected. Additional information regarding sample collection and handling are outlined in 
the Laboratory Manual.  
Samples collected to measure investigational product concentration and metabolism and/or 
protein binding will be retained for as long as legally permitted in the country of origin or 
until Sponsor decision to destroy. 
7.2.8. 
Pharmacodynamic Assessments 
The extent of proteasome activity in whole blood and isolated PBMCs will be assessed in 
blood samples collected as outlined in the Schedule of Assessments (Table 2 and Table 4). 
Proteasome CT-L peptidase activity will be measured by a cleavable fluorogenic substrate 
enzymatic activity assay. KZR-616 occupancy of individual subunits of the proteasome in 
whole blood and PBMCs will be measured by the proteasome constitutive/ 
immunoproteasome subunit enzyme-linked immunosorbent assay (ELISA) (ProCISE), a 
subunit-specific proteasome active site ELISA.   
Additional information regarding sample collection and handling are outlined in the 
Laboratory Manual. 
7.2.9. 
Exploratory Biomarkers 
7.2.9.1. 
Cytokines, Proteomics, and Leukocyte Subsets  
Blood samples will be collected at the times shown in the Schedule of Assessments (Table 2 
and Table 4) for the measurement of cytokines by ELISA including IFNα, IFNβ, IFNγ, IL-2, 
IL-6, IL-12, IL-17A, IL-21, IL-23, CXCL10, BLyS, TNFα, TGFβ; and to profile immune 
cells by flow cytometry including B cell subgroups (naïve, activated, memory), plasma cell 
subgroups (long, short-lived), T cell subgroups (CD4 [Th1, Th17, all, naïve, activated], CD8 
[memory], Treg). Immune cell profiling may also be performed by immune cell subset 
identification by deoxyribonucleic acid (DNA) methylation polymerase chain reaction 
methodology. Additional information regarding sample collection and handling are outlined 
in the Laboratory Manual. 
7.2.9.2. 
Autoantibodies 
Blood samples will be collected at the times shown in the Schedule of Assessments (Table 2 
and Table 4) for the measurement of autoantibodies. Autoantibodies that may be assessed 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 72 of 95 
include the following: myositis autoantibodies: anti-Jo-1, anti-PL-7, anti-PL12, anti-EJ,  
anti-OJ, anti-SRP, anti-Mi-2α, anti-Mi-2β, anti-MDA-5, anti-TIF-1γ, anti-NXP-2, 
anti-HMGCR; other autoantibodies: anti-PM-Scl, anti-U1RNP, anti-SSA, anti-SSB, anti-Ku, 
anti-SAE, anticentromere, and antinuclear.  
Additional information regarding sample collection and handling are outlined in the 
Laboratory Manual. 
7.2.9.3. 
Pharmacogenomics/Gene Expression 
Gene expression (ribonucleic acid [RNA]) profiling and DNA genotyping and methylation 
status may be assessed in blood samples. A whole blood sample will be collected for 
pharmacogenomic analysis for storage and analysis at a later date as specified in the 
Schedule of Assessments (Table 2 and Table 4) and to the extent permitted by the national 
and/or local laws and regulations. 
Samples will be used to conduct retrospective disease or population genetic research as a 
separate analysis not included in this study. Samples may be used to investigate variable 
response to KZR-616 and to investigate genetic or epigenetic variants thought to play a role 
in the diseases under investigation in this study. Assessment of variable response may include 
evaluation of AEs or differences in efficacy. The results may be reported in the separate 
report. 
Additional information regarding sample collection and handling are outlined in the 
Laboratory Manual. 
7.2.9.4. 
Biopsy 
Biopsies will be collected from a subset of enrolled patients; skin biopsies will be performed 
only for selected patients with DM, and muscle biopsies will be performed for selected 
patients with PM or DM. For selected patients, biopsies will be collected from skin and/or 
muscle at the time points shown in the Schedule of Assessments (Table 2 and Table 4). The 
tissue samples may be used for exploratory investigations of treatment-related changes and 
regulation of inflammatory pathways. 
Additional information regarding sample collection and handling are outlined in the 
Laboratory Manual. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 73 of 95 
8. STUDY DISCONTINUATION 
The Investigator must make every reasonable effort to keep each patient on study for the 
whole duration of the study, including through the SFU, lost to follow-up, consent 
withdrawal, or End of Study, whichever occurs first. 
8.1. 
Individual and Study Stopping Rules for Safety 
8.1.1. 
Study Stopping Rules 
If any of the following events occur, the accumulated safety data will be reviewed by the 
DMC. 
 Death in any patient, unless the cause of death is due to obvious alternative etiology 
 Any unexpected or life-threatening SAE, unless due to obvious alternative etiology 
 Any event of TMA, thrombotic thrombocytopenic purpura (TTP), or hemolytic uremic 
syndrome (HUS) 
 Three or more of the same Grade 3 or higher AE (judged by the Investigator, Medical 
Monitor, or Sponsor’s representative), including ISRs, unless due to obvious alternative 
etiology 
 Any event which, in the opinion of the Investigator, Medical Monitor, DMC, or Sponsor, 
contraindicates further dosing of additional patients. 
Based on the review, the DMC will have the ability to recommend the study be continued as 
is, continued with modification, or discontinued. Modifications could include 
eg, implementation of additional monitoring measures or a dose reduction of KZR-616. 
8.1.2. 
Individual Patient Stopping Rules 
If any of the following events occur in an individual patient, administration of study drug to 
the patient should be interrupted until a review of the accumulated safety data is undertaken 
by the DMC. 
 Any event that fulfills criteria for a Study Stopping Rule (per Section 8.1.1), unless due to 
obvious alternative etiology 
 Any event that, in the opinion of the Investigator, Medical Monitor, DMC, or Sponsor, 
contraindicates further dosing 
After such a review, the DMC may recommend the patient resume dosing, including 
consideration for any prophylactic interventions (eg, as per Section 6.1.3); reduce their dose 
(as per Section 6.1.4.1), or discontinue dosing. 
8.2. 
Early Withdrawal of Patients from the Study 
In accordance with applicable regulations, a patient has the right to withdraw from the study, 
at any time and for any reason, without prejudice to future medical care. 
Patients may be withdrawn from the study for the occurrence of any of the following reasons:  

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 74 of 95 
 Patient request/informed consent withdrawn due to an AE 
 Patient request/informed consent withdrawn due to reasons other than an AE 
 Patient becomes pregnant 
 Adverse event (whether or not related to the study drug) that precludes further 
participation in the study in the judgment of the Investigator and/or Sponsor  
 Protocol noncompliance in the judgment of the Investigator and/or Sponsor 
 Lost to follow-up 
 The Investigator or Sponsor considers that it is in the patient’s best interest for the patient 
not to continue participation in the study 
 Administrative decision by the Investigator or Sponsor. 
Patients who withdraw from the study will not be replaced. 
Patients are free to withdraw from the study at any time without providing reason(s) for 
withdrawal and without prejudice to further treatment. The reason(s) for withdrawal will be 
documented in the eCRF. If a patient withdraws consent, all samples obtained will be 
retained for analysis unless the patient confirms that he or she wishes the samples to be 
discarded.  
Patients who withdraw from the study prior to W32 will be requested to undergo the ETV 
procedures within 7 days of the withdrawal, and all patients who withdraw from the study 
prematurely will be requested to return for the SFU Visit 9 weeks (to perform W40 visit 
procedures) after receipt of their last dose of the study drug as per Table 4. Patients 
withdrawing from the study treatment will be encouraged to complete the same final 
evaluations as patients completing the study according to this protocol, particularly safety 
evaluations. The primary reason for withdrawal will be identified and recorded on the 
appropriate eCRF, along with the date of withdrawal.  
Reasonable efforts will be made to contact patients who are lost to follow-up. These efforts 
must be documented in the patient’s file. 
8.3. 
Termination or Suspension of the Study 
The Sponsor has the right to terminate the study at any time if judged necessary for safety, 
regulatory, or other reasons consistent with applicable laws, regulations, and Good Clinical 
Practice (GCP). In this event, the Investigator(s) will be informed of the reason for study 
termination. Should this occur, all data available will also be recorded in the eCRFs. The 
Investigator should notify the relevant Institutional Review Boards (IRBs)/Independent 
Ethics Committees (IECs) in writing of the study’s completion or early discontinuation. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 75 of 95 
9. ADVERSE EVENTS 
9.1. 
Adverse Event Reporting 
9.1.1. 
Definition of an Adverse Event 
An AE is defined as any untoward medical occurrence in a clinical study patient administered 
a medicinal product, which does not necessarily have a causal relationship with this 
treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not it is related to the medicinal 
(investigational) product. This includes an exacerbation of pre-existing conditions or events, 
intercurrent illnesses, drug interaction or the significant worsening of the indication under 
investigation that is not recorded elsewhere in the eCRF under specific efficacy assessments. 
Anticipated fluctuations of pre-existing conditions, including the disease under study, that do 
not represent a clinically significant exacerbation or worsening need not be considered AEs. 
It is the responsibility of the Investigator to document all AEs that occur during the study. 
Adverse events will be elicited by asking the patient a nonleading question, for example, 
“Have you experienced any new or changed symptoms since we last asked/since your last 
visit?” Adverse events should be reported on the appropriate page of the eCRF. 
9.1.2. 
Assessment of Severity 
Severity of AEs will be graded according to National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI-CTCAE) Version 4.03. If there is a change in severity of an 
AE, it must be recorded as a separate event. 
9.1.3. 
Assessment of Causality 
Adverse events will be deemed related to study medication unless clearly unrelated to study 
medication.  
The Investigator will assess the causal relationship between KZR-616 (or placebo) and AE. 
One of the following categories should be selected based on medical judgment, considering 
the definitions below and all contributing factors. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 76 of 95 
Related 
A clinical event, including laboratory test abnormality, occurs in a plausible time 
relationship to treatment administration and which concurrent disease or other drugs 
or chemicals cannot explain. The response to withdrawal of the treatment 
(dechallengea) should be clinically plausible. The event must be definitive 
pharmacologically or phenomenologically, using a satisfactory rechallengeb 
procedure if necessary. 
Unrelated 
A clinical event, including laboratory test abnormality, with little or no temporal 
relationship with treatment administration. May have negative dechallenge and 
rechallenge information. Typically explained by extraneous factors (eg, concomitant 
disease, environmental factors, or other drugs or chemicals). 
a 
Dechallenge: Upon discontinuation of a drug suspected of causing an AE, the symptoms of the 
AE disappear partially or completely, within a reasonable time from drug discontinuation, 
(positive dechallenge), or the symptoms continue despite withdrawal of the drug (negative 
dechallenge). Note that there are exceptions when an AE does not disappear upon 
discontinuation of the drug, yet drug-relatedness clearly exists (for example, as in bone marrow 
suppression, fixed drug eruptions, or tardive dyskinesia). 
b 
Rechallenge: Upon re-administration of a drug suspected of causing an AE in a specific patient 
in the past, the AE recurs upon exposure (positive rechallenge), or the AE does not recur, 
(negative rechallenge). 
9.1.4. 
Action Taken 
The Investigator will describe the action taken with study drug in the appropriate section of 
the eCRF, as follows: 
 None 
 Study drug stopped 
 Study drug temporarily interrupted 
 Study drug dose reduced (only permissible with Medical Monitor confirmation in 
writing) 
 Other, specify. 
9.1.5. 
Follow-up on Adverse Events 
Adverse events are intended to be collected according to the procedures outlined above from 
the time of informed consent and to continue for 30 days following the last dose, or the End 
of Study Visit, whichever occurs later.  
All Investigators should follow up with patients with AEs until the event is resolved or until, 
in the opinion of the Investigator, the event is stabilized or determined to be chronic. Details 
of AE resolution must be documented in the eCRF. 
9.1.6. 
Documentation and Reporting of Adverse Events 
Adverse events (including SAEs) should be reported and documented in accordance with the 
procedures outlined below. All AEs occurring during the study must be documented on the 
relevant eCRF pages. The following data should be documented for each AE: 
 Diagnosed or description of the symptom if diagnosis is not established 
 Classification of ‘serious’ or ‘not serious’ 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 77 of 95 
 Classification as AESI (yes or no) 
 Severity 
 Date of first occurrence and date of resolution (if applicable) 
 Action taken with study drug 
 Causal relationship with study drug 
 Outcome of event (unknown, recovered, not yet recovered, recovered with sequelae, 
death [with date and cause reported]). 
9.2. 
Serious Adverse Events 
9.2.1. 
Serious Adverse Event Definition 
An SAE is any untoward medical occurrence or affect that, at any dose,  
 Results in death 
 Is life-threatening (an AE is life-threatening if the patient was at immediate risk of death 
from the event as it occurred, ie, it does not include a reaction that might have caused 
death if it had occurred in a more serious form) 
 Requires or prolongs inpatient hospitalization. (Complications occurring during 
hospitalization are AEs and are SAEs if they cause prolongation of the current 
hospitalization. Hospitalization for elective treatment of a pre-existing nonworsening 
condition is not, however, considered an AE. The details of such hospitalizations must be 
recorded on the medical history or physical examination page of the eCRF) 
 Results in persistent or significant disability/incapacity. (An AE is incapacitating or 
disabling if it results in a substantial and/or permanent disruption of the patient’s ability 
to carry out normal life functions) 
 Results in a congenital anomaly/birth defect. 
In addition, medical and scientific judgement is required to decide if prompt notification is 
required in situations other than those defined for SAEs above. This may include any event 
that the Investigator regards as serious that did not strictly meet the criteria above but may 
have jeopardized the patient or required intervention to prevent one of the outcomes listed 
above, or that would suggest any significant hazard, contraindication, side effect, or 
precaution that may be associated with the use of the investigational product. 
9.2.2. 
Serious Adverse Event Reporting and Documentation Requirements 
Any SAE must be reported (see Section 9.1.6) by the Investigator if it occurs from the time 
of signed consent through 30 days after the last dose of study drug (KZR-616 or placebo) if 
the patient is withdrawn from the study early or at the SFU, whether or not the SAE is 
considered to be related to the investigational product. After the reporting period, SAEs 
should be reported if the Investigator assesses the event to be related to study drug. An SAE 
report consists of the SAE form, provided separately, along with requested additional source 
documentation as considered necessary.   
Serious adverse events that occur during the reporting period must be reported by the 
Investigator via entry of data into the eCRF within 24 hours from the point in time when the 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 78 of 95 
Investigator becomes aware of the SAE. This will trigger an email notification to the Serious 
Adverse Event Reporting e-mail address (see below) that an SAE has occurred. If the EDC 
system is down or unavailable, a copy of the SAE form should be completed and emailed or 
faxed by the Investigator to the Serious Adverse Event Reporting e-mail address or dedicated 
fax (see below) within 24 hours from the point in time when the Investigator becomes aware 
of the SAE. Once the EDC system is available, the SAE should be entered in the eCRF. The 
Investigator should not wait for additional information to fully document the SAE before 
reporting it, though additional information may be requested. Requested source 
documentation (ie, relevant laboratory results, hospital case records, or autopsy reports) that 
is considered necessary should be provided separately to the Serious Adverse Event 
Reporting e-mail address using a cover sheet. 
Contact Information:  
Serious Adverse Event Reporting E-mail: 
  
Fax: 
 
Instances of death, congenital abnormality, or an event that is of such clinical concern as to 
influence the overall assessment of safety, if brought to the attention of the Investigator at 
any time after cessation of study drug administration and linked by the Investigator to this 
study, should be reported to the study monitor. 
The Sponsor and/or designee will promptly notify all relevant Investigators and the 
regulatory authorities of findings that could adversely affect the safety of patients, impact on 
the conduct of the study, or alter the DMC/IRB/IEC approval/favorable opinion of the study. 
In addition, the Sponsor or designee, will expedite the reporting of all adverse reactions that 
are both serious and unexpected to all concerned Investigators, to the DMC/IRBs/IECs where 
required, and to the regulatory authorities. 
9.3. 
Pregnancy Reporting 
Pregnancy occurring during a clinical investigation must be reported to safety within 
24 hours and entered into the EDC. The outcome of a pregnancy should be followed up 
carefully and any abnormal outcome of the mother or the child should be reported. This also 
applies to pregnancies following the administration of the investigational product to the 
father prior to sexual intercourse. Infants should be followed for a minimum of 8 weeks and 
all findings should be reported to the Sponsor. Study drug is to be discontinued immediately 
upon Investigator knowledge of the pregnancy and reported as per Section 8.2. 
If the outcome of the pregnancy meets a criterion for immediate classification as an SAE—
spontaneous abortion (any congenital anomaly detected in an aborted fetus is to be 
documented), stillbirth, neonatal death, or congenital anomaly—the Investigator should 
repeat the procedures for expedited reporting of SAEs as outlined above. 
Full details will be recorded on the withdrawal page of the eCRF, or an SAE report will be 
completed if the patient has completed the study. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 79 of 95 
9.4. 
New or Worsening Disease Manifestations 
New or worsening manifestation(s) of DM or PM should not be recorded as AEs unless they 
are assessed as serious. 
9.5. 
Adverse Events of Special Interest 
Adverse events of special interest should be reported within 24 hours using the AE eCRF as 
per Section 9.1.6. No additional reporting will be required unless they become SAEs. 
9.5.1. 
Systemic Injection Reactions 
Systemic injection reactions have been observed with KZR-616 and other proteasome 
inhibitors and are considered AESIs. 
Systemic injection reactions have included a number of signs and symptoms including fever, 
chills, myalgia, facial swelling or flushing, vomiting, weakness, hypotension, chest tightness, 
and shortness of breath, as well as abnormalities in laboratory values (eg, creatinine, 
transaminases). The relative roles of the immunoproteasome versus constitutive proteasomes 
to these specific events are not known. Therefore, terms such as eg, the NCI-CTCAE or 
Medical Dictionary for Regulatory Activities (MedDRA) terms of ‘injection related reaction,’ 
‘cytokine release syndrome,’ ‘systemic immune activation,’ ‘drug hypersensitivity,’ 
‘hypersensitivity reaction,’ or ‘allergic reaction’ should not be used. Instead, each sign or 
symptom should be recorded as an individual AE with its own level of severity, even if 
multiple signs or symptoms occur.  
Management of systemic injection reactions is described in Section 6.1.3. 
9.5.2. 
Thrombotic Microangiopathy 
Cases of TMA, including TTP and HUS have been described with the nonspecific 
proteasome inhibitors, bortezomib, carfilzomib, and ixazomib, and are considered AESIs. 
One SAE of TMA has also been reported in a patient with SLE receiving KZR-616. While 
SLE itself is a risk factor for TMA, the contribution of KZR-616 to the event could not be 
ruled out. The clinical presentation of TMA typically includes fever, microangiopathic 
hemolytic anemia (with schistocytes on blood smear), thrombocytopenia, renal failure, 
purpura, and neurological manifestations. Patients should be monitored for signs and 
symptoms of TTP/HUS. If the diagnosis is suspected, interrupt treatment with study drug and 
evaluate (refer to Section 8.1.2). Missed doses should be addressed as per Section 6.1.4.2. If 
the diagnosis of TTP/HUS is excluded, study drug may be resumed. If the diagnosis is 
confirmed, study drug must be permanently discontinued (refer to Section 8.2). 
9.6. 
Unexpected Adverse Reactions 
9.6.1. 
Unexpected Adverse Reaction Definition 
An unexpected adverse reaction is any untoward and unintended response that is related to 
the administration of the study drug at any dose that is not consistent with the applicable 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 80 of 95 
product information (eg, IB for an unauthorized investigational medicinal product or 
prescribing information for an authorized product). 
All suspected unexpected serious adverse reactions (SUSARs) will be subject to expedited 
reporting. The Sponsor or designee shall ensure that all relevant information about a SUSAR 
that is fatal or life-threatening is reported to the relevant competent authorities and IRB/IEC 
within 7 days after knowledge by the Sponsor of such a case and that relevant follow-up 
information is communicated within an additional 8 days. All other SUSARs will be reported 
to the relevant competent authorities and IRB/IEC within 15 days after knowledge by the 
Sponsor of such a case. All Investigators should follow up SUSARs until the event is 
resolved or until, in the opinion of the Investigator, the event is stabilized or determined to be 
chronic. Post study SUSARs that occur after the patient has completed the clinical study 
must be reported by the Investigator to the Sponsor. 
9.7. 
Data Monitoring Committee 
To enhance the safety and integrity of the study data, a study-specific DMC will be 
established for interim safety monitoring. The specific responsibilities and composition of the 
DMC are outlined in a separate DMC Charter. In addition, the details of outputs provided for 
the meetings will be referenced in the separate document. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 81 of 95 
10.  
STATISTICAL ANALYSES 
A detailed Statistical Analysis Plan (SAP) will be prepared for approval by the Sponsor prior 
to performing any unblinded analysis for presentation to personnel designated as being 
blinded to the randomization. 
10.1. Sample Size Calculation 
Prior summary statistics on change from Baseline in TIS score are not available. Hence, 
statistical power is quantified via standardized effect size (mean difference divided by pooled 
standard deviation [SD]). A sample size of 24 patients has 80% power to yield a statistically 
significant (α=0.05 2-sided) improvement from Baseline if the true underlying effect size is 
0.6 (90% power if true effect size is 0.7). The minimum observed effect size that would yield 
statistical significance is 0.42. This level of statistical precision is thought to be adequate for 
this initial trial of KZR-616 in PM and DM. 
10.2. Analysis Populations 
The Safety Analysis Set consists of all patients who receive at least 1 dose of the study drug.  
The Full Analysis Set (FAS) consists of all patients who receive at least 1 dose of the study 
drug and who have a Baseline and post-Baseline observation. This is the primary efficacy 
analysis set for the study.  
The Per Protocol Analysis Set consists of all patients in the FAS, excluding those identified 
as having relevant protocol deviations.  
The PK Analysis Set consists of all patients who received at least 1 dose of KZR-616 and for 
whom the PK data are considered sufficient. Since this is a Phase 2 trial, all analyses and 
summaries will be based on the actual test treatment the respective patients received. 
10.3. Efficacy Analysis 
The primary endpoint is mean change from start to end of KZR-616 treatment in TIS.2. For 
the continuous efficacy parameters, within-patient changes will be analyzed as follows:  
 (1: primary) by comparing the Baseline and post Baseline observations within patients for 
the KZR-616 treatment periods combined, ie, W16 versus W0 for patients allocated to 
the randomized treatment sequence KZR-616 followed by placebo and W32 versus W16 
for patients allocated to the randomized treatment sequence placebo followed by  
KZR-616, combined; 
 (2: secondary) by comparing the change from Baseline in Treatment Period 1 between 
treatments, ie, change from W0 to W16 for patients allocated to the randomized treatment 
sequence KZR-616 followed by placebo versus change from W0 to W16 for patients 
allocated to the randomized treatment sequence placebo followed by KZR-616; and  
 (3: exploratory) by comparing the last response on test treatment between treatments via 
a crossover design analysis, ie, W16 for patients allocated to the randomized treatment 
sequence KZR-616 followed by placebo and W32 for patients allocated to the 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 82 of 95 
randomized treatment sequence placebo followed by KZR-616, combined, versus W16 
for patients allocated to the randomized treatment sequence placebo followed by  
KZR-616 and W32 for patients allocated to the randomized treatment sequence KZR-616 
followed by placebo, combined.   
The rationale for this priority order is as follows. The usual crossover analysis for this design 
is prespecified as exploratory since it is unknown whether that analysis would be confounded 
by carryover effect. In order to maximize the precision for assessment of KZR-616 effect, it 
is assessed primarily via all patients’ Baseline versus post-Baseline KZR-616 assessment and 
secondarily by the Treatment Period 1 between-treatment comparison. Summary statistics, 
including 95% confidence intervals, will be provided for each treatment for each of the 
3 types of analysis. Within-patient changes will be analyzed via paired t-tests and 
corroborated by signed rank tests. Between-patient differences will be analyzed via analysis 
of covariance, with Baseline as a covariate. The crossover analysis will be via a mixed-model 
repeated-measures analysis. Normality will be assessed graphically and via the Shapiro-Wilk 
statistic. If substantial departure from normality is observed, transformations, eg, natural log 
and rank, will be explored. P values will be 2-sided with at the type 1 error level 0.05. 
Binary endpoints will be summarized by counts and percent and 95% confidence intervals 
via Clopper-Pearson method. Additional analyses will be specified in the SAP. 
10.4. Safety Analysis 
The safety analysis set will be used for all presentations of safety endpoints. No statistical 
testing will be used to compare treatment groups for different safety endpoints. Safety data 
will be summarized descriptively for each test treatment. All AEs will be coded using the 
current version of the MedDRA. Treatment emergent AEs will be presented within summary 
presentations, by MedDRA system organ class, preferred term, and treatment group. 
Additional analyses will be specified in the SAP. 
10.5. Pharmacokinetic and Pharmacodynamic Analyses 
Blood samples for assay of KZR-616 plasma concentrations will be collected periodically. 
The plasma KZR-616 and its metabolite KZR-59587 concentrations and PK parameters will 
be listed and summarized by appropriate summary statistics (eg, geometric means, natural 
log-scale SD, medians, quartiles). Further details of the analysis of PK data will be described 
in a PK analysis plan, if appropriate. 
Whole blood samples for determination of proteasome activity will be collected periodically 
and processed to washed whole blood and isolated PBMC pellets. Chymotrypsin-like activity 
and proteasome subunit active site occupancy in each compartment will be assessed and 
presented as absolute and predose-normalized values. Individual proteasome activity and 
PBMC data will be listed for each patient and summarized by nominal sampling time point 
and treatment group with descriptive statistics (sample size [N], arithmetic mean, SD, 
median, minimum, and maximum). A summary of change from Baseline at each protocol 
specified time point by treatment group will also be presented. Individual and summary (by 
treatment group) parameter values over time will also be presented graphically. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 83 of 95 
Additional analyses will be specified in the SAP. 
 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 84 of 95 
11.  
ETHICAL AND ADMINISTRATIVE CONSIDERATIONS 
11.1. Compliance Statement 
The Investigator(s) and all parties involved in this study should conduct the study in 
adherence to the ethical principles based on the Declaration of Helsinki, International 
Conference on Harmonisation (ICH) guidelines for current GCP, and the applicable national 
and local laws and regulatory requirements. 
Relevant study documentation will be submitted to the regulatory authorities of the 
participating countries, according to local/regional/national requirements, for review and 
approval before the beginning of the study. On completion of the study, the regulatory 
authorities will be notified that the study has ended. 
11.2. Institutional Review Board or Independent Ethics Committee 
Before initiation of the study at each study center, the protocol, the informed consent form 
(ICF), other written material given to the patients, and any other relevant study 
documentation will be submitted to the appropriate IRB/IEC. Written approval of the study 
and all relevant study information must be obtained before the study center can be initiated or 
the study drug is released to the Investigator. Any necessary extensions or renewals of 
IRB/IEC approval must be obtained for changes to the study (ie, amendments to the protocol, 
the ICF, or other study documentation). The written approval of the IRB/IEC together with 
the approved ICF must be filed in the study files. 
The Investigator will report promptly to the IRB/IEC any new information that may 
adversely affect the safety of the patients or the conduct of the study. The Investigator will 
submit written summaries of the study status to the IRB/IEC as required. On completion of 
the study, the IRB/IEC will be notified that the study has ended. 
11.3. Informed Consent and Human Patient Protection  
The process of obtaining informed consent must be in accordance with applicable regulatory 
requirement(s) and must adhere to current GCP. 
Patients will provide written informed consent before any study-related procedures are 
performed. 
The Investigator is responsible for ensuring that no patient undergoes any study-related 
examination or activity before that patient has given written informed consent to participate 
in the study. 
The Investigator or designated personnel will inform the patient of the objectives, methods, 
anticipated benefits, and potential risks and inconveniences of the study. The patient should 
be given every opportunity to ask for clarification of any points s/he does not understand and, 
if necessary, ask for more information. At the end of the interview, the patient will be given 
ample time to consider the study. Patients will be required to sign and date the ICF. After 
signatures are obtained, the ICF will be kept and archived by the Investigator in the 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 85 of 95 
Investigator’s study file. A signed and dated copy of the patient ICF will be provided to the 
patient or their authorized representative. 
It should be emphasized that the patient may refuse to enter the study or to withdraw from 
the study at any time, without consequences for their further care or penalty or loss of 
benefits to which the patient is otherwise entitled. Patients who refuse to give or who 
withdraw written informed consent should not be included or continue in the study. 
If new information becomes available that may be relevant to the patient’s willingness to 
continue participation in the study, a new ICF will be approved by the IRB(s)/IEC(s) (and 
regulatory authorities, if required). The study patients will be informed about this new 
information and reconsent will be obtained. 
11.4. Direct Access to Source Data, Source Documents, and Study Reports 
The Sponsor or its representatives may periodically check a sample of the patient data 
recorded against source documents at the study site. The study may be audited by the 
Sponsor, designee, and/or regulatory agencies at any time. Investigators will be given notice 
before an audit occurs. 
The Investigator will keep records of all original source data. This might include laboratory 
tests, medical records, and clinical notes. If requested, the Investigator will provide the 
Sponsor, applicable regulatory agencies, and applicable review boards with direct access to 
the original source documents. 
11.5. Data Collection and Handling 
An EDC system will be used in this study. The site must define and retain all source records 
and must maintain a record of any data where source data are directly entered into the EDC 
system.  
Data systems used for the study will have controls and requirements in accordance with local 
data protection law.   
The purpose and use of patient personal information collected will be provided in a written 
document to the patient by the Sponsor or designee. 
Remaining sample material will be stored off-site at 
, and will be accessible to 
only the Sponsor for up to 2 years after the completion of the study, or until the sample 
material is entirely used up. 
11.6. Confidentiality 
Monitors, auditors, and other authorized agents of the Sponsor and/or its designee, the 
IRB(s)/IEC(s) approving this research, and the Food and Drug Administration (FDA), as well 
as that of any other applicable agency(ies), will be granted direct access to the study patients’ 
original medical records for verification of clinical study procedures and/or data, without 
violating the confidentiality of the patients to the extent permitted by the law and regulations. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 86 of 95 
In any presentations of the results of this study or in publications, the patients’ identity will 
remain confidential. 
All personal data collected and processed for the purposes of this study should be managed 
by the Investigator and his/her staff with adequate precautions to ensure confidentiality of 
those data, and in accordance with the Health Insurance Portability and Accountability Act 
and national, regional and/or local laws and regulations on personal data protection. 
11.7. Financing and Insurance 
Financing and insurance of this study will be outlined in a separate agreement between the 
Sponsor and designee.  
11.8. Audit and Inspection 
Study centers and study documentation may be subject to Quality Assurance audit during the 
course of the study by the Sponsor or its nominated representative. In addition, inspections 
may be conducted by regulatory authorities at their discretion. 
11.9. Monitoring 
Data for each patient will be recorded on an eCRF. Data collection must be completed for 
each patient who signs an ICF. 
In accordance with current GCP and ICH guidelines, the study monitor will carry out source 
document verification at regular intervals to ensure that the data collected in the eCRF are 
accurate and reliable.  
The Investigator must permit the monitor, the IRB/IEC, the Sponsor’s internal auditors, and 
representatives from regulatory authorities’ direct access to all study-related documents and 
pertinent hospital or medical records for confirmation of data contained within the eCRFs. 
11.10. Data Management and Coding 
The Sponsor or designee will be responsible for activities associated with the data 
management of this study. This will include setting up a relevant database and data transfer 
mechanisms, along with appropriate validation of data and resolution of queries. Data 
generated within this clinical study will be handled according to the relevant standard 
operating procedures of the data management and biostatistics departments of Sponsor or 
designee. 
Study centers will enter data directly into an EDC system by completing the eCRF via a 
secure internet connection. Data entered into the eCRF must be verifiable against source 
documents at the study center. Data to be recorded directly on the eCRF will be identified 
and the eCRF will be considered the source document. Any changes to the data entered into 
the EDC system will be recorded in the audit trail and will be FDA CFR 21 Part 11 
compliant. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 87 of 95 
Medical coding will use MedDRA for concomitant diseases and AEs and will use World 
Health Organization (WHO) drug classifications for medications. 
Missing or inconsistent data will be queried in writing to the Investigator for clarification. 
Subsequent modifications to the database will be documented. 
11.11. Reporting and Publication, Including Archiving 
Essential documents are those documents that individually and collectively permit evaluation 
of the study and quality of the data produced. After completion of the study (End of Study 
defined as the date of the last visit of the last patient), all documents and data relating to the 
study will be kept in an orderly manner by the Investigator in a secure study file. This file 
will be available for inspection by the Sponsor or its representatives. Essential documents 
should be retained for 2 years after the final marketing approval in an ICH region or for at 
least 2 years since the discontinuation of clinical development of the investigational product. 
It is the responsibility of the Sponsor to inform the study center when these documents no 
longer need to be retained. The Investigator must contact the Sponsor before destroying any 
study-related documentation. In addition, all patient medical records and other source 
documentation will be kept for the maximum time permitted by the hospital, institution, or 
medical practice. 
The Sponsor must review and approve any results of the study or abstracts for professional 
meetings prepared by the Investigator(s). Published data must not compromise the objectives 
of the study. Data from individual study centers in multicenter studies must not be published 
separately. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 88 of 95 
12.  
REFERENCES 
1. Agarwal S, Kiely PD. Two simple, reliable and valid tests of proximal muscle 
function, and their application to the management of idiopathic inflammatory 
myositis. Rheumatology (Oxford). 2006;45(7):874-9. 
2. Aggarwal R, Rider LG, Ruperto N, Bayat N, Erman B, Feldman B, Oddis C. 2016 
American College of Rheumatology/European League Against Rheumatism criteria 
for minimal, moderate and major clinical response for adult dermatomyositis and 
polymyositis: An International Myositis Assessment and Clinical Studies 
Group/Paediatric Rheumatology International Trials Organisation Collaborative 
Initiative. Ann Rheum Dis. 2017;76(5):792-801. 
3. Alexander T, Sarfert R, Klotsche J, et al. The proteasome inhibitor bortezomib 
depletes plasma cells and ameliorates clinical manifestations of refractory systemic 
lupus erythematosus. Ann Rheum Dis. 2015;74(7):1474-8. 
4. Alexanderson H, Broman L, Tollbäck A, et al. Functional Index-2: validity and 
reliability of a disease-specific measure of impairment in patients with polymyositis 
and dermatomyositis. Arthritis Rheum. 2006;55(1):114-22. 
5. Arastu-Kapur S, Anderl JL, Kraus M, et al. Nonproteasomal targets of the proteasome 
inhibitors bortezomib and carfilzomib: a link to clinical adverse events. Clin Cancer 
Res. 2011;17(9):2734-43. 
6. Atkinson MJ, Kumar R, Cappelleri JC, et al. Hierarchical construct validity of the 
treatment satisfaction questionnaire for medication (TSQM version II) among 
outpatient pharmacy consumers. Value Health. 2005;8(Suppl 1):S9-S24. 
7. Bennett MK, Kirk CJ. Development of proteasome inhibitors in oncology and 
autoimmune diseases. Curr Opin Drug Discov Devel. 2008;11(5):616-25. 
8. Bhattarai S, Ghannam K, Krause S, et al. The immunoproteasomes are key to regulate 
myokines and MHC class I expression in idiopathic inflammatory myopathies. 
J Autoimmun. 2016;75:118-29.  
9. Bogdanov I, Kazandjieva J, Darlenski R, et al. Dermatomyositis: Current concepts. 
Clin Dermatol. 2018;36(4):450-8.  
10. Bross PF, Kane R, Farrell AT, et al. Approval summary for bortezomib for injection 
in the treatment of multiple myeloma. Clin Cancer Res. 2004;10(12 Pt 1):3954-64.  
11. Ciechanover A. Intracellular protein degradation: From a vague idea through the 
lysosome and the ubiquitin-proteasome system and onto human diseases and drug 
targeting. Best Pract Res Clin Haematol. 2017;30(4):341-55.  
12. Clark KEN, Isenberg DA. A review of inflammatory idiopathic myopathy focusing 
on polymyositis. Eur J Neurol. 2018;25(1):13-23. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 89 of 95 
13. Coux O, Tanaka K, Goldberg AL. Structure and functions of the 20S and 26S 
proteasomes. Annu Rev Biochem. 1996;65:801-47. 
14. Cruellas MG, Viana Vdos S, Levy-Neto M, et al. Myositis-specific and  
myositis-associated autoantibody profiles and their clinical associations in a large 
series of patients with polymyositis and dermatomyositis. Clinics (Sao Paulo). 
2013;68(7):909-14. 
15. Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. Lancet. 
2003;362(9388):971-82. 
16. Dalakas MC. Inflammatory muscle diseases. N Engl J Med. 2015;372(18):1734-47. 
17. Dimopoulos MA, Moreau P, Palumbo A, et al. Carfilzomib and dexamethasone 
versus bortezomib and dexamethasone for patients with relapsed or refractory 
multiple myeloma (ENDEAVOR): A randomised, phase 3, open-label, multicentre 
study. Lancet Oncol. 2016;17(1):27-38. 
18. Egerer K, Kuckelkorn U, Rudolph PE, et al. Circulating proteasomes are markers of 
cell damage and immunologic activity in autoimmune diseases. J Rheumatol. 
2002;29(10):2045-52.  
19. Furst DE, Amato AA, Iorga SR, et al. Epidemiology of adult idiopathic inflammatory 
myopathies in a U.S. managed care plan. Muscle Nerve. 2012;45(5):676-83.  
20. Ghannam K, Martinez-Gamboa L, Spengler L, et al. Upregulation of 
immunoproteasome subunits in myositis indicates active inflammation with 
involvement of antigen presenting cells, CD8 T-cells and IFNγ. PLoS One. 
2014;9(8):e104048.  
21. Glynne R, Powis SH, Beck S. et al. A proteasome-related gene between the two ABC 
transporter loci in the class II region of the human MHC. Nature. 
1991;353(6342):357-60. 
22. Guy W (ed). ECDEU assessment manual for psychopharmacology. Rockville, MD: 
U.S. Dept. of Health, Education, and Welfare, Public Health Service, Alcohol, Drug 
Abuse, and Mental Health Administration, National Institute of Mental Health, 
Psychopharmacology Research Branch, Division of Extramural Research Programs, 
1976. 
23. Harvey RD. Incidence and management of adverse events in patients with relapsed 
and/or refractory multiple myeloma receiving single-agent carfilzomib. Clin 
Pharmacol. 2014;6:87-96. 
24. Hay EM. The BILAG index: a reliable and valid instrument for measuring clinical 
disease activity in systemic lupus erythematosus. Q J Medicine. 1993;86:447-58. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 90 of 95 
25. Herndon TM, Deisseroth A, Kaminskas E, et al. U.S. Food and Drug Administration 
approval: carfilzomib for the treatment of multiple myeloma. Clin Cancer Res. 
2013;19(17):4559-63. 
26. Huber EM, Basler M, Schwab R, et al. Immuno- and constitutive proteasome crystal 
structures reveal differences in substrate and inhibitor specificity. Cell. 
2012;148(4):727-38. 
27. Ichikawa HT, Conley T, Muchamuel T, et al. Beneficial effect of novel proteasome 
inhibitors in murine lupus via dual inhibition of type I interferon and  
autoantibody-secreting cells. Arthritis Rheum. 2012;64(2):493-503.  
28. Kalim KW, Basler M, Kirk CJ, Groettrup M. Immunoproteasome subunit LMP7 
deficiency and inhibition suppresses Th1 and Th17 but enhances regulatory T cell 
differentiation. J Immunol. 2012;189(8):4182-93.  
29. Kim HJ, Zeidi M, Bonciani D, et al. Itch in dermatomyositis: the role of increased 
skin interleukin-31. Br J Dermatol 2018;179(3):669-78. 
30. Kirk CJ. Discovery and development of second-generation proteasome inhibitors. 
Semin Hematol. 2012;49(3):207-14. 
31. Kisselev AF, van der Linden WA, Overkleeft HS. Proteasome inhibitors: an 
expanding army attacking a unique target. Chem Biol. 2012;19(1):99-115.  
32. Kocoloski A, Ward C, Koontz D, et al. Functional measures and patient home  
self-assessments in the idiopathic inflammatory myopathies. Arthritis Rheumatol. 
2017;69(Suppl 10). https://acrabstracts.org/abstract/functional-measures-and-patient-
home-self-assessments-in-the-idiopathic-inflammatory-myopathies/. Accessed 
12 Feb 2019. 
33. Leggett LE, Khadaroo RG, Holroyd-Leduc J, et al. Measuring resource utilization: A 
systematic review of validated self-reported questionnaires. Medicine (Baltimore). 
2016;95(10):e2759. 
34. Lundberg IE, Miller FW, Tjarnlund A, et al. Diagnosis and classification of idiopathic 
inflammatory myopathies. J Intern Med. 2016;280(1):39-51. 
35. Martinez CK, Monaco JJ. Homology of proteasome subunits to a major 
histocompatibility complex-linked LMP gene. Nature. 1991;353(6345):664-7. 
36. Muchamuel T, Basler M, Aujay MA, et al. A selective inhibitor of the 
immunoproteasome subunit LMP7 blocks cytokine production and attenuates 
progression of experimental arthritis. Nat Med. 2009;15(7):781-7.  
37. Nandi D, Jiang H, Monaco JJ. Identification of MECL-1 (LMP-10) as the third  
IFN-gamma-inducible proteasome subunit. J Immunol. 1996;156(7):2361-4. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 91 of 95 
38. O'Connor O, Stewart AK, Vallone M, Molineaux CJ, Kunkel LA, Gerecitano JF, 
Orlowski RZ. A phase 1 dose escalation study of the safety and pharmacokinetics of 
the novel proteasome inhibitor carfilzomib (PR-171) in patients with hematologic 
malignancies. Clin Cancer Res. 2009;15(22):7085-92. 
39. Parlati F, Lee SJ, Aujay M, et al. Carfilzomib can induce tumor cell death through 
selective inhibition of the chymotrypsin-like activity of the proteasome. Blood. 
2009;114(16):3439-47. 
40. Pinto D, Robertson MC, Hansen P, et al. Good agreement between questionnaire and 
administrative databases for health care use and costs in patients with osteoarthritis. 
BMC Med Res Methodol. 2011;11:45. 
41. Rider LG, Koziol D, Giannini EH, et al. Validation of manual muscle testing and a 
subset of eight muscles for adult and juvenile idiopathic inflammatory myopathies. 
Arthritis Care Res. 2010;62(4):465–72. 
42. Rider LG, Werth VP, Huber AM, et al. Measures of adult and juvenile 
dermatomyositis, polymyositis, and inclusion body myositis: Physician and 
Patient/Parent Global Activity, Manual Muscle Testing (MMT), Health Assessment 
Questionnaire (HAQ)/Childhood Health Assessment Questionnaire (C-HAQ), 
Childhood Myositis Assessment Scale (CMAS), Myositis Disease Activity 
Assessment Tool (MDAAT), Disease Activity Score (DAS), Short Form 36 (SF-36), 
Child Health Questionnaire (CHQ), physician global damage, Myositis Damage 
Index (MDI), Quantitative Muscle Testing (QMT), Myositis Functional Index-2 (FI-
2), Myositis Activities Profile (MAP), Inclusion Body Myositis Functional Rating 
Scale (IBMFRS), Cutaneous Dermatomyositis Disease Area and Severity Index 
(CDASI), Cutaneous Assessment Tool (CAT), Dermatomyositis Skin Severity Index 
(DSSI), Skindex, and Dermatology Life Quality Index (DLQI). Arthritis Care 
Res. 2011;63(Suppl 11):S118-57.  
43. Robinson AB, Reed AM. Clinical features, pathogenesis and treatment of juvenile 
and adult dermatomyositis. Nat Rev Rheumatol. 2011;7(11):664-75. 
44. Sciorati C, Rigamonti E, Manfredi AA, et al. Cell death, clearance and immunity in 
the skeletal muscle. Cell Death Differ. 2016;23(6):927-37. 
45. Siegel DS. From clinical trials to clinical practice: single-agent carfilzomib adverse 
events and their management in patients with relapsed and/or refractory multiple 
myeloma. Ther Adv Hematol. 2013;4(6):354-65. 
46. Smoyer-Tomic KE, Amato AA, Fernandes AW. Incidence and prevalence of 
idiopathic inflammatory myopathies among commercially insured, Medicare 
supplemental insured, and Medicaid enrolled populations: an administrative claims 
analysis. BMC Musculoskelet Disord. 2012;13:103.  
47. Sultan SM, Allen E, Oddis CV, et al. Reliability and validity of the myositis disease 
activity assessment tool. Arthritis Rheum. 2008; 58(11):3593-9. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 92 of 95 
48. Sultan SM, Allen E, Cooper RG, et al. Interrater reliability and aspects of validity of 
the myositis damage index. Ann Rheum Dis. 2011;70(7):1272-6. 
49. Vancsa A, Gergely L, Ponyi A, et al. Myositis-specific and myositis-associated 
antibodies in overlap myositis in comparison to primary dermatopolymyositis: 
Relevance for clinical classification: retrospective study of 169 patients. Joint Bone 
Spine. 2010;77(2):125-30. 
50. Whiting-O’Keefe QE, Stone JH, Hellmann DB. Validity of a vasculitis activity index 
for systemic necrotizing vasculitis. Arthritis Rheum 1999;42(11):2365-71.  
51. Wilk S, Orlowski M. Evidence that pituitary cation-sensitive neutral endopeptidase is 
a multicatalytic protease complex. J Neurochem. 1983;40(3):842-9. 
52. Yassaee M, Fiorentino D, Okawa L, et al. Modification of the cutaneous 
dermatomyositis disease area and severity index, an outcome instrument. Br J 
Dermatol. 2010;162:669-73. 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 93 of 95 
13.  
APPENDICES 
Appendix A: Recommended Cancer Screenings 
Recommended Cancer Screenings (adapted from American Cancer Society guidelines, 
available at https://www.cancer.org/health-care-professionals/american-cancer-society-
prevention-early-detection-guidelines.html (Last accessed 28 February 2019) 
Breast Cancer 
Ages 40-54:  mammography annually 
Age ≥55:  
mammography every 1 to 2 years 
Enhanced detection methods should be considered (eg, magnetic resonance imaging, 
tomography, or ultrasound). 
Colon and Rectal Cancer and Polyps 
Ages 45-85:  fecal immunochemical test or high sensitivity, guaiac-based fecal occult blood 
test annually or multitarget stool deoxyribonucleic acid (DNA) test every 
3 years  
AND 
flexible sigmoidoscopy or computed tomography (CT) colonography every 
5 years or colonoscopy every 10 years 
Age ≥85:  
testing no longer recommended unless recent (less than 3 years) diagnosis of 
myositis; then the above should be performed 
Cervical Cancer 
For all women with a cervix (eg, no total hysterectomy), and regardless of human papilloma 
virus (HPV) vaccination status: 
Ages 21-29: 
Papanicolaou (Pap) test every 3 years with HPV testing only if result 
abnormal 
Ages 30-65: 
Pap test with HPV test every 5 years or Pap test only every 3 years 
Ages ≥65: 
continued testing with Pap test with HPV test every 5 years or Pap test only 
every 3 years only if test in the prior 10 years has been abnormal or if recent 
diagnosis (less than 3 years) of myositis 
Lung Cancer 
Ages 55-74 and currently smoke or have quit smoking in the past 15 years, and have a 
30 pack-year smoking history: low-dose CT scan yearly 
Prostate Cancer 

Protocol 
Kezar Life Sciences, Inc. 
KZR-616-003 
01 March 2019 
 
 
Confidential 
Page 94 of 95 
Ages ≥50: 
prostate-specific antigen blood test with rectal exam annually (ages ≥45 if 
African American or have a father or brother who had prostate cancer before 
age 65)