A Randomized, Double-blind, Placebo-controlled, Phase 2a Study With Open-label Extension to Evaluate the Safety and Efficacy of Zetomipzomib (KZR-616) in Patients With Autoimmune Hepatitis
Phase: PHASE2
Conditions: Autoimmune Hepatitis
Sponsor: Kezar Life Sciences, Inc.

 
KZR-616-208 
A RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED, PHASE 2A STUDY 
WITH OPEN-LABEL EXTENSION TO 
EVALUATE THE SAFETY AND EFFICACY OF 
ZETOMIPZOMIB (KZR-616) IN PATIENTS 
WITH AUTOIMMUNE HEPATITIS 
 
 
 
 
Clinicaltrials.gov Identifier 
NCT05569759 
Date of protocol: 
26 February 2024 
 
 
 

Confidential  
 
Page 1 of 86 
CLINICAL STUDY PROTOCOL 
Protocol Title: 
A Randomized, Double-blind, Placebo-controlled, Phase 2a 
Study with Open-label Extension to Evaluate the Safety and 
Efficacy of Zetomipzomib (KZR-616) in Patients with 
Autoimmune Hepatitis  
Protocol Number: 
KZR-616-208 
Investigational Medicinal 
Product: 
Zetomipzomib (KZR-616) 
Indication: 
Autoimmune hepatitis (AIH) 
Development Phase: 
2a 
 
 
Sponsor: 
Kezar Life Sciences, Inc. 
4000 Shoreline Court, Suite 300 
South San Francisco, CA 94080 
Telephone: 650-822-5600 
Protocol Version and Date: 
Version 4.0, 26 February 2024 
Version 3.0, 07 March 2023 
Version 2.0, 15 September 2022 
Version 1.0, 22 July 2022 
 
 
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 Council for 
Harmonisation (ICH), Guideline for Good Clinical Practice (GCP), and the applicable country 
and regional (local) regulatory requirements. 
 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 2 of 86 
  
 
STUDY PERSONNEL 
 
Serious Adverse Event Reporting Details (to be used for submitting SAE forms and 
Pregnancy Report Form): 
 
Central Safety Fax: 
 
* = country exit code 
 
Kezar/Clinical Study Lead 
Name 
Title 
 
 
Address 
Telephone No. 
4000 Shoreline Court, Suite 300, South San Francisco, CA 94080 
 
 
Medical Monitor 
Name 
Title 
 
Medical Monitor 
Email 
Telephone No. 
 
 
 
Serious Adverse Event Reporting Contact 
 Safety Lead 
Name 
Title 
 
Senior Project Manager 
Telephone No. 
 
 
 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 3 of 86 
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 Council for 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 Name: 
 
Name of Institution/Site: 
 
Signature: 
 
Date: 
 
 
 
 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 4 of 86 
PROTOCOL SYNOPSIS 
NAME OF INVESTIGATIONAL PRODUCT: 
zetomipzomib (KZR-616) 
NAME OF ACTIVE INGREDIENT: 
zetomipzomib (KZR-616) maleate 
CLINICAL CONDITION(S)/INDICATION(S) 
Autoimmune hepatitis (AIH) 
PROTOCOL NUMBER: KZR-616-208 
PROTOCOL TITLE: 
A Randomized, Double-blind, Placebo-controlled, Phase 2a Study with Open-Label Extension to Evaluate the 
Safety and Efficacy of Zetomipzomib (KZR-616) in Patients with Autoimmune Hepatitis  
SHORT TITLE: Safety and Efficacy of Zetomipzomib (KZR-616) for Autoimmune Hepatitis  
STUDY PHASE: Phase 2a 
STUDY OBJECTIVES: 
Safety: To evaluate the safety and tolerability of zetomipzomib (KZR-616) in patients with autoimmune 
hepatitis (AIH). 
Efficacy: The efficacy objective for the Double-blind Treatment Period is to evaluate the efficacy of zetomipzomib 
in addition to standard-of-care in patients with AIH who have failed standard-of-care treatment, had an incomplete 
biochemical response to ≥3 months of standard-of-care treatment, or had a disease flare after experiencing 
complete remission induced by standard-of-care treatment. The efficacy objective for the OLE Period is to evaluate 
the long-term efficacy of zetomipzomib in patients with AIH. 
STUDY DESIGN: 
This is a Phase 2a, multi-center, randomized, double-blind, placebo-controlled study with an open-label extension 
to evaluate the safety, tolerability, and efficacy of zetomipzomib in patients with AIH who have failed standard-of-
care treatment, had an incomplete biochemical response to ≥3 months of standard-of-care treatment, or had a 
disease flare after experiencing complete remission induced by standard-of-care treatment. 
Double-blind Treatment Period 
In the Double-blind Treatment Period, zetomipzomib or placebo will be administered weekly for a 24-week 
treatment period. A screening period of up to 4 weeks will precede Day 1. Efficacy will be assessed at Weeks 12, 
16, 20, and 24; assessments are discussed in Section 7.2.2. Safety will be assessed throughout the study by 
monitoring of vital signs, clinical laboratory tests, and physical examinations, and by recording and analyzing all 
adverse events (AEs) and serious AEs (SAEs). 
Eligible patients will be randomized in a 2:1 ratio on Day 1 (Visit 2) to receive either standard-of-care 
(glucocorticoids) with zetomipzomib (Active Treatment group), or standard-of-care with Placebo (Control group). 
Zetomipzomib and placebo (ie, sterile water for injection [WFI] in an equivalent volume to the reconstituted 
zetomipzomib dose), will be administered subcutaneously (SC) once weekly by study personnel at the site or by a 
home trial service at the patient’s home or alternate location (eg, place of employment). The first dose of 
investigational medicinal product (IMP) will be 30 mg zetomipzomib or placebo, followed by weekly doses of 
60 mg zetomipzomib or placebo for the remaining 23 weeks of the Double-blind Treatment Period.  
Enrolled patients will be on standard-of-care with a prednisone/prednisone equivalent dose of 20 mg/day on Day 1 
(Visit 2). Following consultation with the Medical Monitor, patients who are taking a prednisone/prednisone 
equivalent dose higher than 20 mg/day at Baseline may also be enrolled in the study provided the 
prednisone/prednisone equivalent dose does not exceed 40 mg/day. Patients are encouraged to undergo a 
glucocorticoid taper of prednisone/prednisone equivalent dose according to the protocol-suggested glucocorticoid 
taper schedule (Table 6) and prednisone equivalent doses (Table 7) as provided in Appendix B. Patients taking 
budesonide who are unwilling to switch to a prednisone/prednisone equivalent for the study may continue to take 
budesonide at the doses shown in Appendix B. For suggested glucocorticoid taper schedule, please see 
Appendix B.  

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 5 of 86 
In addition to prednisone/prednisone equivalent, patients may continue to use up to two additional 
immunosuppressive agents if these agents are already used as baseline therapy: 
a) Oral azathioprine (AZA) or oral mycophenolate mofetil (MMF; including the alternatives mycophenolate 
sodium [MMS] or mycophenolic acid [MPA]) 
and/or 
b) Oral tacrolimus (TAC), cyclosporine A (CsA), or 6-mercaptopurine (6-MP)  
The dose of these immunosuppressants must be stable for at least 4 weeks prior to Screening and must be held 
constant unless tolerability/AEs require dose adjustment and glucocorticoid taper is completed. Following 
completion of the glucocorticoid taper, immunosuppressants may be decreased at the Investigator’s discretion 
(Section 6.2.3). 
During the glucocorticoid taper, patients with signs and symptoms of worsening disease (ie, worsening of alanine 
aminotransferase [ALT] level ≥25% from Baseline for ≥1 week, as verified via repeat laboratory assessments) may 
increase glucocorticoid doses following consultation with the Medical Monitor.  
For patients who are confirmed treatment failures or who experience a disease flare (see Section 2.2.2) during the 
treatment period, IMP may be discontinued upon consultation with the Medical Monitor, and additional care will 
be introduced as medically indicated. Patients who receive rescue therapy (see Section 6.3) will temporarily 
discontinue IMP, complete the Double-blind Period visits, and remain eligible for the OLE Period. Patients who do 
not receive rescue therapy but undergo a temporary interruption in IMP (≤2 consecutive doses or ≤4 total doses) 
should also remain in the study. Patients who discontinue participation in the study due to a disease flare will be 
considered treatment failures. If the patient cannot continue with the planned assessments, the patient will complete 
the Early Termination Visit (ETV; Table 3) followed by the End-of-Study (EOS) visit (Table 3) 4 weeks later. 
Patients who are eligible to roll over to the OLE Period will receive their first SC injection of zetomipzomib at the 
dose and schedule described in the OLE Period section. Patients who are not eligible or choose not to roll over to 
the OLE Period will have an End-of-Study (EOS) visit (see Table 3) 4 weeks after completion of the Double-blind 
Treatment Period. 
A liver biopsy will be performed at the Week 24 visit to assess changes from Baseline in liver histopathology. 
Open-label Extension (OLE) Period 
Patients who complete the Double-blind Period study visits through Week 24 are eligible to roll over to the OLE 
Period. If a patient does not meet eligibility criteria for the OLE Period, then the patient would proceed with the 
EOS visit. The patient would not be considered a screen fail for the OLE Period. 
All patients will receive a SC injection of 30 mg zetomipzomib at the OLE Week 1 visit, followed by weekly SC 
injections of 60 mg zetomipzomib, administered by study personnel at the site or by a home trial service at the 
patient’s home or alternate location (eg, place of employment), for a total of 24 additional weeks of treatment. 
After the OLE Week 1 Visit, additional on-site study visits will occur at least every 4 weeks from OLE Week 4 
through OLE Week 20. An additional on-site visit will occur at OLE Week 25 (End-of-Treatment [EOT] visit). 
At these visits, safety and efficacy assessments will be performed. Patients will have a safety follow-up visit 
(EOS Visit) 4 weeks after their last dose of zetomipzomib, for a maximum potential length of participation in the 
OLE of 28 weeks. 
During the course of the OLE Period, prednisone/prednisone equivalent can continue to be tapered and may be 
withdrawn (see Appendix B for suggested taper schedule). Patients with signs and symptoms of worsening disease 
(ie, worsening of ALT level ≥25% from OLE Baseline for ≥1 week, as verified via repeat laboratory assessments) 
may increase glucocorticoid doses following consultation with the Medical Monitor. For patients who are 
confirmed treatment failures or who experience a disease flare (see Section 2.2.2) during the OLE Treatment 
Period, IMP may be discontinued upon consultation with the Medical Monitor, and additional care will be 
introduced as medically indicated. Patients who receive rescue therapy (see Section 6.3) will temporarily 
discontinue IMP but will remain in the study to complete OLE visits. Patients who do not receive rescue therapy 
but undergo a temporary interruption in IMP (≤2 consecutive doses or ≤4 total doses) should also remain in the 
study. Patients who discontinue participation in the study due to a disease flare will be considered treatment 
failures. If the patient cannot continue with the planned assessments, the patient will complete the ETV (Table 3) 
followed by the End-of-Study (EOS) visit (Table 3) 4 weeks later. 
An optional liver biopsy may be performed at the OLE Week 25 visit to assess changes in liver histopathology. 
The overall study design is shown in Figure 1.  

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 6 of 86 
Independent Data Monitoring Committee (IDMC) 
An Independent Data Monitoring Committee (IDMC) will review safety findings after data are available from the 
Double-blind Treatment Period Week 12 visit for 6, 12, 18, and 24 patients. After all patients have completed at 
least 12 weeks of treatment or have withdrawn early, the IDMC will continue to review safety data every 3 to 
6 months until the last patient completes the study. 
ENDPOINTS: 
Definitions related to study endpoints (eg, complete remission, partial remission, disease flare, etc.) can be found in 
Section 2.2.2. 
Safety Endpoints: 
The primary safety endpoint is the proportion of patients who experience AEs and SAEs. Other safety endpoints 
include: 
• 
Incidence, nature, and severity of AEs and SAEs  
• 
Incidence of AEs leading to IMP discontinuation and dose reduction 
• 
Changes in standard laboratory parameters, vital signs, and ECGs 
Efficacy Endpoints: 
Double-blind Treatment Period 
Primary Efficacy Endpoint 
• 
Proportion of patients who achieve complete remission (CR) by Week 24; analyses will also be performed 
on data collected at Weeks 12, 16, and 20 
Secondary Efficacy Endpoints  
• 
Changes from Baseline in ALT at Weeks 12, 16, 20, and 24 
• 
Proportion of patients who achieve partial remission (PR) at Week 12, 16, 20, and 24 
• 
Time to CR 
• 
Time to PR 
• 
Proportion of patients experiencing a disease flare after CR 
• 
Proportion of patients who are treatment failures 
• 
Proportion of patients who achieve CR or PR with successful glucocorticoid taper by Week 24; analyses 
will also be performed on data collected at Weeks 12, 16, and 20 
Exploratory Efficacy Endpoints: 
• 
Proportion of patients who achieve ALT normalization based on Prati criteria (males, 30 U/L; 
females, 19 U/L) (Prati et al., 2002), with successful glucocorticoid taper, by Week 24  
• 
Mean changes from Baseline in aspartate aminotransferase (AST) at Weeks 12, 16, 20, and 24 
• 
Mean changes from Baseline in immunoglobulin G (IgG) at Weeks 12, 16, 20, and 24 
• 
Mean changes from Baseline in glucocorticoid dose 
• 
Change from Baseline in the Glucocorticoid Toxicity Index (GTI) Cumulative Worsening Score 
(GTI-CWS) and the Aggregate Improvement Score (GTI-AIS) 
• 
Mean changes from Baseline in inflammatory cytokines at Weeks 8, 16, and 24  
• 
Change from Baseline in liver stiffness at Week 24, assessed by vibration-controlled transient 
elastography (VCTE) utilizing Fibroscan® 
• 
Mean change from Baseline in the EuroQol 5-dimension 5-level (EQ-5D-5L) at Weeks 16 and 24 
• 
Mean change from Baseline in Chronic Liver Disease Questionnaire (CLDQ) at Weeks 16 and 24 
• 
Change from Baseline in liver histopathology at Week 24, based on Ishak score (modified Histological 
Activity Index HAI]) scores (Ishak et al., 1995) 
Open-label Extension 
Primary Efficacy Endpoints 
• 
Proportion of patients experiencing a disease flare among the patients who achieved a CR during the 
Double-blind Treatment Period 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 7 of 86 
Exploratory Efficacy Endpoints 
• 
Proportion of patients who have a CR or PR among the patients who did not achieve a CR or PR during 
the Double-blind Treatment Period 
• 
Proportion of patients who have a CR or PR with successful glucocorticoid taper who did not achieve a 
CR or PR during Double-blind Treatment Period 
• 
Proportion of patients who achieve a glucocorticoid-free CR 
• 
Proportion of patients who achieve a glucocorticoid-free PR 
• 
Mean changes in ALT 
• 
Mean changes in AST 
• 
Mean changes in IgG 
• 
Mean change in the EQ-5D-5L 
• 
Mean change in CLDQ 
• 
Change in the GTI-CWS and the GTI-AIS 
• 
Mean change in liver stiffness, assessed by VCTE utilizing Fibroscan® 
• 
Change in liver histopathology, based on Ishak score (modified HAI) scores (Ishak et al., 1995) 
Pharmacokinetic Endpoints: 
• 
Zetomipzomib and its metabolite KZR-59587 pharmacokinetics (PK) (maximum concentration [Cmax], 
time of maximum concentration [Tmax], area under the concentration-time curve [AUC]) 
INVESTIGATIONAL PRODUCT(S), DOSE, AND MODE OF ADMINISTRATION: 
Investigational Medicinal Product: IMPs include zetomipzomib and placebo control. Placebo control will consist 
of sterile WFI in an equivalent volume to the reconstituted zetomipzomib dose. Instructions for the receipt, 
inspection, storage, preparation, administration, and disposal of IMP will be provided in a separate Pharmacy 
Manual.  
Dose and Dose Frequency: An unblinded Pharmacist will prepare and blind the active and placebo doses. During 
the Double-blind Treatment Period, IMP will be administered by SC injection once weekly, according to 
randomization. The first dose will be 30 mg zetomipzomib or placebo, administered at the clinical trial site, 
followed by weekly doses of 60 mg zetomipzomib or placebo for the remaining 23 weeks of the Double-blind 
Treatment Period. During the OLE Period, zetomipzomib will be administered to all patients by SC injection once 
weekly. The first open-label dose will be 30 mg zetomipzomib, followed by weekly doses of 60 mg zetomipzomib 
for the duration of the OLE Period. 
After the first dose, IMP will be administered by study personnel at the site or by a home trial service at the 
patient’s home or alternate location (eg, place of employment). Doses will be administered according to the 
Schedules of Assessments (Table 1 through Table 4). 
Background Medication: 
Patients will take their own supply of glucocorticoids. Enrolled patients will be on standard-of-care with a 
prednisone/prednisone equivalent dose of 20 mg/day on Day 1 (Visit 2). Following consultation with the Medical 
Monitor, patients who are taking a prednisone/prednisone equivalent dose higher than 20 mg/day at Day 1 may 
also be enrolled in the study provided the prednisone/prednisone equivalent dose does not exceed 40 mg/day. 
The prednisone equivalents are outlined in Appendix B. 
In addition to prednisone/prednisone equivalent, patients may continue to use up to two additional 
immunosuppressive agents if these agents are already used as baseline therapy: 
a) Oral AZA or oral MMF (including the alternatives MMS or MPA) 
and/or 
b) Oral TAC, CsA, or 6-MP 
The dose of these immunosuppressants must be stable for at least 4 weeks prior to Screening and must be held 
constant unless tolerability/AEs require dose adjustment and glucocorticoid taper is completed. Following 
completion of the glucocorticoid taper, immunosuppressants may be decreased at the Investigator’s discretion 
(Section 6.2.3). 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 8 of 86 
PATIENT SELECTION: 
Targeted Number of Patients: Approximately 24 patients (randomized in a 2:1 ratio; Active Treatment group: 
Control group) 
Planned Number of Sites: Up to 24 sites 
Inclusion Criteria: 
Double-blind Treatment Period 
1. Must be aged ≥18 years. 
2. Must have a clinical diagnosis of AIH and signs of active disease despite standard-of-care therapy for ≥3 
months or disease flare after experiencing complete remission induced by standard-of-care treatment, 
including: 
a. 
Screening ALT values that are 1.25 to 10 times the upper limit of normal (ULN) 
b. Liver biopsy results with Ishak score (modified HAI) ≥5/18 (Ishak et al., 1995) indicating active 
AIH, from a biopsy performed at Screening or within 6 months prior to Screening 
c. 
Mild or no hepatic impairment (Child-Pugh category A) 
3. Must be willing to use and taper glucocorticoid therapy as described in Section 3.1 and Section 6.2.2.1. 
4. Women of childbearing potential (WOCBP) must have a negative urine or serum pregnancy test prior to 
the first dose of IMP in Study KZR-616-208 and must agree to continue to use a highly effective method 
of birth control until completion of the study (or 30 days following the last dose of IMP in case of early 
withdrawal). For the purposes of this study, WOCBP are defined as fertile 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 or local laboratory and if patient is not on supplementary hormonal 
therapy) or surgically sterile (ie, tubal ligation, hysterectomy, bilateral salpingo-ophorectomy). 
5. Male patients must agree to use an effective contraception method (eg, condom with spermicide) during 
the study, and continue to use this method for 1 week following their last dose of IMP or be congenitally 
or surgically sterile (eg, vasectomy with documented confirmation of post-surgical aspermia). 
6. Must be willing and able to return for all protocol-specified clinic visits and complete all study-required 
procedures. 
Open-label Extension Period 
7. Same as Double-blind Treatment Period Inclusion criteria, except the following modifications to Inclusion 
Criterion 2: 
a. 
ALT value can be normal or, if elevated, in the range of 1.25 to 10 times the ULN  
b. Inclusion Criterion 2b does not apply to the OLE Period 
c. 
Inclusion Criterion 2c must be met  
8. Must have completed the Double-blind Period study visits through Week 24, including all Week 24 Visit 
assessments. 
9. Must be willing to maintain glucocorticoid therapy or continue to taper glucocorticoid therapy as 
described in Section 6.2.2.1. 
Exclusion Criteria: 
Double-blind Treatment Period 
1. Have a concomitant diagnosis of primary biliary sclerosis, primary sclerosing cholangitis, IgG 4-related 
cholangitis, drug-related AIH (at Screening) or a history of drug-related AIH. 
2. Have clinical evidence of significant unstable or uncontrolled diseases other than the disease under study 
(eg, cardiac [including congestive heart failure, hypertension, angina, or myocardial infarction], 
pulmonary [including pulmonary hypertension or interstitial lung disease], hematologic, gastrointestinal, 
endocrinologic, hepatic, renal, neurological, or infectious disease, any ongoing SAE(s), or AE(s) 
≥ Grade 3 by National Cancer Institute Common Terminology Criteria for Adverse Events 
[NCI-CTCAE]) that, in the opinion of the Investigator or Sponsor/designee, could confound the results of 
the study, put the patient at undue risk, or interfere with protocol adherence. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 9 of 86 
3. Are receiving oral or injectable immunomodulating treatment other than permitted concomitant 
medications in Section 6.2.3 prior to enrollment in the study. Patients who have been using such 
treatments must have had the washout periods outlined in Section 6.2.1. 
4. Have an active infection (eg, acute hepatitis E, cytomegalovirus, or Epstein-Barr virus) requiring systemic 
therapy with antibiotic, antiviral, or antifungal treatment, or has had any febrile illness within 7 days prior 
to Day -1. 
5. Have a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test (real-time 
polymerase chain reaction [RT-PCR]) at Screening or Day 1. 
6. Have a history of thyroiditis, celiac disease, or other autoimmune disorder known to be associated with 
transaminitis. 
7. Have a history of primary or acquired immunodeficiency.  
8. Have a history of malignancy of any type, with the exceptions of surgically excised nonmelanoma skin 
cancers, in situ cervical cancer >5 years prior to Baseline (Day 1), prostate cancer that is considered cured 
(normal prostate-specific antigen) for >5 years, colon cancer considered cured >5 years following surgical 
treatment, or lymphoma with >5 years complete remission. 
9. Have a history of solid organ transplant. 
10. Have a history of excessive alcohol use (consumption of 4 or more drinks on any day or 8 or more drinks 
per week for women and 5 or more drinks on any day or 15 or more drinks per week for men) or drug 
abuse in the 1 year prior to Screening, in the opinion of the Investigator. 
11. Have an estimated glomerular filtration rate <60 mL/min/1.73 m2 by the Modification of Diet in Renal 
Disease (MDRD) equation (National Institute of Diabetes and Digestive and Kidney Diseases [NIDDK]). 
12. Have a hemoglobin level <9.0 g/dL, neutrophil count <1200/mm3, or platelet count <120 × 109/L at 
Screening. 
13. Have a prothrombin time above ULN at Screening, or an International Normalized Ratio (INR) >1.2. 
NOTE: Minor changes in prothrombin time that may be attributable to permitted concomitant medications 
and that are not considered clinically significant by the Investigator are allowed. 
14. Have a history of hypercoagulability (including, but not limited to, antiphospholipid antibody syndrome, 
activated protein C resistance, elevated coagulation factor VIII levels, sticky platelet syndrome, protein C 
or S deficiency, homocystinemia, antithrombin deficiency, dysfibrinolysis, or prothrombin G20210A 
mutation), thrombotic events (including, but not limited to, deep vein, femoral vein, superior vena cava, or 
jugular vein thrombosis; thrombotic stroke; pulmonary embolism; myocardial infarction; retinal vein 
occlusion, or thrombotic microangiopathies), or hemolytic uremic syndrome. 
15. Have liver cirrhosis with significant impairment of liver function (Child Pugh category B or C) or have 
decompensated cirrhosis. 
16. Patients with histology confirmed coincident non-alcoholic steatohepatitis. NOTE: Patients with other 
type of non-alcoholic fatty liver disease are NOT excluded from the study. 
17. Have electrocardiogram (ECG) findings of QT corrected for pulse rate (QTcF)>480 msec, newly 
diagnosed (within 6 months prior to Screening) and/or poorly controlled atrial fibrillation (ie, symptomatic 
patients or a ventricular rate above 100 beats/min on ECG), or other clinically significant cardiac 
abnormalities. 
18. Have positive serology results at Screening (human immunodeficiency virus [HIV], hepatitis B [surface 
antigen and core antibodies], hepatitis C [anti-HCV antibody confirmed with hepatitis C RNA]). 
• 
Patients who are hepatitis B virus surface antigen (HBsAg) positive will not be eligible.  
• 
Patients who are HBsAg negative and hepatitis B core antigen antibody (HBcAb) positive will be 
tested for hepatitis B surface antibody (HBsAb) and hepatitis B DNA:  
– 
Patients with HBsAb titer ≥100 IU/L and negative hepatitis B DNA may be enrolled.  
– 
Patients with positive hepatitis B DNA results will be excluded.  
– 
Patients with HBsAb titer <100 IU/L or negative will be excluded. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 10 of 86 
19. Have positive interferon-gamma release assay (IGRA) (eg, T-SPOT tuberculosis [TB] Test, 
QuantiFERON®-TB Gold, or QuantiFERON®-TB Gold Plus (QFT Plus), at Screening, unless the patient 
has latent TB and all of the following conditions are true:  
• 
The chest X-ray does not show evidence suggestive of active TB. 
• 
There are no clinical signs or symptoms of pulmonary and/or extra-pulmonary TB. 
• 
The patient has documented evidence of receiving one of the following prophylactic treatment 
regimens: daily oral isoniazid for 6 months, daily oral rifampin for 6 months, or isoniazid and 
rifapentine weekly for 3 months. 
Note: If a QuantiFERON®-TB Gold/Gold Plus is indeterminate for any reason and a T-SPOT TB test 
is negative, the patient may be enrolled using the local result upon approval of the Sponsor. On a 
case-by-case basis, after discussion and approval by the Sponsor, a local TB test that is negative and 
is considered equivalent to one of the above tests may be used for eligibility. Without a negative test, 
unless treated as noted above, one or more indeterminant tests are not sufficient for the patient to be 
enrolled (see Section 7.2.4.5.1.1 ). 
20. Have taken rituximab, other B- or T-cell depleting agents, or alkylating agents within 6 months of 
Screening, unless B- or T-cells have been shown to return to normal values (B-cells [CD19+] 
>100 cells/μL; T-cells [CD4+] >500 cells/mm3 [0.64 × 109/L]). 
21. Require regular use of medications with known hepatotoxicity (see Section 6.2). 
22. Have previously used a proteasome inhibitor (dual proteasome inhibitors allowed if it has been at least 
1 year since last use). 
23. Have received a live vaccine within 28 days prior to Baseline (Day 1), or plan to receive a live vaccine 
during the study. 
24. Have used another investigational medical therapy, and/or participated in an investigational trial within 
6 months or 5 half-lives (whichever is longer) prior to Screening. 
25. Are females who are breastfeeding or who plan to become pregnant during the study, or who are actively 
trying to conceive at the time of signing of the informed consent form (ICF). 
26. Have known hypersensitivity to zetomipzomib or any of its excipients. 
Open-label Extension Period 
27. Same as the Double-blind Treatment Period exclusion criteria. No need to re-test for HIV, HBV, HCV, 
and TB. 
Patients who do not meet inclusion/exclusion criteria may be rescreened one time. 
Pharmacokinetic Analysis:  
Blood samples for determination of PK parameters (Cmax, Tmax, AUC) for zetomipzomib and its metabolite 
KZR-59587 will be collected from all patients during the Double-blind Treatment Period according to the Schedule 
of Assessments (Table 1).  
STATISTICAL ANALYSIS: 
The statistical analyses of the study data will be descriptive in nature, and no formal hypothesis testing will be 
performed. No formal statistical sample size or power estimation has been performed. The sample size of 
approximately 24 patients was set to allow a preliminary assessment of the potential effect of zetomipzomib with a 
glucocorticoid, and glucocorticoid treatment with placebo, in patients diagnosed with AIH. For example, a sample 
size of 16 patients (in the Active Treatment group) would have a two-sided 90% confidence interval (CI) with a 
half width of 0.188 (0.112–0.488), assuming a sample proportion of 0.30 (corresponding to efficacy and/or safety 
measure). This is a signal-seeking study designed to collect data and perform preliminary assessments on safety 
and efficacy endpoints between treatment groups. 
No interim analyses are planned for this study. The first planned unblinded analysis of the data will be conducted 
after all patients have completed or would have completed the Week 24 visit or EOS visit, whichever occurs later, 
in the Double-blind Treatment Period, data being fully cleaned and database being “soft” locked to limit changes. 
The final data analysis will be conducted after all patients have completed the study (Double-blind Treatment 
Period and OLE Period).  

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 11 of 86 
Patient baseline characteristics, the primary and secondary endpoints, including efficacy, PK, and safety measures, 
will be summarized using simple descriptive statistics. A between-treatment difference value in an efficacy 
endpoint (primary or secondary) will be summarized using a point estimate and a two-sided 95% CI. Statistical 
uncertainty with regard to the efficacy outcome estimate will be presented in a two-sided 95% CI. Change scores 
from Baseline to follow-up visits (ie, Weeks 12, 14, 16, 24, or OLE visits) on the continuous secondary outcome 
parameters may be analyzed using the Wilcoxon signed rank test. Two-sided p-values may be calculated to help 
assess strength of evidence. Due to the explorative nature of this study, no adjustments (in p-values) will be applied 
to perform multiple comparisons. 
Analysis Sets: 
Full Analysis Set (FAS): The FAS for summaries of efficacy endpoints will include all randomized patients who 
receive at least 1 dose of IMP or glucocorticoid in this study and have baseline and at least one post-treatment data 
for the following measures: ALT, AST, IgG, Ishak score, and autoantibodies. All observed data will be included in 
the data summaries. 
Per Protocol (PP): A PP population may be used to analyze select efficacy endpoints and will be based on 
zetomipzomib exposure (time on treatment) and protocol deviations. 
Safety Population: The safety population will include all randomized patients who received at least 1 dose of IMP 
and will be the population used for the analysis of safety data.  
AE data will be coded to system organ class and preferred term using Medical Dictionary for Regulatory Activities 
(MedDRA; Version 25.0 or later). The number and percentage of patients experiencing any treatment-emergent AE 
(TEAE), overall, and by system organ class and preferred term will be tabulated. Values for clinical laboratory 
results, vital signs, weight, and ECG findings will be tabulated for each visit. 
Further details of the statistical methodology, including methods for handling missing data and early withdrawals, 
will be provided in a statistical analysis plan (SAP) that will be finalized prior to any planned unblinded analysis. 
 
 
 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
 
 
 
Page 15 of 86 
g Vital signs (pulse rate, respiratory rate, blood pressure, and body temperature) will be collected prior to dosing. Pulse rate and blood pressure (using a 
calibrated sphygmomanometer) should be collected after the patient has been resting for at least 5 minutes in the seated position (pulse rate first, followed by 
blood pressure). If the blood pressure is elevated on the first measurement at Screening, it should be repeated after at least an additional 5 minutes of rest. It is 
recommended that blood pressure be 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. 
h 12-lead ECG should be performed after the patient has been resting for at least 5 minutes in the supine position. 
i It is recommended that the EQ-5D-5L and CLDQ be completed prior to any other procedures or assessments (other than signing of informed consent) at 
applicable visits. 
j See Section 7.2.4.5 for the list of autoantibodies. In addition to the timepoints specified, samples for autoantibodies will be collected if a patient experiences a 
disease flare. 
k Patients will be in a seated or supine position during blood collection. See Section 7.2.4.5 for assessments. 
l Plasma samples for cytokines and proteomics and blood samples for immune cell profiling will be collected prior to dosing. Samples for proteomics and immune 
cell profiling will be stored for future analysis of chemokines and immune cell subsets.  
m Samples will be collected prior to dosing in patients who have provided the proper informed consent for genetic analyses. 
n Samples for PK analysis will be drawn from all patients prior to IMP administration, at 30 minutes (±10 minutes) after administration, and at 4 hours 
(±15 minutes) after administration. In addition, patients will be randomized 1:1:1 to 3 groups to obtain an additional PK sample at either 15 minutes 
(±5 minutes), 1 hour (±10 minutes), or 2 hours (±15 minutes) after IMP administration. The time of the PK blood draw must be recorded.  
o A 30 mL aliquot should be obtained from the first morning void. All urinalyses will include both macroscopic and microscopic examination. 
p Where local conditions and requirements mandate SARS-CoV-2 testing, these tests will be conducted prior to Visit 2. If testing is conducted, the test must be 
an RT-PCR assay for SARS-CoV-2, with results expected within 24 hours.  
q FibroScan is a device to using VCTE to measure liver stiffness. The scan will be performed at least 2 hours after food intake. 
r Results of a liver biopsy performed within 6 months prior to Screening (or at Screening) will be used as the Baseline liver biopsy. Liver biopsies will be 
performed and analyzed by a local laboratory. 
s See Table 2 for weekly schedule of IMP administration at visits where no study assessments are performed. 
t For patients who roll over immediately to the OLE Period, Study Visit 26 (Table 1) may occur on the same day as Study Visits 27 and 28 (Table 3). Patients 
who are not eligible or choose not to roll over to the OLE Period will have an End-of-Study (EOS) visit (see Table 3) 4 weeks after completion of the Double-
blind Treatment Period. 
 
 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
 
 
 
Page 19 of 86 
h Patients will be in a seated or supine position during blood collection. See Section 7.2.4.5 for assessments. 
i 
A 30 mL aliquot should be obtained from the first morning void. All urinalyses will include both macroscopic and microscopic examination. 
j 
Plasma samples for cytokines and proteomics and blood samples for immune cell profiling will be collected prior to dosing. Samples for proteomics and 
immune cell profiling will be stored for future analysis of chemokines and immune cell subsets.  
k Samples will be collected prior to dosing in patients who have provided the proper informed consent for genetic analyses. 
l 
FibroScan is a device to using VCTE to measure liver stiffness. The scan will be performed at least 2 hours after food intake. 
m See Table 4 for weekly schedule of IMP administration at visits where no study assessments are performed. 
n The EOS (safety follow-up) visit has a ±7 day visit window. 
o If a patient cannot continue with the planned assessments, the patient will complete the ETV followed by the End-of-Study (EOS) visit 4 weeks later. 
 
 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 21 of 86 
TABLE OF CONTENTS 
CLINICAL STUDY PROTOCOL ..................................................................................................1 
STUDY PERSONNEL ....................................................................................................................2 
PROTOCOL ACCEPTANCE PAGE ..............................................................................................3 
PROTOCOL SYNOPSIS ................................................................................................................4 
LIST OF ABBREVIATIONS ........................................................................................................27 
1. 
INTRODUCTION ......................................................................................................30 
1.1. 
Zetomipzomib Background ........................................................................................30 
1.2. 
Rationale for Use of Zetomipzomib in the Proposed Study Populations, and 
Rationale for the Study ...............................................................................................31 
1.3. 
Rationale for Study Endpoints ....................................................................................32 
1.4. 
Summary of Potential Risks and Benefits ..................................................................32 
2. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................35 
2.1. 
Study Objectives .........................................................................................................35 
2.2. 
Study Endpoints ..........................................................................................................35 
2.2.1. 
Safety Endpoints .........................................................................................................35 
2.2.2. 
Definitions Related to Efficacy Endpoints .................................................................35 
2.2.3. 
Efficacy Endpoints ......................................................................................................36 
2.2.3.1. 
Double-blind Treatment Period ..................................................................................36 
2.2.3.2. 
Open-label Extension Period ......................................................................................37 
2.2.4. 
Pharmacokinetic Endpoints ........................................................................................38 
3. 
STUDY DESIGN .......................................................................................................39 
3.1. 
Type and Design of Study ..........................................................................................39 
3.1.1. 
Double-blind Treatment Period ..................................................................................39 
3.1.2. 
Open-label Extension (OLE) Period ...........................................................................40 
3.1.3. 
Study Design Schema .................................................................................................42 
3.1.4. 
Study Design Rationale ..............................................................................................43 
3.2. 
Randomization, Blinding, and Unblinding Procedures ..............................................43 
3.2.1. 
Randomization ............................................................................................................43 
3.2.2. 
Blinding ......................................................................................................................43 
3.2.3. 
Unblinding ..................................................................................................................44 
3.3. 
Number of Sites ..........................................................................................................44 
4. 
PATIENT SELECTION AND ENROLLMENT .......................................................45 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 22 of 86 
4.1. 
Number of Patients .....................................................................................................45 
4.2. 
Inclusion Criteria ........................................................................................................45 
4.3. 
Exclusion Criteria .......................................................................................................46 
5. 
STUDY TREATMENT INFORMATION .................................................................49 
5.1. 
Physical Description of Investigational Medicinal Product .......................................49 
5.2. 
Packaging and Labeling ..............................................................................................49 
5.3. 
Supply, Dispensing, Storage, and Investigational Medicinal Product 
Accountability .............................................................................................................49 
6. 
DOSAGE AND STUDY MEDICATION ADMINISTRATION ..............................51 
6.1. 
Investigational Medicinal Product Administration .....................................................51 
6.1.1. 
Administration Site .....................................................................................................51 
6.1.2. 
Suggested Measures to Improve Investigational Medicinal Product 
Tolerance ....................................................................................................................51 
6.1.3. 
Dose Modification Guidelines ....................................................................................52 
6.1.3.1. 
Dose Reduction ...........................................................................................................52 
6.1.3.2. 
Missed Doses ..............................................................................................................52 
6.2. 
Prior and Concomitant Treatments .............................................................................53 
6.2.1. 
Prior Treatment Restrictions .......................................................................................53 
6.2.2. 
Required Concomitant Medications and Therapies ....................................................53 
6.2.2.1. 
Glucocorticoids ...........................................................................................................53 
6.2.3. 
Permitted Concomitant Medications and Therapies ...................................................54 
6.2.3.1. 
Azathioprine (AZA) ....................................................................................................54 
6.2.3.2. 
Inhibitors of Inosine Monophosphate Dehydrogenase (Mycophenolate 
Mofetil [MMF], Mycophenolate Sodium [MMS] and Mycophenolic Acid 
[MPA]) ........................................................................................................................54 
6.2.3.3. 
Tacrolimus (TAC) ......................................................................................................54 
6.2.3.4. 
Cyclosporine A (CsA) ................................................................................................55 
6.2.3.5. 
6-Mercaptopurine (6-MP) ...........................................................................................55 
6.2.4. 
Prohibited Concomitant Medications .........................................................................55 
6.2.5. 
Potential Drug-Drug Interactions ...............................................................................55 
6.2.6. 
Vaccinations ...............................................................................................................55 
6.2.7. 
Other Restrictions and Prohibitions ............................................................................56 
6.3. 
Rescue Therapy ..........................................................................................................56 
7. 
STUDY EVALUATIONS ..........................................................................................57 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 23 of 86 
7.1. 
Schedule of Assessments ............................................................................................57 
7.1.1. 
Double-blind Treatment Period ..................................................................................57 
7.1.2. 
Open-label Extension Period ......................................................................................57 
7.1.3. 
Unscheduled Visits .....................................................................................................57 
7.1.4. 
Telehealth Visits .........................................................................................................57 
7.2. 
Study Procedures and Assessments ............................................................................58 
7.2.1. 
Medical History ..........................................................................................................58 
7.2.2. 
Efficacy Assessments .................................................................................................58 
7.2.2.1. 
Aminotransferases and Immunoglobulin G ................................................................58 
7.2.2.2. 
Vibration-controlled Transient Elastography .............................................................58 
7.2.2.3. 
Liver Histopathology ..................................................................................................58 
7.2.2.4. 
Glucocorticoid Toxicity Index ....................................................................................59 
7.2.3. 
Patient Reported Outcome Measures..........................................................................59 
7.2.3.1. 
EuroQol 5-Dimension 5-Level ...................................................................................59 
7.2.3.2. 
Chronic Liver Disease Questionnaire .........................................................................59 
7.2.4. 
Safety Assessments .....................................................................................................60 
7.2.4.1. 
Vital Sign Measurements ............................................................................................60 
7.2.4.2. 
Electrocardiograms .....................................................................................................60 
7.2.4.3. 
Weight and Height ......................................................................................................60 
7.2.4.4. 
Physical Examination .................................................................................................60 
7.2.4.5. 
Clinical Laboratory Assessments ...............................................................................60 
7.2.5. 
Exploratory Assessments ............................................................................................62 
7.2.5.1. 
Cytokines and Proteomics ..........................................................................................62 
7.2.5.2. 
Genotyping and Gene Expression ..............................................................................62 
7.2.6. 
Pharmacokinetic Assessments ....................................................................................62 
7.2.7. 
Contraception Requirements and Pregnancy Testing .................................................63 
8. 
STUDY DISCONTINUATION .................................................................................65 
8.1. 
Study and Individual Patient Stopping Rules .............................................................65 
8.1.1. 
Termination or Suspension of the Study ....................................................................65 
8.1.2. 
Individual Patient Stopping Rules ..............................................................................65 
8.1.3. 
Potential Drug-induced Liver Injury ..........................................................................66 
8.2. 
Lost to Follow-Up.......................................................................................................66 
9. 
ADVERSE EVENTS..................................................................................................68 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 24 of 86 
9.1. 
Adverse Event Reporting ............................................................................................68 
9.1.1. 
Definition of an Adverse Event ..................................................................................68 
9.1.2. 
Assessment of Severity ...............................................................................................68 
9.1.3. 
Assessment of Causality .............................................................................................68 
9.1.4. 
Action Taken with Regard to Investigational Medicinal Product ..............................69 
9.1.5. 
Follow-up of Adverse Events .....................................................................................69 
9.1.6. 
Documentation and Reporting of Adverse Events .....................................................69 
9.2. 
Serious Adverse Events ..............................................................................................70 
9.2.1. 
Definition of a Serious Adverse Event .......................................................................70 
9.2.2. 
Serious Adverse Event Reporting and Documentation Requirements .......................70 
9.3. 
Pregnancy Reporting ..................................................................................................71 
9.4. 
New or Worsening Disease Manifestations ................................................................72 
9.5. 
Injection Site Reactions ..............................................................................................72 
9.6. 
Adverse Events of Special Interest .............................................................................72 
9.6.1. 
Systemic Injection Reactions ......................................................................................72 
9.6.2. 
Thrombotic Microangiopathy .....................................................................................73 
9.7. 
Unexpected Adverse Reactions ..................................................................................73 
9.7.1. 
Definition of an Unexpected Adverse Reaction .........................................................73 
9.8. 
Hypersensitivity Reactions .........................................................................................73 
9.9. 
Infections ....................................................................................................................74 
9.10. 
Adrenal Insufficiency .................................................................................................74 
9.11. 
Independent Data Monitoring Committee ..................................................................74 
10. 
STATISTICAL ANALYSES .....................................................................................75 
10.1. 
Overview .....................................................................................................................75 
10.2. 
Study Population Definitions ......................................................................................75 
10.3. 
Sample Size and Power Considerations .....................................................................76 
10.4. 
Background and Demographic Characteristics ..........................................................76 
10.5. 
Patient Disposition ......................................................................................................76 
10.6. 
Efficacy Analysis ........................................................................................................76 
10.6.1. 
Statistical Methods ......................................................................................................77 
10.6.2. 
Multiplicity .................................................................................................................77 
10.6.3. 
Sensitivity Analysis ....................................................................................................77 
10.7. 
Safety Analysis ...........................................................................................................78 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 25 of 86 
10.8. 
Interim Analysis ..........................................................................................................78 
10.9. 
Other Topics ...............................................................................................................78 
10.9.1. 
Biomarker Analysis ....................................................................................................78 
10.9.2. 
Pharmacokinetic Analysis ..........................................................................................78 
10.9.3. 
Subgroup Analyses .....................................................................................................78 
11. 
ETHICAL AND ADMINISTRATIVE CONSIDERATIONS ...................................79 
11.1. 
Compliance Statement ................................................................................................79 
11.2. 
Institutional Review Board or Independent Ethics Committee ..................................79 
11.3. 
Informed Consent and Human Patient Protection ......................................................79 
11.4. 
Direct Access to Source Data, Source Documents, and Study Reports .....................80 
11.5. 
Data Collection and Handling ....................................................................................80 
11.6. 
Confidentiality ............................................................................................................80 
11.7. 
Financing and Insurance .............................................................................................80 
11.8. 
Audit and Inspection ...................................................................................................81 
11.9. 
Monitoring ..................................................................................................................81 
11.10. 
Quality Control and Quality Assurance ......................................................................81 
11.11. 
Data Management and Coding ...................................................................................81 
11.12. 
Reporting and Publication, Including Archiving ........................................................82 
12. 
REFERENCES ...........................................................................................................83 
13. 
APPENDICES ............................................................................................................86 
13.1. 
Appendix A: Protocol History ....................................................................................86 
13.2. 
Appendix B: Suggested Glucocorticoid Taper Schedule and Prednisone 
Equivalents .................................................................................................................86 
 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 26 of 86 
LIST OF TABLES 
Table 1 
Schedule of Assessments (Visits with Study Assessments) – Double-blind 
Treatment Period ........................................................................................................12 
Table 2 
Schedule of Investigational Medicinal Product Administration (Visits with 
no Study Assessments) – Double-blind Treatment Period .........................................16 
Table 3: 
Schedule of Assessments (Visits with Study Assessments) – Open-label 
Extension Period .........................................................................................................17 
Table 4: 
Schedule of Investigational Medicinal Product Administration (Visits with 
no Study Assessments) – Open-label Extension Period .............................................20 
Table 5: 
Causality Categories ...................................................................................................69 
Table 6 
Suggested Glucocorticoid Taper Schedule .................................................................86 
Table 7 
Prednisone Equivalents ...............................................................................................86 
 
 
LIST OF FIGURES 
Figure 1 
Study KZR-616-208 Study Design Schema ...............................................................42 
 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 27 of 86 
LIST OF ABBREVIATIONS 
Abbreviation 
or Term 
Definition 
6-MP 
6-Mercaptopurine 
AASLD 
American Association for the Study of Liver Diseases 
AE 
Adverse event 
AESI 
Adverse event of special interest 
AIDS 
Acquired immune deficiency syndrome 
AIH 
Autoimmune hepatitis 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration-time curve 
AZA 
Azathioprine 
BUN 
Blood urea nitrogen 
CAP 
Controlled attenuation parameter 
CD 
Cluster of differentiation 
CFR 
Code of Federal Regulations 
CI 
Confidence interval  
CLDQ 
Chronic Liver Disease Questionnaire 
Cmax 
Maximum plasma concentration 
CMH 
Cochran-Mantel-Haenszel 
COVID-19 
Coronavirus disease 2019 
CR 
Complete remission 
CsA 
Cyclosporine A 
DILI 
Drug-induced liver injury 
DM 
Dermatomyositis 
DNA 
Deoxyribonucleic acid 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EDC 
Electronic data capture 
ELISA 
Enzyme-linked immunosorbent assay 
EOS 
End-of-Study 
EOT 
End-of-Treatment 
EQ-5D-5L 
EuroQol 5-dimension 5-level 
EQ-VAS 
EuroQol visual analog scale 
ETV 
Early Termination Visit 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 28 of 86 
Abbreviation 
or Term 
Definition 
FSH 
Follicle stimulating hormone 
GCP 
Good Clinical Practice 
GMP 
Good Manufacturing Practice 
GTI 
Glucocorticoid Toxicity Index 
GTI-AIS 
GTI Aggregate Improvement Score 
GTI-CWS 
GTI Cumulative Worsening Score 
HAI 
Histological Activity Index 
HBcAb 
Hepatitis B core antibody 
HBsAb 
Hepatitis B surface antibody 
HBsAg 
Hepatitis B surface antigen 
hCG 
Beta-human chorionic gonadotropin 
HCV 
Hepatitis C virus 
HEENT 
Head, eyes, ears, nose, throat 
HIV 
Human immunodeficiency virus 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IDMC 
Independent Data Monitoring Committee 
IEC 
Independent Ethics Committee 
IgG 
Immunoglobulin G 
IGRA 
Interferon-gamma release assay 
IMP 
Investigational medicinal product 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology  
ISR 
Injection site reaction 
IV 
Intravenous 
LDA 
Longitudinal data analysis 
LMP 
Low molecular mass polypeptide 
LN 
Lupus nephritis 
LSM 
Liver stiffness measurement 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
MLL 
Mixed lineage leukemia 
MMF 
Mycophenolate mofetil 
MMRM 
Mixed model for repeated measures 
MMS 
Mycophenolate sodium 
MPA 
Mycophenolic acid 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 29 of 86 
Abbreviation 
or Term 
Definition 
NIDDK 
National Institute of Diabetes and Digestive and Kidney Diseases 
OLE 
Open-label extension 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic  
PM 
Polymyositis 
PR 
Partial remission 
QTcF 
QC interval corrected for pulse rate by Fridericia’s formula 
QW 
Once weekly 
RNA 
Ribonucleic acid 
RT-PCR 
Real-time polymerase chain reaction 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus 2 
SC 
Subcutaneous  
SD 
Standard deviation 
SLE 
Systemic lupus erythematosus 
SLEDAI-2K 
Systemic Lupus Erythematosus Disease Activity Index 2000 
SUSAR 
Suspected unexpected serious adverse reaction 
TAC 
Tacrolimus 
TB 
Tuberculosis 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time of maximum plasma concentration 
ULN 
Upper limit of normal 
US 
United States 
VCTE 
Vibration-controlled transient elastography 
WFI 
Water for injection 
WHO 
World Health Organization 
WOCBP 
Women of childbearing potential 
 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 30 of 86 
1. 
INTRODUCTION 
Study KZR-616-208 is a randomized, double-blind, placebo-controlled, Phase 2a study with an 
open-label extension (OLE) to evaluate the safety, tolerability, and efficacy of zetomipzomib 
(KZR-616) in patients with autoimmune hepatitis (AIH) who have failed standard-of-care 
treatment, had an incomplete biochemical response to ≥3 months of standard-of-care treatment, 
or had a disease flare after experiencing complete remission induced by standard-of-care 
treatment. The definition of biochemical response is per the current 2020 American Association 
for the Study of Liver Diseases (AASLD) practice guidance for the diagnosis and management 
of AIH in Adults and Children (Mack et al., 2020). 
1.1. 
Zetomipzomib Background 
Zetomipzomib is a first-in-class tripeptide ketoepoxide-based selective inhibitor of the human 
immunoproteasome. Inhibition of the immunoproteasome results in an immunomodulatory 
response characterized by reduction in pro-inflammatory cytokine release, inhibition of 
inflammatory T-cell subsets and a reduction in autoantibody levels and plasma cells in 
preclinical models of autoimmune disease (Muchamuel et al., 2009; Ichikawa et al., 2012; Kalim 
et al., 2012). Based on broad immunomodulatory activity across both the innate and acquired 
immune system, zetomipzomib represents a potential novel therapeutic for multiple disorders of 
the immune system regardless of disease etiology. 
Preclinical studies show that zetomipzomib results in potent and selective inhibition of the 
immunoproteasome in human cells in vitro, in blood and tissues when administered to rodents, 
and in blood when administered to monkeys. Near complete recovery of immunoproteasome 
activity in immune cell rich tissues such as the spleen occurred within 7 days of dosing. 
Inhibition of immunoproteasome active site subunits by zetomipzomib, specifically the low 
molecular mass polypeptide (LMP) subunits LMP7, LMP2, and the multicatalytic endopeptidase 
complex-like (MECL) subunit MECL1, occurs through an irreversible mechanism, similar to 
that for carfilzomib, a Food and Drug Administration (FDA)-approved agent and analog of 
zetomipzomib (Bennett and Kirk, 2008; Huber et al., 2012; KYPROLIS®, 2012). 
Peptide ketoepoxides show no off-target activity (Arastu-Kapur et al., 2011; Kisselev et al., 
2012). Zetomipzomib forms a dual covalent adduct with the N-terminal Thr residue of 
proteasome active sites. There are 8 known N-terminal threonine proteases in the genome, 
7 proteasome active sites (β1, β2, β5, LMP2, LMP7, MECL1, and β5t) and Taspase 1, an 
endopeptidase involved in activity of the mixed lineage leukemia (MLL) gene product. Thus, the 
anti-inflammatory and immunomodulating effects of zetomipzomib is achieved only through 
action on the immunoproteasome. 
To date, 2 studies in healthy volunteers using doses ranging from 7.5 to 75 mg zetomipzomib 
weekly have been completed. In addition, a Phase 1b/2 study in patients with lupus nephritis 
(LN) (KZR-616-002) and a Phase 2 study in patients with dermatomyositis (DM) or 
polymyositis (PM) (KZR-616-003) have recently completed. An OLE study in patients with DM 
or PM, KZR-616-003E, is ongoing. Data from the KZR-616-002 study demonstrated 
improvement in multiple exploratory efficacy measures of disease activity across organ systems 
(including the Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K]), 
proteinuria, and autoantibodies after 24 weeks of treatment, without evidence of significant 
immunosuppression. Topline results of the KZR-616-003 study showed that most patients with 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 31 of 86 
DM or PM saw clinically meaningful improvements in the components of the Total 
Improvement Score (TIS), although zetomipzomib demonstrated no significant differentiation 
from placebo control. Results from zetomipzomib studies to date are discussed in more detail in 
Section 1.4. 
1.2. 
Rationale for Use of Zetomipzomib in the Proposed Study 
Populations, and Rationale for the Study 
AIH is a rare, severe, autoimmune disease that without treatment results in fulminant hepatic 
failure. AIH is the initial stage of serial subsequent liver diseases including cirrhosis and 
hepatocellular carcinoma (Kirstein et al., 2015). The prevalence of AIH ranges from 16 to 
18 cases per 100,000 persons in Europe (Lowe and John, 2018). In the United States (US), AIH 
prevalence is as high as 31.2/100,000, affecting less than 200,000 individuals in the US (Beretta-
Piccoli et al., 2021; Tunio et al., 2021). In Europe and in the US, AIH accounts for 2% to 3% of 
the pediatric and 4% to 6% of the adult liver transplantations (Lowe and John, 2018). 
Current first-line therapy for AIH is chronic administration of high-dose glucocorticoids (Mack 
et al., 2020). The usual treatment paradigms include higher-dose induction therapy followed by 
dose tapering to the lowest tolerated dose that also controls inflammation of the liver and is 
titrated to liver transaminases, specifically alanine aminotransferase (ALT). Patients with AIH 
require anti-inflammatory therapy for life. Second-line induction and maintenance therapies 
include glucocorticoid-sparing treatments such as azathioprine (AZA), mycophenolate mofetil 
(MMF), calcineurin inhibitors, and B-cell depleting therapies (eg, rituximab). 
AIH can respond favorably to standard-of-care, and though most patients accrue some degree of 
hepatic fibrosis, only 10-15% progress to end-stage liver disease with current treatments. 
However, the adverse effects of high-dose glucocorticoid therapies create an additional burden 
for patients resulting in diabetes mellitus, osteoporosis, muscle atrophy, centripetal weight gain, 
Cushing facies, and diminished defense against multiple infections (Poetker and Reh, 2010). 
Thus, there is a high unmet need for glucocorticoid-sparing therapies. 
AIH disease pathophysiology is not well understood, and predictive animal models are lacking 
(Sebode et al., 2018), but contributions of dysregulated B- and T- cells as well as monocytic cells 
likely underlie disease etiology. The immunopathogenesis of AIH comprises (1) autoreactive 
CD4 and CD8 T cells that break self-tolerance to hepatic autoantigens, (2) autoantibodies 
produced by autoreactive B cells in the absence of effective B regulatory cell inhibition (Mack et 
al., 2020), (3) selective immunoglobulin G (IgG) elevation that supports B cell involvement in 
AIH (Sebode et al., 2018), and (4) elevated expression levels of Vav guanine nucleotide 
exchange factor 1 (VAV1) and p21-activated kinase 1 (PAK1) in liver monocytes/Kupffer cells 
which are associated with disease progression (Lin et al., 2016). These effector cells, also 
implicated in the pathogenesis of AIH, have been shown to be targeted by immunoproteasome 
inhibition (Kirk et al., 2021). 
As zetomipzomib is a selective inhibitor of the human immunoproteasome without off-target 
activities, it may achieve immunomodulation by specifically targeting the immunoproteasome, 
and result in similar therapeutic potential to glucocorticoids without any off-target effects or 
frank immunosuppression, thus providing a glucocorticoid-sparing/glucocorticoid-free therapy 
for AIH.  

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 32 of 86 
Study KZR-616-208 will provide proof-of-concept for both remission induction and remission 
maintenance of AIH with zetomipzomib. 
1.3. 
Rationale for Study Endpoints 
The unmet medical needs for AIH are glucocorticoid-sparing/glucocorticoid-free remission 
induction and remission maintenance. Glucocorticoid dose reduction, glucocorticoid-related side 
effects, reduction of liver stiffness, and health-related quality of life assessment have been 
widely used as outcome measures for clinical trials in AIH (Schramm, 2019). According to a 
recent publication regarding effective trial design for AIH, 24 weeks of active treatment is a 
sufficient length of time to achieve remission induction (Schramm, 2019). However, the optimal 
timepoints for zetomipzomib to achieve remission in AIH patients have not been identified. 
Complete biochemical remission (ALT, aspartate aminotransferase [AST], immunoglobulin G 
[if IgG levels are high at Baseline]) is the best surrogate marker for histological remission, and 
thus for a favorable disease course. Therefore, the primary efficacy endpoint for the 
Double-blind Treatment Period of this study is the proportion of patients who achieve 
normalization of ALT, AST, and IgG (complete remission [CR]) by Week 24 or earlier with 
glucocorticoid dose not higher than the starting dose (at Baseline). The primary efficacy endpoint 
will be analyzed at Weeks 12, 16, 20 and 24 to help determine an optimal timepoint for 
achieving remission in AIH patients with zetomipzomib treatment. The key secondary efficacy 
endpoints are the changes from Baseline in ALT level at Weeks 12, 16, 20 and 24, the proportion 
of patients who achieve partial remission (PR), time to CR, and the proportion of patients not 
responding to treatment (ie, treatment failures).  
The OLE Period of the study will allow monitoring of safety and efficacy beyond 24 weeks in 
patients who were randomized to zetomipzomib during the Double-blind Treatment Period. 
Patients who were randomized to placebo in the Double-blind Treatment Period will be treated 
with zetomipzomib for the first time during the OLE Period, and the safety/efficacy will be 
compared with the patient’s experience on 24 weeks of placebo. Key additional efficacy 
endpoints are the proportion of patients experiencing a disease flare among the patients who 
achieved a CR and the patients who have a CR or PR among the patients who did not achieve a 
CR or PR during the Double-blind Treatment Period. The mean changes in 
prednisone/prednisone equivalent dose will also be assessed for zetomipzomib as potential 
glucocorticoid-sparing/glucocorticoid-free medication for the treatment of AIH. 
1.4. 
Summary of Potential Risks and Benefits  
Despite advances in understanding and treatment of AIH, important unmet clinical needs remain 
in both adult and pediatric patient populations (Jones et al., 2018). The current study is to assess 
the safety and efficacy of the first-in-class targeted selective molecule for patients with AIH 
which is designed to reduce organ (liver) inflammation and damage, be safe to be used as 
maintenance therapy, and that could reduce or obviate the need for immunosuppressive 
therapies, including glucocorticoids. 
Zetomipzomib is a selective and irreversible inhibitor of the immunoproteasome, which controls 
key intracellular processes in immune effector cells. The nonclinical pharmacologic, 
pharmacokinetic (PK), and toxicologic properties of zetomipzomib have been thoroughly 
evaluated. This nonclinical data supports investigation of zetomipzomib as a selective and 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 33 of 86 
irreversible inhibitor of the immunoproteasome, which controls key intracellular processes in 
immune effector cells in patients with autoimmune diseases, including but not limited to models 
of rheumatoid arthritis, the progression of nephritis in 2 mouse models of systemic lupus 
erythematosus (SLE), and in the C-protein induced myositis mouse model of myositis. It should 
be noted that no relevant nonclinical model of AIH exists at this time. Zetomipzomib could 
provide a meaningful potent anti-inflammatory treatment potentially without immunosuppression 
or significant off-target effects found with currently available therapies. 
Zetomipzomib showed preliminary evidence of clinical activity in adult patients with SLE and 
LN (KZR-616-002) through improvement in proteinuria, reduction in autoantibodies (anti-ds-
DNA antibodies), and improvements in extra-renal disease activity.  
Nonclinical toxicity studies of zetomipzomib include single- and repeat-dose studies in rats and 
monkeys, immunotoxicity, safety pharmacology, embryofetal development, fertility, local 
irritation study in pigs, and genotoxicity studies. Of note, especially for patients with 
autoimmune disease who are often of childbearing potential, no teratogenicity was demonstrated. 
Repeat-dose toxicity studies of zetomipzomib in rats and monkeys involved once weekly 
subcutaneous (SC) administration for 6- and 9-months duration, respectively. No signs of 
hepatotoxicity or immunotoxicity were noted in these studies. 
Across separate studies in healthy volunteers to evaluate safety, tolerability, PK and 
pharmacodynamics (PD) (KZR-616-001 and KZR-616-004), zetomipzomib was administered to 
100 subjects as single and weekly intravenous (IV) or SC doses ranging from 7.5 to 75 mg. 
Exposure to zetomipzomib is dose proportional across this range of doses and total exposure at 
75 mg is roughly equivalent to that seen in 6-month repeat dose toxicity study in rats. 
Zetomipzomib is cleared rapidly following single SC administration with a mean terminal 
half--life of ~5 hr and extrahepatic clearance based on IV administration. No accumulation of 
zetomipzomib was noted with repeated weekly SC administration. Metabolism occurs via 
microsomal epoxide hydrolase, a ubiquitously expressed enzyme which is non-saturable. 
The predominant metabolite found in human plasma is the inactive diol. At doses ≥30 mg, 
zetomipzomib induces selective inhibition of immunoproteasome enzymatic activity exceeding 
80% with recovery occurring between weekly doses and no impact of repeat dosing on PD. 
At doses of 45 and 60 mg, the level of inhibition is at or near the lower limit of quantitation, 
while inhibition of the constitutive protease is <40%, demonstrating selectivity for the 
immunoproteasome in humans. 
Patients will be closely monitored for safety. For adult patients with autoimmune diseases who 
were treated with zetomipzomib, systemic injection reaction is an important potential risk. 
Systemic injection reaction has presented as hypotension, tachycardia, nausea, vomiting, 
dizziness, headache, pyrexia, rigors, and/or chills. In addition, the most common adverse events 
(AEs) at any dose were predominantly injection site reactions such as erythema, induration, and 
tenderness (pain), which were generally mild and transient in nature and did not appear to 
increase in severity or frequency with repeated dosing of zetomipzomib. Injection site reaction is 
an identified risk for zetomipzomib. Patients will be monitored for the aforementioned signs and 
symptoms.  
The effects of zetomipzomib on embryogenesis, reproduction, and spermatogenesis in humans 
are unknown. No formal studies have been conducted with zetomipzomib in pregnant women or 
during breastfeeding. In nonclinical studies, zetomipzomib tested positive for mammalian 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 34 of 86 
chromosomal aberration, but did not have clastogenic activity in animal studies and was not 
found to have direct teratogenic effects in rats and rabbits. In addition, zetomipzomib had no 
toxicological effect on mating or fertility in male and female rats. Study patients should be 
advised to use effective contraception during and after zetomipzomib treatment as described in 
respective protocols.  
The potential risks identified in association with zetomipzomib are justified by the anticipated 
benefits that may be afforded to patients with AIH. Given the modulatory action on immune 
effector cells without suppressive effects on cell generation, zetomipzomib is well positioned to 
be a meaningful anti-inflammatory agent and potentially glucocorticoid-sparing treatment option 
for patients with AIH. 
For additional information, please refer to the current version of the zetomipzomib (KZR-616) 
Investigator’s Brochure. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 35 of 86 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
2.1. 
Study Objectives 
The safety objective is to evaluate the safety and tolerability of zetomipzomib in patients with 
AIH. 
The efficacy objective for the Double-blind Treatment Period is to evaluate the efficacy of 
zetomipzomib in addition to standard-of-care in patients with AIH who have failed standard-of-
care treatment, had an incomplete biochemical response to ≥3 months of standard-of-care 
treatment, or had a disease flare after experiencing complete remission induced by standard-of-
care treatment. The efficacy objective for the OLE Period is to evaluate the long-term efficacy of 
zetomipzomib in patients with AIH. 
2.2. 
Study Endpoints 
2.2.1. 
Safety Endpoints 
The primary safety endpoint for both the Double-blind Treatment Period and the OLE Period is 
the proportion of patients who experience AEs and serious adverse events (SAEs). Other safety 
endpoints include: 
• Incidence, nature, and severity of AEs and SAEs  
• Incidence of AEs leading to investigational medicinal product (IMP) discontinuation 
and dose reduction 
• Changes in standard laboratory parameters, vital signs, and ECGs 
2.2.2. 
Definitions Related to Efficacy Endpoints 
The Baseline ALT, AST, and IgG values will be calculated as the mean of all collected 
Screening and Day 1 values. Relative reduction in ALT, AST, and IgG (if IgG level is elevated 
at Baseline) will be calculated as the percentage change from the Baseline value. 
Successful glucocorticoid taper: Prednisone/prednisone equivalent dose tapered from the 
starting dose (at Baseline) to a prednisone/prednisone equivalent dose of ≤10 mg/day by 
Week 24 or earlier.  
Complete biochemical remission (CR): Normal ALT, AST, and IgG values (if IgG level is 
elevated at Baseline) with glucocorticoid dose not higher than starting dose (at Baseline).  
Partial biochemical remission (PR): ALT, AST, and IgG values (if IgG level is elevated at 
Baseline) with glucocorticoid dose not higher than starting dose (at Baseline) meeting one of the 
following criteria: 
• > upper limit of normal (ULN) but <2 × ULN (values must be lower than Baseline) 
• >ULN with >80% improvement from Baseline. 
Responder: Patients who achieve a reduction from Baseline in ALT, AST, and IgG (if IgG level 
is elevated at baseline) of ≥25% with glucocorticoid dose not higher than starting dose 
(at Baseline). 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 36 of 86 
Sustained responder: Responders in the Double-blind Treatment Period who have sustained or 
further improved ALT, AST and IgG (if IgG level is elevated at Baseline) levels throughout the 
OLE Period with glucocorticoid dose not higher than starting dose (at Baseline). 
Non-responder: Patients who do not achieve a reduction from Baseline in ALT or AST of 
≥25%. Patients who have insufficient data for response determination at a time point will be 
considered non-responders for that time point. 
Treatment failure:  
• Patient’s ALT or AST level worsened ≥2 times that of the Baseline value that is sustained 
for ≥1 week as verified via repeat laboratory assessments, despite compliance with 
standard of care (ie, with regard to inclusion criteria) or protocol-defined therapy.  
• If a glucocorticoid dose is increased above the Baseline dose, it may be considered a 
treatment failure unless attributed to an adverse event not relating to AIH.  
Disease flare: Elevation of ALT after achieving CR that meets all the following criteria: 
• is ≥25% above the CR value 
• is ≥1.25 ULN 
• is sustained for ≥1 week as verified via repeat laboratory assessments 
• requires the patient to re-start or escalate glucocorticoid therapy 
• is not due to other identifiable causes (eg, viral hepatitis, concomitant medications, 
alcoholic liver injury, etc.) 
2.2.3. 
Efficacy Endpoints 
2.2.3.1. 
Double-blind Treatment Period 
2.2.3.1.1. Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of patients who achieve CR by Week 24; 
analyses will also be performed on data collected at Weeks 12, 16, and 20. 
2.2.3.1.2. Secondary Efficacy Endpoints 
• Change from Baseline in ALT at Weeks 12, 16, 20, and 24 
• Proportion of patients who achieve PR at Week 12, 16, 20, and 24 
• Time to CR 
• Time to PR 
• Proportion of patients experiencing a disease flare after CR  
• Proportion of patients who are treatment failures 
• Proportion of patients who achieve CR or PR with successful glucocorticoid taper by 
Week 24; analyses will also be performed on data collected at Weeks 12, 16, and 20. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 37 of 86 
2.2.3.1.3. Exploratory Efficacy Endpoints 
• Proportion of patients who achieve ALT normalization based on Prati criteria (males, 
30 U/L; females, 19 U/L) (Prati et al., 2002), with successful glucocorticoid taper, by 
Week 24 
• Mean changes from Baseline in AST at Weeks 12, 16, 20, and 24 
• Mean changes from Baseline in IgG at Weeks 12, 16, 20, and 24 
• Mean changes from Baseline in glucocorticoid dose 
• Change from Baseline in the Glucocorticoid Toxicity Index (GTI) Cumulative 
Worsening Score (GTI-CWS) and the Aggregate Improvement Score (GTI-AIS) 
• Mean changes from Baseline in inflammatory cytokines at Weeks 8, 16, and 24 
• Change from Baseline in liver stiffness at Week 24, assessed by vibration-controlled 
transient elastography (VCTE) utilizing Fibroscan®  
• Mean change from Baseline in the EuroQol 5-dimension 5-level (EQ-5D-5L) at 
Weeks 16 and 24 
• Mean change from Baseline in the Chronic Liver Disease Questionnaire (CLDQ) at 
Weeks 16 and 24 
• Change from Baseline in liver histopathology at Week 24, based on Ishak score 
(modified Histological Activity Index [HAI]) scores (Ishak et al., 1995) 
2.2.3.2. 
Open-label Extension Period 
2.2.3.2.1. Primary Efficacy Endpoints 
• Proportion of patients experiencing a disease flare among the patients who achieved a 
CR during the Double-blind Treatment Period 
2.2.3.2.2. Exploratory Efficacy Endpoints 
• Proportion of patients who have a CR or PR among the patients who did not achieve a 
CR or PR during the Double-blind Treatment Period 
• Proportion of patients who have a CR or PR with successful glucocorticoid taper who 
did not achieve a CR or PR during Double-blind Treatment Period 
• Proportion of patients who achieve a glucocorticoid-free CR 
• Proportion of patients who achieve a glucocorticoid-free PR 
• Mean changes in ALT 
• Mean changes in AST 
• Mean changes in IgG 
• Mean change in the EQ-5D-5L 
• Mean change in CLDQ 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 38 of 86 
• Change in the GTI-CWS and the GTI-AIS 
• Mean change in liver stiffness, assessed by VCTE utilizing Fibroscan® 
• Change in liver histopathology, based on Ishak score (modified HAI) scores (Ishak et 
al., 1995) 
2.2.4. 
Pharmacokinetic Endpoints 
• Zetomipzomib and its metabolite KZR-59587 PK (maximum concentration [Cmax], 
time of maximum concentration [Tmax], area under the concentration-time 
curve [AUC]) 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 39 of 86 
3. 
STUDY DESIGN 
3.1. 
Type and Design of Study 
This is a Phase 2a, multi-center, randomized, double-blind, placebo-controlled study with an 
OLE Period to evaluate the safety, tolerability, and efficacy of zetomipzomib in patients with 
AIH who have failed standard-of-care treatment, had an incomplete biochemical response 
to ≥3 months of standard-of-care treatment, or had a disease flare (relapse) after experiencing 
complete remission induced by standard-of-care treatment. Incomplete biochemical response is 
defined as an improvement of laboratory and histological findings that are insufficient to satisfy 
criteria for remission (Mack et al., 2020). Disease flare or relapse is defined as an exacerbation 
of disease activity after induction of remission and drug withdrawal (or nonadherence) (Mack et 
al., 2020). 
Independent Data Monitoring Committee (IDMC) will review safety findings as described in 
Section 9.11.  
3.1.1. 
Double-blind Treatment Period 
In the Double-blind Treatment Period, zetomipzomib or placebo will be administered weekly for 
a 24-week treatment period. Patients will be evaluated for eligibility according to the entry 
criteria (see Section 4) within 4 weeks prior to the first dose of IMP on Day 1 (Visit 2). Efficacy 
assessments will be performed for all patients at Weeks 12, 16, 20, and 24; these assessments are 
discussed in Section 7.2.2. Safety will be assessed throughout the study by monitoring of vital 
signs, clinical laboratory tests, and physical examinations, and by recording and analyzing all 
AEs and SAEs.  
Eligible patients will be randomized in a 2:1 ratio on Day 1 (Visit 2) to receive either standard-
of-care (glucocorticoids) with zetomipzomib (Active Treatment group), or standard-of-care with 
Placebo (Control group). Zetomipzomib and placebo (ie, sterile water for injection [WFI] in an 
equivalent volume to the reconstituted zetomipzomib dose) will be administered SC once weekly 
by study personnel at the site or by a home trial service at the patient’s home or alternate location 
(eg, place of employment). The first dose of IMP will be 30 mg zetomipzomib or placebo, 
followed by weekly doses of 60 mg zetomipzomib or placebo for the remaining 23 weeks of the 
Double-blind Treatment Period. 
Enrolled patients will be on standard-of-care with a prednisone/prednisone equivalent dose of 
20 mg/day on Day 1 (Visit 2). Following consultation with the Medical Monitor, patients who 
are taking a prednisone/prednisone equivalent dose higher than 20 mg/day at Baseline may also 
be enrolled in the study provided the prednisone/prednisone equivalent dose does not exceed 
40 mg/day. Patients are encouraged to undergo a glucocorticoid taper of prednisone/prednisone 
equivalent dose according to the protocol-suggested glucocorticoid taper schedule (Table 6) and 
prednisone equivalent doses (Table 7) as provided in Appendix B. Patients taking budesonide 
who are unwilling to switch to a prednisone/prednisone equivalent for the study may continue to 
take budesonide at the doses shown in Appendix B.  

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 40 of 86 
In addition to prednisone/prednisone equivalent, patients may continue to use up to two 
additional immunosuppressive agents if these agents are already used as baseline therapy: 
a) Oral AZA or oral MMF (including the alternatives mycophenolate sodium [MMS] or 
mycophenolic acid [MPA]) 
and/or 
b) Oral tacrolimus (TAC), cyclosporine A (CsA), or 6-mercaptopurine (6-MP) 
The dose of these immunosuppressants must be stable for at least 4 weeks prior to Screening and 
must be held constant unless tolerability/AEs require dose adjustment and glucocorticoid taper is 
completed. Following completion of the glucocorticoid taper, immunosuppressants may be 
decreased at the Investigator’s discretion (Section 6.2.3). 
During the glucocorticoid taper, patients with signs and symptoms of worsening disease 
(ie, worsening of ALT level ≥25% from Baseline for ≥1 week, as verified via repeat laboratory 
assessments) may increase glucocorticoid doses following consultation with the Medical 
Monitor. 
For patients who are confirmed treatment failures or who experience a disease flare 
(see Section 2.2.2) during the treatment period, IMP may be discontinued upon consultation with 
the Medical Monitor, and additional care will be introduced as medically indicated. Patients who 
receive rescue therapy (see Section 6.3) will temporarily discontinue IMP, complete the 
Double-blind Period visits, and remain eligible for the OLE Period. Patients who do not receive 
rescue therapy but undergo a temporary interruption in IMP (≤2 consecutive doses or ≤4 total 
doses) should also remain in the study. Patients who discontinue participation in the study due to 
a disease flare will be considered treatment failures. If the patient cannot continue with the 
planned assessments, the patient will complete the Early Termination Visit (ETV; Table 3) 
followed by the End-of-Study (EOS) visit (Table 3) 4 weeks later. 
A liver biopsy will be performed at the Week 24 visit to assess any changes from Baseline in 
liver histopathology. 
Patients who are eligible to roll over to the OLE Period will receive their first SC injection of 
zetomipzomib at the dose and schedule described in the OLE Period section (Section 3.1.2). 
Patients who are not eligible or choose not to roll over to the OLE Period will have an 
End-of-Study (EOS) visit (assessments shown in Table 3) 4 weeks after completion of the 
Double-blind Treatment Period. 
3.1.2. 
Open-label Extension (OLE) Period 
Patients who complete the Double-blind Period study visits through Week 24 are eligible to roll 
over to the OLE Period. If a patient does not meet eligibility criteria for the OLE Period, then the 
patient would proceed with the EOS visit. The patient would not be considered a screen fail for 
the OLE Period. 
All patients will receive a SC injection of 30 mg zetomipzomib at the OLE Week 1 visit, 
followed by weekly SC injections of 60 mg zetomipzomib, administered by study personnel at 
the site or by a home trial service at the patient’s home or alternate location (eg, place of 
employment), for a total of 24 additional weeks of treatment. After the OLE Week 1 Visit, 
additional on-site study visits will occur every 4 weeks from OLE Week 4 through OLE 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 41 of 86 
Week 20. An additional on-site visit will occur at OLE Week 25 (EOT visit). At these visits, 
safety and efficacy assessments will be performed according to the OLE Schedule of 
Assessments (Table 3). Patients will have a safety follow-up visit (EOS Visit) 4 weeks after their 
last dose of zetomipzomib, for a maximum potential length of participation in the OLE of 
28 weeks. 
During the course of the OLE Period, prednisone/prednisone equivalent can continue to be 
tapered and may be withdrawn (see Appendix B for suggested taper schedule). Patients with 
signs and symptoms of worsening disease (ie, worsening of ALT level ≥25% from OLE Baseline 
for ≥1 week, as verified via repeat laboratory assessments) may increase glucocorticoid doses 
following consultation with the Medical Monitor. For patients who are confirmed treatment 
failures or who experience a disease flare (see Section 2.2.2) during the OLE Period, IMP may 
be discontinued upon consultation with the Medical Monitor, and additional care will be 
introduced as medically indicated. Patients who receive rescue therapy (see Section 6.3) will 
temporarily discontinue IMP but will remain in the study to complete OLE visits. Patients who 
do not receive rescue therapy but undergo a temporary interruption in IMP (≤2 consecutive doses 
or ≤4 total doses) should also remain in the study. Patients who discontinue participation in the 
study due to a disease flare will be considered treatment failures. If the patient cannot continue 
with the planned assessments, the patient will complete the ETV (Table 3) followed by the 
End-of-Study (EOS) visit (Table 3) 4 weeks later. 
An optional liver biopsy may be performed at the OLE Week 25 visit to assess changes in liver 
histopathology. 
 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
 
 
 
Page 42 of 86 
3.1.3. 
Study Design Schema 
Figure 1 
Study KZR-616-208 Study Design Schema 
 
 
 
Abbreviations: AIH=autoimmune hepatitis; EOS=End-of-Study; EOT=End-of-Treatment; QW=once weekly; OLE=open-label extension; SC=subcutaneous; 
SoC=standard-of-care 
Note: Patients who are not eligible or choose not to roll over to the OLE Period will have an EOS visit (safety follow up) 4 weeks after completion of the 
Double-blind Treatment Period. * For protocol-suggested glucocorticoid taper schedule, refer to Table 6 and Table 7 for prednisone equivalents in Appendix B. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 43 of 86 
3.1.4. 
Study Design Rationale 
This is a Phase 2a, multi-center, randomized, double-blind, placebo-controlled study with an 
OLE Period to evaluate the safety and efficacy of zetomipzomib in patients with AIH. The study 
will consist of a 24-week Double-blind Treatment Period, a 24-week OLE Period, and a 4-week 
off-treatment safety follow-up period.  
Zetomipzomib is a first-in-class selective inhibitor of the human immunoproteasome that may 
offer distinct advantages to the treatment and care of patients with AIH. The pathophysiology of 
AIH is attributed to autoimmune based dysfunction that involves T-cells, B-cells, and 
monocyte/macrophages including resident Kupffer cells. The foundation of current care is high-
dose glucocorticoids given chronically over years or given with glucocorticoid-sparing therapies. 
The current standard of care is immunosuppressive agents, which are associated with significant 
comorbidities and toxicities. Zetomipzomib given once weekly results in an immunomodulatory 
effect that does not deplete cell lines or interfere with important immune-signaling targets. 
Zetomipzomib activity is highly specific, targeting N-terminal threonine proteases, which are 
only found within the immunoproteasome; thus, no off-target activities are predicted or have 
been seen in clinical trials to date.  
Zetomipzomib is metabolized by extrahepatic epoxide hydrolase enzymes, so its metabolism 
would likely not be impacted by patients with liver dysfunction. The current study design 
enables evaluation of the safety and efficacy of zetomipzomib in patients with AIH. This study 
will also begin to describe potential glucocorticoid-sparing attributes, as a protocol-suggested 
glucocorticoid taper is included. This study should provide sufficient evidence of the safety and 
efficacy of zetomipzomib to inform a later phase trial of zetomipzomib for the treatment and 
prevention of disease flares in AIH. 
3.2. 
Randomization, Blinding, and Unblinding Procedures 
3.2.1. 
Randomization 
This is a Phase 2a, multi-center, randomized, double-blind, placebo-controlled study with an 
OLE Period. Once patients have consented, undergone all screening procedures, and been 
determined to be eligible for the study, they will return for the Baseline (Day 1) Visit to be 
randomized in a 2:1 ratio to receive weekly SC administration of zetomipzomib plus standard-of-
care or placebo control plus standard-of-care during the Double-blind Treatment Period.  
Patients will be stratified by glucocorticoid use at Screening (ie, glucocorticoid use, no 
glucocorticoid use at Screening).  
Additional details on randomization procedures will be provided in the Interactive Response 
Technology (IRT) Manual. 
3.2.2. 
Blinding 
To preserve the double-blind design, patients randomized to the placebo group will receive a SC 
injection in an equivalent volume to the active treatment IMP. The dosing schedule in the 
placebo group will be the same as that of the active treatment IMP. Thus, the double-blind nature 
of this study preserves the blind with respect to active study treatment and placebo. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 44 of 86 
All study personnel and study patients will be blinded to the IMP administered during the 
Double-blind Treatment Period. Zetomipzomib and placebo will be identical in volume (see 
Section 5.1). An unblinded Pharmacist will prepare and blind the IMP (see Section 6.1). 
The randomization code key will not be available to the Study Monitors, project statisticians, or 
the project team at Kezar or its representatives. The site personnel, Monitors, and study patients 
will remain blinded to Double-blind Treatment Period IMP assignment until the end of the study. 
In case of emergency, the unblinding process in Section 3.2.3 should be followed. Measures will 
be in place at the Sponsor to prevent unblinding by laboratory measurements. 
3.2.3. 
Unblinding 
In the rare event that a treatment-emergent adverse event (TEAE) or pregnancy occurs for which 
knowledge of the IMP administered is necessary to manage the patient’s condition, the code for 
that patient may be broken and the test substance identified via the IRT system. Procedures for 
unblinding will be provided in the IRT Manual. 
If emergency unblinding is required, the Investigator should contact the Medical Monitor prior to 
unblinding whenever possible. However, the Investigator is strongly advised to discuss options 
with the Medical Monitor or appropriate Sponsor study personnel prior to unblinding. The reason 
for unblinding must be documented and captured directly within the IRT system. The IRT 
system will automatically store the date and time of unblinding.  
Individual patient data will be unblinded for pharmacovigilance regulatory reporting purposes. 
Patients whose data have been unblinded for pharmacovigilance regulatory reporting purposes 
only will not be discontinued from further receipt of IMP. 
In the case of accidental unblinding, immediate measures must be taken to contain the 
unblinding. The accidental unblinding should be promptly documented and reported to the 
Sponsor, who will advise on further actions. 
3.3. 
Number of Sites 
Up to 24 sites are planned to participate in this study. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 45 of 86 
4. 
PATIENT SELECTION AND ENROLLMENT 
4.1. 
Number of Patients 
Approximately 24 patients (randomized in a 2:1 ratio; Active Treatment group: Control group) 
will be enrolled in the study. 
Patients will be evaluated for eligibility in the study according to the eligibility criteria. 
The Investigator will ensure that the patient has provided written informed consent before 
administration of study medication. 
Once informed consent is obtained, the evaluations may begin to assess study eligibility 
(inclusion/exclusion criteria). Patients who do not meet inclusion/exclusion criteria may be 
rescreened one time. 
4.2. 
Inclusion Criteria 
Only individuals who meet all of the following criteria may be enrolled in the study. 
Double-blind Treatment Period 
1. Must be aged ≥18 years.  
2. Must have a clinical diagnosis of AIH and signs of active disease despite standard-of-care 
therapy for ≥3 months or disease flare after experiencing complete remission induced by 
standard-of-care treatment, including: 
a. Screening ALT values that are 1.25 to 10 times ULN 
b. Liver biopsy results with Ishak score (modified HAI) ≥5/18 (Ishak et al., 1995) 
indicating active AIH, from a biopsy performed at Screening or within 6 months prior 
to Screening. 
c. Mild or no hepatic impairment (Child-Pugh category A) 
3. Must be willing to use and taper glucocorticoid therapy as described in Section 3.1 and 
Section 6.2.2.1. 
4. Women of childbearing potential (WOCBP) must have a negative urine or serum 
pregnancy test prior to the first dose of IMP in KZR-616-208, and must agree to continue 
to use a highly effective method of birth control until completion of the study (or 30 days 
following the last dose of IMP in case of early withdrawal). For the purposes of this 
study, WOCBP are defined as fertile 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 or local laboratory and if 
patient is not on supplementary hormonal therapy) or surgically sterile (ie, tubal ligation, 
hysterectomy, bilateral salpingo-ophorectomy). See Section 7.2.7 for detailed 
requirements for WOCBP. 
5. Male patients must agree to use an effective contraception method (eg, condom with 
spermicide) during the study, and continue to use this method for 1 week following their 
last dose of IMP or be congenitally or surgically sterile (eg, vasectomy with documented 
confirmation of post-surgical aspermia).  

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 46 of 86 
6. Must be willing and able to return for all clinic visits and to complete all study-required 
procedures. 
Open-label Extension Period 
7. Same as Double-blind Treatment Period Inclusion criteria, except the following 
modifications to Inclusion Criterion 2: 
a. ALT value can be normal or, if elevated, in the range of 1.25 to 10 times the ULN  
b. Inclusion Criterion 2b does not apply to the OLE Period 
c. Inclusion Criterion 2c must be met  
8. Must have completed the Double-blind Period study visits through Week 24, including 
all Week 24 Visit assessments. 
9. Must be willing to maintain glucocorticoid therapy or continue to taper glucocorticoid 
therapy as described in Section 6.2.2.1. 
4.3. 
Exclusion Criteria 
Only individuals who do not meet any of the following criteria may be enrolled in the study. 
Double-blind Treatment Period 
1. Have a concomitant diagnosis of primary biliary sclerosis, primary sclerosing cholangitis, 
IgG 4-related cholangitis, or drug-related AIH (at Screening) or a history of 
drug-related AIH. 
2. Have clinical evidence of significant unstable or uncontrolled diseases other than the 
disease under study (eg, cardiac [including congestive heart failure, hypertension, angina, 
or myocardial infarction], pulmonary [including pulmonary hypertension or interstitial 
lung disease], hematologic, gastrointestinal, endocrinologic, hepatic, renal, neurological, 
or infectious disease, any ongoing SAE(s), or AE(s) ≥ Grade 3 by National Cancer 
Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE]) that, in the 
opinion of the Investigator or Sponsor/designee, could confound the results of the study, 
put the patient at undue risk, or interfere with protocol adherence. 
3. Are receiving oral or injectable immunomodulating treatment other than permitted 
concomitant medications in Section 6.2.3 prior to enrollment in the study. Patients who 
have been using such treatments must have had the washout periods outlined in 
Section 6.2.1. 
4. Have an active infection (eg, acute hepatitis E, cytomegalovirus, or Epstein-Barr virus) 
requiring systemic therapy with antibiotic, antiviral, or antifungal treatment, or has had 
any febrile illness within 7 days prior to Day -1. 
5. Have a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test 
(real-time polymerase chain reaction [RT-PCR]) at screening or Day 1. 
6. Have a history of thyroiditis, celiac disease, or other autoimmune disorder known to be 
associated with transaminitis. 
7. Have a history of primary or acquired immunodeficiency. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 47 of 86 
8. Have a history of malignancy of any type, with the exceptions of surgically excised 
nonmelanoma skin cancers, in situ cervical cancer >5 years prior to Baseline (Day 1), 
prostate cancer that is considered cured (normal prostate-specific antigen) for >5 years, 
colon cancer considered cured >5 years following surgical treatment, or lymphoma with 
>5 years complete remission. 
9. Have a history of solid organ transplant. 
10. Have a history of excessive alcohol use (consumption of 4 or more drinks on any day or 8 
or more drinks per week for women and 5 or more drinks on any day or 15 or more 
drinks per week for men) or drug abuse in the 1 year prior to Screening, in the opinion of 
the Investigator. 
11. Have an estimated glomerular filtration rate <60 mL/min/1.73 m2 by the Modification of 
Diet in Renal Disease (MDRD) equation (National Institute of Diabetes and Digestive 
and Kidney Diseases [NIDDK]). 
12. Have a hemoglobin level <9.0 g/dL, neutrophil count <1200/mm3, or platelet count 
<120 × 109/L at Screening. 
13. Have a prothrombin time above ULN at Screening, or an International Normalized Ratio 
(INR) >1.2. 
NOTE: Minor changes in coagulation parameters that may be attributable to permitted 
concomitant medications and that are not considered clinically significant by the 
Investigator are allowed. 
14. Have a history of hypercoagulability (including, but not limited to, antiphospholipid 
antibody syndrome, activated protein C resistance, elevated coagulation factor VIII 
levels, sticky platelet syndrome, protein C or S deficiency, homocystinemia, antithrombin 
deficiency, dysfibrinolysis, or prothrombin G20210A mutation), thrombotic events 
(including, but not limited to, deep vein, femoral vein, superior vena cava, or jugular vein 
thrombosis; thrombotic stroke; pulmonary embolism; myocardial infarction; retinal vein 
occlusion, or thrombotic microangiopathies), or hemolytic uremic syndrome. 
15. Have liver cirrhosis with significant impairment of liver function (Child Pugh category B 
or C), or have decompensated cirrhosis. 
16. Patients with histology confirmed coincident non-alcoholic steatohepatitis. NOTE: 
Patients with other type of non-alcoholic fatty liver disease are NOT excluded from the 
study. 
17. Have electrocardiogram (ECG) findings of QT corrected for pulse rate (QTcF) 
>480 msec, newly diagnosed (within 6 months prior to Screening) and/or poorly 
controlled atrial fibrillation (ie, symptomatic patients or a ventricular rate above 
100 beats/min on ECG), or other clinically significant cardiac abnormalities. 
18. Have positive serology results at Screening (human immunodeficiency virus [HIV], 
hepatitis B [surface antigen and core antibodies], hepatitis C [anti-HCV antibody 
confirmed with hepatitis C RNA]). 
• Patients who are hepatitis B virus surface antigen (HBsAg) positive will not 
be eligible. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 48 of 86 
• Patients who are HBsAg negative and hepatitis B core antigen antibody (HBcAb) 
positive will be tested for hepatitis B surface antibody (HBsAb) and hepatitis B DNA: 
− Patients with HBsAb titer ≥100 IU/L and negative hepatitis B DNA may be 
enrolled. 
− Patients with positive hepatitis B DNA results will be excluded. 
− Patients with HBsAb titer <100 IU/L or negative will be excluded. 
19. Have positive interferon-gamma release assay (IGRA) (eg, T-SPOT tuberculosis [TB] 
Test, QuantiFERON®-TB Gold, or QuantiFERON®-TB Gold Plus (QFT Plus), at 
Screening, unless the patient has latent TB and all of the following are true: 
• The chest X-ray does not show evidence suggestive of active TB. 
• There are no clinical signs or symptoms of pulmonary and/or extra-pulmonary TB. 
• The patient has documented evidence of receiving one of the following prophylactic 
treatment regimens: daily oral isoniazid for 6 months, daily oral rifampin for 6 
months, or isoniazid and rifapentine weekly for 3 months. 
Note: If a QuantiFERON®-TB Gold/Gold Plus is indeterminate for any reason and a 
T-SPOT TB test is negative, the patient may be enrolled using the local result upon 
approval of the Sponsor. On a case-by-case basis, after discussion and approval by the 
Sponsor, a local TB test that is negative and is considered equivalent to one of the above 
tests may be used for eligibility. Without a negative test, unless treated as noted above, 
one or more indeterminant tests are not sufficient for the patient to be enrolled 
(see Section 7.2.4.5.1.1). 
20. Have taken rituximab, other B- or T-cell depleting agents, or alkylating agents within 
6 months of screening, unless B- or T-cells have been shown to return to normal values 
(B-cells [CD19+] >100 cells/μL; T-cells [CD4+] >500 cells/mm3). 
21. Require regular use of medications with known hepatotoxicity (see Section 6.2). 
22. Have previously used a proteasome inhibitor (dual proteasome inhibitors allowed if it has 
been at least 1 year since last use). 
23. Have received a live vaccine within 28 days prior to Baseline (Day 1), or plan to receive 
a live vaccine during the study. 
24. Have used another investigational medical therapy, and/or participated in an 
investigational trial within 6 months or 5 half-lives (whichever is longer) prior to 
Screening. 
25. Are females who are breastfeeding or who plan to become pregnant during the study, or 
who are actively trying to conceive at the time of signing of the informed consent form 
(ICF). 
26. Have known hypersensitivity to zetomipzomib or any of its excipients. 
Open-label Extension Period 
27. Same as Double-blind Treatment Period exclusion criteria. No need to re-test for 
antiphospholipid antibody, HIV, HBV, HCV, and TB. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 49 of 86 
5. 
STUDY TREATMENT INFORMATION 
Instructions for the receipt, inspection, storage, preparation, administration, and disposal of IMP 
will be provided in a separate Pharmacy Manual at each site. 
5.1. 
Physical Description of Investigational Medicinal Product 
Active IMP (zetomipzomib) is supplied as sterile lyophilized solids in single-use glass vials. 
Each vial is reconstituted with sterile WFI diluent prior to administration. Details of the 
zetomipzomib drug product formulation are provided in the Investigator's Brochure. 
Placebo control will consist of sterile WFI in an equivalent volume to the reconstituted 
zetomipzomib dose.  
Commercially available sterile WFI may be used as diluent for active IMP reconstitution and as 
placebo. Commercially available sterile WFI should be stored as per the manufacturer’s 
recommendation. 
5.2. 
Packaging and Labeling 
Active IMP will be packaged in cartons. All active IMP will be manufactured, packaged, and 
labeled according to Good Manufacturing Practice (GMP) and relevant regulatory guidelines. 
All manufacturing, packaging, and labeling operations will be performed according to Good 
Manufacturing Practice (GMP) and relevant regulatory requirements. 
5.3. 
Supply, Dispensing, Storage, and Investigational Medicinal Product 
Accountability 
Refer to the most current version of the Investigator’s Brochure and Pharmacy Manual for 
storage conditions for active IMP. The current recommended storage condition for active IMP is 
2°C to 8°C. 
Upon receipt of active IMP, the Investigator (or designee) will conduct an inventory of the 
supplies and verify that they are received in acceptable condition and in the correct amounts. 
The Clinical Site Monitor (Monitor) may verify the study supplies at each study center at any 
time during the study. 
The Investigator or designee must confirm that appropriate temperature conditions have been 
maintained during transit for all active IMP received and that any discrepancies are reported and 
resolved before use of the active IMP. 
Only patients enrolled in the study may receive IMP. All IMP should be stored in an 
environmentally controlled and monitored (manual or automated) area in accordance with the 
labeled storage conditions. Unless communicated as permissible by Sponsor, excursions from 
labeled storage conditions must be reported and resolved before use. Access to IMP must be 
limited to the investigator and authorized site personnel. 
The Investigator or the head of the medical institution (where applicable) is responsible for 
accountability, reconciliation, and record maintenance (such as receipt, reconciliation, and final 
disposition records) of IMP. It is the responsibility of the Monitor to ensure that the Investigator 
(or designee) has correctly documented the amount of IMP received, dispensed, and returned in a 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 50 of 86 
dispensing log. A full accountability log will be maintained at the site at all times. The Monitor 
will perform an inventory of IMP at the closeout visit to the site. All discrepancies must be 
accounted for and documented. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 51 of 86 
6. 
DOSAGE AND STUDY MEDICATION ADMINISTRATION 
6.1. 
Investigational Medicinal Product Administration 
An unblinded Pharmacist will prepare and blind the active and placebo doses. During the 
Double-blind Treatment Period, IMP (active zetomipzomib or volume-matched placebo) will be 
administered by SC injection once weekly, according to randomization. The first dose will be 
30 mg zetomipzomib or placebo, administered at the clinical trial site, followed by weekly doses 
of 60 mg zetomipzomib or placebo for the remaining 23 weeks of the Double-blind Treatment 
Period. During the OLE Period, zetomipzomib will be administered to all patients by SC 
injection once weekly. The first open-label dose will be 30 mg zetomipzomib, followed by 
weekly doses of 60 mg zetomipzomib for the duration of the OLE Period. 
After the first dose, IMP will be administered by study personnel at the site or by a home trial 
service at the patient’s home or alternate location (eg, place of employment). 
Weekly doses will be administered according to the Schedules of Assessments (Table 1 through 
Table 4). 
Further details regarding drug product formulation, preparation, and administration of IMP will 
be provided in a separate Pharmacy Manual. 
6.1.1. 
Administration Site 
SC 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 anatomic site, if 
possible. 
6.1.2. 
Suggested Measures to Improve Investigational Medicinal Product Tolerance  
Initial SC administration of zetomipzomib at doses of 60 mg or above is occasionally associated 
with at least one of the following signs/symptoms: hypotension, tachycardia, nausea, vomiting, 
dizziness, headache, pyrexia, rigors and/or chills. These signs/symptoms typically begin within 
8 to 24 hours after dosing, and usually resolve within 48 hours after dosing. 
Although the numbers are small, the percentage of patient reporting TEAEs of the above 
signs/symptoms appears to be lower in patients who received zetomipzomib as step-up doses 
and/or with pre-/post-dose prophylaxis, suggesting that these methods are effective at tolerizing 
patients to higher doses of zetomipzomib. 
Step-up Dosing 
All patients will receive an initial SC step-up dose of 30 mg zetomipzomib or placebo, followed 
weekly by the target dose of 60 mg SC zetomipzomib or placebo.  
Pre/Post Dose Prophylaxis 
Prophylactic measures may be considered if any of the signs and/or symptoms listed above 
develop, and may be used as treatment. Measures that have been demonstrated to reduce the 
incidence and severity of SC administration-related reactions include the following: 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 52 of 86 
• Fluid hydration, eg, 250-500 mL oral (or IV if necessary) of an electrolyte solution up 
to 48 hours prior to dosing, or up to 24 hours after dosing if symptoms are present 
• Antiemetics, non-sedating antihistamines, and/or acetaminophen are permitted if 
patients are prone to specific symptoms. 
If additional guidance for improving initial tolerability symptoms is required, the Medical 
Monitor should be consulted. Home trial service providers do not provide or administer any of 
the fluids or medications listed above. 
6.1.3. 
Dose Modification Guidelines 
6.1.3.1. 
Dose Reduction 
If the Investigator is concerned that a patient needs a dose reduction due to safety or tolerability, 
the Medical Monitor should be consulted for a reduction of IMP. The dose may then be reduced 
to a 45 mg or 30 mg dose of zetomipzomib or placebo in a blinded manner during the Double-
blind Treatment Period, or to a 45 mg or 30 mg dose of zetomipzomib during the OLE Period.  
Written approval from the Medical Monitor should be obtained in advance of implementing dose 
reduction, when possible. After dose reduction is implemented, patients should remain on the 
reduced dose for at least 2 doses, after which the dose may be re-escalated to a 60 mg dose of 
zetomipzomib or placebo. If the 60 mg zetomipzomib or placebo dose is not tolerated after 
re-escalation, the reduced dose may be continued for the remainder of the study, or re-escalation 
to a 60 mg dose of zetomipzomib or placebo may be re-attempted after written approval from the 
Medical Monitor. Any dose modifications should be documented in the electronic case report 
form (eCRF) as per Section 9.1.4. 
6.1.3.2. 
Missed Doses 
Doses should be administered within the visit windows as per the Schedule of Assessments 
(Section 7.1). Any doses administered outside of the visit window will be considered a protocol 
deviation; however, if necessary to avoid missing a dose, doses may be administered up to 3 days 
from the date of scheduled administration with a minimum of 4 days required between doses. 
Patients who meet individual patient stopping rules (Section 8.1.2) may resume dosing after 
discussion between the Investigator and Medical Monitor. Upon resumption of dosing, 
subsequent doses should be timed according to the original dosing schedule based on Day 1. 
Missed doses should be documented in the eCRF as per Section 9.1.4. Patients who are 
discontinued for missed doses should have their discontinuation recorded in the eCRF based on 
the reason the doses were missed, eg, AE, protocol noncompliance. The Investigator should 
contact the Medical Monitor if a patient misses >2 consecutive doses or >4 total doses to 
determine whether the patient should resume administration of IMP. 
If IMP is permanently discontinued due to an AE, the planned assessments (see Schedule of 
Assessments in Table 1 and Table 3) should continue for the protocol-specified time period. 
If the patient cannot continue with the planned assessments, the patient will complete the ETV 
(Table 3) followed by the safety follow-up (EOS) visit (Table 3) 4 weeks later. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 53 of 86 
6.2. 
Prior and Concomitant Treatments 
A concomitant medication is any prescription or over-the-counter preparation, including 
vitamins and supplements. A concomitant therapy is any therapy that may be used, eg, physical 
therapy, surgery, or medication. Except as described in Section 6.2.1, prior and concomitant 
medications and therapies will be recorded on the eCRF for 60 days prior to Screening and 
continuing for 30 days following the last dose, or the EOS visit, whichever occurs later. Details 
to be recorded include, but are not limited to, the concomitant medication generic name, dose, 
route, frequency of administration, and indication.  
6.2.1. 
Prior Treatment Restrictions 
All prior AIH treatments (eg, glucocorticoids, immunosuppressants, antimalarials, and biologics) 
will be recorded, from at least 24 weeks prior to Screening. When possible, all prior biologics 
should be recorded. Details to be recorded include, but are not limited to, the concomitant 
medication generic name, dose, route, frequency of administration, and indication. Patients 
taking immunologic response modifiers must have completed the washout periods shown below 
prior to enrolling in the study. 
≥2 weeks prior to Screening: 
Methotrexate, dapsone, intravenous immunoglobulin, 
anakinra, etanercept, sirolimus, or any other 
immunosuppressant not elsewhere mentioned  
4 weeks prior to Screening 
Thioguanine 
12 weeks prior to Screening: 
Infliximab, adalimumab, golimumab, abatacept, tocilizumab, 
certolizumab, secukinumab, plasmapheresis 
6 months prior to Screening: 
Anti-CD20 drugs such as rituximab, ofatumumab, or other 
long-acting biologics, proteasome inhibitors such as 
carfilzomib or bortezomib 
A shorter washout period is allowed for anti-CD20 treatments if there is documented B cell 
reconstitution. 
6.2.2. 
Required Concomitant Medications and Therapies 
6.2.2.1. 
Glucocorticoids 
Oral prednisone/prednisone equivalent is a required concomitant medication during this study. 
Enteric-coated glucocorticoids are not permitted. Patients will take their own supply of 
glucocorticoids. Patients should be informed of and follow appropriate local practice for this 
medication including monitoring for adverse effects.  
Enrolled patients will be on standard-of-care with a prednisone/prednisone equivalent dose of 
20 mg/day on Day 1 (Visit 2). Following consultation with the Medical Monitor, patients who 
are taking a prednisone/prednisone equivalent dose higher than 20 mg/day at Day 1 may also be 
enrolled in the study provided the prednisone/prednisone equivalent dose does not exceed 
40 mg/day. For the Double blind Treatment period, patients are encouraged to undergo a 
glucocorticoid taper of prednisone/prednisone equivalent dose according to the 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 54 of 86 
protocol-suggested glucocorticoid taper schedule (Table 6) and prednisone equivalent doses 
(Table 7) as provided in Appendix B Patients taking budesonide who are unwilling to switch to a 
prednisone/prednisone equivalent for the study may continue to take budesonide at the doses 
shown in Appendix B. For suggested glucocorticoid taper schedule, please see Appendix B. 
During the glucocorticoid taper, patients with signs and symptoms of worsening disease 
(ie, worsening of ALT level ≥25% from Baseline for ≥1 week, as verified via repeat laboratory 
assessments) may increase glucocorticoid doses following consultation with the Medical 
Monitor.  
During the OLE Period, prednisone/prednisone equivalent can continue to be tapered and may be 
withdrawn (see Appendix B for suggested taper schedule). Investigators are encouraged to 
further taper to discontinuation if clinically appropriate throughout the study, particularly during 
the OLE Period. 
6.2.3. 
Permitted Concomitant Medications and Therapies 
Concomitant therapies for comorbid conditions are permitted; these therapies should be recorded 
in the eCRF. Details regarding physical therapy, occupational therapy, or exercise should also be 
recorded in the eCRF. 
Concomitant use of cholesterol lowering medications (ie, statins) at prescribed doses and 
acetaminophen (Tylenol®) below 4,000 mg per day during the study are permitted if the patient’s 
elevated ALT level is not related to the use of these medications in the Investigator’s opinion.  
Concomitant medications in the following subsections are allowed throughout the study as 
described in Section 3.1.1. 
6.2.3.1. 
Azathioprine (AZA) 
Patients who are taking AZA in addition to prednisone/prednisone equivalent as part of their 
usual care may continue, but no more 150 mg per day (Mack et al., 2020). The AZA dose is to be 
held constant unless tolerability/AEs require dose adjustment, or decreased after completion of 
glucocorticoid taper, at the Investigator’s discretion. Evolving leukopenia or thrombocytopenia 
warrants dose reduction or drug withdrawal. AZA should be discontinued if the cytopenia does 
not recover in 1-2 weeks. 
6.2.3.2. 
Inhibitors of Inosine Monophosphate Dehydrogenase (Mycophenolate Mofetil 
[MMF], Mycophenolate Sodium [MMS] and Mycophenolic Acid [MPA]) 
Patients who are taking MMF or equivalent, such as mycophenolic acid and mycophenolate 
sodium, in addition to prednisone/prednisone equivalent as part of their usual care may continue, 
and the dose is to be held constant unless tolerability/AEs require dose adjustment, or decreased 
after completion of glucocorticoid taper, at the Investigator’s discretion. Twice daily, 3 times 
daily, or 4 times daily (if needed due to gastrointestinal AEs) dosing are permitted. Doses of 
MMF or equivalent from 1 g/day to 3 g/day are permitted per the Investigator’s discretion. 
6.2.3.3. 
Tacrolimus (TAC) 
Patients who are taking oral TAC in addition to prednisone/prednisone equivalent as part of their 
usual care may continue, and the dose is to be held constant unless tolerability/AEs require dose 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 55 of 86 
adjustment, or decreased after completion of glucocorticoid taper, at the Investigator’s discretion. 
Doses from 1 mg/day to 8 mg/day are permitted per the Investigator’s discretion (Efe et al., 
2017). 
6.2.3.4. 
Cyclosporine A (CsA) 
Patients who are taking oral CsA in addition to prednisone/prednisone equivalent as part of their 
usual care may continue, and the dose is to be held constant unless tolerability/AEs require dose 
adjustment, or decreased after completion of glucocorticoid taper, at the Investigator’s discretion. 
Doses from 1 to 2 mg/kg body weight, twice a day, are permitted per the Investigator’s discretion 
(Nasseri-Moghaddam et al., 2013). 
6.2.3.5. 
6-Mercaptopurine (6-MP) 
Patients who are taking oral 6-MP in addition to prednisone/prednisone equivalent as part of 
their usual care may continue, and the dose is to be held constant unless tolerability/AEs require 
dose adjustment, or decreased after completion of glucocorticoid taper, at the Investigator’s 
discretion. Doses from 25 to 50 mg/day or more if therapy is tolerated, are permitted per the 
Investigator’s discretion (Hübener et al., 2016).  
6.2.4. 
Prohibited Concomitant Medications 
Concomitant use of any immunosuppressant medication other than glucocorticoids and AZA, 
MMF or equivalent, TAC, CsA, or 6-MP during the study is prohibited (eg, those listed in 
Section 6.2.1). Patients who need other immunosuppressant therapy during the study should be 
withdrawn from study participation. In addition, concomitant medications associated with AIH 
(eg, minocycline, allopurinol, nitrofurantoin) are prohibited. 
6.2.5. 
Potential Drug-Drug Interactions 
Zetomipzomib has a half-life of ~5 hours in humans and is metabolized extra-hepatically by the 
ubiquitously expressed epoxide hydrolase. A very weak inhibition of CYP-Pg has been observed 
but is unlikely to be of clinical significance. No drug-drug interactions are predicted, but all 
efforts will be made to observe if any occur. 
6.2.6. 
Vaccinations 
Zetomipzomib is not anticipated to impact the response to vaccinations. It is strongly 
recommended that patients be up to date on immunizations per current AASLD guidelines 
(Mack et al., 2020) prior to Screening. If vaccinations are recommended and received during the 
study, they should be recorded in the eCRF. Live vaccinations are not permitted during the study. 
If vaccination against herpes zoster is required during the study, Shingrix or other non-live 
vaccine (if available) is preferred over live vaccines. Similarly, vaccination against influenza 
virus with inactivated vaccine is preferred. If a patient requires the vaccine against coronavirus 
disease 2019 (COVID-19) during the study, no interruption of IMP treatment is required for the 
purpose of vaccination. If it is possible to schedule COVID-19 vaccine administration with 
respect to IMP administration, the following is recommended when feasible: 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 56 of 86 
• If IMP is administered in an extremity, the vaccine should be administered in an 
extremity other than the one used for IMP injection that week. 
• If symptoms related to IMP administration are present, it is recommended to time the 
administration of the vaccine when the symptoms are resolved or resolving 
• For patients who have received at least 3 doses of IMP, ideally 2 days should separate 
administration of IMP and the vaccination to permit sufficient time to distinguish 
potential adverse effects. 
• For patients who have received less than 3 doses of IMP, ideally 3 days should 
separate administration of IMP and the vaccination to permit sufficient time to 
distinguish potential adverse effects. 
6.2.7. 
Other Restrictions and Prohibitions 
For patients requiring surgery, or for any planned surgery during the study, the Medical Monitor 
should be consulted to discuss IMP dosing. 
6.3. 
Rescue Therapy  
Rescue therapy is defined as any modification to the background AIH treatment, including dose 
or frequency increases in concomitant medications or initiation of a new medication. 
Rescue medications may include, but are not limited to systemic glucocorticoids, AZA, MMF, 
calcineurin inhibitor, and other immunosuppressants according to the guideline (Mack et al., 
2020). While rescue therapy is typically restricted or prohibited per protocol (Section 6.2.4), 
patients may receive rescue therapy during the study at the discretion of the Investigator when 
deemed medically necessary for the safety of the patient. Examples of situations that might 
require rescue therapy include: 
• Patients who meet the definition for treatment failure or disease flare that requires 
higher than the maximum protocol-allowed prednisone/prednisone equivalent dose 
(Section 3.1) or addition of other immunosuppressant medication(s) 
• Patients requiring hospitalization due to signs of acute liver failure 
• Patients with evidence of a coagulation abnormality (eg, INR ≥1.5) 
• Patients with any degree of mental alteration (encephalopathy) without pre-existing 
cirrhosis and with an illness of <26 weeks duration (Polson et al., 2005). 
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 will temporarily discontinue IMP, complete the Double-blind Period visits, and remain 
eligible for the OLE Period.  

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 57 of 86 
7. 
STUDY EVALUATIONS 
7.1. 
Schedule of Assessments 
7.1.1. 
Double-blind Treatment Period 
The Schedule of Assessments is presented in Table 1, and the Schedule of IMP Administration 
(for visits at which no assessments are scheduled) is presented in Table 2. 
Screening assessments should be performed between Day -28 and Day -1. The Screening period 
may be extended to 35 days upon approval by the Sponsor or designee. Patients who do not meet 
inclusion/exclusion criteria may be rescreened one time. 
Study visits will occur according to Table 1 and Table 2. Glucocorticoid tapering will be 
evaluated from the Week 2 visits. 
At on-site study visits, safety and efficacy assessments will be performed and IMP will be 
administered according to the Schedule of Assessments (Table 1). All other study visits may 
occur either at the site or at patients’ homes or alternate location (eg, place of employment) via 
home trial service (Table 2). 
7.1.2. 
Open-label Extension Period 
At on-site study visits, safety and efficacy assessments will be performed and IMP will be 
administered according to the Schedule of Assessments (Table 3). All other study visits may 
occur either at the site or at patients’ homes or alternate location (eg, place of employment) via 
home trial service (Table 4). 
For patients who roll over immediately to the OLE Period, Study Visit 26 (Table 1) may occur 
on the same day as Study Visits 27 and 28 (Table 3). For patients who initiate the OLE Period 
within 4 weeks after the Week 24 Visit of the Double-blind Treatment Period, the most recently 
reported assessments from Week 20 or later in the Double-blind Treatment Period may serve as 
the eligibility assessments for the OLE Period (ie, OLE Visit 27 assessments do not need to be 
repeated). For patients who roll into the OLE Period >4 weeks and <12 weeks after the Week 24 
Visit of the Double-blind Treatment Period, Visit 27 assessments must be performed within 
28 days prior to first open-label IMP administration to confirm eligibility for the OLE. 
7.1.3. 
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 
other reasons, as warranted. During an unscheduled visit, information regarding concomitant 
medications and AEs (at a minimum) will be collected. Any of the other procedures listed for the 
Week 24 visit may also be performed at the Investigator’s discretion.  
7.1.4. 
Telehealth Visits 
While the study visits in Table 1 and Table 3 are mandatory, in the event of constraints imposed 
by the COVID-19 pandemic, sites may elect to use a combination of telemedicine (as permitted 
by their institutions) and/or home trial service to conduct these visits. Weekly IMP injections 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 58 of 86 
listed on Table 2 and Table 4 may occur at the site or at patients’ homes or alternate location 
(eg, place of employment) via home service. 
For telehealth visits, weight will not be measured, and a limited physical examination will be 
performed. All other assessments should be performed, if feasible. Samples for clinical 
laboratory assessments will be collected by home trial service providers and sent to the central 
laboratory. 
7.2. 
Study Procedures and Assessments 
All patients must be provided an ICF describing the study with sufficient information for them to 
make an informed decision regarding their participation as per Section 11.3. Informed consent 
must be signed prior to any procedures for the study. All study procedures and assessments 
should be performed according to the schedules presented in Table 1 through Table 4. 
If a patient is not able to come to the site for an on-site visit as per the Schedule of Assessments 
(Table 1 and Table 3), a telehealth visit should occur (see Section 7.1.4).  
7.2.1. 
Medical History 
Documentation of the patient’s medical history should contain the patient’s full medical history 
including past and concomitant illnesses/diseases, year of diagnosis, date and results of liver 
biopsy or biopsies, prior and concomitant medications, demographic data (race, ethnicity, date of 
birth, and gender), and social history (tobacco use, drugs of abuse, and alcohol use). 
7.2.2. 
Efficacy Assessments  
Efficacy assessments will be performed for all patients, unless indicated otherwise, at the visits 
shown in the Schedule of Assessments (Table 1 and Table 3). 
7.2.2.1. 
Aminotransferases and Immunoglobulin G 
ALT, aspartate aminotransferase (AST) and IgG will be collected as part of the clinical 
laboratory assessments (see Section 7.2.4.5) and used for analysis of the related efficacy 
endpoints. 
7.2.2.2. 
Vibration-controlled Transient Elastography 
Liver stiffness will be assessed using a Fibroscan® ultrasound device, which is a non-invasive 
method of determining liver fibrosis. The test will be performed on an empty stomach, at least 
2 hours after food intake. The patient will be instructed to lie supine. An ultrasound-like probe 
will be placed on the skin over the liver area, typically in the right mid-axillary line. The liver 
fibrosis stage will be assessed using the liver stiffness measurement (LSM) scores recorded as 
kilopascal (kPA) as well as controlled attenuation parameter (CAP) recorded as decibels/meter 
(dB/m), which is a marker of hepatic steatosis, graded as 0, 1, 2 and 3 (Siddiqui et al., 2019). 
7.2.2.3. 
Liver Histopathology 
If a liver biopsy is not available from within 6 months prior to Screening, a liver biopsy sample 
will be collected at Screening. Local reports of the liver biopsy are sufficient for inclusion. 
Results from a liver biopsy with Ishak histological grading and staging scores (Ishak et al., 1995) 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 59 of 86 
performed at Screening or within 6 months prior to Screening will be used as the Baseline for 
comparison with the liver biopsy collected at Week 24 of the Double-blind Treatment Period as 
well as the optional liver biopsy collected at OLE Week 25. Review of liver biopsies will be 
done at a local laboratory. A central review of liver biopsies may also be performed as an 
optional exploratory analysis. 
7.2.2.4. 
Glucocorticoid Toxicity Index 
The GTI is a comprehensive, outcome-based glucocorticoid toxicity-monitoring instrument 
developed by a multidisciplinary team of international experts (Jayne et al., 2021). 
The instrument calculates a composite index score from data captured related to the following 
domains: body mass index, glucose tolerance, blood pressure, lipids, steroid myopathy, skin 
toxicity, neuropsychiatric toxicity, and infection. In addition, reports of any of the following 
toxicities are included in the index: endocrine (adrenal insufficiency), gastrointestinal 
(perforation, peptic ulcer disease), musculoskeletal (ruptured tendon, avascular necrosis), and 
ocular (retinopathy, increase in ocular pressure, posterior subcapsular cataract). 
The GTI instrument uses 2 GTI scores: the Cumulative Worsening Score and the Aggregate 
Improvement Score, referred to as GTI-CWS and GTI-AIS, respectively. 
7.2.3. 
Patient Reported Outcome Measures 
7.2.3.1. 
EuroQol 5-Dimension 5-Level  
The EQ-5D-5L 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-5L consists of a descriptive system and the EuroQol visual analog scale (EQ-VAS). 
The descriptive system comprises 5 levels of severity for each of 5 dimensions (ie, mobility, 
self-care, usual activities, pain/discomfort, and anxiety/depression). The EQ-VAS records the 
patient’s self-rated health on a vertical visual analog scale. 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 converted to a single summary index number 
(utility) reflecting preferability compared to other health profiles. 
7.2.3.2. 
Chronic Liver Disease Questionnaire 
The CLDQ is the most widely validated disease-specific health-related quality-of-life instrument 
for patients with chronic liver disease (Younossi et al., 1999). It has been cross-culturally 
validated and translated, and has demonstrated validity and reliability in patients with chronic 
liver disease across a variety of cultural and socioeconomic differences. The CLDQ produces 
both a summary score and domain score, and correlates with the severity of liver disease. 
The instrument contains 29 items within 6 domains including abdominal symptoms (items 1, 5, 
17), fatigue (items 2, 4, 8, 11, 13), systemic symptoms (items 3, 6, 21, 23, 27), activity (items 3, 
6, 21, 23, 27), emotional function (items 10, 12, 15, 16, 19, 20, 24, 26) and worry (items 18, 22, 
25, 28, 29). A Likert scale response format is used for all items ranging from 1 (most 
impairment) to 7 (least impairment). Scoring of the questionnaire is performed by dividing each 
domain score by the number of items per domain (Younossi et al., 1999).  

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 60 of 86 
7.2.4. 
Safety Assessments  
Safety will be assessed throughout the study by monitoring of vital signs, ECG, physical 
examinations, and laboratory tests; and by recording and analyzing all AEs and SAEs. 
7.2.4.1. 
Vital Sign Measurements 
Blood pressure, pulse rate, respiratory rate, and temperature will be measured at the visits shown 
in the Schedules of Assessments (Table 1 and Table 3). 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, it should be repeated after at least 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. 
7.2.4.2. 
Electrocardiograms 
A 12-lead ECG will be performed at the on-site visits specified on the Schedule of Assessments 
(Table 1 and Table 3). The ECG should be performed after the patient has rested for at least 
5 minutes in a supine position. 
The Investigator or qualified designee will review and indicate whether the ECG is normal or 
abnormal, specify the abnormality, and whether clinically significant. Any clinically significant 
ECG result will be recorded as medical history or an AE per the Investigator’s judgement. 
7.2.4.3. 
Weight and Height 
When possible, body weight will be recorded as part of the full physical examination at the 
on-site visits shown in the Schedule of Assessments (Table 1 and Table 3). Body weight, with 
the patient wearing light clothing and the shoes and jacket or coat removed, will be measured 
and recorded in kilograms. 
Height will be measured at Visit 2 only. 
7.2.4.4. 
Physical Examination 
Complete physical examinations will be performed at the on-site visits specified on the Schedule 
of Assessments (Table 1 and Table 3). A complete physical examination should include 
assessments of at least the following: general appearance, skin, head, ears, eyes, nose and throat, 
heart, chest/breast, abdomen, neurological system (briefly), lymph nodes, spine, and skeletal 
extremities. 
At other visits (including other on-site visits and unscheduled visits), an abbreviated physical 
examination, symptom-directed as determined by the Investigator, may be performed to include 
general appearance, cardiovascular, gastrointestinal, and pulmonary systems. Medically 
significant changes from physical examination will be recorded as AEs.  
7.2.4.5. 
Clinical Laboratory Assessments 
Clinical laboratory tests for safety, including hematology, clinical chemistry, immunoglobulins, 
autoantibodies, and clinical laboratory assessments for efficacy measures will be performed at a 
central laboratory at the visits shown on the Schedules of Assessment (Table 1 and Table 3).  

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 61 of 86 
Hematology: complete blood count with differential 
Coagulation: prothrombin time, INR, activated partial thromboplastin time, antiphospholipid 
antibodies (Screening only)  
Clinical chemistry: Non-fasting chemistry panel including electrolytes, AST, ALT, alkaline 
phosphatase (ALP) and total bilirubin; lactate dehydrogenase, blood urea nitrogen (BUN), 
albumin, total protein, creatinine, glucose, low-density lipoproteins (LDL), amylase, lipase, 
triglycerides, hemoglobin A1c (HgbA1c), and C-reactive protein.  
LDL, ALP, amylase, lipase, triglycerides, and HgbA1c are only required at Day 1 (pre-dose) and 
Week 24 of the Double-blind Treatment Period, and OLE Week 25. 
IgG: Immunoglobulin G 
Autoantibodies: Antinuclear antibodies (ANA), smooth muscle antibody (SMA), liver kidney 
microsome type 1 (anti-LKM-1) antibody, anti-liver cytosol type 1 (LC1) antibodies, 
anti-soluble liver antigen/liver pancreas (SLA/LP) antibodies 
Urinalysis: macroscopic and microscopic examination 
Additional blood will be sent for biomarker studies as per Section 7.2.5.  
Unscheduled or additional laboratory samples may be collected and analyzed by local 
laboratories if immediate results are necessary for management of TEAEs or dosing 
determination. Urine pregnancy tests will be performed locally. 
Unless otherwise noted, when scheduled simultaneously with a dosing visit, samples for 
laboratory evaluations should be collected prior to administration of IMP. 
Clinical laboratory results the Investigator deems clinically significantly abnormal should be 
repeated within 48 to 72 hours from when the result became available, when possible. 
7.2.4.5.1. Infectious Disease Blood Tests 
Infectious disease blood tests screening for HBsAg, HBcAb, hepatitis C antibody, and HIV will 
be performed at Screening only. Positive screening results may require additional testing. 
For HBcAb-positive patients permitted to enter the study (HBcAb positive, HBsAg negative, 
HBsAb titer ≥100 IU/L, and negative hepatitis B DNA), additional assessments for hepatitis B 
DNA will be performed as described in Inclusion Criterion 18 (Section 4.3). 
7.2.4.5.1.1. Tuberculosis Test 
Evaluation of all patients by QuantiFERON®-TB Gold/Gold Plus test will be performed by the 
central clinical laboratory. On a case-by-case basis upon approval by the Sponsor, negative 
results on a local TB test that is considered equivalent to one of the above tests may be used for 
eligibility. Use of the T-SPOT® TB test will also be permitted locally. 
Latent TB: If the Screening QuantiFERON-TB Gold/Gold Plus (or a local T-SPOT TB) test is 
negative and there is no known history of recent exposure to individuals with active TB and the 
chest x-ray shows no evidence of active TB, the patient may be enrolled. If the Screening 
QuantiFERON-TB Gold/Gold Plus test is positive and/or the patient is diagnosed with latent TB, 
they must have a chest x-ray that shows no evidence of active TB, no clinical signs and 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 62 of 86 
symptoms of TB, and documentation confirming completion of appropriate prophylactic 
treatment prior to being permitted to enroll. 
An indeterminate QuantiFERON-TB Gold/Gold Plus test at Screening must be repeated at least 
once as soon as possible by the central laboratory (QuantiFERON-TB Gold/Gold Plus test) or 
local laboratory (QuantiFERON-TB Gold/Gold Plus or T-SPOT TB). If the result remains 
indeterminate (or borderline on T-SPOT TB test), the patient is not eligible for enrollment into 
the study, unless already treated for latent TB as described above for a positive test. The site, if it 
has performed the T-SPOT TB test locally and if it has the appropriate equipment and laboratory 
kits, may perform the QuantiFERON-TB Gold Plus test centrally if a repeat test needs to be 
performed. 
7.2.5. 
Exploratory Assessments 
Additional blood and plasma will be collected and may be sent for biomarker studies. Biomarker 
assessments may be reported separately. Detailed instructions for sample collection, processing, 
storage, and shipment will be provided in the Laboratory Manual. 
7.2.5.1. 
Cytokines and Proteomics 
Plasma samples will be collected at the times shown in the Schedule of Assessments (Table 1 
and Table 3) for the measurement of cytokines and other circulating proteins by 
electrochemiluminescent (Meso Scale Discovery) or enzyme-linked immunosorbent assay 
(ELISA). Blood samples will be collected for immune cell profiling performed by flow 
cytometry. Samples for proteomics and immune cell profiling will be stored for future analysis 
of chemokines and immune cell subsets. Additional information regarding sample collection and 
handling are outlined in the Laboratory Manual. 
7.2.5.2. 
Genotyping and Gene Expression 
Gene expression (ribonucleic acid [RNA]) profiling and DNA genotyping may be assessed in 
blood samples. A whole blood sample will be collected for gene expression analysis for storage 
and analysis at a later date as specified in the Schedule of Assessments (Table 1 and Table 3) 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 zetomipzomib 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. 
7.2.6. 
Pharmacokinetic Assessments 
Blood samples will be collected from all patients during the Double-blind Treatment Period 
according to the Schedule of Assessments (Table 1). Samples will be used to measure the plasma 
concentration of zetomipzomib and its metabolite KZR-59587 (AUC, Cmax, Tmax, and other 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 63 of 86 
PK calculations). Additional information regarding sample collection and handling are outlined 
in the Laboratory Manual. 
Samples collected to measure investigational product concentration and metabolism will be 
retained for as long as legally permitted in the country of origin or until Sponsor decision to 
destroy. 
Measures will be in place at the Sponsor to prevent unblinding by laboratory measurements. 
7.2.7. 
Contraception Requirements and Pregnancy Testing 
WOCBP must agree to use highly effective and medically acceptable methods of contraception 
to prevent pregnancy during the study and for 4 weeks after administration of the last dose of 
IMP. For the purposes of this study, WOCBP are defined as fertile female patients, unless the 
patient is postmenopausal (defined by amenorrhea for at least 2 years or amenorrhea for at least 
1 year with confirmatory FSH level in the postmenopausal range, as documented historically or 
measured by the central or local laboratory and if patient is not on supplementary hormonal 
therapy) or surgically sterile (ie, bilateral tubal ligation, hysterectomy, bilateral 
salpingo-ophorectomy). 
Highly effective contraception is defined as the use of an intrauterine device or hormonal 
contraceptives (eg, implant or oral) or having a vasectomized partner. In regions where it is 
considered highly effective contraception, 2 barrier methods (eg, female diaphragm and male 
condom OR 1 barrier method with spermicide) may be used. 
If using a hormonal form of contraception, use must have been stable for at least 4 weeks prior to 
the Baseline (Day 1), and if using concomitant mycophenolate, the patient must use another 
highly effective nonhormonal form of 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. 
For WOCBP, urine pregnancy testing will be performed at the time points shown in Table 1 and 
Table 3. IMP should not be administered prior to confirmation of a negative test at visits at 
which pregnancy tests are performed. Positive urine pregnancy tests should be confirmed by a 
serum pregnancy test. 
Samples for FSH testing may be collected at any time during the study to confirm 
postmenopausal status in female patients whose childbearing potential status has changed since 
the Screening Visit. Only after confirmation of postmenopausal status is pregnancy testing not 
required. 
Male patients must use an effective contraception method (eg, condom with spermicide) during 
the study, and continue to use the method for 1 week following the last dose of IMP or be 
congenitally or surgically sterile (eg, vasectomy with documented confirmation of post-surgical 
aspermia). The requirement for 1 week of post-treatment contraception for male patients is 
supported by the short half-life of zetomipzomib (<2 hours), full recovery of immunoproteasome 
inhibition within 3 days of dosing, lack of mutagenic potential as determined in vitro and in vivo 
nonclinical studies, and lack of reproductive organ findings in the 6- and 9-month rodent and 
monkey repeat-dose toxicity studies. Additionally, no teratogenic effects were found in the 
definitive embryofetal toxicity studies in rats and rabbits. As per International Council for 
Harmonisation (ICH) M3 (R2) guidance, lack of reproductive and teratogenic findings in general 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 64 of 86 
toxicity and embryofetal toxicity studies is sufficient to support the treatment of male patients in 
Phase 1 and 2 trials prior to conducting fertility studies.  

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 65 of 86 
8. 
STUDY DISCONTINUATION  
The Investigator must make every reasonable effort to keep each patient on study for the 
duration of the study, including through the safety follow-up, lost to follow-up (see Section 8.2 
for additional details), consent withdrawal, or end of study, whichever occurs first. 
8.1. 
Study and Individual Patient Stopping Rules 
8.1.1. 
Termination or Suspension of the Study 
The Sponsor has the right to terminate the study at any time, for any reason, including safety or 
administrative reasons. In all cases, all necessary measures will be taken to guarantee appropriate 
safety follow-up of patients already included in the trial. Reasons for terminating the study may 
include, but are not limited to, the following: 
• The incidence or severity of AEs indicates a potential health hazard to patients. 
• Patient enrollment is unsatisfactory, and the Sponsor wishes to stop the study. 
• IDMC recommendation due to safety concerns. 
The IDMC will hold periodic meetings to undertake thorough reviews of the accumulated safety 
data. The IDMC can recommend stopping the study based on their review and findings 
(see Section 9.11). Further information about the IDMC’s role and oversight will be detailed in 
the IDMC charter. 
In the event that the Sponsor terminates the study, Investigators will be informed of the reason 
for study termination. Should the study be terminated due to safety reasons, the Investigator must 
contact all study patients promptly, complete the EOS procedures, and return the IMP. 
8.1.2. 
Individual Patient Stopping Rules 
The Investigator and Sponsor may discontinue the patient from study participation at any time if 
discontinuation would be in the patient’s best interest. If a patient meets any of the stopping 
criteria listed below, the patient will complete the assessments for the EOT Visit and return 
4 weeks after the last dose for the EOS Visit. Reasons for discontinuing a patient are not 
necessarily limited to the criteria below. 
• Development of AIH manifestations or intercurrent liver disease (eg, viral hepatitis) 
while on IMP that threaten the patient’s life or liver function (ie, AST, ALT or total 
bilirubin values ≥10 × ULN that has been verified via repeat laboratory assessment 
and is sustained for ≥1 week) 
• Grade 4 (life-threatening) TEAE, unless due to an obvious alternative etiology 
• Serious allergic reaction to IMP, including anaphylaxis 
• Confirmed thrombotic microangiopathy (TMA) 
• HIV/acquired immune deficiency syndrome (AIDS), viral hepatitis (B and C) 
infection occurring during the study 
• Pregnancy 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 66 of 86 
• Any medical condition or personal circumstance that, in the opinion of the 
Investigator, exposes the patient to risk if the patient continues with IMP or that 
prevents the patient’s adherence to the protocol 
• Protocol deviation involving inclusion or exclusion criteria that, in the Investigator’s 
and Sponsor’s judgment, would significantly compromise data interpretation 
or patient safety 
• Investigators should grade and report injection site reactions (ISRs). If a patient 
develops a CTCAE Grade ≥3 ISR, or if a Grade 2 ISR worsens, the patient’s IMP will 
be discontinued. 
Furthermore, zetomipzomib or placebo should be interrupted, and the patient should be evaluated 
if there is a suspected diagnosis of thrombotic microangiopathy, such as with any acute changes 
in renal function, thrombocytopenia, or intravascular hemolytic anemia. 
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 source document and 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 withdrawing from study treatment will complete the ETV (Table 3) followed by the 
End-of-Study (EOS) visit (Table 3) 4 weeks later to complete the final evaluations according to 
this protocol, particularly safety evaluations. The aim is to record data in the same way as for 
patients who complete the study. 
8.1.3. 
Potential Drug-induced Liver Injury 
Possible drug-induced liver injury (DILI) will be evaluated throughout the study according to the 
Guidance for Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation (2009). 
Note that it may be difficult to distinguish DILI from signs of active AIH, and every effort 
should be made to do so. Patients with significant rises in enzymes consistent with possible 
hepatocellular injury or cholestatic injury will be considered possible DILI. 
Patients meeting the criteria for possible DILI will undergo a pause in IMP administration until a 
diagnosis can be established. If there is no apparent etiology other than DILI, the patient will be 
treated according to the treatment guidelines for DILI (Giordano et al., 2014). 
8.2. 
Lost to Follow-Up 
The Investigator must make reasonable efforts to contact patients who fail to return for scheduled 
visits so that they will not be declared “lost to follow-up.” Patients will be considered “lost to 
follow-up” only after reasonable, documented attempts to reach the patient prove unsuccessful. 
These attempts include, but are not limited to, the following: 
1. Attempt contact at all telephone numbers for the patient and his/her listed contacts (to be 
collected in the source documents at the patient’s entry into the study), as applicable. 
2. Contact the patient’s primary care physician, referring specialist, or other healthcare 
professional, as applicable. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 67 of 86 
3. Send emails and texts, and certified letters through the postal service to all the patient’s 
addresses and contacts, as applicable. 
4. Review available medical records/notes for details of hospitalizations, clinic visits, or 
other procedures that may indicate the status of the patient, as applicable. 
5. Perform an internet search for additional contact information, as applicable. 
6. Check local, regional, and national public records to locate the patient or search for 
mortality status as allowed by law, as applicable. 
The information and dates of attempted contact must be recorded in the patient’s records and the 
patient’s final status recorded in the appropriate eCRF. Once all attempts to contact the patient 
have been exhausted and documented, the Sponsor or Sponsor’s designee should be contacted 
for additional guidance. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 68 of 86 
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 IMP. 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. Hypersensitivity reactions are not anticipated given the structure and mechanism of 
action of zetomipzomib, but potential hypersensitivity to an excipient could occur. 
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. 
It is the responsibility of the Investigator to document all AEs that occur during the study. 
AEs will be elicited by asking the patient a nonleading question such as, “Have you experienced 
any new or changed symptoms since we last asked/since your last visit?” AEs should be reported 
on the appropriate page of the eCRF. 
9.1.2. 
Assessment of Severity 
Severity of AEs will be graded according to the National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI-CTCAE) (Version 5.0). If there is a change in severity of an AE, 
it must be recorded as a separate event. 
9.1.3. 
Assessment of Causality 
AEs will be deemed related to IMP unless clearly unrelated to IMP. 
The Investigator will assess the causal relationship between IMP and the AE. One of the 
categories in Table 5 should be selected based on medical judgment, considering the definitions 
and all contributing factors. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 69 of 86 
Table 5: 
Causality Categories 
Related 
A clinical event, including laboratory test abnormality, that occurs in a plausible time 
relationship to treatment administration, and that 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 to treatment administration. May have negative dechallengea and 
rechallengeb information. Typically explained by extraneous factors (eg, concomitant 
disease, environmental factors, or other drugs or chemicals). 
Abbreviations: AE=adverse event 
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 (eg, 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 with Regard to Investigational Medicinal Product 
The Investigator will describe the action taken with IMP in the appropriate section of the eCRF, 
as follows: 
• None 
• IMP stopped 
• IMP temporarily interrupted 
• IMP dose reduced (with written confirmation from Medical Monitor) 
• Other (specify) 
9.1.5. 
Follow-up of Adverse Events 
Adverse events are intended to be collected according to the procedures outlined above from the 
time of informed consent and continuing for 30 days following the last dose, or the EOS Visit, 
whichever occurs later. 
All Investigators should follow up with patient 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 
AEs (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. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 70 of 86 
• Diagnosis, or description of the symptoms if a diagnosis is not established 
(see Section 9.6.1 for specific instructions considered related to IMP tolerability) 
• Classification of ‘serious’ or ‘not serious’ 
• Severity 
• Date of first occurrence and date of resolution (if applicable) 
• Action taken with regard to IMP 
• Outcome of the event (unknown, recovered, not yet recovered, recovered with 
sequelae, death [with date and cause reported]) 
9.2. 
Serious Adverse Events 
9.2.1. 
Definition of a Serious Adverse Event 
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 considered SAEs if they cause prolongation of the 
current hospitalization. Hospitalization for elective treatment of a pre-existing 
non-worsening 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. 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the patient and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
9.2.2. 
Serious Adverse Event Reporting and Documentation Requirements 
An 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 IMP, whether or not the SAE is considered 
to be related to IMP. After the reporting period, SAEs should be reported if the Investigator 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 71 of 86 
assesses the event to be related to IMP. An SAE report consists of the SAE form, provided 
separately, along with requested additional source documentation as considered necessary. 
SAEs that occur during the reporting period must be reported by the Investigator to the Safety 
Reporting email address 
or dedicated fax number 
 
 on the Study Personnel page and entered into the EDC system within 24 hours from the 
time the Investigator becomes aware of the SAE. A copy of the SAE form should also be 
emailed or faxed within 24 hours for the attention of the study safety lead 
(see Study Personnel page).  
The Investigator should not wait for additional information to fully document the event before 
notification of an SAE, though additional information may be requested. Where applicable, 
information from relevant laboratory results, hospital case records, and autopsy reports should be 
obtained. Follow-up information should be submitted in the same manner as the original 
SAE report. 
Instances of death, congenital abnormality, or an event 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 IMP administration and considered by the Investigator to be related to participation 
in this study, should be reported to the Medical 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 the conduct of the 
study, or alter the IDMC/Institutional Review Board (IRB)/Independent Ethics Committee (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 IDMC/IRBs/IECs where required, and to relevant regulatory authorities. 
For SAEs that have been reported in the zetomipzomib development program, please refer to the 
most current zetomipzomib (KZR-616) Investigator’s Brochure. 
9.3. 
Pregnancy Reporting 
Pregnancy occurring in female patients or female partners of male patients participating in the 
study or during a clinical investigation must be reported to 
 (email address: 
; dedicated fax number: 
) via the Pregnancy 
Report Form (see Study Personnel page) within 24 hours and entered into the EDC. The outcome 
of a pregnancy should be followed up carefully, and any abnormal outcome for the mother or the 
child should be reported. Infants should be followed for a minimum of 8 weeks, and all findings 
should be reported to the Sponsor. IMP is to be discontinued immediately upon Investigator 
knowledge of the pregnancy in a female patient. 
If the outcome of the pregnancy meets a criterion for immediate classification as an SAE 
(ie, spontaneous abortion [for which any congenital anomaly detected in an aborted fetus is to be 
documented], stillbirth, neonatal death, or congenital anomaly), the Investigator should follow 
the procedures for expedited reporting of SAEs as outlined in Section 9.2.2. 
Any SAE experienced by a patient during pregnancy must be reported as an SAE. 
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 Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 72 of 86 
9.4. 
New or Worsening Disease Manifestations 
New or worsening manifestation(s) of AIH should not be recorded as AEs unless they are 
assessed as serious. 
9.5. 
Injection Site Reactions 
In study participants who have received zetomipzomib SC, ISRs, including bruising, 
discoloration, discomfort, erythema, induration, pain, pruritus and/or swelling, have been 
described in the majority of participants in zetomipzomib studies to date; these events have been 
transient and predominantly mild. No interventions have been formally studied to prevent or treat 
these reactions; however, local therapy such as topical antihistamines or glucocorticoids may be 
helpful, and/or systemic antihistamines, anti-inflammatory drugs, and/or glucocorticoids may be 
appropriate in more severe cases. The Medical Monitor should be consulted prior to use of 
glucocorticoids. Investigators should grade and report ISRs. If a patient develops a CTCAE 
Grade ≥3 ISR, or if a Grade 2 ISR worsens, IMP will be discontinued. 
9.6. 
Adverse Events of Special Interest 
An AE of special interest (AESI) is one that is of scientific and medical concern specific to the 
Sponsor's product or program, for which ongoing monitoring and rapid communication by the 
Investigator to the Sponsor can be appropriate, regardless of the seriousness, expectedness, or 
relatedness of the AE to the administration of a product or compound. Systemic injection 
reactions and thrombotic microangiopathy have been identified as AESIs, and should be closely 
monitored and reported within 24 hours using the AE eCRF. 
9.6.1. 
Systemic Injection Reactions 
In clinical studies of zetomipzomib, systemic injection reactions associated with SC injections 
have been reported as TEAEs, consisting of one or more of the following symptoms: 
hypotension, tachycardia, nausea, vomiting, dizziness, headache, pyrexia, rigors, and/or chills. 
The events are associated with an acute phase-like response, including leukocytosis and elevated 
C-reactive protein, occur approximately 8 to 24 hours after dosing, and usually resolve within 
48 hours of dosing. While most commonly associated with an initial dose of zetomipzomib at 
60 mg SC and reduced in frequency when initially dosed with 30 mg SC, any or all of these 
events could occur with lower doses of zetomipzomib or with subsequent higher doses of 
zetomipzomib. The events are similar to those described for infusion-related reactions observed 
with the currently approved proteasome inhibitor carfilzomib, which generally occur in the first 
cycle of dosing.  
In reporting TEAEs related to zetomipzomib tolerability, terms such as the NCI-CTCAE terms 
of ‘infusion-related reaction,’ ‘cytokine release syndrome,’ ‘acute infusion reaction,’ or ‘allergic 
or hypersensitivity reaction’ should not be used. Instead, each sign or symptom should be 
recorded as an individual TEAE. If multiple signs or symptoms occur with a given systemic 
injection-related event, each sign or symptom should be recorded separately with its own level 
of severity. 
Management of these symptoms is described in Section 6.1.2. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 73 of 86 
9.6.2. 
Thrombotic Microangiopathy 
Cases of thrombotic microangiopathy, including thrombocytopenic purpura and hemolytic 
uremic syndrome, have been described with the proteasome inhibitors, bortezomib, carfilzomib, 
and ixazomib. The clinical presentation of thrombotic microangiopathy 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 thrombocytopenic purpura/hemolytic uremic syndrome. If the diagnosis is 
suspected, interrupt treatment with IMP and evaluate. Missed doses should be addressed as per 
Section 6.1.3.2. If the diagnosis of thrombocytopenic purpura/hemolytic uremic syndrome is 
excluded, IMP may be resumed. If the diagnosis is confirmed, IMP must be 
permanently discontinued. 
9.7. 
Unexpected Adverse Reactions 
9.7.1. 
Definition of an Unexpected Adverse Reaction 
An unexpected adverse reaction is any untoward and unintended response that is related to the 
administration of IMP at any dose that is not consistent with the applicable product information 
(eg, the Reference Safety information of the zetomipzomib [KZR-616] Investigator’s Brochure). 
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. 
9.8. 
Hypersensitivity Reactions 
Hypersensitivity reactions are exaggerated or inappropriate immunologic responses occurring in 
response to an antigen or allergen. Drugs may cause allergic reactions by any mechanism of 
hypersensitivity. For example, penicillin may cause anaphylaxis, which is IgE-mediated, but 
most responses are trivial. Hypersensitivity reactions to zetomipzomib are not anticipated given 
its structure and mechanism of action; however, potential hypersensitivity to an excipient could 
occur. Studies in compound ONX 0914, an analog of zetomipzomib, demonstrated inhibition of 
T-helper 2 cell response and allergic reactions in foreign ovalbumin- and house dust mite-
induced allergic airway inflammation in mouse models.  
Known risk factors for developing a hypersensitivity reaction include allergic reaction history, 
concomitant diseases such as chronic respiratory diseases, cardiovascular diseases, mastocytosis 
or clonal mast cell disorders, and severe atopic disease. Some concurrent medications such as 
beta-adrenergic blockers and angiotensin-converting enzyme inhibitors might also increase the 
risk. Patients in Study KZR-616-208 should be closely monitored. Should any signs and 
symptoms of suspected hypersensitivity reactions occur, the Investigator will diagnose per 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 74 of 86 
clinical guideline. Anaphylaxis will be defined and managed using the National Institute of 
Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network criteria (Sampson et al., 
2006), which are outlined in the zetomipzomib Investigator’s Brochure. IMP may be temporarily 
withheld. If the diagnosis of hypersensitivity is confirmed, IMP must be permanently 
discontinued, and the patient will be treated per guidelines.  
9.9. 
Infections 
The usual clinical care for patients with AIH who use chronic immunosuppressives includes 
surveillance for severe or opportunistic infections, given the increased incidence in this setting. 
Patients with recent serious or ongoing infections are excluded from the study (Section 4.3). 
While zetomipzomib has not been associated with new onset or more severe infections to date in 
patients with similar risk factors, patients will be monitored for new infections, and potential 
infections (bacterial, viral, or fungal) will be fully evaluated. The periodic physical examination 
assessments in this study include capturing new onset signs and symptoms. Patients should be 
encouraged to contact the Investigator if they develop any new signs or symptoms between 
physical assessments. Clinical care will be provided for any newly diagnosed infection. Patients 
who use chronic prophylactic or suppressive therapy (eg, chronic antivirals for herpes simplex 
virus) as part of their usual care are permitted to continue with their usual therapies. Infections 
will be captured as AEs. In addition to inclusion in the safety data base, the data on infections 
will be analyzed as part of the glucocorticoid toxicity index (GTI) (Section 7.2.2.4). 
9.10. 
Adrenal Insufficiency 
Adrenal insufficiency may be caused by autoimmune diseases such as AIH or by a reduction or 
discontinuation of exogenous glucocorticoids. The most common symptoms are fatigue, muscle 
weakness, loss of appetite, weight loss, and abdominal pain. Patients will be educated to 
recognize the symptoms of adrenal insufficiency. When such symptoms occur, the patient should 
seek immediate medical care. 
9.11. 
Independent Data Monitoring Committee 
The IDMC will convene for safety data review meetings after clinical data are available from the 
Double-blind Treatment Period Week 12 visit for 6, 12, 18, and 24 patients. After all patients 
have completed at least 12 weeks of treatment or have withdrawn early, the IDMC will continue 
to review safety data every 3 to 6 months until the last patient completes the study. Records for 
AEs, laboratory values (especially ALT), and vital signs will be reviewed. The IDMC may 
recommend the trial be terminated if major safety concerns related to zetomipzomib are found.  
IDMC meetings will be held at mutually agreeable dates and times between the Sponsor and the 
IDMC members. The Sponsor and the IDMC Chairperson will coordinate the agenda with 
advance notice to attendees. Meetings may be convened as conference calls or in person. The 
Sponsor, in consultation with the IDMC Chairperson, may request additional ad hoc meetings of 
the IDMC with a full quorum should questions of patient safety arise between scheduled 
meetings. The specific responsibilities and composition will be outlined in a separate 
IDMC Charter.  

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 75 of 86 
10. 
STATISTICAL ANALYSES  
10.1. 
Overview 
Key elements of the statistical analyses for this study are described in this section; details will be 
documented in a statistical analysis plan (SAP). The statistical analyses for this study will be the 
responsibility of the Biostatistics department of the Sponsor or 
. 
The first treatment period of this study will be conducted as a double-blind, randomized study 
with blinding procedures. For the purpose of the final data analysis, the official, final database 
will be locked after medical/scientific review has been conducted, protocol deviations have been 
identified, the data have been declared final and complete, and an SAP has been written and 
approved. The randomization schedule will be generated and implemented by the external 
vendor of the study interactive response technology. 
No interim analyses are planned for this study. The first planned unblinded analysis of the data 
will be conducted after all patients have or would have completed the Week 24 visit or EOS 
visit, whichever occurs later, in the Double-blind Treatment Period, data being fully cleaned and 
database being “soft” locked to limit changes. The final data analysis will be conducted after all 
patients have completed the study (Double-blind Treatment Period and OLE Period). 
Data will be summarized for all patients as well as the following groups of patients based on 
treatment received in the Double-blind Treatment Period: 
• Group 1: Patients receiving zetomipzomib in the Double-blind Treatment Period and 
continuing with zetomipzomib in the OLE Period 
• Group 2: Patients receiving placebo in the Double-blind Treatment Period followed 
by zetomipzomib in the OLE Period 
10.2. 
Study Population Definitions 
Full Analysis Set (FAS): The FAS is defined as all randomized patients who receive at least 
1 dose of IMP or glucocorticoid in this study and have baseline and at least one post-treatment 
data for the following measures: ALT, AST, IgG, Ishak score, and autoantibodies. For variables 
with post-baseline missing data, analyses will be carried out using the missing data handling 
method (to be outlined in the SAP). All observed data will be included in the statistical 
summaries.  
Per Protocol (PP): A PP population may be used to analyze select efficacy endpoints and will be 
based on zetomipzomib exposure (time on treatment) and protocol deviations. 
Safety Population: The safety population will include all randomized patients who received at 
least one dose of IMP and will be the population used for the analysis of safety data. Adverse 
event data will be coded to system organ class and preferred term using Medical Dictionary for 
Regulatory Activities (MedDRA). 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 76 of 86 
10.3. 
Sample Size and Power Considerations 
The statistical analyses of the study data will be descriptive in nature, and no formal hypothesis 
testing will be performed. No formal statistical sample size or power estimation has been 
performed. 
The sample size of approximately 24 patients was set to allow a preliminary assessment of the 
potential effect of zetomipzomib with a glucocorticoid, and glucocorticoid treatment with 
placebo, in patients diagnosed with AIH. This is a signal-seeking study designed to collect data 
and perform preliminary assessments on safety and efficacy endpoints between treatment groups. 
10.4. 
Background and Demographic Characteristics 
Age, height, weight, and other continuous variables will be summarized using descriptive 
statistics (n, mean, standard deviation [SD], median, minimum, and maximum), while sex, race 
and other categorical variables will be provided using frequency tabulations. Medical history 
data, including prior medications and coding methodology, will be summarized using frequency 
tabulations by MedDRA system organ class and preferred term. 
10.5. 
Patient Disposition 
Patient disposition (analysis population allocation, screened, randomized, completed, 
discontinued, along with primary reason for discontinuation) will be summarized using 
frequency and percent. A summary of patients enrolled by site will be provided. 
Protocol deviations will be summarized using frequency tabulations. 
10.6. 
Efficacy Analysis 
The statistical analyses of the study data will be descriptive in nature, and no formal hypothesis 
testing will be performed. No formal statistical sample size estimation has been performed.  
Descriptive statistics for continuous variables will be summarized (n, mean, SD, median, 
interquartile range, minimum, and maximum). Summaries will be presented for the change from 
Baseline, when appropriate. Categorical variables will be summarized using number of 
observations (n), frequency and percentages of patients. All percentages will be based on the 
number of patients in the population unless specified otherwise.  
For time-to-event variables (eg, time to CR, time to PR, and time to flare), the Kaplan-Meier 
method will be used.  
Continuous efficacy endpoints (ie, change or percentage change from Baseline in ALT, AST, 
IgG by visit) will be analyzed using the longitudinal data analysis method based on a mixed 
model for repeated measures (MMRM) approach. Continuous endpoints will be assessed for 
normality and log-transformed values may be used if data is not normally distributed. This model 
will include fixed effect terms for randomized treatment, timepoint (ie, visit) and randomized 
treatment by timepoint interaction. Within subject error will be modelled by use of an 
unstructured variance-covariance matrix. Baseline value will be included as a covariate and the 
randomization stratification factors will be included as class terms. 
The Baseline value for ALT, AST, and IgG is defined as the mean of all collected Screening and 
Day 1 (pre-dose) values. When only one ALT, AST, or IgG result from the Screening visit is 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 77 of 86 
available, that single value will be used for the Baseline. Unless specified otherwise, the baseline 
value for other parameters, including laboratory data, is defined as the last value prior to the first 
dose of zetomipzomib or placebo. 
All analyses will be performed in SAS® v9.4 for Microsoft® Windows®. 
Further details of the statistical methodology, including methods for handling missing data and 
early withdrawals, will be provided in the SAP that will be finalized prior to any planned 
unblinded analysis. 
10.6.1. 
Statistical Methods 
The statistical analyses of the study data will be descriptive in nature, and no formal hypothesis 
testing will be performed. No formal statistical sample size estimation has been performed.  
Patient baseline characteristics, and the primary and secondary endpoints (Section 2.2), including 
efficacy, PK, and safety measures, will be summarized using descriptive statistics. A 
between-treatment difference value in an efficacy endpoint (primary or secondary) will be 
summarized using a point estimate and a two-sided 95% CI. Statistical uncertainty regarding the 
efficacy outcome estimate will be presented in a two-sided 95% CI. Change scores from 
Baseline to follow-up visits (ie, Weeks 12, 14, 16, 24, or OLE visits) on the continuous 
secondary outcome parameters may be analyzed using the Wilcoxon signed rank test or by log-
transformations if data is not normally distributed. Two-sided p-values may be calculated to help 
assess strength of evidence.  
Binary endpoints may be analyzed by the Cochran-Mantel-Haenszel (CMH) test stratified by the 
randomization stratification factor (ie, glucocorticoid use at Screening, no glucocorticoid use at 
Screening). Patients who have insufficient data for response determination for a time point will 
be considered non-responders for that time point. 
A longitudinal data analysis (LDA) model (Liu et al., 2009; Liang and Zeger, 2000) may be used 
to analyze continuous endpoints. This model assumes a common mean across treatment groups 
at Baseline and a different mean for each treatment group at each of the post-Baseline time 
points. In this model, the response vector consists of the Baseline and post-Baseline values. 
Time is treated as a categorical variable so that no restriction is imposed on the trajectory of the 
means over time. The model will also adjust for randomization stratification factors (ie, 
glucocorticoid use at Screening, no glucocorticoid use at Screening). The continuous endpoints 
may be log-transformed if they are not normally distributed. 
Time to event data (eg, time to CR or PR) will be summarized using the Kaplan-Meier approach.  
10.6.2. 
Multiplicity 
Due to the explorative nature of this study, no adjustments will be applied to perform multiple 
comparisons. 
10.6.3. 
Sensitivity Analysis 
Sensitivity analyses will be performed to support the primary analysis of the primary and key 
secondary endpoints. These analyses use missing data handling methods, where appropriate, 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 78 of 86 
including multiple imputation (Rubin, 1988), all observed data, and tipping point analysis (Yan 
et al., 2009; Yuan, 2011; Campbell et al., 2011). 
10.7. 
Safety Analysis 
Safety and tolerability will be assessed by clinical review of all relevant parameters including 
TEAEs, laboratory tests, vital signs, weight, and ECGs. No inferential testing for statistical 
significance will be performed. 
TEAEs will be classified using the MedDRA classification system (Version 25.0 or later). 
All TEAEs will be summarized by system organ class, preferred term, severity, and relationship 
to IMP. TEAEs leading to death or to discontinuation from treatment and serious TEAEs will 
also be tabulated. In the by-patient analysis, patients having the same event more than once will 
be counted only once and by greatest severity. 
Summary measure(s) of TEAEs (eg, cumulative incidence rate, exposure-adjusted incidence 
rate) will be provided. Risk difference in events of interest (eg, AESIs), along with point estimate 
and 95% CI may be calculated.  
Laboratory, vital signs, weight, and ECG data will be summarized descriptively by time point. 
In addition, shift tables showing the number of patients with low, normal, and high values 
compared to the normal ranges at Baseline versus post-Baseline will be provided for 
laboratory tests. 
10.8. 
Interim Analysis 
No interim analyses are planned for this study. Periodic evaluations of safety data will be 
performed throughout this study by the IDMC. 
10.9. 
Other Topics 
10.9.1. 
Biomarker Analysis 
Gene transcriptional and proteomic changes following IMP treatment will be assessed. 
Biomarker profiles of patients in the Active Treatment group and the Control group will be 
compared. Correlation of clinical outcome and Baseline biomarker profile and longitudinal 
changes after treatment will also be assessed. 
10.9.2. 
Pharmacokinetic Analysis 
Descriptive statistics will be provided for PK assessments of zetomipzomib and its metabolite 
KZR-59587, and the results will be presented in tabular and graphic form as appropriate. 
10.9.3. 
Subgroup Analyses 
Subgroup analyses of key efficacy endpoints by category of the randomization stratification 
factors, baseline demographic, and disease characteristics will be provided to explore the 
consistency of the treatment effect across various subgroups and specified in the SAP. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 79 of 86 
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, ICH guidelines for current Good 
Clinical Practice (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 conduct, the regulatory authorities will be 
notified that the study has ended. 
11.2. 
Institutional Review Board or Independent Ethics Committee 
Prior to initiation of the study at each study center, the protocol, 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, and before IMP can be 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 documented in the 
study files. 
The Investigator will promptly report any new information that may adversely affect the safety 
of the patients or the conduct of the study to the IRB/IEC. The Investigator will submit written 
summaries of the study status to the IRB/IEC as required, and will inform them when 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 Investigator’s study file. 
A signed and dated copy of the patient ICF will be provided to the patient. 
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. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 80 of 86 
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 consent will be re-obtained. 
11.4. 
Direct Access to Source Data, Source Documents, and Study Reports 
The Sponsor or its representatives may periodically check a sample of patient data recorded 
against source documents at the 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 may 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. 
The Sponsor or its designee is responsible for preparing a clinical study report. Study results will 
be provided to the Investigator. 
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.  
The remaining biological 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, other authorized agents of the Sponsor and/or its designee, the IRB(s)/IEC(s) 
approving this study, the US FDA, and any other applicable agency(ies) will be granted direct 
access to the 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. 
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. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 81 of 86 
11.8. 
Audit and Inspection 
Study centers and study documentation may be subject to Quality Assurance audit during 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. The Monitor will carry out source document verification in accordance 
with current GCP and ICH guidelines 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. 
Details for monitoring will be provided in a Clinical Monitoring Plan. 
11.10. 
Quality Control and Quality Assurance 
All aspects of the study will be carefully monitored by the Sponsor or its authorized 
representative(s) for compliance with applicable government regulations with respect to current 
GCP and SOPs. 
11.11. 
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 into the EDC system by completing the eCRF via a secure internet 
connection. Data transcribed 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 (eSource concept). Any changes to the data entered into the 
EDC system will be recorded in the audit trail and will be compliant with FDA Code of Federal 
Regulations (CFR) 21 Part 11. 
An essential element of the eSource concept is that the clinical assessment data and other source 
data is entered during the clinical visit in an eSource EDC system. When designing the system 
there are some fundamental aspects to be respected: 
• The ability of the physician to record clinical information in the patient medical 
record should not be limited or constrained 
• Information should be recorded in line with the current practice at the site 
• The integrity of the medical records should not be compromised 
• The Sponsor should have access only to pseudonymized information mandated by 
the protocol 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 82 of 86 
This guidance does not include direct data input from tablets, mobile phones, or other 
electronic devices. 
Medical coding will use MedDRA for concomitant diseases and AEs, and will use the 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. 
11.12. 
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 conduct (ie, following 
the last patient’s last visit), 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 after the discontinuation of clinical 
development of zetomipzomib. It is the Sponsor’s responsibility 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 follows local regulatory requirements related to clinical trial registration and results 
disclosure. Within the United States, the Sponsor complies with the requirements of the Food 
and Drug Administration Amendments Act of 2007 to register and post results of applicable 
clinical trials in a timely manner. 
The Sponsor is committed to submit for publication in peer-reviewed scientific literature, the 
results of registered clinical trials involving the Sponsor’s products. The Sponsor reserves the 
right to determine if the results of a registered trial will be submitted for publication and may 
post the results for registered trials on a clinical trials websites such as www.clinicaltrials.gov or 
www.clinicaltrialsregister.eu/ as a substitute for a peer-reviewed publication. 
The Sponsor often works with clinical trial investigators to produce high-quality manuscripts for 
publication in various formats including but not limited to abstracts, posters, or presentations. 
The final clinical study report is intended to form the basis for a manuscript intended for 
publication in a peer-reviewed scientific journal. The authorship, timetable, and any 
arrangements for review by the participating investigators will be coordinated by the Sponsor. 
No partial subset of data from individual investigational sites can be presented or published until 
after the primary manuscript for the entire study has been accepted for publication in a 
peer-reviewed scientific journal, with Sponsor consent. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 83 of 86 
12. 
REFERENCES 
Arastu-Kapur S, Anderl JL, Kraus M, et al. (2011) Nonproteasomal targets of the proteasome 
inhibitors bortezomib and carfilzomib: a link to clinical adverse events. Clin Cancer Res 17(9): 
2734-2743. 
Bennett MK and Kirk CJ (2008) Development of proteasome inhibitors in oncology and 
autoimmune diseases. Curr Opin Drug Discov Devel 11(5): 616-625. 
Beretta-Piccoli BT, Mieli-Vergani G and Vergani D (2021) Autoimmmune hepatitis. Cellular & 
Molecular Immunology 19: 158-176. 
Campbell G, Pennello G and Yue L (2011) Missing data in the regulation of medical devices. J 
Biopharm Stat 21(2): 180-195. 
Edsbacker S and Andersson T (2004) Pharmacokinetics of budesonide (Entocort EC) capsules 
for Crohn's disease. Clin Pharmacokinet 43(12): 803-821. 
Efe C, Hagström H, Ytting H, et al. (2017) Efficacy and safety of mycophenolate mofetil and 
tacrolimus as second-line therapy for patients with autoimmune hepatitis. Clin Gastroenterol 
Hepatol 15(12): 1950-1956. e1951. 
Giordano C, Rivas J and Zervos X (2014) An Update on Treatment of Drug-Induced Liver 
Injury. J Clin Transl Hepatol 2(2): 74-79. 
Hübener S, Oo YH, Than NN, et al. (2016) Efficacy of 6-mercaptopurine as second-line 
treatment for patients with autoimmune hepatitis and azathioprine intolerance. Clin 
Gastroenterol Hepatol 14(3): 445-453. 
Huber EM, Basler M, Schwab R, et al. (2012) Immuno- and constitutive proteasome crystal 
structures reveal differences in substrate and inhibitor specificity. Cell 148(4): 727-738. 
Ichikawa HT, Conley T, Muchamuel T, et al. (2012) Beneficial effect of novel proteasome 
inhibitors in murine lupus via dual inhibition of type I interferon and autoantibody-secreting 
cells. Arthritis Rheum 64(2): 493-503. 
Ishak K, Baptista A, Bianchi L, et al. (1995) Histological grading and staging of chronic 
hepatitis. J Hepatol 22(6): 696-699. 
Jayne DRW, Merkel PA, Schall TJ, et al. (2021) Avacopan for the Treatment of ANCA-
Associated Vasculitis. N Engl J Med 384(7): 599-609. 
Jones D, Manns MP, Terracciano L, et al. (2018) Unmet needs and new models for future trials 
in autoimmune hepatitis. The Lancet Gastroenterology & Hepatology 3(5): 363-370. 
Kalim KW, Basler M, Kirk CJ, et al. (2012) Immunoproteasome subunit LMP7 deficiency and 
inhibition suppresses Th1 and Th17 but enhances regulatory T cell differentiation. J Immunol 
189(8): 4182-4193. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 84 of 86 
Kirk CJ, Muchamuel T, Wang J, et al. (2021) Discovery and Early Clinical Development of 
Selective Immunoproteasome Inhibitors. Cells 11(1). 
Kirstein MM, Metzler F, Geiger E, et al. (2015) Prediction of short- and long-term outcome in 
patients with autoimmune hepatitis. Hepatology 62(5): 1524-1535. 
Kisselev AF, van der Linden WA and Overkleeft HS (2012) Proteasome inhibitors: an expanding 
army attacking a unique target. Chem Biol 19(1): 99-115. 
KYPROLIS® (2012) Carfilzomib) [Prescribing Information]. 
https://www.pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-
com/kyprolis/kyprolis_pi.pdf.: AMGEN (Thousand Oaks, CA). 
Liang K and Zeger S (2000) Longitudinal data analysis of continuous and discrete responses for 
pre-post designs. . The Indian Journal of Statistics (Series B) 62: 134-148. 
Lin R, Zhang J, Zhou L, et al. (2016) Altered function of monocytes/macrophages in patients 
with autoimmune hepatitis. Mol Med Rep 13(5): 3874-3880. 
Liu GF, Lu K, Mogg R, et al. (2009) Should baseline be a covariate or dependent variable in 
analyses of change from baseline in clinical trials? Stat Med 28(20): 2509-2530. 
Lowe D and John S (2018) Autoimmune hepatitis: Appraisal of current treatment guidelines. 
World J Hepatol 10(12): 911-923. 
Mack CL, Adams D, Assis DN, et al. (2020) Diagnosis and Management of Autoimmune 
Hepatitis in Adults and Children: 2019 Practice Guidance and Guidelines From the American 
Association for the Study of Liver Diseases. Hepatology 72(2): 671-722. 
Muchamuel T, Basler M, Aujay MA, et al. (2009) A selective inhibitor of the 
immunoproteasome subunit LMP7 blocks cytokine production and attenuates progression of 
experimental arthritis. Nat Med 15(7): 781-787. 
Nasseri-Moghaddam S, Nikfam S, Karimian S, et al. (2013) Cyclosporine-A versus prednisolone 
for induction of remission in auto-immune hepatitis: interim analysis report of a randomized 
controlled trial. Middle East Journal of Digestive Diseases 5(4): 193. 
Poetker DM and Reh DD (2010) A comprehensive review of the adverse effects of systemic 
corticosteroids. Otolaryngol Clin North Am 43(4): 753-768. 
Polson J, Lee WM and American Association for the Study of Liver D (2005) AASLD position 
paper: the management of acute liver failure. Hepatology 41(5): 1179-1197. 
Prati D, Taioli E, Zanella A, et al. (2002) Updated definitions of healthy ranges for serum alanine 
aminotransferase levels. Ann Intern Med 137(1): 1-10. 
Rubin DB (1988) An overview of multiple imputation. Proceedings of the survey research 
methods section of the American statistical association. Citeseer, 79-84. 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 85 of 86 
Sampson HA, Munoz-Furlong A, Campbell RL, et al. (2006) Second symposium on the 
definition and management of anaphylaxis: summary report--Second National Institute of 
Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network symposium. J Allergy 
Clin Immunol 117(2): 391-397. 
Schramm C (2019) Autoimmune hepatitis beyond steroids: Effective trial design and attention to 
quality of life. Clinical Liver Disease 14(1): 33. 
Sebode M, Hartl J, Vergani D, et al. (2018) Autoimmune hepatitis: From current knowledge and 
clinical practice to future research agenda. Liver Int 38(1): 15-22. 
Siddiqui MS, Vuppalanchi R, Van Natta ML, et al. (2019) Vibration-Controlled Transient 
Elastography to Assess Fibrosis and Steatosis in Patients With Nonalcoholic Fatty Liver Disease. 
Clin Gastroenterol Hepatol 17(1): 156-163 e152. 
Tunio NA, Mansoor E, Sheriff MZ, et al. (2021) Epidemiology of Autoimmune Hepatitis (AIH) 
in the United States Between 2014 and 2019: A Population-based National Study. J Clin 
Gastroenterol 55(10): 903-910. 
Yan X, Lee S and Li N (2009) Missing data handling methods in medical device clinical trials. J 
Biopharm Stat 19(6): 1085-1098. 
Younossi ZM, Guyatt G, Kiwi M, et al. (1999) Development of a disease specific questionnaire 
to measure health related quality of life in patients with chronic liver disease. Gut 45(2): 295-
300. 
Yuan Y (2011) Multiple Imputation Using SAS Software. J Stat Softw 45(6): 1-25. 
 

Protocol Version 4.0 
Kezar Life Sciences, Inc. 
KZR-616-208  
26 February 2024 
 
Confidential  
 
Page 86 of 86 
13. 
APPENDICES 
13.1. 
Appendix A: Protocol History 
Protocol Version 
Date Issued 
Rationale for Update 
Original Protocol, Version 1.0 
22 July 2022 
N/A 
Version 2.0  
15 September 2022 
 
Version 3.0 
07 March 2023 
Added an open-label extension (OLE) 
treatment period, added options for 
background medications, and made additional 
corrections and clarifications. 
Version 4.0 
26 February 2024 
Aligned study efficacy endpoints and 
associated recommended corticosteroid dose 
with AASLD AIH guidelines and made 
additional corrections and clarifications. 
13.2. 
Appendix B: Suggested Glucocorticoid Taper Schedule and 
Prednisone Equivalents 
Table 6 
Suggested Glucocorticoid Taper Schedule  
Study 
Week(s) 
Prednisone equivalent dose (mg/day) 
for Both Treatment Groups 
Budesonide dose for Both Treatment 
Groupsa 
0-2 
20.0 
6 mg/day 
3-4 
17.5 
6 mg/day 
5-6 
15.0 
3 mg/ day 
7-8 
12.5 
3 mg day 
9-11 
10.0 
6 mg/every other day 
12-13 
7.5 
6 mg/every other day 
14-24b 
5.0 
3 mg/every other day 
a Edsbäcker S, Andersson T. Pharmacokinetics of budesonide (Entocort EC) capsules for Crohn’s disease. Clin Pharmacokinet 
2004; 43(12): 803-21 (Edsbacker and Andersson, 2004) 
b After Week 16, the glucocorticoid dose may be tapered further, including discontinuation, at the Investigator’s discretion. 
Table 7 
Prednisone Equivalents 
Glucocorticoid 
Prednisone Equivalent (mg) 
Prednisone 
20 
Betamethasone 
2.4 
Cortisone acetate 
100 
Dexamethasone 
3 
Hydrocortisone 
80 
Methylprednisolone 
16 
Prednisolone 
20 
Triamcinolone 
16 
 

Signature Page for 
Signature Page for 
Approval Task
28-Feb-2024 17:44:06 GMT+0000
Approval Task
28-Feb-2024 18:14:47 GMT+0000
Approval Task
28-Feb-2024 20:53:19 GMT+0000
Approval Task
28-Feb-2024 23:33:07 GMT+0000