A Phase 2, Randomized, Double-blind, Placebo-controlled Study With Additional Open-label, Single-blind and Placebo-controlled Cohorts to Assess the Safety, Tolerability, and Efficacy of NGM282 in Patients With Nonalcoholic Steatohepatitis
Phase: PHASE2
Conditions: Nonalcoholic Steatohepatitis (NASH)
Sponsor: NGM Biopharmaceuticals, Inc

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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group 
Multiple-Center Study with Additional Open-Label Single-Blind and 
Placebo-Controlled 24-Week Histology Cohorts to Evaluate the Safety, Tolerability, 
and Efficacy of NGM282 Administered for Up to 24 Weeks in Patients with 
Histologically Confirmed Nonalcoholic Steatohepatitis (NASH) 
Protocol Number 15-0105 
for 
NGM Biopharmaceuticals Australia Pty Ltd 
Original Protocol    16 January 2015 
Amendment 1    27 May 2015 
Amendment 2    2 September 2015 
Amendment 3    20 June 2016 
Amendment 4    8 November 2016 
Amendment 5    24 January 2017 
Amendment 6    23 August 2017 
Amendment 7    14 February 2018 
Amendment 8    4 June 2018 
Amendment 9    29 March 2019 
Confidentiality Statement: 
This document contains proprietary and confidential information of NGM Biopharmaceuticals Australia Pty Ltd. 
Acceptance of this document constitutes agreement by the recipient that no previously unpublished information 
contained herein will be published or disclosed without the prior written approval of NGM Biopharmaceuticals 
Australia Pty Ltd with the exception that this document may be disclosed to study personnel under your 
supervision who need to know the contents for conducting the study and appropriate Institutional Review 
Boards/Ethics Committees under the condition that the personnel have agreed to keep this information 
confidential. The foregoing shall not apply to disclosure required by governmental regulations or laws; however, 
NGM Biopharmaceuticals Australia Pty Ltd shall be promptly notified of any such disclosure. 
NCT02443116

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3 
Table of Contents 
Title Page ......................................................................................................................................................... 1 
1 
Study Identification ........................................................................................................................... 2 
2 
Summary of Changes ........................................................................................................................ 3 
9.9.2 Magnetic Resonance Imaging (MRI) ..................................................................................... 6 
10.3 Study-Drug Storage and Appendix D ...................................................................................... 6 
Appendix D ..................................................................................................................................... 7 
Appendix E ...................................................................................................................................... 7 
3 
Table of Contents .............................................................................................................................. 8 
3.1 
List of Tables ........................................................................................................................... 10 
3.2 
List of Appendices ................................................................................................................... 10 
3.3 
List of Abbreviations ............................................................................................................... 11 
4 
Synopsis .......................................................................................................................................... 13 
5 
Introduction ..................................................................................................................................... 24 
5.1 
Background .............................................................................................................................. 24 
5.1.1 
Nonalcoholic Steatohepatitis (NASH) ............................................................................ 24 
5.1.2 
Treatment of NASH ........................................................................................................ 25 
5.1.3 
Therapeutic Rationale for NGM282 in NASH ................................................................ 26 
5.2 
Nonclinical Studies .................................................................................................................. 30 
5.2.1 
Nonclinical Safety Assessment ....................................................................................... 30 
5.3 
Clinical Studies ........................................................................................................................ 31 
5.4 
Rationale for Dose Selection of NGM282 for NASH .............................................................. 31 
5.5 
Rationale for the Use of Rosuvastatin for Lipid Management in NGM282-treated Subjects .. 33 
5.6 
Rationale for MRI-PDFF, LiverMultiScanTM and MRE Assessments ..................................... 33 
5.7 
Rationale for a Liver Biopsy at Weeks 12 or 24 ...................................................................... 34 
6 
Study Objectives ............................................................................................................................. 36 
7 
Study Design ................................................................................................................................... 38 
7.1 
Study-Stop Criteria .................................................................................................................. 41 
8 
Enrollment Criteria .......................................................................................................................... 41 
8.1 
Double-blind, Open-label Single-blind and Placebo-controlled 24 Week Histology Cohorts . 41 
8.1.1 
Inclusion Criteria ............................................................................................................. 41 
8.1.2 
Exclusion Criteria ............................................................................................................ 44 
8.2 
Discontinuation of Study Treatment for an Individual Subject ................................................ 46 
8.3 
Discontinuation of Subjects from Study Participation ............................................................. 47 
9 
Study Methods ................................................................................................................................ 48 
9.1 
Schedule of Study Procedures for Double-blind Cohort .......................................................... 48 
9.2 
Study Visit Procedures for Double-blind cohort ...................................................................... 51 
9.2.1 
Day –28 to Day –1 (Screening) Procedures .................................................................... 51 
9.2.2 
Day 1 Procedures ............................................................................................................ 51 
9.2.3 
Week 1 Procedures .......................................................................................................... 53 
9.2.4 
Week 2 Procedures .......................................................................................................... 54 
9.2.5 
Week 4 Procedures .......................................................................................................... 54 
9.2.6 
Week 8 Procedures .......................................................................................................... 55 
9.2.7 
Week 12 (End of Treatment)/Early Withdrawal Procedures ........................................... 56 
9.2.8 
Week 16 (End of Study) Procedures ............................................................................... 57 
9.3 
Schedule of Study Procedures for Open-label Single-blind Cohort ......................................... 58 
9.4 
Study Visit Procedures for Open-label cohort ......................................................................... 61 
9.4.1 
Day –28 to Day –1 (Screening) Procedures .................................................................... 61 
9.4.2 
Day 1 Procedures ............................................................................................................ 62 
9.4.3 
Week 2 Procedures .......................................................................................................... 63 
9.4.4 
Week 4 Procedures .......................................................................................................... 64 
9.4.5 
Week 6 Procedures .......................................................................................................... 65 
9.4.6 
Week 8 Procedures .......................................................................................................... 67 
9.4.7 
Week 12 (End of Treatment)/Early Withdrawal Procedures ........................................... 68 

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9.4.8 
Week 18 (End of Study) Procedures ............................................................................... 69 
9.5 
Schedule of Study Procedures for Placebo-controlled 24-Week Histology Cohort ................. 71 
9.6 
Study Visit Procedures for Placebo-controlled 24-week Histology Cohort ............................. 74 
9.6.1 
Day –28 to Day –1 (Screening) Procedures .................................................................... 74 
9.6.2 
Day 1 Procedures ............................................................................................................ 74 
9.6.3 
Week 2 Procedures .......................................................................................................... 75 
9.6.4 
Week 4 Procedures .......................................................................................................... 76 
9.6.5 
Week 6 Procedures .......................................................................................................... 77 
9.6.6 
Week 8 Procedures .......................................................................................................... 78 
9.6.7 
Week 12 Procedures ........................................................................................................ 79 
9.6.8 
Week 18 Procedures ........................................................................................................ 80 
9.6.9 
Week 24/Early Withdrawal (End of Treatment) Procedures ........................................... 81 
9.6.10 
Week 30 (End of Study) Procedures ............................................................................... 82 
9.7 
Prior and Concomitant Medications ......................................................................................... 83 
9.8 
Diet and Activity Control ......................................................................................................... 85 
9.9 
Clinical Evaluations ................................................................................................................. 85 
9.9.1 
Liver Biopsy .................................................................................................................... 85 
9.9.2 
Magnetic Resonance Imaging (MRI) .............................................................................. 86 
9.9.3 
Pharmacokinetic Blood Sample Collection and Processing ............................................ 88 
9.9.4 
Clinical Laboratory Evaluations ...................................................................................... 88 
9.9.5 
12-Lead Electrocardiograms ........................................................................................... 89 
9.9.6 
Vital Signs ....................................................................................................................... 89 
9.9.7 
Physical Examinations .................................................................................................... 89 
9.9.8 
Weight, Body Mass Index, and Waist Circumference Measurements ............................ 90 
9.9.9 
Local Injection-Site Symptom Assessments (LISSA)..................................................... 90 
10 
Study Drug ...................................................................................................................................... 91 
10.1 
Clinical Supplies ...................................................................................................................... 91 
10.1.1 
NGM282 ......................................................................................................................... 91 
10.1.2 
Rosuvastatin .................................................................................................................... 91 
10.1.2.1 Drug Supply for Open-Label Single-Blind Cohort ......................................................... 91 
10.1.2.2 Drug Supply for Placebo-Controlled 24-Week Histology Cohort .................................. 91 
10.2 
Study-Drug Accountability ...................................................................................................... 92 
10.3 
Study-Drug Storage.................................................................................................................. 92 
10.4 
Dose Preparation and Administration ...................................................................................... 92 
10.4.1 
NGM282 ......................................................................................................................... 92 
10.4.2 
Rosuvastatin .................................................................................................................... 93 
10.4.2.1 Rosuvastatin Treatment Algorithm – Statin Naïve ......................................................... 94 
10.4.2.2 Rosuvastatin Treatment Algorithm – Statin Experienced ............................................... 95 
10.5 
Removal of Study Blind ........................................................................................................... 95 
11 
Adverse Events ............................................................................................................................... 96 
11.1 
Definition and Grading Intensity of Adverse Events ............................................................... 96 
11.2 
Criteria for Determining Relationship to Drug ........................................................................ 97 
11.3 
Reporting ................................................................................................................................. 97 
11.4 
Cardiovascular Adjudication .................................................................................................... 98 
12 
Data Analysis and Statistical Considerations .................................................................................. 98 
12.1 
Sample Size .............................................................................................................................. 99 
12.2 
Randomization and Enrollment .............................................................................................. 100 
12.3 
Test of Hypothesis and Significance Levels .......................................................................... 101 
12.4 
Study Populations .................................................................................................................. 101 
12.4.1 
Intent-to-Treat Population ............................................................................................. 101 
12.4.2 
All Patients Population .................................................................................................. 102 
12.4.3 
Safety Population .......................................................................................................... 102 
12.4.4 
Efficacy Population ....................................................................................................... 102 
12.4.5 
Per Protocol Population ................................................................................................. 102 
12.4.6 
Liver Histology Population ........................................................................................... 102 
12.4.7 
Pharmacokinetic Population .......................................................................................... 103 
12.5 
Treatment Exposure ............................................................................................................... 103 

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12.6 
Patient Disposition ................................................................................................................. 103 
12.7 
Protocol Deviations ................................................................................................................ 103 
12.8 
Demographic Analysis ........................................................................................................... 103 
12.9 
Efficacy and Pharmacodynamics ........................................................................................... 104 
12.9.1 
Efficacy and Pharmacodynamic Endpoints ................................................................... 104 
12.9.2 
Analysis of Primary Endpoint ....................................................................................... 105 
12.9.3 
Analysis of Secondary Endpoints ................................................................................. 106 
12.9.4 
Analysis of Exploratory Endpoints ............................................................................... 106 
12.10 
Safety ..................................................................................................................................... 107 
12.10.1 Adverse Events ............................................................................................................. 107 
12.10.2 Clinical Laboratory Evaluations .................................................................................... 107 
12.10.3 Physical Examinations .................................................................................................. 107 
12.10.4 Vital Signs ..................................................................................................................... 108 
12.10.5 Pregnancy Test .............................................................................................................. 108 
12.10.6 Electrocardiogram ......................................................................................................... 108 
12.10.7 Injection-Site Reactions ................................................................................................ 108 
12.10.8 Concomitant Medications ............................................................................................. 108 
12.11 
Pharmacokinetics ................................................................................................................... 108 
12.11.1 Trough Serum Concentrations (All Subjects) ............................................................... 108 
12.11.2 Single-Dose Pharmacokinetics (Open-Label Single-Blind Subjects) ........................... 109 
12.11.3 Multiple-Dose Pharmacokinetics (Open-label Single-blind Subjects) .......................... 110 
12.12 
Interim Analysis ..................................................................................................................... 110 
13 
Administrative Aspects ................................................................................................................. 111 
13.1 
Protocol Adherence ................................................................................................................ 111 
13.2 
Disclosure .............................................................................................................................. 111 
13.3 
Monitoring ............................................................................................................................. 111 
13.4 
Ethics Committee ................................................................................................................... 112 
13.5 
Informed Consent ................................................................................................................... 112 
13.6 
Records .................................................................................................................................. 112 
13.7 
Financing and Insurance ........................................................................................................ 113 
Investigator Protocol Review and Signature Form ...................................................................................... 114 
Sponsor Protocol Approval and Signature Page .......................................................................................... 115 
14 
References ..................................................................................................................................... 116 
14.1 
Clinical Study References ...................................................................................................... 116 
14.2 
Nonclinical Study References ................................................................................................ 116 
14.3 
Literature References ............................................................................................................. 117 
15 
Appendices .................................................................................................................................... 121 
 
3.1 
List of Tables 
Table 1. 
Estimated Safety Exposure Margin of NGM282 ..................................................................... 31 
Table 2. 
Schedule of Study Procedures for Double-Blind Cohort ......................................................... 49 
Table 3. 
Schedule of Study Procedures for Open-Label Single-Blind Cohort ....................................... 59 
Table 4. 
Schedule of Study Procedures for Placebo-Controlled 24-Week Histology Cohort ................ 72 
 
3.2 
List of Appendices 
Appendix A. 
NASH Clinical Research Network (CRN) NAFLD Activity Score and Fibrosis Score ........ 121 
Appendix B. 
Food and Drug Administration Toxicity Grading Scale: Clinical Abnormalities in Local 
Injection-Site Symptom Assessments .................................................................................... 122 
Appendix C. 
Rosuvastatin Package Insert .................................................................................................. 123 
Appendix D. 
Ezetimibe Package Insert ....................................................................................................... 124 
Appendix E. 
Prohibited Hepatotoxic Agents .............................................................................................. 125 
 
 

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3.3 
List of Abbreviations 
Abbreviation Definition/Term 
AAV 
Adeno-associated virus 
ADA 
Anti-drug antibody 
AE 
Adverse event 
AFP 
Alpha fetoprotein 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
AUC 
Area under the concentration–time curve 
AUS 
Australia 
BMI 
Body mass index 
C2h post-dose 
Concentration at 2 hours post-dose 
C4 
7-alpha-hydroxy-4-cholesten-3-one 
CBC 
Complete blood count (hematology clinical laboratory evaluations) 
CHMP 
Committee for Medicinal Products for Human Use (European Medicines Agency) 
CI 
Confidence interval 
CL/F 
Clearance divided by the bioavailable fraction 
Cmax 
Maximum drug concentration 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRN 
Clinical Research Network 
Ctrough 
Trough concentration 
CTCAE 
Common Terminology Criteria for Adverse Events 
DIO 
Diet-induced obese 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
ELF 
Enhanced liver fibrosis 
EOS 
End of study 
EOT 
End of treatment 
ER 
Emergency room 
FDA 
Food and Drug Administration 
FFA 
Free fatty acid 
FGF19 
Fibroblast growth factor 19 
FXR 
Farnesoid X receptor 
GGT 
Gamma-glutamyl transpeptidase 
GI 
Gastrointestinal 
GLP 
Good Laboratory Practice 
GLP1 
Glucagon-like peptide-1 
GRE 
Gradient recalled echo 
HCC 
Hepatocellular carcinoma 
HCV 
Hepatitis C virus 
HDL 
High-density lipoprotein 
HDL-C 
High-density lipoprotein-cholesterol 
HIV 
Human immunodeficiency virus 
HOMA-IR 
Homeostasis model assessment–estimated insulin resistance 
hr 
Hour(s) 
 
 
IA 
Interim analysis 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
IL-6 
Interleukin 6 
INR 
International Normalized Ratio 
ISR 
Injection-site reaction 

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Abbreviation Definition/Term 
ITT 
Intent-to-treat 
IWRS 
Interactive Web Response System 
LDL 
Low-density lipoprotein 
LDL-C 
Low-density lipoprotein-cholesterol 
LIF 
Liver Inflammation Fibrosis 
LISSA 
Local injection-site symptom assessment 
LLT 
Lowest Level Term (MedDRA) 
MAD 
Multiple ascending dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRE 
Magnetic resonance elastography 
MRI 
Magnetic resonance imaging 
MRI-PDFF Magnetic resonance imaging–proton density fat fraction 
NAb 
Neutralizing antibody 
NAFLD 
Nonalcoholic fatty liver disease 
NAS 
NAFLD Activity Score 
NASH 
Nonalcoholic steatohepatitis 
NGM 
NGM Biopharmaceuticals, Inc. 
NGM282 
Recombinant protein of 190 amino acids; engineered variant of humanized FGF19  
NIH 
National Institutes of Health 
No. 
Number 
NOAEL 
No-observed-adverse-effect level 
NPO 
Nothing by mouth  
NZW 
New Zealand White 
OCA 
Obeticholic acid 
PBC 
Primary biliary cirrhosis 
PD 
Pharmacodynamics; pharmacodynamic 
PDFF 
Proton density fat fraction 
PI 
Principal Investigator 
PK 
Pharmacokinetics; pharmacokinetic 
PT 
Preferred term 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous 
SD 
Standard deviation 
SE 
Standard error 
SOC 
System organ class 
SOP 
Standard Operating Procedure 
t1/2 
Apparent terminal elimination half-life 
T2D 
Type 2 diabetes 
TEAE 
Treatment-emergent adverse event 
TG 
Triglyceride 
TGF-β 
Transforming growth factor beta 
Tmax 
Time to maximum concentration 
UA 
Urinalysis 
ULN 
Upper limit of normal 
U.S. 
United States 
Vz/F 
Volume of distribution based on the terminal portion of the concentration–time curve divided 
by the bioavailable fraction 
Wk 
Week 
 
 

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4 
Synopsis 
Title of Study: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group 
Multiple-Center Study with Additional Open-Label Single-Blind and 
Placebo-Controlled 24-Week Histology Cohorts to Evaluate the Safety, Tolerability, 
and Efficacy of NGM282 Administered for Up to 24 Weeks in Patients with 
Histologically Confirmed Nonalcoholic Steatohepatitis (NASH) 
Protocol Number: 
15-0105 
 
Phase: 
2 
 
Investigational 
Product: 
NGM282 
 
Objectives: 
Primary Objective:  
• 
Evaluate the treatment effect of NGM282 on absolute liver fat content as 
measured by magnetic resonance imaging–proton density fat fraction  
(MRI-PDFF) in patients with histologically confirmed NASH. 
Secondary Objectives: 
• 
Assess the safety and tolerability of NGM282 in patients with NASH with 
up to 24 weeks of treatment with NGM282. 
• 
Evaluate the percentage change in absolute liver fat content at End of 
Treatment (EOT). 
o 
In the open-label single-blind cohort, additional evaluations will be 
performed at Weeks 6 and 18 weeks 
o 
In the placebo-controlled 24-week histology cohort, additional 
evaluations will be performed at Weeks 6, 24, and 30 weeks 
• 
Evaluate the percentage of normalization for liver fat content at EOT. 
• 
Evaluate the change in liver fat content response rate as defined by a ≥ 5% 
decrease in absolute liver fat content. 
• 
Evaluate the absolute and percentage changes from Baseline to EOT as well 
as the percentage of normalization of the following parameters: ALT, AST, 
triglycerides, bilirubin (total and direct), and GGT. Percentage of 
normalization will also be investigated for a clinically meaningful threshold 
for triglycerides. 
• 
Evaluate the absolute and percentage changes from Baseline to EOT of the 
following (if collected as part of the cohort): 
o 
Total cholesterol, HDL-cholesterol (HDL-C), LDL-cholesterol 
(LDL-C), triglycerides, and lipoprotein particles  
 
In addition, evaluate the absolute and percentage change 
from Baseline to End of Study (EOS) of the above lipid 
parameters in the open-label single-blind cohort. 
o 
 
o 
Fasting blood glucose, insulin levels, 
 
, and homeostasis model assessment–estimated 
insulin resistance (HOMA-IR) 
o 
PRO-C3 and ELF Score (Placebo Controlled 24 Week Histology 
Cohorts)  
o 
Body weight, body mass index (BMI), and waist circumference 
o 
7-alpha-hydroxy-4-cholesten-3-one (C4) and serum bile acids 

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Methodology/ 
Study Design: 
This is a multiple-center evaluation of NGM282 in a randomized, double-blind, 
placebo-controlled, parallel-group cohort with additional open-label single-blind and 
placebo-controlled 24-week histology cohorts when administered for up to 24 weeks 
as an SC injection in patients with histologically confirmed NASH. 
In the double-blind cohort, ~75 patients will be randomized across ~20 sites 
worldwide. 
Patients to be studied will have histologically confirmed NASH as defined by the 
NIH NASH Clinical Research Network and determined by a qualified local 
pathologist. Historical biopsy results within 6 months of Screening may be used for 
inclusion into the study; otherwise, a liver biopsy must be obtained for assessment. 
Patients must have a nonalcoholic fatty liver disease (NAFLD) activity score (NAS) 
of at least 4, with 1 point in each of the three components, along with the presence of 
fibrosis. Patients with cirrhosis will be excluded from this study. Patients will 
undergo an MRI during the Screening period, which must demonstrate at least 8% 
total fat content.  

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Methodology/ 
Study Design 
(cont’d): 
On Day 1, subjects will be randomized into one of the three treatment arms 
(NGM282 3 mg, NGM282 6 mg, or placebo) in a 1:1:1 ratio. Subjects will be 
stratified at randomization according to non-diabetic and diabetic status at Day 1 to 
ensure an even distribution across the three groups. Study-drug self-administration 
instructions and training will be provided to the subjects and a weekly study-drug kit 
will be dispensed. Treatment assignment will be blinded to the sites, study subjects, 
sponsor, and Medical Monitor throughout the study period. The first dose (Day 1) 
and doses at Weeks 1, 2, 4, 8, and 12 will be self-administered in the clinic, with all 
other doses through Week 12 self-administered at home. Self-administration should 
occur in the morning for every dose in both the clinic and at home. Subjects will 
return to the clinic on Weeks 1, 2, 4, and 8 for on-treatment assessments and to 
receive weekly NGM282 study-drug kits. Week 12 will be the EOT clinic visit. 
Subjects will return to the clinic at Week 16 (or 4 weeks after last dose) for an EOS 
follow-up visit. Subjects are requested to undergo MRI performed during Screening 
and at Week 12 (EOT)/Early Withdrawal visit. 
In the open-label single-blind cohort, up to 100 patients (25 per dosing group) will 
be enrolled from ~6–8 U.S. sites. Subjects will be required to meet enrollment 
criteria similar to those of the double-blind cohort with the exception of the 
following, specifically defined in protocol Section 8.1.2: 1) historical biopsy window 
extended to 12 months; 2) limitations on the use of glucagon-like peptide-1 (GLP1) 
agonists; 3) glycated hemoglobin (HbA1c) level ≤ 9.5%; 4) LDL levels at Screening 
need to be ≤ 165 mg/dL; 5) exclusion of specific lipid-lowering therapies prior to and 
during study period; 6) no contraindications to receiving statins. The single-blind 
cohort is not randomized. At Day 1 eligible patients will be sequentially enrolled into 
the study and categorized as either statin-naïve versus statin experienced with no 
more than 8 statin experienced subjects within each dosing group. Subjects will be 
enrolled sequentially initially into the dosing Group 1 and enrollment will be 
continuous within the dosing group. Sequencing of the subsequent 2 dosing groups 
will be based on PD and safety parameters from dosing Group 1. The subsequent 
2 dosing groups may run in parallel. A fourth optional dosing group may be 
conducted based on the safety/tolerability, imaging data, and histology (dosing 
Group 3 only) data from the prior 3 dosing groups. Dosing Group 4 will be initiated 
only after all subjects in Dosing Group 3 have been enrolled and a minimum of 
10 subjects have completed 12 weeks of treatment in order to do a preliminary 
review of key data. Individual subject treatment assignment will be blinded only to 
the study subjects throughout the study period. 
The first dose of NGM282 (Day 1) and doses at Weeks 2, 4, 6, 8, and 12 study visits 
will be self-administered in the clinic, with all other doses throughout the treatment 
period self-administered at home. Self-administration of NGM282 should occur in 
the morning for every dose in both the clinic and at home. Subjects will return to the 
clinic on Weeks 2, 4, 6, and 8 for on-treatment assessments and to receive weekly 
NGM282 study-drug kits. LDL-C will be evaluated at Weeks 2, 4, and 8 in all 
subjects for possible increases in lipid levels associated with NGM282 
administration. Rosuvastatin will be started in subjects meeting specific LDL-C level 
criteria. The specific dosing and administration of rosuvastatin will be based on 
whether the subject is statin naïve versus statin experienced and LDL-C levels at 
Weeks 2, 4, and 8. The dosing algorithms are specifically outlined in Section 10.4 of 
the study protocol. Bottles of rosuvastatin tablets will be dispensed at Weeks 2, 4, 
and 8, depending on observed lipid levels and dosing algorithm in Section 10.4. 
Week 12 will be the EOT clinic visit and subjects will return to the clinic at Week 18 
(or 6 weeks after last dose) for an EOS follow-up visit. Subjects are required to 
undergo MRI performed during Screening and at Weeks 6, 12 (EOT)/Early 
Withdrawal, and 18 (EOS) visits. 
Dosing Groups 3 or 4 will have two other assessments performed to assess liver 
histology in addition to MRI-PDFF. LiverMultiScanTM will be performed during the 
MRI assessments at the same time as the MRI-PDFF assessments (Screening and 

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Number of Patients: 
 
Approximately 75 patients (25 per treatment group) will be randomized in the 
double-blind cohort. Up to 100 additional patients (25 per treatment group) will be 
enrolled in the open-label single-blind cohort. Approximately 75 additional subjects 
(50 active, 25 placebo) will be enrolled in the placebo-controlled 24-week cohort. 
 
Number of Study 
Sites: 
 
Double-blind cohort: ~20 sites worldwide  
Open-label single-blind cohort: ~6–8 U.S. sites  
Placebo-controlled 24-week histology cohort : ~10 U.S. sites 
 
Test Product(s), 
Dose, and 
Mode of 
Administration: 
For the double-blind cohort, the NGM282 final product will be supplied in pre-filled 
syringes intended to deliver 0.3 mL (3 mg) or 0.6 mL (6 mg) for SC injection. 
Placebo will be provided in volume-matched syringes (0.3 mL and 0.6 mL). For the 
open-label cohort, NGM282 final product will be supplied in pre-filled syringes 
intended to deliver 0.3 mL (0.3 mg, 1 mg, and 3 mg) for SC injection. For the 
placebo-controlled 24-week histology cohort, NGM282 final product will be 
supplied in pre-filled syringes intended to deliver 0.3 mL (1 mg) dose for SC 
injection. All subjects will be instructed to dose NGM282 each morning and to skip 
the dose if it is past 12:00 noon and administer the next dose as planned the 
following morning.  
The open-label single-blind and placebo-controlled 24-week histology cohorts will 
also include treatment with rosuvastatin for subjects meeting pre-specified LDL-C 
criteria. Study-labeled rosuvastatin 20-mg tablets will be supplied in order to deliver 
either 20 mg or 40 mg total daily doses as outlined in Section 10.4 to manage 
possible LDL-C increase during NGM282 treatment.   
The placebo-controlled 24-week histology cohort only will also include treatment 
with ezetimibe co-therapy that will be prescribed by the Investigator when subjects 
have not achieved an adequate LDL-C response or when subjects are unable to 
tolerate rosuvastatin.  Ezetimibe is formulated as 10 mg tablets and can be 
administered with or without food at the same time as rosuvastatin and NGM282 or 
placebo 
 
Duration of 
Treatment: 
In all cohorts, patients will sign the Informed Consent Form at the Screening Visit, 
and will undergo screening assessments to verify eligibility for the study for up to 
4 weeks from consent date. In the double-blind cohort, all subjects will be treated 
with NGM282 or placebo for 12 weeks and will be monitored for 4 weeks after 
completing their final dose of NGM282 or placebo. In the open-label single-blind 
cohort, subjects will receive NGM282 in 0.3 mg, 1 mg, or 3 mg doses for 12 weeks 
and be monitored for 6 weeks after completing final study-drug dose. In the 
placebo-controlled 24-week histology cohort, subjects will receive NGM282 or 
matching placebo at 1mg dose for 24 weeks and be monitored for 6 weeks after 
completing final study-drug dose. 
The total duration of individual participation will be ~20 weeks for the double-blind 
cohort, ~22 weeks for the open-label single-blind cohort, and ~34 weeks for the 
placebo-controlled 24-week histology cohort. 
 
Criteria for 
Evaluation: 
Safety 
In all study cohorts, safety and tolerability will be assessed by monitoring adverse 
events (AEs) and concomitant medications, conducting local injection-site symptom 
assessments (LISSAs), measuring vital signs and electrocardiograms (ECGs), and 
collecting and analyzing clinical laboratory blood and urine samples. 
 

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Criteria for 
Evaluation: 
Pharmacokinetics  
In the double-blind cohort, PK will be analyzed to determine the steady-state trough 
and 2-hour post-dose NGM282 levels in NASH subjects and to compare to the levels 
in normal volunteers and in subjects with type 2 diabetes (T2D), and to explore 
PK/PD correlations in terms of drug efficacy (change in hepatic fat content), toxicity, 
and other parameters of the disease. 
In the open-label single-blind cohort, the same PK parameters and comparisons will 
be performed as outlined for the double-blind cohort. In addition, approximately 
8 subjects per dosing group will be given the option to participate in further PK 
sampling at pre-dose and at 1, 2, 4, 8, and 12 hours after dosing on Day 1 and 
Week 6 in order to further characterize the PK in this population. 
In the placebo-controlled 24-week histology cohort, the same PK parameters and 
comparisons will be performed as outlined for the double-blind cohort.  
 

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Sample Size 
Determination 
(cont’d): 
The sample size of the placebo-controlled 24-week histology cohort is based on 1) 
12-week histologic response data from the 3-mg cohort and 2) estimated placebo 
histologic response rates from controlled Phase 2 studies in NASH. Preliminary 
12-week histologic response data (n=16) demonstrated that 50% of subjects had a 
1-stage improvement in fibrosis with no worsening of NASH or resolution of NASH 
with no worsening of fibrosis. The placebo histologic response rates from recent 
Phase 2b trials of obeticholic acid, cenicriviroc, liraglutide, and selonsertib were 
14%–20% at timepoints ranging from 24 to 72 weeks. Based on these data, the 
assumptions of calculated sample-size estimates for 24-week efficacy used an 
NGM282 response of 50% versus 15% for placebo utilizing 80% power and 
alpha=0.05 with a 2:1 randomization scheme. Assuming a 15% drop-out rate, the 
planned sample size of 50 NGM282-treated subjects and 25 placebo subjects is 
sufficient to evaluate efficacy and support powering estimates for late-stage clinical 
trials. 
Statistical Methods: 
All patients who receive any amount of study drug will be included in the analyses, 
including those who withdraw prematurely from the study. Patients will be 
summarized within five analysis populations:  
• 
Intent-to-treat (ITT) population: all randomized patients (for the double-blind 
and placebo-controlled 24-week histology cohorts) 
• 
All Patients population: all enrolled patients (single-blind cohort only) 
• 
Safety population: all randomized/enrolled patients who receive at least one dose 
(full or partial) and have at least one post-dose safety evaluation 
• 
Efficacy population: all randomized/enrolled patients who receive at least 
one dose (full or partial) of study drug and have at least one valid, non-missing 
post-dose efficacy/PD parameter value  
• 
Per Protocol (PP) population: subset of patients in the Efficacy population; will 
include patients who have at least one valid, non-missing post-dose liver fat 
content measurement and excludes those patients who deviate from the conduct 
of the study or have an AE deemed by the medical monitor to be impactful on 
the primary endpoint 
• 
Liver histology population: subset of patients in the Efficacy population; will 
include patients who have at least one valid, non-missing Baseline and EOT 
biopsy and excludes those patients who deviate from the conduct of the study or 
have an AE deemed by the medical monitor to be impactful on the primary 
endpoint 
• 
PK population: all randomized/enrolled patients who receive at least one dose 
(full or partial) of drug, with a pre-dose (Baseline) blood draw, and at least 
one qualified (above the limit of quantification) post-dose sample 
The patient disposition will be presented by randomized treatment group for the 
double-blind and placebo-controlled 24-week histology cohorts and by enrolled 
treatment group for the single-blind cohort. The reasons for discontinuation will also 
be summarized. Treatment exposure will be summarized as extent of exposure to the 
study drug. Measures of extent of exposure will include the total number of doses per 
patient and compliance. Treatment exposure will be summarized using the Safety 
population by actual treatment group. Demographic and Baseline characteristics will 
be descriptively summarized by treatment group. Patient disposition, demographic, 
and Baseline characteristics will be summarized using the ITT population for the 
double-blind and placebo-controlled 24-week histology cohorts and using the All 
Patients population for the single-blind cohort. 
 

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Statistical Methods 
(cont’d): 
The primary efficacy endpoint is the absolute change in liver fat content as measured 
by MRI-PDFF from Baseline to EOT. The absolute change from Baseline to EOT 
will be compared between treatment groups using an analysis of covariance 
(ANCOVA) model with treatment group and diabetic status (double-blind cohort 
only) as cofactors and Baseline absolute liver fat content as a covariate at the 5% 
level of significance. The primary endpoint will be evaluated using the Efficacy 
population and the analysis will be repeated using the Per Protocol population. 
The secondary and exploratory PD endpoints will be measured as an absolute as well 
as percentage change (for specific identified parameters) from Baseline to EOT. The 
secondary and exploratory PD endpoint analyses will utilize the Efficacy population. 
The absolute change and percentage change from Baseline to EOT will be compared 
between treatment groups using an ANCOVA model with treatment group and 
diabetic status (double-blind cohort only) as cofactors and Baseline endpoint value as 
a covariate at the 5% level of significance. In cases where the parameters do not 
follow a normal distribution, a non-parametric approach will be followed to analyze 
the difference between treatment groups. Categorical secondary endpoints 
(percentage of normalization) will be analyzed through a chi-square test. 
 
Further covariates/cofactors and correlations may be included in the modeling 
depending on the relevance to the endpoint analyzed and will be further described in 
the Statistical Analysis Plan. 
Safety and tolerability will be assessed by the following parameters: AEs, LISSAs, 
clinical laboratory tests, physical examinations, ECGs, vital signs, prior and 
concomitant medications. All safety analyses will be conducted using the Safety 
population. Apart from the lipid profile (total cholesterol, HDL-C, LDL-C, and 
lipoprotein particles), which will be analyzed as described for the primary and 
secondary endpoints above based on the safety population, all other safety endpoints 
will be analyzed descriptively only. 
Interim Analyses: 
A single interim analysis (IA) is planned to be conducted for the double-blind cohort 
after ~12 patients per arm have completed 12 weeks of treatment. The final analysis 
of the double-blind cohort will be conducted after all double-blind cohort patients 
have completed Week 16. The IA will include review of all safety and selected 
efficacy endpoints and is for internal planning purposes. The final analysis of the 
double-blind cohort will review all endpoints (safety, efficacy, and exploratory). The 
double blind will be maintained for the IA as the results in the summary tables will 
be presented only by treatment group. 
There will be no formal interim analysis of the open-label single-blind cohort. 
A single IA is planned to be conducted in the placebo-controlled 24-week cohort 
after at least 50% of the subjects (2:1 randomization) have completed 24 weeks of 
treatment.  The IA will include review of safety and selected efficacy endpoints by 
treatment group. The IA is being conducted for internal planning purposes and the 
study will not be stopped early based on the results of the IA. Therefore, no formal 
hypothesis testing will occur with no effect on available alpha for the final planned 
analyses. The final analysis is planned to be conducted after all subjects have 
completed Week 30.  Results for individual subjects will not be shared with study 
investigators. 
Further details of the IAs and final analyses, including statistical considerations and 
analyses, will be included in the SAP. 
 
 
 
 

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5 
Introduction 
5.1 
Background 
5.1.1 
Nonalcoholic Steatohepatitis (NASH) 
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of disease ranging from 
simple steatosis to inflammatory steatohepatitis (NASH). The estimated global prevalence of 
NASH has risen rapidly in parallel with the dramatic rise in population levels of obesity and 
diabetes, resulting in NAFLD now representing the most common cause of liver disease in 
the Western world (Swinburn 2011, Centers for Disease Control US Obesity Trends 2014). 
The prevalence of NASH is estimated to be between 2% and 5% in Western adults, rising to 
as high as 40%–50% in the morbidly obese patients with type 2 diabetes (T2D) (Argo 2009, 
Williams 2011). The histologic criteria for the diagnosis of adult NASH include 
macrovesicular steatosis, hepatocyte ballooning, and mild lobular inflammation 
(Kleiner 2005, Brunt 2009). Portal and periportal fibrosis followed by bridging fibrosis and 
cirrhosis are seen in patients with the progression of NASH. Steatosis may be absent in cases 
of bridging fibrosis or cirrhosis (“burnt-out NASH”) and is often misdiagnosed as 
cryptogenic cirrhosis (Caldwell 2004). The NAFLD Activity Score (NAS) is a validated 
score used to grade disease activity in patients with NAFLD and NASH (Appendix A). The 
NAS is the sum of the biopsy's individual scores for steatosis (0–3), lobular inflammation 
(0-2), hepatocellular ballooning (0–2), and fibrosis (0–4). Fibrosis staging is assessed using a 
separate scoring system from the NAS (Kleiner 2005).  
Most patients with NASH are asymptomatic, although some patients may present with 
fatigue, malaise, and vague right-upper abdominal discomfort. Patients are more likely to 
initially be identified by elevated liver aminotransferases on routine exams or hepatic 
steatosis detected incidentally on abdominal imaging. Patients with NASH often have one or 
more components of the metabolic syndrome such as obesity, hypertension, dyslipidemia, 
and insulin resistance or T2D, with NASH considered to be the hepatic manifestation of 
metabolic syndrome (Torres 2012). Most patients are diagnosed with NASH in their forties 
or fifties. Studies vary with regard to the sex distribution of NASH, with some studies 
suggesting it is more common in women while others suggest it is more common in men 
(Pan 2014). There appear to be ethnic differences in the prevalence of NASH, with a higher 
prevalence of hepatic steatosis in Hispanics compared with whites or blacks (Pan 2014).  
The pathogenesis of NASH and progression to fibrosis/cirrhosis is not yet fully understood, 
despite recent advances in understanding complex metabolic and inflammatory pathways that 
are likely involved in disease progression. The most widely supported theory implicates 
insulin resistance as the key mechanism leading to hepatic steatosis and subsequent NASH 
(Cusi 2012). This is likely followed by oxidative injury resulting in the necroinflammatory 
component of NASH (Cusi 2012). Hepatic iron, antioxidant deficiency, and intestinal 

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bacteria have all been suggested as potential oxidative stressors (Cusi 2012). Several other 
factors known to be involved in the progression of NASH include inflammatory cytokines, 
adipokines, lipotoxicity, autophagy, and mitochondrial dysfunction (Tsochatzis 2009). There 
is also growing evidence of a genetic component for the progression of NAFLD to NASH as 
well as fibrogenesis in patients with NASH (Mehta 2014). 
The natural history of NASH is variable from patient to patient and the NAS does not appear 
to be predictive of disease progression. The presence of fibrosis has been the only highly 
predictive factor of patients who will progress to cirrhosis. Approximately 10%–20% of 
patients with NAFLD will progress to NASH over a 7-year period (Argo 2009, Bhala 2013). 
Of these patients, roughly 20% will progress to cirrhosis over a 20-year period (Bhala 2013). 
A recent meta-analysis of paired biopsy studies in NASH patients demonstrated an annual 
fibrosis progression rate of 0.14 fibrosis stages in patients with NASH and 1 stage of 
progression over 7.1 years for patients with NASH (Singh 2014). The mortality rate of 
patients with NASH has been estimated at 1%–2% per year in patients with fibrosis, largely 
due to cardiovascular disease followed by liver-related causes (Kim 2013). Patients with 
NASH-related cirrhosis can progress to decompensated liver disease, complications of portal 
hypertension, and hepatocellular carcinoma (HCC). Recently, a growing number of cases of 
HCC in NASH patients have been reported without bridging fibrosis or cirrhosis, suggesting 
an independent pathogenic mechanism in this population (Paradis 2009). NASH is rapidly 
growing as the primary cause of end-stage liver disease in the U.S. and European populations 
and is expected to be the primary indication for liver transplantation by 2020 (Charlton 2011, 
Afzali 2012). 
5.1.2 
Treatment of NASH 
The identification of a single therapeutic target has been complicated by the complexity of 
the pathogenesis of NASH. The treatment goals for NASH have focused on the prevention or 
reversal of liver injury either by treating the underlying metabolic and inflammatory 
conditions or through directly targeting fibrogenic pathways. Early-stage disease treatments 
have focused on insulin sensitization, decreasing lipids, and antioxidant activity. The 
endpoints for these treatments have been both improvements in biochemical parameters and 
histologic improvement in the components of NAS with no worsening or improvement of 
fibrosis. More recently, the resolution of NASH on biopsy has been considered a more 
clinically meaningful treatment endpoint. Antifibrotic agents have targeted the advanced 
fibrosis and cirrhotic populations but have little activity on the underlying disease causing the 
chronic hepatic injury.  
Weight loss through lifestyle management is considered the first-line treatment strategy for 
NASH and is associated with improvement in liver histology and a reduction in 
cardiovascular and metabolic complications (Promrat 2010; Glass 2015). However, the 
majority of patients are unsuccessful in achieving or maintaining adequate weight loss and 

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require other interventions. In cases of morbid obesity, bariatric surgery has been successful 
in reversing the metabolic and hepatic injury associated with NASH (Cazzo 2014). Currently, 
no agents have been approved by regulatory authorities for the treatment of NASH; the 
majority of interventions have utilized agents approved for other indications. However, the 
interpretation of the data with many of these agents has been complicated by the study 
designs and endpoints. The majority of studies are uncontrolled or retrospective cohorts, have 
small sample sizes and/or are insufficiently powered, were comprised of heterogeneous 
populations, have treatment durations too short (<12 months) to demonstrate a treatment 
effect, and lack consistent definitions of response. Evaluated agents including metformin, 
fibrates, ursodeoxycholic acid, and orlistat have failed to show a significant histologic benefit 
in NASH (Torres 2012). Pilot studies with PPAR-γ agonists (pioglitazone, rosiglitazone) 
have been undertaken based on their effects on insulin resistance, inflammatory signaling, 
and fibrogenesis. Both agents have demonstrated improvements in ALT and steatosis with 
pioglitazone having a marginally better anti-inflammatory and anti-fibrotic activity 
(Belfort 2006, Neuschwander-Tetri 2003). Vitamin E has also been evaluated in NASH 
patients based on its antioxidant properties. Small pilot studies have demonstrated histologic 
improvement with daily doses of 400–800 IU (Harrison 2003). The PIVENS trial comparing 
pioglitazone or vitamin E to placebo was the first well-controlled study to show an impact on 
steatosis, inflammation, hepatocyte ballooning, and fibrosis, with vitamin E having slightly 
better improvements in fibrosis (Sanyal 2010). Although a treatment benefit was 
demonstrated in this study, the improvements in fibrosis were modest. Additionally, 
near- and long-term safety and tolerability concerns were observed with both pioglitazone 
(weight gain, edema, bone fractures, malignancy) and vitamin E (hemorrhagic stroke, 
inhibition of platelet aggregation, malignancy). More recently, the farnesoid X receptor 
(FXR) agonist obeticholic acid (OCA) was evaluated in the FLINT trial in a population 
similar to that in the PIVENS study with comparable primary and secondary endpoints 
(Neuschwander-Tetri 2014). OCA demonstrated results comparable to vitamin E versus 
placebo in terms of improvements in NAS and fibrosis whereas vitamin E and pioglitazone 
demonstrated better results compared to OCA in terms of resolution of NASH. Additionally, 
significant increases in pruritus and lipids (requiring treatment on study) were associated 
with OCA. Although these agents have demonstrated some histologic improvement in 
NASH, a significant medical need for new effective therapies with favorable safety and 
tolerability profiles remains. 
5.1.3 
Therapeutic Rationale for NGM282 in NASH 
The pathogenesis of NASH involves complex interactions of insulin resistance, dysregulation 
of lipid and triglyceride metabolism, and bile acid synthesis that leads to steatohepatitis and 
fibrogenic activity. The biologic activity of the fibroblast growth factor 19 (FGF19) can 

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potentially impact all of these mechanisms to a varying degree, supporting the evaluation of 
the therapeutic applications of this pathway for the treatment of NASH.  
FGF19 is a naturally occurring protein selectively expressed and secreted in the 
gastrointestinal (GI) tract. Studies have shown that the predominant expression is in the 
ileum with some expression observed in the brain, retina, cartilage, and skin (Schauer 2003, 
Cummings 2007). 
FGF19 acts as an endocrine hormone to regulate systemic glucose homeostasis and bile acid 
synthesis (Schauer 2003). FGF19 is released postprandially from the distal small intestine 
into the circulation and functions as a hormone to govern hepatic glycogen synthesis and 
gluconeogenesis without stimulation of lipogenesis (Kir 2011, Potthoff 2011). In normal 
human subjects, the basal level of systemic FGF19 concentration ranges between 200 and 
400 pg/mL (Lundasen 2006, Stejskal 2008). Systemic FGF19 levels are decreased in patients 
with T2D or metabolic syndrome and are normalized after bariatric surgery in diabetic 
human subjects (Mingrone 2012). 
In mouse models of diabetes and/or obesity, transgenic or viral-mediated FGF19 expression 
resulted in profound metabolic benefits (similar to gastric bypass surgery), including the 
rapid resolution of hyperglycemia and hyperinsulinemia (Xie 1999). Transgenic mice 
over-expressing FGF19 are resistant to diet-induced obesity and have decreased body fat 
mass and improved insulin sensitivity, glucose disposal, and plasma lipid profiles 
(Tomlinson 2002). Subcutaneous (SC) administration of recombinant FGF19 protein into 
leptin-deficient mutant obese or diet-induced obese (DIO) mice results in similar metabolic 
effects (Fu 2004). Similar to insulin, FGF19 stimulates hepatic protein and glycogen 
synthesis but does not induce lipogenesis (Schauer 2012). 
FGF19 has also been found to be associated with disease progression in NASH. Adult 
patients with biopsy-proven NAFLD and NASH have decreased serum levels of FGF19 
(Eren 2012, Bechmann 2013). Additionally, decreased FGF19 serum levels are inversely 
correlated with severity of fibrosis/cirrhosis NASH-related liver disease (Alisi 2013). 
Although normal intestinal secretion of FGF19 occurs in NASH, hepatic β-klotho expression 
is reduced and hepatic response to FGF19 is impaired, and a correlation exists between 
increased hepatocyte ballooning and increased FGF19 levels (Schreuder 2010, Wojcik 2012). 
The increased understanding of the role of bile acids in the pathogenesis of NASH further 
supports the therapeutic potential of FGF19. Nonclinical models demonstrate a significant 
role of dysregulation of bile acid synthesis in the pathogenesis of NASH (Tanaka 2012, 
Jia 2013). Increased bile acid synthesis as well as serum bile acid and 
7-alpha-hydroxy-4-cholesten-3-one (C4) concentrations, a key marker of CYP7A1 activity, 
correlate with NASH disease severity and fibrotic activity (Bechmann 2013). Altered bile 
acid composition has been observed in patients with NASH, with a compensatory transition 
from CYP7A1-mediated classic pathway (toxic bile acids) to the less toxic alternative 

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pathway (Lake 2013). Increased hepatic concentrations of bile acids are also associated with 
increased apoptosis, Fas, and TNF-R1 activity resulting in hepatocyte injury and stellate cell 
activation (Faubion 1999, Higuchi 2003). A significant correlation also exists between 
increases in specific bile acids and severity of NASH-related hepatic injury (Aranha 2008). 
Based on the identified beneficial metabolic and bile acid synthetic activities of FGF19 in 
animal models, the associated reduction of FGF19 levels with obesity and diabetes in 
patients, the associated increase in plasma levels after gastric bypass in humans, and the 
clinical associations of FGF19 deficiency in NASH patients, the FGF19 biologic pathway 
represents a potentially important therapeutic target for the treatment of NASH.  
NGM282 is a recombinant protein of 190 amino acids with a molecular weight of 21.3 kDa 
and an amino acid sequence 95.4% identical to that of human FGF19. Extensive in vivo 
structure–activity relationship analyses have been conducted to define and manipulate the 
distinct functional domains in FGF19 protein that are responsible for its metabolic and 
proliferative features. More than 160 variants of human FGF19 were engineered, of which 
NGM282 was selected as the clinical candidate based on robust efficacy with no evidence of 
the proliferative activity previously observed in db/db mice. 
NGM282 effectively mimics the actions of FGF19 on glucose homeostasis as demonstrated 
in a series of in vitro and in vivo pharmacology studies. In vitro, NGM282 binds to the 
extracellular portion of mouse and human FGFR1c–β-klotho co-receptor complexes, with 
high nanomolar affinity (Study 11-MP-NGM282-1002). NGM282 has been shown to 
potently trigger FGFR1c-mediated intracellular signaling in mouse- and human-cultured 
adipocytes (Study 11-MP-NGM282-1001). NGM282 also activates intracellular signaling 
pathways in L6 cells transfected with FGFR1c–β-klotho complexes of the mouse, rat, rabbit, 
cynomolgus monkey (Macaca fascicularis), or human (Study 13-MP-NGM282-1004). 
In vivo, daily administration of NGM282 to ob/ob mice for 14 days resulted in significant 
dose-dependent reductions in the levels of non-fasting blood glucose 
(Study 11-PD-NGM282-1003). In DIO mice, fasted blood glucose levels were significantly 
reduced following a 14-day treatment regimen in response to NGM282 as low as the lowest 
dose tested (0.1 mg/kg) (Study 11-PD-NGM282-1004). NGM282 also effectively mimics the 
actions of FGF19 on bile acid synthesis through the binding of FGFR4c–β-klotho co-receptor 
(Study 12-MP-NGM282-1006). Bile acid homeostasis is regulated through gene expression 
of the CYP7A1 enzyme in hepatocytes by bile-acid–dependent synthesis of FGF15/19 in the 
intestine. In vitro studies have demonstrated that NGM282 binds to human hepatocytes with 
affinity similar to that of FGF19 (Studies 11-MP-NGM282-1002 and 
13-MP-NGM282-1005). Additionally, NGM282 specifically inhibits only CY7A1 activity 
without inhibiting other bile-acid–synthetic enzymes (Study 12-MP-NGM282-1006). In vivo 
studies have shown that systemic administration NGM282 can potently and rapidly suppress 
the expression of the Cyp7a1 gene in db/db mice (Study 11-PD-NGM282-1001). NGM282 

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has demonstrated a dose-dependent decrease of Cyp7a1 levels. Consistent with reduction in 
Cyp7a1 levels, serum C4 levels were also reduced in the 28-day monkey toxicology study 
(Study 11-TX-NGM282-1002) and 26-week toxicology study in monkeys 
(Study 13-TX-NGM282-1004). Significant reductions in serum C4 levels were also observed 
after administration of NGM282 in normal volunteers (Study 12-0101). 
NGM282 has also been evaluated in two distinct animal models of NASH. Adeno-associated 
virus (AAV)–mediated delivery of NGM282 transgenes into FXR-deficient mice 
demonstrated improvement in the histologic, biochemical, and fibrogenic biomarkers 
associated with NASH-related hepatic injury (Study 13-PD-NGM282-1007). Similarly, AAV 
administration of NGM282 in the STAMTM model of NASH in mice showed a significant 
reduction in steatosis, inflammation, ballooning, and overall body weight versus placebo 
(data on file). 
The safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of NGM282 
have been studied in a blinded, placebo-controlled, single-ascending-dose 
(SAD)/multiple-ascending-dose (MAD) study in normal subjects (Study 12-0101). NGM282 
or placebo was administered to 119 normal subjects as a daily SC injection in escalating 
doses of 0.1–30 mg in the SAD module and 0.1–20 mg in the MAD module. Multiple-dose 
PK were consistent with single-dose PK parameters, with no evidence of drug accumulation. 
NGM282 was safe and well tolerated with no serious adverse events (SAEs) or clinically 
relevant laboratory abnormalities. Mild to moderate injection-site reactions (ISRs) were the 
most common drug-related adverse events (AEs), observed mainly with higher doses and 
larger injection volumes. NGM282 had a favorable safety profile and highly predictable PK 
that support once-daily dosing.  
NGM282 has recently been evaluated in 80 patients with T2D, many of whom have 
presumptive NASH (Study 13-0102). NGM282 was administered for 28 consecutive days in 
patients randomized into one of the four treatment conditions (NGM282 at doses of 2, 5, or 
10 mg; or placebo). Dose-dependent improvement in insulin sensitivity and body weight, as 
well as decreases in triglycerides and ALT, were observed compared to placebo as well as a 
trend to a decrease in fasting blood glucose and a slight increase in HDL. Total cholesterol 
and low-density lipoprotein (LDL) were modestly increased with NGM282 at Day 28. This 
increase appears to represent an acute change at Day 14, followed by a decrease from Day 14 
to Day 28, consistent with a mitigation of this rise over time. C4 was suppressed by > 95% in 
subjects treated with the 2- and 5-mg doses. NGM282 was well tolerated with no SAEs or 
safety signals observed during the study. Mild to moderate GI symptoms (nausea, loose 
stools) as well as mild ISRs were the most frequently reported AEs, both of which were seen 
more frequently at the higher doses. In general, NGM282 was well tolerated in a population 
with characteristics similar to those in patients with NASH. 

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Based on the identified activities in animal models as well as the PK and favorable safety and 
tolerability profiles in normal volunteers and T2D patients, NGM282 represents a potentially 
important therapeutic option for the treatment of NASH through enhanced FGF19 signaling.  
5.2 
Nonclinical Studies 
NGM has completed a series of in vitro and in vivo nonclinical studies supportive of the 
clinical development of NGM282 in patients with NASH. Please refer to the Investigator’s 
Brochure (IB) for additional information on these studies. 
5.2.1 
Nonclinical Safety Assessment 
The nonclinical safety of NGM282 has been assessed in general toxicity studies in CD-1 
mice and cynomolgus monkeys for up to 26 weeks of treatment and in embryo–fetal toxicity 
studies in CD-1 mice and New Zealand White (NZW) rabbits. NGM282 was 
pharmacologically active in the mouse and monkey for up to 26 weeks of treatment. 
In the monkey, NGM282 was clinically well tolerated as clinical signs were limited to 
increased hair loss at doses ≥ 0.1 mg/kg and slight reductions in body-weight gain at 1 mg/kg 
at 26 weeks of treatment. In the mouse, NGM282 produced transient clinical signs (e.g., 
hypoactivity or partial eye closure) at doses ≥ 1 mg/kg that were not dose limiting and 
resolved with continued treatment for up to 26 weeks. In the mouse, microscopic findings 
were limited to the liver (minimal to moderate hepatocellular hypertrophy) that was 
associated with slight increases in albumin, total protein, and liver weight. These changes 
were not considered adverse and were reversible.  
In the mouse and rabbit, NGM282 did not produce any adverse effects on embryo–fetal 
development at the highest doses tested (10 mg/kg). In the rabbit, the 
no-observed-adverse-effect level (NOAEL) was 1 mg/kg due to maternal toxicity associated 
with body-weight gain reduction and associated reduction in fetal uterine weight at 10 mg/kg. 
Based on the cumulative nonclinical safety profile of NGM282 for up to 26 weeks of 
treatment, the NOAELs in the mouse and monkey were determined to be 1 and 3 mg/kg, 
respectively. A sufficient safety margin exists for NGM282 at the proposed maximal clinical 
dose of 6 mg (0.0864 mg/kg) where estimated exposure is estimated to be 2- or 14-fold 
below that at the NOAELs in the mouse or monkey, respectively (see Table 1). 

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Table 1. 
Estimated Safety Exposure Margin of NGM282 
Nonclinical 
Species 
NOAEL 
(mg/kg) a 
Plasma AUC 
(hr  ng/mL) b 
Exposure Margin Relative to 
Maximum Human Therapeutic Dose c 
Monkey 
1 
6610 
̴ 14X 
Mouse 
3 
1062 
̴ 2X 
AUC = area under the concentration–time curve; hr = hour; NOAEL = no-observed-adverse-effect level. 
a Determined from the 6-month chronic toxicity studies. 
b Systemic exposure at Day 1 after a single dose was used as the most conservative estimate of exposure given 
the presence of anti-drug antibody formation with repeat dosing in animals leading to drug accumulation 
(plasma AUC 7-fold above Day 1 levels).  
c Based on a maximal therapeutic dose of 6 mg (0.0864 mg/kg based on a 70-kg patient) where plasma AUC is 
projected to be 482 hr  ng/mL (Study 12-0101). 
 
5.3 
Clinical Studies 
To date, NGM has completed a Phase 1 clinical study in healthy volunteers and Phase 2 
clinical studies in T2D and primary biliary cirrhosis (PBC) supportive of the clinical 
development of NGM282 in patients with NASH. Additionally, blinded safety data from the 
ongoing Phase 2 clinical trial in NASH patients are also available to further support the 
open-label single-blind cohort. Please refer to the IB for additional detailed information on 
these studies.  
5.4 
Rationale for Dose Selection of NGM282 for NASH 
The doses selected for the Phase 2 study are supported by both the nonclinical and clinical 
data generated to date. The dose range for the first-in-human Phase 1 clinical trial  
(0.1–30 mg) was based on a broad approach to dose calculation considering the 
pharmacology of FGF19, beyond sole reliance on the NOAEL obtained in the GLP 28-day 
toxicology program. The dose range also took into consideration safe starting-dose principles 
for first-in-human administration as outlined in both FDA and CHMP Guidance. 
Dose-proportional changes in PK parameters were observed with both single and multiple 
dosing in the Phase 1 study, consistent with predictions from animal models. All doses were 
safe and well tolerated, thus establishing the initial clinical safety of this dose range. 
The proposed doses of 0.3, 1, 3, and 6 mg for evaluation in the double-blind as well as the 
single-blind cohorts are based on a cumulative broad approach to dose calculation 
considering the pharmacology of FGF19 in NASH, clinical data from normal volunteers and 
patients with T2D, and exposure safety margins obtained in the GLP 26-week toxicology 
program relative to the clinical doses proposed. The proposed doses for both cohorts are 
within the current safety margins in both monkeys and mice (Table 1). The drug exposure is 
comparable between normal volunteers and T2D patients and, therefore, expected to be 
comparable in the NASH population. 

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The selection of the 0.3, 1, 3, and 6 mg doses is further supported by the efficacy, safety, and 
tolerability observed in the T2D study in which NGM282 doses of 2, 5, or 10 mg were 
evaluated. The T2D study patients represent a population similar to the NASH population 
expected to be enrolled in the NASH Phase 2 study. In patients with T2D, doses > 2 mg are 
associated with greater decreases in body weight, fasting blood glucose, triglycerides, HDL, 
and ALT, all of which are parameters associated with potential therapeutic activity in NASH. 
The subsequent decreases in LDL at Day 28 after initial increases at Day 14 are greater with 
doses > 2 mg. A trend toward increased frequency and severity of GI symptoms and ISRs in 
patients treated with 10 mg was noted; therefore, lower doses were selected for tolerability. 
Lastly, bile acid synthesis as measured by suppression of C4 levels is greatest at doses of 
3 mg based on the data from the Phase 1 normal volunteer study. Furthermore, C4 was 
suppressed by > 95% in T2D patients treated with the 2- and 5-mg doses of NGM282. Based 
on the above data, the selected doses should allow a balance of optimizing biologic activity 
versus safety and tolerability in the studied population. 
The selection of the lower doses (0.3 mg and 1 mg) for study in the open-label single-blind 
cohort was based on the robust results of the double-blind cohort demonstrating comparable 
improvements in the non-invasive markers of NASH at 3 mg and 6 mg, with improved 
tolerability with the 3 mg dose. Subjects enrolled in the open-label single-blind cohort 
received 0.3 mg or 1 mg for 12 weeks in order to establish a minimally effective dose, based 
on non-invasive measures of liver fat, inflammation, and fibrosis. Additionally, based on the 
rapidity of the treatment effect demonstrated with 3 mg and 6 mg, 
 
 
This demonstrated significant 
improvement in both NAS and fibrosis scores with 3 mg for 12 weeks. In order to assess the 
histologic response and utility of 1 mg, a 12-week biopsy dosing group (Group 4) is ongoing.  
The selection of the 1 mg dose for the placebo-controlled 24-week histology cohort is based 
on a comparative evaluation of the histologic response, non-invasive parameters, and safety 
in the previous cohorts in Study 15-0105. Preliminary data from the first 10 subjects at 
12 weeks from the 1 mg histology dosing group (Group 4) demonstrated comparable changes 
in non-invasive parameters (MRI-PDFF, LMS and ALT) and histology to the 3 mg histology 
dosing group (Group 3). Additionally, there were no new safety signals observed in either 
cohort. The 1 mg cohort had fewer injection site reactions as well as less persistent GI 
symptoms. Therefore, the 1 mg dose was selected to move forward into the placebo-
controlled 24 week histology cohort based on the assessment of comparative risk benefit of 
the 1 mg and 3 mg doses. 

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5.5 
Rationale for the Use of Rosuvastatin for Lipid Management in 
NGM282-treated Subjects 
NGM282 specifically inhibits CYP7a similar to FGF19 through binding to  
FGFR4c–β-klotho complexes causing a potent and rapid suppression of cholesterol 
metabolism and a subsequent decrease in bile acid synthesis. The biologic activity of 
NGM282 is similar to FGF19 and has been shown to cause an increase in serum levels of 
total cholesterol and LDL-C to a varying degree in cynomolgus monkeys (data on file) as 
well as in normal volunteers (Study 12-0101) and T2D patients (Study 13-0102). More recent 
data from the blinded safety review in Study 15-0105 demonstrated similar elevations in 
NASH patients. The clinical outcomes associated with long-term elevations in LDL-C 
associated with NGM282 are unknown. However, the evaluation of lipid-lowering therapies, 
in particular statins, is warranted given the increased cardiovascular risk associated with the 
NASH patient population. The ability of statin therapy to mitigate FGF-19–mediated 
increases in LDL-C has been demonstrated in both primate and human studies. Recent data 
from obese insulin-resistant primates demonstrated that the increase in LDL-C levels seen 
with NGM282 was substantially reduced with rosuvastatin to pre-treatment baseline levels 
(data on file). OCA is an FXR agonist shown to cause increases in LDL-C in NASH patients 
(Neuschwander-Tetri 2014). The use of statins was demonstrated to be safe and well 
tolerated in this population receiving OCA; in addition, LDL-C levels decreased to near 
baseline. The co-administration of OCA and statins is currently being studied in a 
randomized, double-blinded clinical trial (NCT02633956). Therefore, the impact of statin 
co-therapy with NGM282-induced LDL-C elevations is warranted. Rosuvastatin was selected 
for its potency and demonstrated clinical effect on cardiovascular outcomes. Doses of 20 and 
40 mg will be studied in order to evaluate any dose-dependent differences in activity in 
NGM282-treated subjects.  
5.6 
Rationale for MRI-PDFF, 
 Assessments 
Improvements in steatosis have been demonstrated to be a key component of a therapeutic 
response and resolution of NASH. NGM is utilizing a change in total liver fat content of at 
least 5% as measured by magnetic resonance imaging–proton density fat fraction 
(MRI-PDFF) as a primary efficacy endpoint in the Phase 2 Study 15-0105 in NASH patients. 
MRI-PDFF has been determined to be more sensitive than histology for detecting changes in 
liver fat content in several natural history and therapeutic trials (Meisamy 2011). 
Additionally, it is non-invasive and provides quantitative estimates of fat content throughout 
the entire liver and is less operator dependent and more sensitive than either ultrasound or CT 
scan (Kang 2011, Permutt 2012). A reduction of at least 5% in absolute liver fat and 29% 
relative reduction in liver fat was associated with histologic improvements in NASH and is 
currently being utilized in several completed and ongoing clinical studies in NASH 
(Patel 2016). The double-blind cohort in Study 15-0105 is measuring change in liver fat by 

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MRI-PDFF at Baseline and Week 12 to assess the primary treatment effect. Data from T2D 
patients treated with NGM282 who had elevated liver enzymes demonstrated a rapid 
reduction in both liver enzymes and C4 after initiating treatment. Based on the rapid biologic 
activity observed, an additional on-treatment MRI has been added to the open-label 
single-blind cohort at Week 6 in order to assess the kinetics of fat loss at mid-treatment. An 
off-treatment MRI at Week 18 (EOS) has been added to this cohort as well in order to assess 
the reversibility of fat loss after stopping therapy. These effects will be further assessed over 
an extended duration in the placebo-controlled 24-week histology cohort with MRI-PDFF 
assessments collected at Screening and Weeks 6, 12, 24 (EOT), and 30 (EOS).  
 
 
 The software uses 
the images of the liver to calculate parameters that have been shown to correlate with 
histological measures of steatosis, hepatic iron overload, and fibrosis of the liver 
(Banerjee 2014). Additionally, a Liver Inflammation Fibrosis (LIF) score and corrected cT1 
valueare also calculated, both of which have been correlated to liver histology as well as 
predicting liver-related outcomes (Banerjee 2014, Pavlides 2016, Perspectum Diagnostics, 
data on file). 
 
 
 There are no current imaging techniques 
that can directly detect the specific stage of fibrosis. Most attempt to detect fibrosis indirectly 
using proposed biomarkers which include: stiffness, diffusion, perfusion, metabolites, and 
image texture with the leading biomarker being liver stiffness (Younossi 2017). 
 
 
 
 
 
5.7 
Rationale for a Liver Biopsy at Weeks 12 or 24 
Liver biopsy remains the gold standard for assessing treatment effect in NASH patients, as 
measured by a resolution of steatohepatitis and/or an improvement in fibrosis. However, 
several non-invasive imaging technologies and biochemical markers have also correlated 
with improvements in liver histology. MRI-PDFF is a highly sensitive measure of steatosis 
with decreases in absolute and relative liver fat of 4.1% and 29.3%, respectively, correlating 
to > 2 point improvement in NAS after 24 weeks of ezetimibe (Patel 2016). On-treatment 
decline in ALT was associated with the resolution of NASH and no worsening of fibrosis in 
patients treated with elafibranor for 52 weeks (Ratziu 2016a). Similarly, a decrease in 

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triglycerides correlated with resolution of NASH after 96 weeks of pioglitazone or vitamin E 
(Corey 2015). Increased classic-pathway bile acid synthesis is associated with increased 
NASH severity and fibrosis (Bechmann 2013; Lake 2013). Decreases in bile acid synthesis, 
as measured by C4 levels, is observed with FGF19 activity seen with NGM282 and other 
investigational therapies (Marschall 2012, Djedjos 2016).  
NGM282 was studied in 81 patients with type 2 diabetes (many with presumptive NASH) for 
28 days at doses of 2, 5, or 10 mg versus placebo (Study 13-0102). Rapid and 
dose-dependent improvements in ALT, triglycerides, and C4 were observed compared to 
placebo, supportive of further evaluation in NASH. An analysis of the double-blind cohort of 
Study 15-0105 was performed on 43 subjects completing 12 weeks of treatment 
(Harrison 2017). Significant reductions in both absolute and relative liver fat were observed 
after only 12 weeks compared to placebo, with the majority of subjects normalizing liver fat 
content. ALT levels also declined rapidly, with significant reductions observed as soon as 
Week 2 and over 50% of subjects normalizing ALT by Week 12. Significant reductions of 
ALT, C4, and other key biochemical parameters associated with histologic response were 
also observed in NGM282-treated patients. In addition to the results of the non-invasive 
efficacy data, 12-week histology has also been evaluated in the 3-mg cohort using the 
FDA-accepted endpoints. Preliminary 12-week histologic response data demonstrated 50% 
of subjects had a 1-stage improvement in fibrosis with no worsening of NASH or resolution 
of NASH with no worsening of fibrosis. Histology assessments will be conducted at 
Week 12 in the open-label single-blind dosing Groups 3 and 4 and at Week 24 in the 
placebo-controlled 24-week histology cohort. The clinical data from these cohorts will 
provide information on the long-term safety and efficacy (histological and noninvasive) of 
NGM282 and support the late-stage development of NGM282 for treatment of NASH with 
fibrosis. 
Although there are currently no approved therapies for the treatment of NASH, several 
late-stage compounds have demonstrated modest improvements in the resolution of NASH 
and/or fibrosis as well as decreases in key markers that correlate with these histologic 
changes. However, the treatment duration to achieve these changes is 24–72 weeks 
(Sanyal 2010, Neuschwander-Tetri 2014, Patel 2016, Ratziu 2016b, Sanyal 2016, 
Loomba 2016). The changes in MRI-PDFF, ALT, triglycerides, and C4 are significantly 
more rapid and of a greater magnitude by Week 12 versus other therapies for longer 
treatment periods. Therefore, early changes in histology may be observed supporting an early 
time-point for post-treatment liver histology assessment.  
The primary objective of this additional histologic assessment in dosing Groups 3 or 4 of the 
open-label single-blind cohort and the placebo-controlled 24-week histology cohort is to 
evaluate if the rapid changes in steatosis and biomarkers consistent with the resolution of 
observed NASH translates to similar clinically meaningful changes in liver histopathology. 
Additional correlative analyses will be performed between liver histology and the various 

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liver imaging studies and exploratory serum biomarkers collected during the study. The 
results of these data will be used to support the development of non-invasive tools for 
monitoring treatment. Additionally, these results may also be useful for predicting early 
response and stopping rules.  
6 
Study Objectives 
The objectives of this study are as follows: 
Primary Objective:  
• Evaluate the treatment effect of NGM282 on absolute liver fat content as measured 
by MRI-PDFF in patients with histologically confirmed NASH. 
 
Secondary Objectives: 
• Assess the safety and tolerability of NGM282 in patients with NASH with up to 
24 weeks of treatment with NGM282. 
• Evaluate the percentage change in absolute liver fat content at End of Treatment 
EOT. 
o In the open-label single-blind cohort, additional evaluations will be performed 
at 6 and 18 weeks. 
o In the placebo-controlled 24-week histology cohort, additional evaluations 
will be performed at 6, 24, and 30 weeks. 
• Evaluate the percentage of normalization for liver fat content at EOT. 
• Evaluate the change in liver fat content response rate as defined by a ≥ 5% decrease 
in absolute liver fat content. 
• Evaluate the absolute and percentage changes from Baseline to EOT as well as the 
percentage of normalization of the following parameters: ALT, AST, triglycerides, 
bilirubin (total and direct), and GGT. Percentage of normalization will also be 
investigated for a clinically meaningful threshold for triglycerides. 
• Evaluate the absolute and percentage changes from Baseline to EOT of the following 
(if collected as part of the cohort): 
o Total cholesterol, HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), 
triglycerides, and lipoprotein particles  
 In addition, evaluate the absolute and percentage change from Baseline 
to EOS of the above lipid parameters in the open-label single-blind 
cohort. 
o 
 

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o Fasting blood glucose, insulin levels, 
 
, and homeostasis model assessment–estimated insulin resistance 
(HOMA-IR) 
o Pro-C3 and ELF score (Placebo Controlled 24 Week Histology Cohort) 
o Body weight, body mass index (BMI), and waist circumference 
o C4 and serum bile acids 
o Bile-mediated absorption as measured by vitamin D, International Normalized 
Ratio (INR), and fecal fat content 
 
• Evaluate the liver histologic response in Placebo Controlled 24 Week Histology Cohort 
o Improvement in liver fibrosis by ≥ 1 stage by NASH Clinical Research Network 
(CRN) criteria with no worsening of steatohepatitis 
o Resolution of NASH (defined as an NAS score of 0 or 1 for inflammation and 
0 for ballooning) with no worsening of fibrosis as determined by the NASH 
CRN criteria.   
• Evaluate the exposure of NGM282 in patients with NASH.  
o In the double-blind and placebo-controlled 24-week histology cohorts, 
NGM282 exposure will be compared to placebo at 2 hours post-dose at Day 1 
and EOT and pre-dose at all on-treatment study visits. 
o In the open-label single-blind cohort, NGM282 exposure will be evaluated at 
2 hours post-dose at Day 1 and EOT and pre-dose at all on-treatment study 
visits. Additional PK samples will be collected at Baseline and 1, 2, 4, 8, and 
12 hours post-dose on Day 1 and Week 6 in a subset of subjects in each 
dosing group. 
o Exposure of all doses from all cohorts will be compared to each other as well 
as to exposure in other study populations treated with NGM282 
(Studies 12-0101, 13-0102, 13-0103, 14-0104, and 15-0106). 
• 
Evaluate the efficacy and safety of rosuvastatin administered in response to increases 
in total cholesterol and LDL-C from NGM282 treatment (open-label single-blind and 
placebo-controlled 24-week histology cohorts only). 
• Compare the dose-related changes in the safety, tolerability, PK, and PD parameters 
within and across the double-blind and open-label single-blind cohorts. 
 
Exploratory Objectives 
The exploratory objectives of this study are: 
• 
  
 
 

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requested to undergo MRI performed during Screening and at Week 1 (EOT) Early 
Withdrawal visit.  
In the open-label single-blind cohort, up to 100 patients (25 per dosing group) will be 
enrolled from ~6–8 U.S. sites. Subjects will be required to meet enrollment criteria similar to 
those of the double-blind cohort with the exception of the following, specifically defined in 
protocol Section 8.1.2: 1) historical biopsy window extended to 12 months; 2) limitations on 
the use of glucagon-like peptide-1 (GLP1) agonists; 3) glycated hemoglobin (HbA1c) level 
≤ 9.5%; 4) LDL levels at Screening need to be ≤ 165 mg/dL; 5) exclusion of specific 
lipid-lowering therapies prior to and during study period; 6) no contraindications to receiving 
statins. The single-blind cohort is not randomized. At Day 1 eligible patients will be 
sequentially enrolled into the study and categorized as either statin-naïve versus statin 
experienced with no more than 8 statin experienced subjects within each dosing group. 
Subjects will be enrolled sequentially initially into the dosing Group 1 and enrollment will be 
continuous within the dosing group. Sequencing of the subsequent 2 dosing groups will be 
based on PD and safety parameters from dosing Group 1. The subsequent 2 dosing groups 
may run in parallel. A fourth optional dosing group may be conducted based on the 
safety/tolerability, imaging data, and histology (dosing Group 3 only) data from the prior 
3 dosing groups. Dosing group sequence and individual subject treatment assignment will be 
blinded only to the study subjects throughout the study period. 
The first dose of NGM282 (Day 1) and doses at the Weeks 2, 4, 6, 8, and 12 study visits will 
be self-administered in the clinic, with all other doses throughout the treatment period 
self-administered at home. Self-administration of NGM282 should occur in the morning for 
every dose in both the clinic and at home. Subjects will return to the clinic on Weeks 2, 4, 6, 
and 8 for on-treatment assessments and to receive weekly NGM282 study-drug kits. LDL-C 
will be evaluated at Weeks 2, 4, and 8 in all subjects for possible increases in lipid levels 
associated with NGM282 administration. Rosuvastatin will be started in subjects meeting 
specific LDL-C level criteria. The specific dosing and administration of rosuvastatin will be 
based on whether the subject is statin naïve versus statin experienced and LDL-C levels at 
Weeks 2, 4, and 8. The dosing algorithms are specifically outlined in Section 10.4 of the 
study protocol. Bottles of rosuvastatin tablets will be dispensed at Weeks 2, 4, and 8, 
depending on observed lipid levels and dosing algorithm in Section 10.4. Week 12 will be 
the EOT clinic visit and subjects will return to the clinic at Week 18 (or 6 weeks after last 
dose) for an EOS follow-up visit. Subjects are required to undergo MRI performed during 
Screening and at Weeks 6, 12 (EOT)/Early Withdrawal, and 18 (EOS) visits. 
Dosing Groups 3 or 4 will have two other assessments performed to assess liver histology in 
addition to MRI-PDFF. LiverMultiScanTM will be performed during the MRI assessments at 
the same time as the MRI-PDFF assessments (Screening and Weeks 6, 12, and 18). 
An additional post-treatment liver biopsy will be performed at Week 12. The purpose of this 
biopsy is to assess early changes in liver histopathology (including changes in the NAS, 

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resolution of NASH, and changes in fibrosis) and compare and correlate to the liver imaging 
studies and key serum biomarkers collected during the study. The historical liver biopsy 
window for this subset of subjects will be 3 months prior to Screening. Subjects who wish to 
participate in the study but do not agree to the second biopsy will be allowed to Screen and 
enroll for other dosing groups if still open and they meet enrollment criteria. Dosing Group 4 
will be initiated only after all subjects in Cohort 3 have been enrolled and a minimum of 
10 subjects have completed 12 weeks of treatment in order to do a preliminary review of key 
data.  
In the placebo-controlled 24-week histology cohort, up to 75 subjects (50 active at a single 
dose of NGM282; 25 placebo) will be enrolled from ~10 U.S. sites and treated for 24 weeks 
with a 6-week safety follow-up. Subjects will be required to meet enrollment criteria similar 
to those of the open-label single-blind cohort as specifically defined in protocol Section 8.1.1 
with the exception of the following: 1) only subjects with Stages 2 and 3 fibrosis at Screening 
will be enrolled. At Day 1 eligible subjects will be randomized into the study and stratified as 
either fibrosis stage 2 or 3.  The dose of NGM282 to be studied will be 1 mg based on 
comparative evaluation of the safety, non-invasive efficacy parameters, and histology from 
the completed 3 mg 12-week histology dosing group (Group 3) and preliminary data from a 
subset of subjects from the ongoing 1 mg 12-week histology dosing group (Group 4) in the 
open-label single-blind cohort. The active dose selection for this cohort will be blinded to the 
study site and subjects throughout the study period. 
The first dose of NGM282 (Day 1) and doses at Weeks 2, 4, 6, 8, 12, 18, and 24 study visits 
will be self-administered in the clinic, with all other doses throughout the treatment period 
self-administered at home. Self-administration of NGM282 or placebo should occur as close 
as possible to the same time each day for every dose.  Subjects will return to the clinic on 
Weeks 2, 4, 6, 8, 12, 18 and 24 for on-treatment assessments and to be dispensed NGM282 
or placebo study-drug kits through Week 18.  LDL-C (LDL-direct may be used if LDL-C 
was not able to be analyzed) will be evaluated at Weeks 2, 4, 8, and 12 in all subjects for 
possible increases in lipid levels associated with NGM282 or placebo administration. 
Rosuvastatin will be started in subjects meeting specific LDL-C level criteria. The specific 
dosing and administration of rosuvastatin will be based on whether the subject is statin naïve 
versus statin experienced and LDL-C levels at Weeks 2, 4, and 8. A decision about possible 
second-line lipid-lowering therapy with ezetimibe will be made on a case by case basis for 
subjects that have not achieved an adequate response or are unable to tolerate rosuvastatin.  
Bottles of rosuvastatin tablets will be dispensed to all subjects initially and instructions to 
initiate dosing are dependent on observed lipid levels according to the dosing algorithm in 
Section 10.4. Week 24 will be the EOT clinic visit and subjects will return to the clinic at 
Week 30 (or 6 weeks after last dose) for an EOS follow-up visit. Subjects are required to 
undergo MRI performed during Screening and at Weeks 6, 12, 24 (EOT)/Early Withdrawal, 
and 30 (EOS) visits. 

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This cohort will have two other assessments performed to assess liver histology in addition to 
MRI-PDFF.  
 
 An additional 
post-treatment liver biopsy will be performed at Week 24. The purpose of this biopsy is to 
assess changes in liver histopathology (including changes in the NAS, resolution of NASH, 
and changes in fibrosis) and compare and correlate to the liver imaging studies and key 
serum biomarkers collected during the study. 
7.1 
Study-Stop Criteria 
The entire study or a single dosing arm may be discontinued or not initiated at the discretion 
of the Sponsor based on the occurrence of the following: 
• AEs with respect to their nature, frequency, severity, and/or duration 
• Medical or ethical reasons affecting the continued performance of the study 
• Difficulties in the recruitment of patients 
• Cancellation of drug development 
The entire study will be discontinued by the sponsor if there are three or more related 
Grade 3 or Grade 4 treatment-emergent adverse events (TEAEs) of the same Common 
Terminology Criteria for Adverse Events (CTCAE) category. 
8 
Enrollment Criteria 
8.1 
Double-blind, Open-label Single-blind and Placebo-controlled 
24 Week Histology Cohorts 
8.1.1 
Inclusion Criteria 
Patients who meet the following criteria may be included in the study: 
1.   Males and females between 18 and 75 years of age (except self-identified of Asian 
descent), able to comprehend and willing to sign an Informed Consent Form (ICF). 
2. 
Histologically confirmed NASH diagnosis as defined by the NIH NASH Clinical 
Research Network (see Appendix A, Kleiner 2005) and liver biopsy criteria outlined 
below.  A historical biopsy is acceptable if performed within the required time period 
and tissue slides are available for a qualified pathology read. 
Double-Blind Cohort: 
a. NAS of at least 4 with 1 point in each component 
b. Histologic evidence of fibrosis without cirrhosis 
i. 
 Fibrosis stage 1-3  
c. Liver biopsy within 6 months of Screening.  
Open-Label Single Blind Cohort: 

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a. NAS of at least 4 with 1 point in each component 
b. Histologic evidence of fibrosis without cirrhosis 
i. 
Fibrosis stage 1-3  
c. Liver biopsy within 12 months of Screening.  
i. 
Dosing Groups 3 or 4 must have a liver biopsy within 3 months of 
Screening in order to serve as the baseline comparison for the 
additional EOT biopsy. 
Placebo-Controlled 24 Week Histology Cohort: 
a. NAS of at least 4 with 1 point in each component 
b. Histologic evidence of fibrosis without cirrhosis 
i. 
Fibrosis stage 2-3  
c. Liver biopsy within 3 months of Screening in order to serve as the baseline 
comparison for the additional EOT biopsy. 
3. 
Total liver fat content of ≥ 8% as measured by MRI-PDFF (MRI may be used for up to 
8 weeks from the date of the original scan, including use for re-screened subjects) 
4. 
Insulin-resistant or stable T2D  
Double-Blind Cohort: 
a. Stable T2D is defined as HbA1c ≤ 8.5% at Screening. 
b. Diabetes medications: require a stable regimen for at least 3 months prior to 
Day 1 and throughout the study. 
c. Insulin resistance will be based on fasting insulin level ≥ 10uIU/mL. 
Open-Label Single Blind: 
a. Stable T2D is defined as HbA1c ≤ 9.5% at Screening. 
b. Diabetes medications (except GLP1 agonists):  require a stable regimen for at 
least 3 months prior to Day 1 and throughout the study.  
c. GLP1 agonists: require a stable regimen for at least 12 months prior to Day 1 
and throughout study 
d. Insulin resistance will be based on fasting insulin level ≥10uIU/mL. 
Placebo-Controlled 24 Week Histology Cohort: 
Patients with T2D or insulin resistance will be allowed to enroll under the following 
conditions listed below and patients who do not have T2D or insulin resistance can be 
enrolled as long as all other criteria are met. 
 
a. HbA1c ≤ 9.0% at Screening 
b. Patients taking diabetes medications (except GLP1 agonists) require a “stable” 
regimen for at least 3 months prior to Day 1 and throughout study.  
i. GLP1 agonists and pioglitazone: require a stable regimen for at least 
12 months prior to Day 1 and throughout the study.  

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ii. Stable insulin dosing is defined as reasonable dosage adjustments to 
maintain glucose control. 
5. 
Other therapies for NAFLD or NASH: requires a stable regimen for at least 3 months 
prior to the Screening biopsy of record and throughout the study. May include vitamin 
E, milk thistle, thiazolidinediones and pentoxifylline. 
Double-Blind Cohort: 
Includes statins. 
Open-Label Single Blind and Placebo Controlled 24 Week Histology Cohorts: 
Includes statins if the conditions below are met. Other therapies may include 
vitamin E (> 800 IU Placebo cohort only), milk thistle, thiazolidinediones (open-
label, single-blind only) or pentoxifylline.   
a. Patient can be defined as statin naïve or experienced at Screening based on 
the following definitions: 
i. 
Statin-naïve: no administration of statins within 3 months prior to 
enrollment. 
ii. 
Statin experienced: administration of < 50% of the maximal dose 
of current statin therapy. 
b. Requires a stable regimen for at least 3 months prior to Screening through 
Week 2. 
The following are the acceptable daily doses of approved statin therapies, including 
combination preparations of statins and other lipid lowering agents.  Also listed under 
Concomitant Medications in Section 9.7.  
• Atorvastatin: < 40 mg/d 
• Fluvastatin: < 40 mg/d 
• Lovastatin: < 40 mg/d (immediate release), < 30 mg/d (extended release) 
• Pitavastatin: < 2 mg/d 
• Pravastatin: < 40 mg/d 
• Rosuvastatin: < 20 mg/d (Note: must be < not < 20 mg/d) 
• Simvastatin: < 40 mg/d 
6. 
The following liver enzyme parameters must be met at Screening: 
a. ALT and AST < 250 IU/L 
b. Abnormal ALT defined as: ≥ 30 IU in males and ≥ 19 IU in females 
d. AST ≥ 30 IU/L except for patients with a historical biopsy within 3 months of 
screening with NAS of at least 4 with 1 point in each component and fibrosis 
stage 2 or 3 (Placebo-Controlled Cohort only) 
 
7. 
The following additional laboratory parameters must also be met at Screening: 

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a. Total bilirubin must be within normal range.  For patients diagnosed with 
Gibert’s Syndrome, please contact medical monitor/designee 
b. INR ≤ 1.3 (in the absence of warfarin or other anticoagulant therapy) 
c. Creatinine clearance ≥ 90 mL/min as calculated by Cockcroft-Gault equation  
d. Alpha fetoprotein (AFP) < 100 ng/mL 
e. LDL C ≤ 185 mg/dL (except Double-blind cohort and ≤ 165 mg/dL for the 
Open-Label Single Blind ) 
f. LDL-C must also be ≥ 50 mg/dL for statin naïve patients (Placebo cohort 
only) 
g. Platelet count must be within normal limits 150-450 K/uL (Placebo-
Controlled Cohort only) 
8. 
Female patients must be of non-childbearing potential defined as women who have had 
a hysterectomy, bilateral oophorectomy, medically documented ovarian failure, or are 
documented postmenopausal (follicle stimulating hormone > 40 mIU/mL). 
9. 
Female patients of childbearing potential defined as including women < 55 years of age 
with 2 years of amenorrhea (absence of menstruation) must have a negative serum 
pregnancy test at Screening and urine pregnancy test at the Day 1 visit prior to dosing. 
10. Female patients of childbearing potential and male patients with a female partner of 
childbearing potential must agree to consistent and adequate birth control from 
Screening to 30 days after the last dose of study medication.  
One of the following forms of contraception is required and male patients must also use 
a condom. 
a. Hormone-containing contraceptive 
b. Intrauterine device with a failure rate < 1% per year 
c. Cervical cap or diaphragm with spermicidal agent 
d. Sterilization (tubal ligation or vasectomy) 
11. Able and willing to comply with the dosing instructions for study-drug administration 
and able to complete the study schedule of assessments.  
8.1.2 
Exclusion Criteria 
The following criteria will exclude patients from the study: 
1. 
Clinically significant acute or chronic liver disease of an etiology other than NASH 
2. 
Evidence of drug-induced steatohepatitis secondary to amiodarone, corticosteroids, 
estrogens, methotrexate, tetracycline, or other medications known to cause hepatic 
steatosis 
3. 
History or presence of cirrhosis (compensated or decompensated) as determined by 
histology, relevant medical complications, and/or laboratory parameters 

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4. 
Prior liver transplantation 
5. 
Any acute cardiovascular event (e.g. myocardial infarction, stroke, severe arrhythmia or 
hospitalization for any cardiac related event) or evidence of active cardiovascular 
disease within 6 months of Screening 
6. 
History of bypass or bariatric surgery or planned procedure during the study period.  
Removal of a gastric balloon or lap band is permitted if surgery performed within 6 
months prior to Day 1. 
7. 
Type 1 diabetes  
8. 
History of clinically significant unstable or untreated illness or any other major medical 
disorder that may interfere with patient treatment, assessment, or compliance with the 
protocol 
9. 
Any contraindication or inability to obtain an MRI  
10. Inability to obtain or any contraindication to liver biopsy (if a historical biopsy with 
viable tissue slides are not available within the required time period) 
11. Screening ECG with clinically significant abnormalities as determined by the 
Investigator 
12. Positive for HBsAg, anti-HIV, or anti-HCV plus HCV-RNA. Patients who are 
anti-HCV positive but HCV-RNA negative (secondary to treatment or viral clearance) 
are eligible as long as there is evidence of viral negativity for a minimum of 12 weeks.  
13. History of malignancy diagnosed or treated within 2 years (recent localized treatment of 
squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in 
situ is allowed if appropriately treated prior to Screening); patients under evaluation for 
malignancy are not eligible. 
14. Clinically-relevant drug or alcohol abuse within 12 months of screening. A positive 
drug screen will exclude patients unless it can be explained by a prescribed medication; 
the diagnosis and prescription must be approved and documented as such by the 
Investigator. 
15. Use of any prohibited concomitant medications as described in Section 9.7 prior to 
Day1. 
16. Prior participation in a clinical trial of NGM282 
Double Blind Cohort:  
Prior participation in a clinical trial of NGM282 is excluded. 
Open Label Single Blind and Placebo Controlled 24 Week Histology Cohorts: 
Prior participation in a clinical trial of NGM282 is excluded unless previously 
enrolled into a placebo arm of the trial. 
17. Patient with severe allergic or anaphylactic reactions to recombinant therapeutic 
proteins, fusion proteins, or chimeric, human, or humanized antibodies. 
18. Participation in a study of another investigational agent within 28 days or five half-lives 
of the drug (whichever is longer) prior to Screening 

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19. Any acute or chronic condition that, in the opinion of the Investigator, would limit the 
patient’s ability to complete and/or participate in this clinical study. 
20. Pregnancy or lactation 
21. Use of ezetimibe, colesevelam, cholestyramine, niacin, PCSK9 inhibitors, or other 
lipid-lowering agents within 3 months of Screening (except Double-blind cohort).  
Placebo-Controlled 24 Week Histology Cohort Only 
Use of any other lipid lowering agents or combination preparation of statins 
except ezetimibe when approved by MM/designee as second line lipid 
management therapy, within 3 months of Screening and throughout study 
a. colesevelam, cholestyramine, niacin, PCSK9 inhibitors (evolocumab or 
alirocumab), colestid, fibrates, fenofibrates, pharmacologic/prescribed fish 
oil 
22. History or presence of ALT elevations or significant side effects indicative of statin 
intolerance (except Double-blind cohort). 
23. Use of weight loss medications including: orlistat, phentermine, topiramate, qsymia, 
lorcaserin hydrochloride, naltrexone hydrochloride, liraglutide (use is for weight loss 
not T2D, e.g. Saxenda), benzphentamine, diethylpropion and phendimetrazine, within 
3 months of screening and throughout study 
 
Additionally for all cohorts, the Investigator has discretion to repeat assessments if he/she 
believes there is a good chance the results were spurious and do not accurately represent the 
patient’s true values. Repeat assessments must be conducted within the Screening Period. 
8.2 
Discontinuation of Study Treatment for an Individual Subject 
Study treatment will be discontinued if any of the following CTCAE categories are observed: 
• Any related Grade 3 TEAE 
• Any Grade 4 or higher TEAE 
Additionally, subjects will be evaluated for possible discontinuation if the following changes 
in liver-related laboratory parameters are observed: 
• Elevation of ALT > 2x above subject-specific baseline value (calculated using the 
median of the Screening and Day 1 value) and total bilirubin > 2x ULN: 
o ALT, AST, and total bilirubin must be re-tested within 72 hours.  
o Subjects with persistent elevations above the defined thresholds should be 
evaluated for discontinuation of study drug(s), independent of whether they 
are symptomatic or not. 
• Elevation of only ALT > 2x above subject-specific baseline:  
o ALT, AST, and total bilirubin must be re-tested within 72 hours.  

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o Subjects with persistent elevations above the defined thresholds who are 
symptomatic should be evaluated for discontinuation of study drug(s). 
o Subjects with persistent elevations above the defined thresholds who are 
asymptomatic may continue treatment under protocol-defined close 
observation criteria. 
o Subjects continuing treatment under close observation should implement 
study procedures and assessments as part of the study conduct: 
1. Repeat liver enzyme and serum bilirubin tests two or three times weekly. 
The frequency of retesting can decrease to once a week or less if 
abnormalities stabilize or the trial drug has been discontinued and the 
subject is asymptomatic.  
2. Repeat additional tests to evaluate liver synthetic function (e.g., INR, 
direct bilirubin) as appropriate. 
3. Obtain a detailed history of symptoms and prior or concurrent diseases. 
4. Obtain a history of concomitant drug use (including nonprescription 
medications and herbal and dietary supplement preparations), alcohol use, 
recreational drug use, environmental toxin exposure, and special diets. 
5. Rule out acute viral hepatitis and other acute or chronic hepatobiliary 
diseases. 
For the double-blind cohort, dose reductions will be allowed on a case by case basis for 
subjects receiving 6 mg or matched 6 mg placebo for safety or tolerability, but must be 
approved by the Medical Monitor. If approved, the subject will be decreased to 3 mg or the 
matched 3 mg placebo to be aligned with whether they were initially receiving active drug or 
placebo prior to the dose reduction. Subjects receiving 3 mg or matched 3 mg placebo will 
not be allowed to dose-reduce during the study period. 
For the open-label single-blind cohort, no dose reductions will be allowed.  
For the placebo-controlled 24-week histology cohort no dose reductions will be allowed. 
Additionally, ALT, AST, and all lipid laboratory results are blinded starting with Week 2 
onward.  The Medical Monitor will be reviewing and monitoring all laboratory results and if 
any of the liver related testing parameters are observed, investigators will be notified 
immediately to discuss further evaluation. 
8.3 
Discontinuation of Subjects from Study Participation 
Subjects will be informed that they are free to withdraw from the study at any time and for 
any reason. The Principal Investigator (PI) may remove a subject from the study if, in the 
PI’s opinion, it is not in the best interest of the subject to continue the study. Subjects may be 
discontinued due to a change in compliance with an inclusion/exclusion criterion that is 
clinically relevant and affects subject safety, occurrence of AEs, occurrence of pregnancy, or 

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administration of non-permitted concomitant medication that might affect subject safety or 
study assessments/objectives. Notification of discontinuation will be made immediately to 
the Sponsor’s Medical Monitor. In case of premature discontinuation of study participation, 
efforts will be made to perform all final EOT and EOS visits/assessments. The date the 
subject is withdrawn from the study and the reason for discontinuation will be recorded on 
the subject’s Case Report Form (CRF). All withdrawn subjects will be followed until 
resolution of any AEs or until any unresolved AEs are judged by the PI to have stabilized. 
9 
Study Methods 
9.1 
Schedule of Study Procedures for Double-blind Cohort 
The Schedule of Study Procedures for the double-blind cohort is shown in Table 2. The visits 
should occur as close to the intended dates as possible. However, there is an acceptable 
± 3 day window for individual scheduled visits. Subjects attending any visits out of windows 
from Day 1 to Week 12/Early Withdrawal (EOT) visit should be brought back into 
compliance with the overall study-visit schedule as soon as possible thereafter. Subjects will 
then return to the clinic at Week 16 (or 4 weeks after last dose) for an EOS follow-up visit. 
The Investigator has discretion to repeat assessments if he/she believes the results do not 
accurately represent the patient’s true values. Repeat assessments must be conducted within 
the 4-week (±5 days) Screening Period. 
 
 
 

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Table 2. 
Schedule of Study Procedures for Double-Blind Cohort  
Study Procedure 
Days –28 to –1 
(Screening) a 
Day 1 
Wk 1 
Wk 2 
Wk 4 
Wk 8 
Wk 12 (EOT)/ 
EW 
Wk 16 
(EOS) 
Informed consent 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
Body weight, BMI, waist 
circumference 
X 
X 
 
 
 
 
X 
X 
Physical exam 
X 
X  
 
X 
X 
X 
X 
X 
12-lead ECG 
X 
X 
 
X 
 
 
X 
X 
Vital signs  
X 
X 
X 
X 
X 
X 
X 
X 
Liver biopsy b (or tissue slides) 
X 
 
 
 
 
 
 
 
MRI c 
X 
 
 
 
 
 
X 
 
Prior and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization  
 
X 
 
 
 
 
 
 
Study drug self-administration 
training 
 
X 
X 
X 
X 
 
 
 
Dispense study drug 
 
X 
X 
X 
X 
X 
 
 
Medication compliance  
 
 
X 
X 
X 
X 
X 
 
Adverse event (AE) evaluations  
 
X 
X 
X 
X 
X 
X 
X 
LISSA evaluations d 
 
X 
X 
X 
X 
X 
X 
X 
PK blood samples e 
 
X 
X 
X 
X 
X 
X 
X 
Chemistry [fasted ≥ 10 hours] 
X 
X 
X 
X 
X 
X 
X 
X 
Complete blood count (CBC) 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis (UA) 
X 
X 
 
 
X 
 
X 
X 
Fasting lipid panel  
 
X 
 
 
X 
 
X 
 
Lipoprotein particles 
 
X 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
HbA1c 
X 
X 
 
 
 
 
X 
 
Insulin level and HOMA-IR 
X 
X 
 
 
 
 
X 
 
Stool sample 
 
X 
 
 
 
 
X 
 
Hepatitis and HIV screen 
X 
 
 
 
 
 
 
 
Urine drug screen 
X 
 
 
 
 
 
 
 
 

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9.2 
Study Visit Procedures for Double-blind cohort 
9.2.1 
Day –28 to Day –1 (Screening) Procedures 
Subjects will report to this visit fasted. The following screening procedures will be performed 
for all potential subjects at a visit (or visits) conducted within 28 days prior to dosing: 
• Obtain informed consent. 
• Collect demographic data. 
• Ascertain medical history. 
• Assess inclusion/exclusion criteria. 
• Measure height. 
• Measure body weight, BMI, and waist circumference. 
• Conduct physical examination.  
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Obtain MRI (prior to any histologic evaluation). 
• Obtain viable tissue slides from eligible historical liver biopsy or undergo a liver biopsy 
procedure to obtain new tissue. 
• Record prior and concomitant medications. 
• Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• Complete blood count (CBC) 
• HbA1c 
• Insulin 
• HOMA-IR calculation 
• INR 
• AFP 
• Serum pregnancy test (all female subjects) 
• Obtain clinical laboratory samples for HIV antibody and hepatitis screen. 
• Obtain urine samples for the following: 
• Urinalysis (UA) 
• Selected drugs of abuse 
9.2.2 
Day 1 Procedures 
Subjects will report to this visit fasted. The Day 1 visit should be a minimum of 14 days from 
the Screening visit in order to allow for adequate separation of the repeated Chemistry (liver 
function tests) and INR assessments. The following procedures will be performed at the 
Day 1 Visit: 

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Pre-dose: 
• Reassess inclusion/exclusion criteria. 
• Measure body weight, BMI, and waist circumference. 
• Conduct physical examination. 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Record concomitant medications. 
• Record AEs. 
• Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• CBC 
• Lipid panel  
• Lipoprotein particles 
• 
 
• HbA1c 
• Insulin  
• HOMA-IR calculation 
• C4 and serum bile acids 
• Vitamin D 
• INR 
• 
 
• Cytokines 
• 
 
• PK (pre-dose) 
• Anti-drug antibodies (ADAs) 
• Neutralizing antibodies (NAbs) 
• Exploratory biomarkers 
• Obtain stool sample for microbiome and fecal fat assessment. 
• Obtain urine samples for the following: 
• Pregnancy test 
• UA 
 
In-clinic dosing: 
• 
Confirm inclusion/exclusion criteria and no change in clinical symptoms or other 
evidence of a significant change in liver function from Screening. 
• 
Perform randomization. 
• 
Dispense initial study-drug kit/diary (for recording of date/time of study-drug dosing). 

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• 
Provide study-drug self-administration training. 
• 
Oversee subject’s study-drug self-administration. 
 
Before clinic discharge: 
• Obtain 2-hour post-dose PK sample. 
• Record AEs. 
• Perform local injection-site symptom assessment (LISSA) evaluation. 
• Schedule subject for Week 1 visit. 
9.2.3 
Week 1 Procedures 
Subjects will report to this visit fasted and not dosed with NGM282. The following 
procedures will be performed at the Week 1 visit: 
Pre-dose: 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Record concomitant medications. 
• Record AEs. 
• Perform LISSA evaluation.  
• Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• CBC 
• PK (pre-dose) 
 
In-clinic dosing: 
• Collect old study-drug kit/diary and conduct reconciliation. 
• Dispense new study-drug kit/diary. 
• Oversee subject’s study-drug self-administration (from new kit).  
 
Before clinic discharge (20 minutes after dosing): 
• Record AEs. 
• Perform LISSA evaluation. 
• Schedule subject for Week 2 visit. 

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9.2.4 
Week 2 Procedures 
Subjects will report to this visit fasted and not dosed with NGM282. The following 
procedures will be performed at the Week 2 visit: 
Pre-dose: 
• Conduct physical examination. 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Record concomitant medications. 
• Record AEs. 
• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• CBC 
• PK (pre-dose) 
• ADAs 
• NAbs 
• Perform LISSA evaluation. 
 
In-clinic dosing: 
• Collect old study-drug kit/diary and conduct reconciliation. 
• Dispense new study-drug kit/diary. 
• Oversee subject’s study-drug self-administration (from new kit).  
 
Before clinic discharge (20 minutes after dosing): 
• Record AEs. 
• Perform LISSA evaluation. 
• Schedule subject for Week 4 visit. 
 
9.2.5 
Week 4 Procedures 
Subjects will report to this visit fasted and not dosed with NGM282. The following 
procedures will be performed at the Week 4 visit: 
Pre-dose: 
• Conduct physical examination. 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Record concomitant medications. 

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• Record AEs. 
• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• CBC 
• Lipid panel 
• 
 
• Cytokines 
• PK (pre-dose) 
• ADAs 
• NAbs 
• Obtain urine samples for UA. 
 
In-clinic dosing: 
• Collect old study-drug kit/diary and conduct reconciliation. 
• Dispense new study-drug kit/diary. 
• Oversee subject’s study-drug self-administration (from new kit).  
 
Before clinic discharge (20 minutes after dosing): 
• Record AEs. 
• Perform LISSA evaluation. 
• Schedule subject for Week 8 visit. 
9.2.6 
Week 8 Procedures 
Subjects will report to this visit fasted and not dosed with NGM282. The following 
procedures will be performed at the Week 8 visit: 
Pre-dose: 
• Conduct physical exam. 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Record concomitant medications. 
• Record AEs. 
• Perform LISSA evaluation.  
• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• CBC 
• PK (pre-dose) 
• ADAs 
• NAbs 

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In-clinic dosing: 
• Collect old study-drug kit/diary and conduct reconciliation. 
• Dispense new study-drug kit/diary. 
• Oversee subject’s study-drug self-administration (from new kit).  
 
Before clinic discharge (20 minutes after dosing): 
• Record AEs. 
• Perform LISSA evaluation. 
• Schedule subject for Week 12 (End of Treatment) visit. 
9.2.7 
Week 12 (End of Treatment)/Early Withdrawal Procedures 
Subjects will report to this visit fasted and not dosed with NGM282. The following 
procedures will be performed at the Week 12/Early Withdrawal Visit: 
Pre-dose: 
• Measure body weight, BMI, and waist circumference. 
• Conduct physical examination. 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Obtain a MRI examination. 
• Record concomitant medications. 
• Record AEs. 
• Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• CBC 
• Lipid panel  
• Lipoprotein particles 
• 
 
• C4 and serum bile acids 
• Vitamin D 
• HbA1c 
• Insulin level 
• HOMA-IR calculation 
• INR 
• 
 
• Cytokines 
• 
 

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• Serum pregnancy test (all female subjects) 
• PK (pre-dose) 
• ADAs 
• NAbs 
• Exploratory biomarkers 
 
• Obtain stool sample for microbiome and fecal fat assessment. 
• Obtain urine sample for UA. 
• Perform LISSA evaluation. 
 
In-clinic dosing: 
• Collect old study-drug kit/diary and conduct reconciliation. 
• Oversee subject’s study-drug self-administration (from old kit) (not applicable for Early 
Withdrawal subjects). 
 
Before clinic discharge (and approximately 20 minutes after dosing): 
• Obtain 2-hour post-dose PK sample. 
• Record AEs. 
• Perform LISSA evaluation. 
• Schedule subject for Day Week 16 (End of Study) Visit. 
 
(NOTE: Before-clinic-discharge assessments [PK sampling, AE recording, and LISSA 
evaluation] are not applicable for Early Withdrawal subjects. However, Early 
Withdrawal subjects should be scheduled for a 4-week Follow-up Visit.)  
9.2.8 
Week 16 (End of Study) Procedures 
This visit will be performed 4 weeks after the last dose of study medication. Subjects will 
report to this visit fasted. The following procedures will be performed at the Week 16 visit: 
• Measure body weight, BMI, and waist circumference. 
• Conduct physical examination. 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Record concomitant medications. 
• Record AEs. 
• Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• CBC 

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• PK 
• Vitamin D 
• INR 
• 
 
• Serum pregnancy test (all female subjects) 
• ADAs 
• NAbs 
 
• Obtain urine sample for UA. 
• Perform LISSA evaluation. 
 
9.3 
Schedule of Study Procedures for Open-label Single-blind Cohort 
The Schedule of Study Procedures for the open-label single-blind cohort is shown in Table 3. 
The visits should occur as close to the intended dates as possible. However, there is an 
acceptable ± 3-day window for individual scheduled visits. Subjects attending any visits out 
of windows from Day 1 to Week 12/Early Withdrawal (EOT) visit should be brought back 
into compliance with the overall study-visit schedule as soon as possible thereafter. Subjects 
will then return to the clinic at Week 18 (or 6 weeks after last dose) for an EOS follow-up 
visit. 
The Investigator has discretion to repeat assessments if he/she believes the results do not 
accurately represent the patient’s true values. Repeat assessments must be conducted within 
the Screening Period. 
 
 

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Table 3. 
Schedule of Study Procedures for Open-Label Single-Blind Cohort  
Study Procedure 
Days –28  
to –1 
(Screening) a Day 1 
Wk 2 
Wk 4 
Wk 6 
Wk 8 
Wk 12 
(EOT) /EW 
Wk 18 
(EOS) 
Informed consent 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
Body weight, BMI, waist 
circumference 
X 
X 
 
 
 
 
X 
X 
Physical exam 
X 
X  
X 
X 
X 
X 
X 
X 
12-lead ECG 
X 
X 
 
 
X 
 
X 
X 
Vital signs  
X 
X 
X 
X 
X 
X 
X 
X 
MRI b 
X 
 
 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
Liver biopsy d 
X 
 
 
 
 
 
Xc 
 
IWRS screening registration 
X 
 
 
 
 
 
 
 
IWRS enrollment registration 
 
X 
 
 
 
 
 
 
Prior and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event (AE) evaluations  
 
X 
X 
X 
X 
X 
X 
X 
LISSA evaluations e 
 
X 
X 
X 
X 
X 
X 
X 
Chemistry 
[fasted ≥ 10 hours] 
X 
X 
X 
X 
X 
X 
X 
X 
Complete blood count (CBC) 
X 
X 
X 
X 
X 
X 
X 
X 
HbA1c 
X 
X 
 
 
 
 
X 
X 
Insulin level and HOMA-IR 
X 
X 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
International Normalized Ratio 
(INR) 
X 
X 
 
 
 
 
X 
X 
Alpha fetoprotein (AFP) 
X 
 
 
 
 
 
 
 
Pregnancy test f 
X 
X 
 
 
 
 
X 
X 
Hepatitis and HIV screen 
X 
 
 
 
 
 
 
 
Urinalysis (UA) 
X 
X 
 
 
X 
 
X 
X 
Urine drug screen 
X 
 
 
 
 
 
 
 
Fasting lipid panel  
X 
X 
X 
X 
X 
X 
X 
X 
Lipoprotein particles 
 
X 
 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
Lipase 
 
X 
 
X 
X 
X 
X 
X 
Stool sample  
 
X 
 
 
 
 
X 
 
 
 

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9.4 
Study Visit Procedures for Open-label cohort 
9.4.1 
Day –28 to Day –1 (Screening) Procedures 
Subjects will report to this visit fasted. The following screening procedures will be performed 
for all potential subjects at a visit (or visits) conducted within 28 days prior to dosing: 
• Obtain informed consent. 
• Collect demographic data. 
• Ascertain medical history. 
• Assess inclusion/exclusion criteria. 
• Measure height. 
• Measure body weight, BMI, and waist circumference. 
• Conduct physical examination.  
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Obtain an MRI assessment (preferably prior to any histologic evaluation unless a 
historical biopsy is available). 
• Obtain a LiverMultiScanTM reading (dosing Groups 3 or 4 only). 
• Obtain viable tissue slides from eligible historical liver biopsy or undergo a liver biopsy 
procedure to obtain new tissue. 
• Conduct Interactive Web Response System (IWRS) screening registration. 
• Record prior and concomitant medications. 
• Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• CBC 
• Lipid panel 
• HbA1c 
• Insulin 
• HOMA-IR calculation 
• INR 
• AFP 
• Serum pregnancy test (all female subjects) 
• Obtain clinical laboratory samples for HIV antibody and hepatitis screen. 
• Obtain urine samples for the following: 
• UA 
• Selected drugs of abuse 

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9.4.2 
Day 1 Procedures 
Subjects will report to this visit fasted. The Day 1 visit should be a minimum of 14 days from 
the Screening visit in order to allow for adequate separation of the repeated Chemistry (liver 
function tests) and INR assessments. The following procedures will be performed at the 
Day 1 Visit: 
Pre-dose: 
• Reassess inclusion/exclusion criteria. 
• Measure body weight, BMI, and waist circumference. 
• Conduct physical examination. 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Record concomitant medications. 
• Record AEs.  
• Perform LISSA evaluation. 
• Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry  
• CBC 
• HbA1c 
• Insulin  
• HOMA-IR calculation 
• 
 
• Lipid panel  
• Lipoprotein particles 
• 
 
• Lipase 
• C4 and serum bile acids 
• Vitamin D 
• INR 
• 
 
• Cytokines 
• PK (pre-dose) 
• ADAs 
• NAbs 
• Exploratory biomarker #1 
• Exploratory biomarker #2 
• Enhanced liver fibrosis (ELF) panel 

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• 
 
 
  
 
• Obtain stool sample for microbiome and fecal fat assessment. 
• Obtain urine samples for the following: 
• Pregnancy test 
• UA 
 
In-clinic dosing and assessments: 
• 
Confirm inclusion/exclusion criteria and no change in clinical symptoms or other 
evidence of a significant change in liver function from Screening. 
• 
Confirm no new medications have been started or dose changes of medications during 
Screening 
• 
Register subject in IWRS for study-drug kit assignment.  
• 
Dispense initial NGM282 study-drug kit/diary (for recording of date/time of study-drug 
dosing). 
• 
Provide NGM282 study-drug self-administration training. 
• 
Oversee subject’s NGM282 study-drug self-administration. 
• 
In a subset of subjects, PK samples will be collected at pre-dose and 1, 2, 4, 8, and 
12 hours after dosing.  
 
Before clinic discharge (and approximately 20 minutes after dosing: 
• Obtain 2-hour post-dose PK sample (only in subjects not participating in the PK 
sub-study). 
• Record new AEs after NGM282 dosing. 
• Perform LISSA evaluation. 
• Schedule subject for Week 2 visit. 
9.4.3 
Week 2 Procedures 
Subjects will report to this visit fasted and not dosed with NGM282. The following 
procedures will be performed at the Week 2 visit: 
Pre-dose: 
• Conduct physical examination. 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Record concomitant medications. 
• Record AEs.  
• Perform LISSA evaluation. 

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• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• CBC 
• Lipid panel 
• PK (pre-dose) 
• ADAs 
• NAbs 
 
In-clinic dosing and dispensing: 
• Collect old NGM282 study-drug kit/diary and conduct reconciliation. 
• Dispense new NGM282 study-drug kit/diary 
• Dispense new rosuvastatin study drug (if indicated as outlined in Section 10.4) 
• Oversee subject’s NGM282 study-drug self-administration (from new kit).  
 
Before clinic discharge (and approximately 20 minutes after dosing): 
• Record new AEs after NGM282 dosing. 
• Perform LISSA evaluation. 
• Schedule subject for Week 4 visit. 
 
Lipid-Lowering Therapy Assessment: 
• Evaluate LDL-C level from Week 2 visit when available. 
• Based on the Week 2 LDL-C level, initiate/switch rosuvastatin therapy as outlined in 
Section 10.4 of the study protocol. The subject should be called by the study site 
personnel to instruct on the specific administration of the rosuvastatin therapy. 
 
9.4.4 
Week 4 Procedures 
Subjects will report to this visit fasted and not dosed with NGM282. The following 
procedures will be performed at the Week 4 visit: 
Pre-dose: 
• Conduct physical examination. 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Record concomitant medications. 
• Record AEs. 
• Perform LISSA evaluation. 
• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 

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• CBC 
• Lipid panel 
• Lipase 
• PK (pre-dose) 
• ADAs 
• NAbs 
 
In-clinic dosing and dispensing: 
• Collect old NGM282 study-drug kit/diary and conduct reconciliation. 
• Collect old rosuvastatin bottle and conduct reconciliation. 
• Dispense new NGM282 study-drug kit/diary 
• Dispense new rosuvastatin study drug. 
• Oversee subject’s NGM282 study-drug self-administration (from new kit).  
 
Before clinic discharge (and approximately 20 minutes after dosing): 
• Record new AEs after NGM282 dosing. 
• Perform LISSA evaluation. 
• Schedule subject for Week 6 visit. 
 
Lipid-Lowering Therapy Assessment: 
• Evaluate LDL-C level from Week 4 visit when available. 
• Based on the Week 4 LDL-C level, initiate/switch/continue/dose increase rosuvastatin 
therapy as outlined in Section 10.4 of the study protocol. The subject should be called by 
the study site personnel to instruct on the specific administration of the rosuvastatin 
therapy. 
9.4.5 
Week 6 Procedures 
Subjects will report to this visit fasted and not dosed with NGM282. The following 
procedures will be performed at the Week 6 visit: 
Pre-dose: 
• Conduct physical examination. 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Obtain an MRI assessment (preferably prior to any histologic evaluation unless a 
historical biopsy is available). 
• Obtain a LiverMultiScanTM reading (dosing Groups 3 or 4 only). 
• Record concomitant medications. 

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• Record AEs. 
• Perform LISSA evaluation. 
• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• CBC 
• Lipid panel 
• Lipoprotein particles 
• Lipase 
• C4 and serum bile acids 
• 
 
• Cytokines 
• PK (pre-dose) 
• ADAs 
• NAbs 
• Exploratory biomarker #1 
• Exploratory biomarker #2 
• ELF panel 
• 
 
 
 
 
• Obtain urine samples for UA. 
 
In-clinic dosing and dispensing: 
• Collect old NGM282 study-drug kit/diary and conduct reconciliation. 
• Dispense new NGM 282 study-drug kit/diary. 
• Oversee subject’s NGM282 study-drug self-administration (from new kit).  
 
Before clinic discharge (and approximately 20 minutes after dosing): 
• Record new AEs after NGM282 dosing. 
• Perform LISSA evaluation. 
• In a subset of subjects, PK samples will be collected at pre-dose and 1, 2, 4, 8, and 
12 hours after dosing. 
• Schedule subject for Week 8 visit. 

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9.4.6 
Week 8 Procedures  
Subjects will report to this visit fasted and not dosed with NGM282. The following 
procedures will be performed at the Week 8 visit: 
Pre-dose: 
• Conduct physical exam. 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Record concomitant medications. 
• Record AEs. 
• Perform LISSA evaluation.  
• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• CBC 
• Lipid panel 
• Lipase 
• PK (pre-dose) 
• ADAs 
• NAbs 
 
In-clinic dosing and dispensing: 
• Collect old NGM282 study-drug kit/diary and conduct reconciliation. 
• Collect old rosuvastatin study-drug and conduct reconciliation. 
• Dispense new NGM282 study-drug kit/diary 
• Dispense new rosuvastatin study-drug. 
• Oversee subject’s NGM282 study-drug self-administration (from new kit).  
 
Before clinic discharge (and approximately 20 minutes after dosing): 
• Record new AEs after NGM282 dosing. 
• Perform LISSA evaluation. 
• Schedule subject for Week 12 (End of Treatment) visit. 
 
Lipid-Lowering Therapy Assessment: 
• Evaluate LDL-C level from Week 8 visit when available. 
• Based on the Week 8 LDL-C level, initiate/switch/continue/dose increase rosuvastatin 
therapy as outlined in Section 10.4 of the study protocol. The subject should be called by 
the study site personnel to instruct on the specific administration of the rosuvastatin 
therapy. 

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9.4.7 
Week 12 (End of Treatment)/Early Withdrawal Procedures 
Subjects will report to this visit fasted and not dosed with NGM282. The following 
procedures will be performed at the Week 12/Early Withdrawal Visit: 
Pre-dose: 
• Measure body weight, BMI, and waist circumference. 
• Conduct physical examination. 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Obtain an MRI assessment (preferably prior to any histologic evaluation unless a 
historical biopsy is available). 
• Obtain a LiverMultiScanTM reading (dosing Groups 3 or 4 only). 
• Undergo a liver biopsy procedure to obtain new tissue (dosing Groups 3 or 4 only). 
• Record concomitant medications. 
• Record AEs. 
• Perform LISSA evaluation. 
• Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• CBC 
• HbA1c 
• Insulin level 
• HOMA-IR calculation 
• 
 
• INR 
• Serum pregnancy test (all female subjects) 
• Lipid panel  
• Lipoprotein particles 
• 
 
• Lipase 
• C4 and serum bile acids 
• Vitamin D  
• 
  
• Cytokines 
• PK (pre-dose) 
• ADAs 
• NAbs 
• Exploratory biomarker #1 

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• Exploratory biomarker #2 
• ELF panel 
• 
 
 
 
 
• Obtain stool sample for microbiome and fecal fat assessment. 
• Obtain urine sample for UA. 
 
In-clinic dosing: 
• Collect old NGM282 study-drug kit/diary and conduct reconciliation. 
• Collect old rosuvastatin bottle and conduct reconciliation. 
• Dispense new rosuvastatin (only for subjects who were on statin therapy at Baseline). 
• Oversee subject’s NGM282 study-drug self-administration (from old kit) (not applicable 
for Early Withdrawal subjects). 
 
Before clinic discharge (and approximately 20 minutes after dosing): 
• Obtain 2-hour post-dose PK blood sample. 
• Record AEs. 
• Perform LISSA evaluation. 
• Schedule subject for Week 18 (End of Study) Visit. 
 
(NOTE: Before-clinic-discharge assessments [PK sampling, AE recording, and LISSA 
evaluation] are not applicable for Early Withdrawal subjects. However, Early 
Withdrawal subjects should be scheduled for a 6-week Follow-up Visit.)  
9.4.8 
Week 18 (End of Study) Procedures 
This visit will be performed 6 weeks after the last dose of study medication. Subjects will 
report to this visit fasted. The following procedures will be performed at the Week 18 visit: 
• Measure body weight, BMI, and waist circumference. 
• Conduct physical examination. 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Obtain an MRI assessment (preferably prior to any histologic evaluation unless a 
historical biopsy is available). 
• Obtain a LiverMultiScanTM reading (dosing Groups 3 or 4 only). 
• Record concomitant medications. 
• Record AEs. 

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• 
Obtain 10-hour fasted clinical laboratory samples for the following:  
• Chemistry 
• CBC 
• HbA1c 
• Insulin level 
• HOMA-IR calculation 
• 
 
• INR 
• Serum pregnancy test (all female subjects) 
• Lipid panel  
• Lipoprotein particles 
• 
 
• Lipase 
• C4 and serum bile acids 
• Vitamin D  
• 
  
• Cytokines 
• PK (pre-dose) 
• ADAs 
• NAbs 
• Exploratory biomarker #1 
• Exploratory biomarker #2 
• ELF panel 
• 
 
 
 
 
• Obtain urine sample for UA. 
• Perform pre-dose LISSA evaluation only. 
• Collect old rosuvastatin bottle and conduct reconciliation (only for subjects who were on 
statin therapy at Baseline). 
 
 

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9.5 
Schedule of Study Procedures for Placebo-controlled 24-Week 
Histology Cohort 
The Schedule of Study Procedures for the placebo-controlled 24-week histology cohort is 
shown in Table 4. The visits should occur as close to the intended dates as possible. 
However, there is an acceptable ± 3-day window for individual scheduled visits unless 
stipulated otherwise for specific procedures.   
The screening window may be extended an additional 2 weeks (for a total window of 42 
days) if additional time is needed to complete procedures.  Medical Monitor/designee 
approval will be required and will not be considered a protocol deviation: 
Subjects attending any visits out of windows from Day 1 to Week 24/Early Withdrawal 
(EOT) visit should be brought back into compliance with the overall study-visit schedule as 
soon as possible thereafter. Subjects will then return to the clinic at Week 30 (or 6 weeks 
after last dose) for an EOS follow-up visit. 
The Investigator has discretion to repeat assessments if he/she believes the results do not 
accurately represent the patient’s true values. Repeat assessments must be conducted within 
the Screening Period. 
 
 

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Table 4. 
Schedule of Study Procedures for Placebo-Controlled 24-Week Histology 
Cohort  
Study Procedure 
D –28 to –1 
(Screening) a D 1 W 2 W 4 W 6 W 8 W 12 W 18 
W 24/ EW 
(EOT) 
W 30 
 (EOS) 
Visit Window (Days) 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
± 3 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Prior and concomitant 
medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
Body weight, BMI, waist 
circumference 
X 
X 
 
 
 
 
X 
 
X 
X 
Physical exam 
X 
X  
 
X 
 
X 
X 
X 
X 
X 
12-lead ECG 
X 
X 
 
 
 
 
X 
 
X 
X 
Vital signs  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events (AEs) k  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chemistry [fasted ≥ 10 hrs] 
X  
X je X e 
X e 
X e 
X e 
X e 
X e 
X e 
X e 
Complete blood count (CBC) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HbA1c 
X 
X 
 
 
 
 
X 
 
X 
X 
Insulin level and HOMA-IR 
X 
X 
 
 
 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
International Normalized Ratio 
(INR) 
X 
X 
 
 
 
 
X 
 
X 
X 
Alpha fetoprotein (AFP) 
X 
 
 
 
 
 
 
 
 
 
Pregnancy test f 
X 
X 
 
 
 
 
 
 
X 
X 
Hepatitis and HIV screen 
X 
 
 
 
 
 
 
 
 
 
Urinalysis (UA) 
X 
X 
 
 
 
 
X 
 
X 
X 
Urine drug screen 
X 
 
 
 
 
 
 
 
 
 
Fasting lipid panel  
X 
X e 
X e 
X e 
X e 
X e 
X e 
X e 
X e 
X e 
Lipoprotein particles 
 
X 
 
X 
 
X 
X 
 
X 
X 
Lipase 
 
X 
 
X 
 
X 
X 
 
X 
X 
C4 and serum bile acids 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vitamin D 
 
X 
 
 
 
 
X 
 
X 
X 
PK blood samples g 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-drug antibodies (ADAs) 
 
X 
X X 
X 
X 
X 
X 
X 
X 
Neutralizing antibodies (NAbs) 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ELF Panel 
 
X 
 
 
X 
 
X 
 
X 
X 
Exploratory plasma biomarkers 1, 2  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 

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i Compliance with Rosuvastatin will be assessed at Week 30 for statin-experienced subjects only 
j Baseline ALT reported result calculated using the median of the Screening and Day 1 value 
k Adverse events will be monitored and recorded from patient signing informed consent through follow-up. 
l Subjects will be instructed to self-inject NGM282 or placebo as close to the same time as possible each day in the abdomen  
  and administer the next dose the following morning. Subjects will not self-inject NGM282 at home on clinic visit days. 
9.6 
Study Visit Procedures for Placebo-controlled 24-week Histology 
Cohort 
9.6.1 
Day –28 to Day –1 (Screening) Procedures 
Subjects will report to clinic fasted. The following screening procedures should be performed 
within 28 days prior to dosing. The screening window may be extended an additional 
2 weeks (for a total window of 42 days) if additional time is needed to complete procedures. 
Medical Monitor/designee approval will be required and will not be considered a protocol 
deviation: 
• Obtain informed consent. 
• Collect demographic data. 
• Ascertain medical history. 
• Record prior and concomitant medications. 
• Assess inclusion/exclusion criteria. 
• Measure height. 
• Measure body weight, BMI, and waist circumference. 
• Conduct physical examination.  
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Obtain blood and urine for 10-hour fasted laboratory sample collection  
• Obtain an MRI assessment (preferably prior to any histologic evaluation unless a 
historical biopsy is available).  Re-screen subjects may use previously obtained MRI if 
within 8 weeks from original procedure. 
• 
 
 
• Obtain viable tissue slides from historical liver biopsy (within 3 months of screening) or 
undergo a liver biopsy procedure to obtain new tissue. 
• Record AEs (starting from the when the patient signs informed consent) 
• Register screened subject in IWRS 
9.6.2 
Day 1 Procedures 
Subjects will report to clinic fasted or be rescheduled.  The Day 1 visit should be a minimum 
of 14 days from the Screening visit in order to allow for adequate separation of repeated 

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chemistry (liver function tests) and INR laboratory assessments as necessary. The following 
procedures will be performed at the Day 1 Visit: 
Pre-dose: 
• Reassess inclusion/exclusion criteria. 
• Measure body weight, BMI, and waist circumference. 
• Conduct physical examination. 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Record concomitant medications. 
• Record new and/or changes to AEs.  
• Obtain blood and urine for 10-hour fasted laboratory samples 
– Reminder to perform urine pregnancy test for females of child bearing potential 
 
In-clinic dosing and assessments: 
• 
Reconfirm eligibility and no change in clinical symptoms or other evidence of a 
significant change in liver function from Screening. 
• 
Confirm no new or changes to medications  
• 
Randomize subject in IWRS for NGM282 study drug kit assignment.  
• 
Dispense initial NGM282 study drug kits (2) and home diary  
• 
Provide NGM282 study drug self-administration training.  
• 
Oversee subject’s NGM282 study drug self-administration. 
• Perform LISSA evaluation. 
 
Before clinic discharge: 
• Obtain 2-hour post-dose PK sample.  
• Remind subject to bring study drug kits/diary and to not self-inject NGM282 at home on 
clinic visit days 
• Schedule Week 2 visit and remind subject for home dosing to administer NGM282 or 
placebo as close as possible to the same time each day 
9.6.3 
Week 2 Procedures 
Subjects will report to clinic fasted and not dosed with NGM282. The following procedures 
will be performed: 
Pre-dose: 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 

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• 
Obtain blood for 10-hour fasted clinical laboratory samples (if not fasted, chemistries and 
lipid panel will need to be retested) 
– Results are blinded for ALT, AST, Total Cholesterol, LDL, HDL and  
triglycerides 
• Record concomitant medications. 
• Record new and/or changes to AEs.  
 
In-clinic dosing and dispensing: 
• Collect old NGM282 study-drug kit/diary and conduct reconciliation. 
• Dispense new NGM282 study-drug kits (2) and diary. 
• Dispense rosuvastatin medication/diary  
• Oversee subject’s NGM282 study-drug self-administration (from new kit).  
• Perform LISSA evaluation. 
 
Before clinic discharge: 
• Remind subject to bring study drug kits/diary and to not self-inject NGM282 at home on 
clinic visit days. 
• Schedule Week 4 visit and remind subject for home dosing to administer NGM282 or 
placebo as close as possible to the same time each day 
 
Lipid-Lowering Therapy Assessment: 
• NGM Medical Monitor/designee will evaluate LDL-C level as outlined in Section 10.4 
and inform site to: 
– Start or not start rosuvastatin therapy 
– Continue with current therapy 
– Switch to rosuvastatin therapy  
• The site will then contact the subject with further instructions 
9.6.4 
Week 4 Procedures 
Subjects will report to clinic fasted and not dosed with NGM282. The following procedures 
will be performed: 
Pre-dose: 
• Conduct physical examination. 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 

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• 
Obtain blood for 10-hour fasted clinical laboratory samples (if not fasted chemistries and 
lipid panel will need to be retested) 
– Results are blinded for ALT, AST, Total Cholesterol, LDL, HDL and  
triglycerides 
• Record concomitant medications. 
• Record new and/or changes to AEs. 
 
In-clinic dosing and dispensing: 
• Collect old NGM282 study-drug kit/diary and conduct reconciliation. 
• Collect old rosuvastatin medication bottle/diary and conduct reconciliation. 
• Dispense new NGM282 study-drug kits (2) and diary. 
• Dispense new rosuvastatin medication/diary. 
• Oversee subject’s NGM282 study-drug self-administration (from new kit).  
• Perform LISSA evaluation. 
 
Before clinic discharge: 
• Remind subject to bring study drug kits/diary and to not self-inject NGM282 at home on 
clinic visit days. 
• Schedule Week 6 visit and remind subject for home dosing to administer NGM282 or 
placebo as close as possible to the same time each day 
 
Lipid-Lowering Therapy Assessment: 
• NGM Medical Monitor/designee will evaluate LDL-C level as outlined in Section 10.4 
and inform site to: 
– Start or not start rosuvastatin therapy 
– Continue current therapy 
– Titrate rosuvastatin therapy 
– Switch to rosuvastatin therapy  
• The site will then contact the subject with further instructions 
9.6.5 
Week 6 Procedures 
Subjects will report to clinic fasted and not dosed with NGM282. The following procedures 
will be performed: 
Pre-dose: 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 

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• 
Obtain blood for 10-hour fasted clinical laboratory samples (if not fasted, chemistries and 
lipid panel will need to be retested) 
– Results are blinded for ALT, AST, Total Cholesterol, LDL, HDL and  
triglycerides 
• Obtain an MRI assessment.  
• Record concomitant medications. 
• Record new and/or changes to AEs. 
 
In-clinic dosing and dispensing: 
• Collect old NGM282 study-drug kit/diary and conduct reconciliation. 
• Dispense new NGM 282 study-drug kits (2) and diary. 
• Oversee subject’s NGM282 study-drug self-administration (from new kit).  
• Perform LISSA evaluation. 
 
Before clinic discharge: 
• Remind subject to bring study drug kits/diary and to not self-inject NGM282 at home on 
clinic visit days. 
• Schedule Week 8 visit and remind subject for home dosing to administer NGM282 or 
placebo as close as possible to the same time each day 
9.6.6 
Week 8 Procedures  
Subjects will report to clinic fasted and not dosed with NGM282. The following procedures 
will be performed: 
Pre-dose: 
• Conduct physical exam. 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• 
Obtain blood for 10-hour fasted clinical laboratory samples (if not fasted, chemistries and 
lipid panel will need to be retested) 
– Results are blinded for ALT, AST, Total Cholesterol, LDL, HDL and  
triglycerides 
• Record concomitant medications. 
• Record new and/or changes to AEs. 
 
In-clinic dosing and dispensing: 
• Collect old NGM282 study-drug kit/diary and conduct reconciliation. 
• Collect old rosuvastatin medication bottle/diary and conduct reconciliation. 
• Dispense new NGM282 study-drug kits (4) and diary. 

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• Dispense new rosuvastatin medication/diary. 
• Oversee subject’s NGM282 study-drug self-administration (from new kit).  
• Perform LISSA evaluation.  
 
Before clinic discharge: 
• Remind subject to bring study drug kits/diary and to not self-inject NGM282 at home on 
clinic visit days. 
• Schedule Week 12 visit and remind subject for home dosing to administer NGM282 or 
placebo as close as possible to the same time each day 
 
Lipid-Lowering Therapy Assessment: 
• NGM Medical Monitor/designee will evaluate LDL-C level as outlined in Section 10.4 
and inform site to: 
– Continue with current therapy 
– Titrate rosuvastatin therapy 
• The site will then contact the subject with further instructions 
9.6.7 
Week 12 Procedures 
Subjects will report to clinic visit fasted and not dosed with NGM282. The following 
procedures will be performed: 
 
Pre-dose: 
• Measure body weight, BMI, and waist circumference. 
• Conduct physical examination. 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• 
Obtain blood and urine for 10-hour fasted clinical laboratory samples (if not fasted, 
chemistries and lipid panel will need to be retested) 
– Results are blinded for ALT, AST, Total Cholesterol, LDL, HDL and  
triglycerides 
• 
Obtain an MRI assessment.  
• Record concomitant medications. 
• Record new and/or changes to AEs. 
 
In-clinic dosing and dispensing: 
• Collect old NGM282 study-drug kit/diary and conduct reconciliation. 
• Collect old rosuvastatin medication bottle/diary and conduct reconciliation. 

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• Dispense new NGM282 study-drug kits (5) and diary. 
• Dispense new rosuvastatin medication/diary.  
• Oversee subject’s NGM282 study-drug self-administration (from new kit).  
• Perform LISSA evaluation. 
 
Before clinic discharge: 
• Obtain 2-hour post-dose PK blood sample. 
• Remind subject to bring study drug kits/diary and to not self-inject NGM282 at home on 
clinic visit days. 
• Schedule Week 18 visit and remind subject for home dosing to administer NGM282 or 
placebo as close as possible to the same time each day 
 
Lipid-Lowering Therapy Assessment: 
• NGM Medical Monitor/designee will evaluate LDL-C level as outlined in Section 10.4 
and inform site to: 
– Continue with current therapy 
– Evaluate additional lipid-lowering therapy with ezetimibe for statin non-
responder 
– For subjects taking statins, evaluate tolerability and if deemed necessary, subject 
may be considered for alternative second-line lipid lowering therapy with 
ezetimibe . 
• The site will then contact the subject with further instructions 
9.6.8 
Week 18 Procedures  
Subjects will report to clinic fasted and not dosed with NGM282. The following procedures 
will be performed: 
Pre-dose: 
• Conduct physical examination.  
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Record concomitant medications. 
• Record new and/or changes to AEs. 
• 
Obtain blood for 10-hour fasted clinical laboratory samples (if not fasted chemistries and 
lipid panel will need to be retested) 
– Results are blinded for ALT, AST, Total Cholesterol, LDL, HDL and  
triglycerides 
 
In-clinic dosing and dispensing: 

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• Collect old NGM282 study-drug kit/diary and conduct reconciliation. 
• Collect old rosuvastatin medication bottle/diary and conduct reconciliation. 
• If subject is taking statins, evaluate tolerability and continue therapy to Week 24 for 
statin naïve or Week 30 for statin experienced 
• Dispense new NGM282 study-drug kits (5) and diary. 
• Dispense new rosuvastatin medication/diary. 
• Oversee subject’s NGM282 study-drug self-administration (from new kit).  
• Perform LISSA evaluation.  
 
Before clinic discharge: 
• Remind subject to bring study drug kits/diary and to not self-inject NGM282 at home on 
clinic visit days. 
• Schedule Week 24 (End of Treatment) visit and remind subject for home dosing to 
administer NGM282 or placebo as close as possible to the same time each day 
  
9.6.9 
Week 24/Early Withdrawal (End of Treatment) Procedures 
Subjects will report to clinic fasted and not dosed with NGM282. The following procedures 
will be performed: 
Pre-dose: 
• Measure body weight, BMI, and waist circumference. 
• Conduct physical examination. 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
 
• 
Obtain blood and urine for 10-hour fasted clinical laboratory samples (if not fasted, 
chemistries and lipid panel will need to be retested)  
– Results are blinded for ALT, AST, Total Cholesterol, LDL, HDL and 
triglycerides 
• 
Obtain an MRI assessment 
– MRI should be obtained before the last dose of NGM282 (standard Table 4 visit 
window applies)  
• 
  
• Undergo a liver biopsy procedure to obtain new tissue 
– Results will be blinded.  
– Biopsy should be obtained before the last dose of NGM282 with a visit window 
of -7 days and +3 days 

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• Record concomitant medications. 
• Record new and/or changes to AEs. 
 
In-clinic dosing and dispensing: 
• Collect old NGM282 study-drug kit/diary and conduct reconciliation. 
• Collect old rosuvastatin medication bottle/diary and conduct reconciliation. 
• If stain experienced subject is taking statins, evaluate tolerability and continue therapy to 
Week 30  
• Statin naïve subjects taking statins are to discontinue therapy 
• Dispense new rosuvastatin medication/diary to statin experienced subjects taking therapy  
• Oversee subject’s NGM282 study-drug self-administration (from old kit) (not applicable 
for Early Withdrawal subjects). 
• Perform LISSA evaluation. 
 
Before clinic discharge: 
• Obtain 2-hour post-dose PK blood sample (except early withdrawal subjects). 
• Schedule Week 30 (End of Study) Visit. 
 
9.6.10 
Week 30 (End of Study) Procedures 
This visit will be performed 6 weeks after the last dose of study medication. Subject will 
report to clinic fasted.  The following procedures will be performed: 
• Measure body weight, BMI, and waist circumference. 
• Conduct physical examination. 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes). 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse). 
• Obtain blood and urine for 10-hour fasted clinical laboratory samples  
– Results are blinded for ALT, AST, Total Cholesterol, LDL, HDL and  
triglycerides 
• Obtain an MRI assessment  
• Record concomitant medications. 
• Record new and/or changes to AEs. 
• Perform LISSA evaluation. 
• Collect old rosuvastatin medication bottle/diary and conduct reconciliation for statin 
experienced subjects taking therapy  

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9.7 
Prior and Concomitant Medications 
Concomitant therapies are any prescription or over-the-counter preparations used by a 
subject while participating in this study and must be recorded from 28 days prior to Day 1 
until end of study.   
Subjects should refrain from the use of any new medications or products or change in the 
dose or frequency of existing therapies during Screening and throughout the study.  The 
Medical Monitor should be informed of any changes or addition of medications during this 
time period.  
Prohibited Medications from 28 days prior to Day 1 and throughout study: 
• Investigational agents, other than NGM282, or devices for any indication 
• Known hepatotoxic agents 
• Agents used for the treatment of any condition listed in the exclusionary enrollment 
criteria (see Section 8.1.2) 
• Any hepatotoxic herbal medications other than standard vitamin supplements 
Placebo-Controlled 24 Week Histology Cohort Only: 
• Investigational agents, other than NGM282, or devices for any indication 
• Agents used for the treatment of any condition listed in the exclusionary enrollment 
criteria (see Section 8.1.2) 
• Hepatotoxic agents outlined in (Appendix E). 
o All other hepatotoxic agents will be left to the discretion of the PI. 
There should be clear documentation in the patient study records of PI 
approval of use. 
 
Prohibited Medications within 3 months of Screening and throughout study: 
• Ezetimibe, colesevelam, cholestyramine, niacin, PCSK9 inhibitors, or other 
lipid-lowering agents (except Double-blind) 
Placebo-Controlled 24 Week Histology Cohort Only: 
• Contraindicated medications according to rosuvastatin package insert 
(Appendix C) 
o Includes cyclosporine, gemfibrozil, protease inhibitors (atazanavir, 
ritonavir, lopinavir, simeprevir), coumarin anticoagulants, fenofibrates, 
niacin and colchicine 
• Contraindicated medications according to ezetimibe package insert (Appendix D) 
o Includes cyclosporine, fenofibrate, cholestyramine and coumarin 
anticoagulants 

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• Use of any other lipid lowering agents or combination preparation of statins, 
within 3 months of Screening and throughout study, except ezetimibe when 
approved by MM/designee as second line lipid management therapy. 
o colesevelam, cholestyramine, niacin, PCSK9 inhibitors (evolocumab or 
alirocumab), colestid, fibrates, fenofibrates, pharmacologic/prescribed fish 
oil 
o Use of weight loss medications including: orlistat, phentermine, 
topiramate, qsymia, lorcaserin hydrochloride, naltrexone hydrochloride, 
liraglutide (for weight loss not T2D, e.g. Saxenda), benzphentamine, 
diethylpropion and phendimetrazine 
 
Acceptable Medications that require a stable regimen prior to and throughout study: 
Double-Blind and Single-Blind, Open-Label Cohorts:  
• Diabetes medications (except GLP1 agonists): requires a stable regimen for at 
least 3 months prior to Day 1. 
• GLP1 agonists:  requires a stable regimen 12 months prior to Day 1. 
• Weight-loss medications: requires stable regimen for at least 3 months prior to 
Day 1 with no safety or tolerability events. 
• Other therapies for NAFLD or NASH: requires a stable regimen for at least 
6 months prior to Screening biopsy and throughout the study. May include 
vitamin E, milk thistle, thiazolidinediones and pentoxifylline. 
 
Placebo-Controlled 24 Week Histology Cohort Only: 
• GLP1 agonists and pioglitazone:  requires a stable regimen 12 months prior to 
Day1. 
• Procedural Medications use (e.g. Anti-anxiety medication for MRI scan, 
anesthetic for liver biopsy) will be at the discretion of the PI and documented 
accordingly. 
• Other therapies for NAFLD or NASH: requires a stable regimen for at least 
3 months prior to Screening biopsy and throughout the study. May include 
vitamin E (>800 IU), milk thistle, and pentoxifylline. 
 
Statin Use: 
Double-Blind Cohort: 
Includes statins. 

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Open-Label Single-Blind and Placebo-Controlled 24 Week Histology Cohorts: 
Includes statins if the following conditions are met: 
1. Subject can be defined as statin naïve or experienced at Screening based on 
the following definitions: 
a. Statin-naïve: no administration of statins within 3 months prior to 
enrollment. 
b. Statin experienced: administration of < 50% of the maximal dose of 
current statin therapy. 
2. Requires a stable regimen for at least 3 months prior to Screening through 
Week 2. 
The following are the acceptable daily doses of currently approved statin therapies, 
including combination preparations of statins and other lipid-lowering agents. 
• Atorvastatin: < 40 mg/d 
• Fluvastatin: < 40 mg/d 
• Lovastatin: < 40 mg/d (immediate release), < 30 mg/d (extended release) 
• Pitavastatin: < 2 mg/d 
• Pravastatin: < 40 mg/d 
• Rosuvastatin: < 20 mg/d (Note: must be < not < 20 mg/d) 
• Simvastatin: < 40 mg/d 
 
9.8 
Diet and Activity Control 
Subjects should maintain their normal level of physical activity, diet, and lifestyle throughout 
the entire study (i.e., will not begin a new exercise program or participate in any unusually 
strenuous physical exertion).  
9.9 
Clinical Evaluations 
9.9.1 
Liver Biopsy 
Subjects who meet the Screening criteria of an available liver biopsy tissue specimen within 
6 months of Screening for the double-blind cohort and 12 months for the single-blind 
open-label cohort will not be required to undergo a liver biopsy. For the dosing Groups 3 or 4 
of the open-label single-blind cohort and for the placebo-controlled 24-week histology 
cohort, the liver biopsy must be performed within 3 months of Screening in order to serve as 
the Baseline comparison for the additional Week 12 biopsy. All other subjects will be 
required to undergo a liver biopsy per the study site’s local standard-of-care procedure during 
the Screening period and prior to randomization. Tissue from all subjects will be prepped and 
read by a qualified pathologist for review for the absence/presence of NASH. Liver biopsies 

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with histologically confirmed NASH will be further assessed by a qualified pathologist using 
the NAS and Fibrosis Score established and validated by the NASH Clinical Research 
Network (see Appendix A). Liver biopsies will be assessed for degree of steatosis (0–3), 
lobular inflammation (0–3), hepatocellular ballooning (0–2), and fibrosis (0-4). The first 
three components will be added together to determine the NAS that ranges from 0 to 8. 
Liver biopsies with a NAS of < 4 will be considered exclusionary. Subjects with liver 
biopsies with Stage 0 (no fibrosis) or Stage 4 fibrosis (cirrhosis) will be excluded from this 
study. For the placebo-controlled 24-week histology cohort, only subjects with Stage 2 or 
Stage 3 fibrosis will be allowed to enroll into the study. 
The Screening and EOT biopsies for dosing Groups 3 or 4 of the open-label single-blind 
cohort and all subjects in the placebo-controlled 24-week histology cohort will be read by a 
single central pathologist. The biopsies will be read and scored using the same NASH 
Clinical Research Network (CRN) scores as the inclusion biopsies. These will be read 
unpaired and blinded to subject and reported separately from the inclusion biopsy.  
For the placebo-controlled 24-week histology, only the Week 24 biopsy results will be 
blinded to the site and subject.  Screening biopsy results will not be blinded.  The Week 24 
biopsy should be obtained before the last dose of NGM282 with a visit window of -7 days 
and +3 days. 
9.9.2 
Magnetic Resonance Imaging (MRI) 
All enrolled subjects will have a Baseline (from the Screening result) and EOT MRI of the 
liver to evaluate liver volume and liver fat. Open-label single-blind cohort subjects are 
requested to undergo an additional MRI at Weeks 6 and 18.  
Subjects in the placebo controlled 24–week histology cohort will have an MRI performed at 
Screening and at Weeks 6, 12, 24, and 30. None of the treatment or post treatment MRI 
results (other than incidental findings) will be provided to the sites.  MRI-PDFF should be 
performed before the last dose of NGM282 
MRI-PDFF will be reported on all MRI imaging scans. Scans should be performed at high 
field strength (3T preferred, 1.5T acceptable), without the administration of oral or 
intravenous contrast material. MRI examinations will include a six-echo gradient recalled 
echo (GRE) sequence (2D preferred, 3D acceptable), 
 
 
The initial study MRI examination will be performed during the Screening period prior to 
randomization. An MRI-PDFF value of > 8% at Screening as assessed by the central 
radiology core is one of the inclusion criteria for the study. Therefore, for patients who 
require a liver biopsy as part of the trial (for whom no recent liver biopsy is available), it is 

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recommended that liver biopsy be scheduled no sooner than 7 business days after (electronic) 
transmission of the screening MRI examination to the central radiology core to allow 
adequate time for processing and reporting of the result. MRI-PDFF results will be reported 
to the individual site no more than 5 business days after the MRI examination is received. 
For both Screening and EOT/Early Withdrawal MRI examinations, subjects should consume 
nothing by mouth (NPO) for 4 hours prior to their MRI appointment. Medications and small 
amounts of water are acceptable. 
Prior to MRI, all subjects should undergo safety assessment per institutional protocols and 
per the guidelines of the local Institutional Review Board. Subjects should be questioned 
regarding claustrophobia, pregnancy or potential pregnancy, size or weight exceeding the 
capabilities of the MRI system, metal implants, and other potential safety issues.  
Detailed instructions for MRI procedures and provision of examination to a central reader 
will be presented in a separate MRI Manual.  
LiverMultiScanTM imaging will be also be collected during the MRI to obtain the MRI-PDFF 
assessments in dosing Groups 3 or 4 of the open-label single-blind cohort and all subjects in 
the placebo-controlled 24-week histology cohort. This scan is optional and will only be 
performed where the imaging technology is available and adequate. The subjects will be 
required to stay in the MRI machine approximately 10 minutes longer than the standard MRI 
procedure. The software uses the images of the liver to calculate parameters that have been 
shown to correlate with histological measures of steatosis, hepatic iron overload, and fibrosis 
of the liver (Banerjee 2014). Additionally, an LIF score and corrected cT1 value are also 
calculated, both of which have been correlated to liver histology as well as predicting 
liver-related outcomes (Banerjee 2014, Pavlides 2016, Perspectum Diagnostics, data on file). 
Detailed instructions for the LiverMultiScanTM software and provision of the imaging to a 
central reader will be presented in a separate manual. 
 
 
. There are no current imaging techniques 
that can directly detect the specific stage of fibrosis. Most attempt to detect fibrosis indirectly 
using proposed biomarkers which include: stiffness, diffusion, perfusion, metabolites, and 
image texture with the leading biomarker being liver stiffness (Younossi 2017). 
 
 
 
 

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9.9.3 
Pharmacokinetic Blood Sample Collection and Processing 
In all cohorts, blood samples for PK analysis of NGM282 levels will be collected before 
dosing on all study visits. On Day 1 and Week 12, an additional PK blood sample will be 
collected 2 hours post-dose (±20 mins). Additionally, in the open-label single-blind cohort, 
up to 8 subjects per dosing group in the single-blind open-label cohort will be given the 
option to participate in further PK sampling at pre-dose (Baseline) and at 1, 2, 4, 8, and 
12 hours (±20 mins) after dosing on Day 1 (Baseline) and Week 6. Subjects participating in 
the PK sub-study will not obtain an additional 2-hour post-dose sample. 
Processing, storage, and shipping instructions for these PK blood samples will be presented 
in the study Lab Manual. 
9.9.4 
Clinical Laboratory Evaluations 
Clinical laboratory evaluations including chemistry (fasted at least 10 hours), CBC, and UA 
will be collected as outlined in the respective Schedules of Study Procedures (double-blind, 
Table 2; open-label, Table 3; placebo-controlled 24-week histology, Table 4). 
Laboratory assessments of fasted lipid panel (total cholesterol, LDL, HDL, and TG), 
lipoprotein particles, HbA1c, insulin, HOMA-IR, and FFAs will be performed as outlined in 
the respective Schedules of Study Procedures (double-blind, Table 2; open-label, Table 3; 
placebo-controlled 24-week histology, Table 4). For the placebo-controlled 24 week 
histology, test results will be monitored by the sponsor’s medical monitor/designee, but are 
blinded to the site and subject for ALT, AST, Total Cholesterol, LDL, HDL and triglycerides 
for Week 2 – Week 30 sample collections.  LDL-direct may be used if LDL-C was not able 
to be analyzed. 
Laboratory assessments for C4 and serum bile acids will be performed as outlined in the 
respective Schedules of Study Procedures (double-blind, Table 2; open-label, Table 3; 
placebo-controlled 24-week histology, Table 4).  
Laboratory assessments for changes in bile-mediated absorption as measured by vitamin D 
and INR will be performed as outlined in the respective Schedules of Study Procedures 
(double-blind, Table 2; open-label, Table 3; placebo-controlled 24-week histology, Table 4).  
 
 
Cytokines (IL-6, and TGF-β) and hs-CRP will be assessed as outlined in the respective 
Schedules of Study Procedures (double-blind, Table 2; open-label, Table 3).  
Hepatitis screen and HIV antibody screen will be performed at Screening.  
A urine screen for drugs of abuse will be performed at Screening.  

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A stool sample will be collected at Day 1 and Week 12 in only the double-blind and 
open-label single-blind cohorts. Stool samples will be analyzed for microbiome (bacterial 
composition) and fecal fat content (double-blind, Table 2; open-label, Table 3). 
A serum qualitative pregnancy test (all female patients of child bearing potential) will be 
performed at Screening and Week 24/EOT and Week 30/EOS. A urine pregnancy test (all 
female patients of child bearing potential) will be performed at Day 1 (pre-dose). 
AFP will be measured at Screening. 
Samples for analysis of ADAs, NAbs, and exploratory biomarkers will be collected as 
outlined in the respective Schedules of Study Procedures (double-blind, Table 2; open-label, 
Table 3; placebo-controlled 24-week histology, Table 4). All NAb samples will be collected 
as scheduled, and analyzed only if necessary based on ADA results.  
Exploratory biomarkers, ELF panel, 
 will be assessed as 
outlined in the respective Schedules of Study Procedures (open-label, Table 3; 
placebo-controlled 24-week histology, Table 4).  
Processing, storage, and shipping instructions for the above will be presented in a separate 
Lab Manual. 
9.9.5 
12-Lead Electrocardiograms 
12-lead ECGs will be performed after the subject has been supine for at least 5 minutes, and 
as outlined in the respective Schedules of Study (double-blind, Table 2; open-label, Table 3; 
placebo-controlled 24-week histology, Table 4).  
9.9.6 
Vital Signs 
Vital signs (including temperature, respiratory rate, and seated blood pressure and pulse) will 
be obtained at Screening and at all study visits as outlined in the respective Schedules of 
Study Procedures (double-blind, Table 2; open-label, Table 3; placebo-controlled 24-week 
histology, Table 4). 
Seated blood pressure and pulse will be measured after the subject has been seated for at least 
5 minutes. 
9.9.7 
Physical Examinations 
A routine physical examination will be performed at selected study visits in each of the 
cohorts as outlined in the Schedule of Study Procedures (double-blind, Table 2; open-label, 
Table 3; placebo-controlled 24-week histology, Table 4. 

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9.9.8 
Weight, Body Mass Index, and Waist Circumference Measurements 
Subjects will be weighed, BMI calculated, and waist circumference measured at Screening, 
and selected study visits as outlined in the Schedule of Study Procedures (double-blind, 
Table 2; open-label, Table 3; placebo-controlled 24-week histology, Table 4). Formal 
instructions for recording weight and measuring waist circumference will be provided to 
sites. 
9.9.9 
Local Injection-Site Symptom Assessments (LISSA) 
Injection-site evaluation will be made and documented (including photographs, as needed) by 
the PI or clinic staff using a LISSA (Appendix B). 
The LISSA is to be administered pre- and post-dose (approximately 20 minutes after 
injection) at Day 1 through EOT in the double-blind and open-label single-blind cohorts. 
A single assessment will be performed at the Week 16 (double-blind cohort) or Week 18 
(open-label single-blind cohort), to assess any prior dose injection site reactions. 
For the placebo-controlled 24-week histology cohort, LISSA evaluations are to be performed 
at each clinic visit from Day 1 through Week 30.   
The instructions below are to be followed for the pre-dose LISSA: 
• The injection site area(s) should be examined for any ISRs at every visit. 
• If a single ISR is observed, the LISSA should be used to rate that ISR. 
• If multiple ISRs are observed, the LISSA should be used to rate the most severe ISR. 
• The study visit note should document the total number of ISRs seen on examination. 
The LISSA is intended to be a “snapshot” of the ISRs at the time of clinic assessment. The 
LISSA is not intended to capture ISR data (frequency, severity, duration, etc.) in between 
clinic visits. As with any other potential AE, Investigator judgment should be used as to 
whether any ISR is recorded as an AE. Mild to Severe Reactions (LISSA Grades 1–3) are 
reported as AEs at the discretion of the investigator unless standard SAE criteria are met and 
then must be reported as an SAE. Life-threatening (LISSA Grade 4) meet SAE criteria and 
must be reported as such. 
LISSAs may be performed if necessary and as clinically indicated by the PI to capture ISRs 
outside of the routine scheduled assessment time points. 
The 2007 FDA Toxicity Grading Scale (Appendix B) will be used to assess any ISRs (U.S. 
Department of Health and Human Services 2007). The documented record will include all of 
the symptoms, severity, and any local reaction (including pain, tenderness, redness, and 
swelling) and size of injection-site skin reactions identified and observed by the subject or 
clinic personnel. LISSA scores will be documented on the subject’s CRF.  

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10 
Study Drug 
10.1 
Clinical Supplies 
10.1.1 
NGM282 
NGM282 is formulated in aqueous isosmotic buffer solution with 0.01% polysorbate-20. It is 
filled into 1-mL, type I glass syringes, with a 29-g staked needle, needle shield, grey rubber 
plunger, and plastic plunger rod. Filled syringes are labeled and packaged into trays and 
cardboard cartons.  
In the double-blind cohort, NGM282 is provided as a sterile solution for injection in a 
single-use, pre-filled syringe for SC administration at doses of 3 and 6 mg, and 
volume-matched placebo. In the single-blind cohort, NGM282 is provided as a sterile 
solution for injection in a single-use, pre-filled syringe for SC administration at doses of 0.3, 
1, and 3 mg. In the placebo-controlled 24-Week histology cohort NGM282 is provided as a 
sterile solution for injection in a single-use, pre-filled syringe for SC administration at 1 mg 
dose and volume-matched placebo. 
The drug product is manufactured for NGM under current Good Manufacturing Practice 
regulations 
 
that has undergone FDA inspection. 
10.1.2 
Rosuvastatin 
10.1.2.1 
Drug Supply for Open-Label Single-Blind Cohort 
For the open-label single-blind cohort, rosuvastatin will be supplied as 20-mg pink, round, 
convex-shaped, coated tablets with “RU20” on one side and blank on the other side in bottles 
of 30 tablets (NDC 16252-617-30). The active ingredient is rosuvastatin calcium and inactive 
ingredients include microcrystalline cellulose, lactose monohydrate, sodium carbonate 
monohydrate, sodium lauryl sulfate, crospovidone, magnesium stearate, titanium dioxide, 
polyethylene glycol, polyvinyl alcohol, talc, ferric oxide yellow, ferric oxide red, FD&C Red 
40, and indigotindisulfonate sodium.  
10.1.2.2 
Drug Supply for Placebo-Controlled 24-Week Histology Cohort 
For the placebo-controlled 24-week histology cohort, rosuvastatin will be supplied. 
Rosuvastatin calcium tablets 20 mg are light pink colored, round, biconvex, film coated 
tablets debossed with '1181' on one side and plain on other side in bottles of 90 tablets (NDC 
13668-181-90). The active ingredient is rosuvastatin calcium and inactive ingredients include 
crospovidone, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline 
cellulose, titanium dioxide, triacetin and ferric oxide red. 

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10.2 
Study-Drug Accountability 
The PI is responsible for ensuring that a current record of inventory/drug accountability 
(NGM282 and rosuvastatin) is maintained. Inventory records must be readily available for 
inspection by the study monitor and are open to inspection by regulatory authorities at any 
time. Each shipment of drug supply for the study will contain a shipping manifest to assist 
the PI in maintaining current and accurate inventory records. 
Upon receipt of the investigational drug, the designated site personnel will visually inspect 
the shipment, verify the number and condition of study drug received, and confirm receipt of 
study drug.  
At the completion of the study and after all drug accountability has been performed by the 
site CRA, all unused study-drug supplies will be returned to the Sponsor (or designee) or 
disposed of by the clinic, per the Sponsor’s (or designee’s) written instructions. 
10.3 
Study-Drug Storage 
NGM282 syringes are to be stored at the clinical site in the provided packaging and 
refrigerated at 2°C–8°C (36°F–46°F) in a secure, controlled-access location protected from 
light. At the subject’s home, NGM282 syringes are to be stored in the provided packaging 
protected from light and refrigerated.  All drug excursions should be reported immediately to 
Sponsor to confirm NGM 282 stability. 
Rosuvastatin calcium tablets should be stored at room temperature, at 68°F–77°F  
(20°C– 25°C) and in a dry place.  Excursions are permitted to 59°F–86°F (15°C– 30°C) 
Please refer to package insert USP Controlled Room Temperature.  (Appendix D) 
Subjects will be instructed to take care in keeping both study drugs out of the reach of 
children and other family members. 
10.4 
Dose Preparation and Administration 
10.4.1 
NGM282 
Subjects will be instructed to dose with NGM282 at relatively the same time each day.  For 
visit days in the clinic, subjects will not dose at home. 
Study-drug syringes should be brought to room temperature (~15-20 minutes) prior to use 
and administered as a SC injection in the abdomen. On Day 1, subjects will be trained on SC 
self-injecting. During the on-treatment visits, SC self-injecting will occur in the clinic under 
observation by clinic staff. Re-training will be provided as required. Written dose preparation 
and administration instructions will be provided to subjects. Subjects will be required to 
complete a daily study-drug administration diary.  

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10.4.2 
Rosuvastatin 
Only subjects in the open-label single-blind and placebo-controlled 24-week histology 
cohorts who meet specific on-treatment criteria will be instructed to dose rosuvastatin based 
on the LDL-C levels at Weeks 2, 4, and 8 or at the discretion of the medical monitor. 
Additionally, subjects in the placebo-controlled 24-week histology cohort who have not 
achieved an adequate response or are unable to tolerate statin therapy may be considered for 
second-line lipid-lowering therapy with ezetimibe at the discretion of the medical monitor.  
Ezetimibe is formulated as 10mg tablets and can be administered with or without food at the 
same time as rosuvastatin.  This must be approved by the Sponsor’s Medical Monitor prior to 
dosing with ezetimibe and will be prescribed by the Investigator. The specific treatment 
algorithms will be based on whether subjects are statin naïve (Section 10.4.2.1) versus statin 
experienced (Section 10.4.2.2) at Baseline as outlined in the following figures for subjects in 
both the open-label single-blind and placebo-controlled 24-week histology cohorts: 

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11 
Adverse Events 
11.1 
Definition and Grading Intensity of Adverse Events 
An AE is defined as any untoward medical occurrence in a subject of clinical investigational 
participation administered a pharmaceutical product, whether or not considered drug related. 
A TEAE is an AE that is reported after a dose of study drug. 
AEs include the following: 
• Unfavorable changes in general condition 
• Subjective or objective signs/symptoms 
• Concomitant diseases or accidents 
• Clinically relevant adverse changes in laboratory parameters observed in a subject 
in the course of a clinical study 
AEs comprise all disturbances of general health status, subjective and objective disease 
symptoms (including laboratory abnormalities), and accidents observed in the context of a 
clinical trial, irrespective of a possible causal relationship with the administration of the trial 
substance. Events occurring in the framework of a clinical trial during drug-free and 
post-treatment periods or under placebo are also to be designated as AEs. 
All AEs regardless of how identified (e.g., volunteered, elicited, noted on physical 
examination) will be recorded throughout the study from the time the patient signs informed 
consent through Follow-up.  
Subjects will be followed for resolution of AEs, by querying the subjects for an ongoing AE 
until resolved or until any unresolved AEs are judged by the PI to have stabilized or if lost to 
follow-up. Resolution of all AEs will be promptly documented by the clinic on the subject’s 
CRF. 
Any pregnancy diagnosed during the study must be reported immediately to the PI and 
Sponsor, including pregnancy in female partners of male subjects. The pregnancy will be 
followed to term and/or outcome and this outcome must be reported to the Sponsor. 
Pregnancy, in and of itself, is not regarded as an AE or SAE unless the birth results in a 
congenital anomaly/birth defect or there is suspicion that the study medication may have 
interfered with the effectiveness of a contraceptive medication or method. 
The PI will rate the severity of AEs using the CTCAE v4.03 to grade the severity. Each 
CTCAE v4.03 term is a Medical Dictionary for Regulatory Activities (MedDRA) Lowest 
Level Term (LLT). The CTCAE displays Grades 1 through 5 with unique clinical 
descriptions of severity for each AE. Not all Grades are appropriate for all AEs. Therefore, 
some AEs are listed with fewer than five options for Grade selection. Grade 5 (Death) is not 
appropriate for some AEs and, therefore, is not an option.  

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11.2 
Criteria for Determining Relationship to Drug 
The PI will make a blinded determination of the relationship of the AE to NGM282 
(including placebo) in the double-blind cohort. An open-label determination of the 
relationship of the AE to NGM282 and a separate open-label determination of the 
relationship of the AE to rosuvastatin will be made in the open-label single-blind cohort. The 
PI will make a blinded determination of the relationship of the AE to NGM282 (including 
placebo) and a separate open-label determination of the relationship of the AE to rosuvastatin 
in the placebo-controlled 24-week histology cohort. All determinations of relationship will be 
made using a four-category system (not related, possible, probable, or definite) according to 
the following guidelines: 
• NOT RELATED = an AE that does not follow a reasonable temporal sequence from 
administration of the drug and that can be reasonably explained by other factors, 
including underlying disease, complications, concomitant drugs, or concurrent 
treatment; 
• POSSIBLE = an AE that follows a reasonable temporal sequence from the 
administration of the drug (including the course after withdrawal of the drug) and that 
cannot be excluded as being possibly caused by the drug (e.g., existence of similar 
reports attributed to the drug and/or its analogues; reactions attributable to the 
pharmacological effect of the drug), although other factors such as underlying disease, 
complications, concomitant drugs, or concurrent treatment are presumable; 
• PROBABLE = an AE that follows a reasonable temporal sequence from administration 
of the drug (including the course after withdrawal of the drug) and that can be excluded 
as being possibly caused by other factors, such as underlying disease, complications, 
concomitant drugs, or concurrent treatment. 
• DEFINITE = an AE that follows a reasonable temporal sequence from administration 
of the drug (including the course after withdrawal of the drug), follows a known or 
hypothesized cause–effect relationship, and (if appropriate) satisfies the following: 
• Positive results obtained in drug sensitivity tests 
• Toxic level of the drug present in blood or other body fluids 
11.3 
Reporting 
An SAE is any untoward medical occurrence at any dose that results in any of the following 
outcomes: 
• Death 
• A life-threatening event (i.e., places the subject, in the view of the PI, at immediate risk 
of death) 
• Inpatient hospitalization or prolongation of existing hospitalization 

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• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• A congenital anomaly/birth defect 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
An unexpected adverse drug event is any adverse drug event the specificity or severity of 
which is not consistent with the current IB or, if an IB is not required or available, the 
specificity or severity of which is not consistent with the risk information described in the 
general investigational plan or elsewhere in the current application. 
An AE is associated with the use of the drug if a reasonable possibility exists that the event 
may have been caused by the drug. 
SAEs that are unexpected and related to either NGM282 or rosuvastatin are reportable to 
Regulatory Authorities. All SAEs will be reported by the PI to the Sponsor and will be 
reported to the responsible Ethics Committee (EC) in accordance with local requirements. 
The Sponsor’s assigned Safety Representative will be notified in writing (e.g., email or 
facsimile) within 24 hours of when an SAE is first recognized or reported. The Safety 
Representative will subsequently notify the Sponsor and the Sponsor’s assigned Medical 
Monitor of all reported SAEs. 
11.4 
Cardiovascular Adjudication 
An external independent Cardiovascular Adjudication Committee (CAC) will adjudicate 
serious adverse events (SAEs). The CAC members will be independent of the Sponsor, the 
clinical study sites and Investigators. The blinded medical review of known or suspected 
Major Adverse Cardiovascular Event (MACE) will primarily focus on CV death, myocardial 
infarction, cerebrovascular accident (stroke), and hospitalization for heart failure.  Sites may 
be asked to provide additional source documentation relevant to any event reported to the 
CAC as they would to study safety personnel for any serious safety event.  Further details are 
retained in the CAC Charter for the NGM282 Program. 
 
12 
Data Analysis and Statistical Considerations 
Data analysis will be performed according to the Sponsor’s or its representatives’ Standard 
Operating Procedures (SOPs). 

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Details of statistical parameters and methods to be applied will be provided in a detailed 
Statistical Analysis Plan (SAP) prior to database lock (unblinding). The general analytical 
approach for all endpoints will be descriptive in nature.  
Unless otherwise stated, the following statistical approaches will be taken: 
• Continuous variables: Descriptive statistics will include the number of non-missing 
values, mean, standard deviation (SD), median, minimum, and maximum. The minimum 
and maximum values will be presented to the same number of decimal places as recorded 
in the CRF; mean, median, and SD will be presented to one more decimal place than the 
raw data. 
• Categorical variables: Descriptive statistics will include frequency counts and 
percentages per category. Percentages will be rounded to one decimal place, with the 
denominator being the number of subjects in the relevant population. 
• Imputation: No missing data will be imputed. 
• PK data: Descriptive statistics will include the coefficient of variation. Arithmetic mean 
and SD will be substituted with geometric mean and SD for all PK-concentration 
descriptive statistics. 
• Confidence intervals (CIs): CIs will be two-sided and will use 95% confidence levels. 
Any analyses requiring significance testing will use a two-sided test at the 5% 
significance level. 
• Baseline: Baseline will be defined for each patient and will be defined as the last 
available, valid, non-missing assessment prior to start of first study-drug administration. 
Unknown, Not Done, Not Applicable, and other classifications of missing data will not 
be considered when calculating Baseline observations. However, valid categorical 
observations will be considered for Baseline calculations. 
• Analyses: Parametric tests will be used where all statistical requirements are met (e.g., 
normal distribution). In the event that statistical requirements are not met, non-parametric 
alternatives will be utilized. 
12.1 
Sample Size 
For the double-blind cohort, a sample size of 75 subjects was selected (25 subjects per 
treatment arm). 
Allowing for a dropout rate of 10% the following sample-size sensitivity calculations were 
based on a minimum number of 22 subjects per treatment group completing the trial.  
A 5% difference in total liver fat content is the minimal appreciable difference that would be 
considered clinically relevant between the active treatment arms and the placebo treatment 
group. If the NGM282 3-mg and 6-mg groups are assumed to have at least a 6% reduction in 
liver fat when compared to Baseline along with a reduction of 1% or less from Baseline in 
the placebo group, with a 5% level of significance, the following illustrates sample-size 

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power calculations based on varying common standard deviations to achieve an overall 
(overall F-test) statistically significant treatment effect: 
Method 
Mean Absolute Change from Baseline 
Common 
SD 
Effect 
Size 
Power 
NGM282 
6 mg  
NGM282 
3 mg 
Placebo 
One-way 
analysis of 
variance 
(equal n’s) 
6% 
6% 
1% 
8% 
0.0868 
54% 
6% 
6% 
1% 
7% 
0.1134 
66% 
6% 
6% 
1% 
6% 
0.1543 
80% 
6% 
6% 
1% 
5% 
0.2222 
92% 
SD = standard deviation. 
 
A maximum sample size of 100 subjects was selected (with a minimum of 15 subjects per 
treatment arm, up to a maximum of 25 subjects per treatment arm) for the single-blind cohort 
design. 
The sample size for the open-label single-blind cohort was not based on a formal sample-size 
calculation. Instead, it was based on the results of the interim analysis that was conducted 
when ~15 subjects per arm had completed 12 weeks of treatment. Although the results of this 
interim analysis are still blinded, the magnitude of the treatment differences observed 
indicate that a sample size of 15–20 subjects per treatment arm is sufficient to give an initial 
indication of efficacy for further exploration.  
The sample size of the placebo-controlled 24-week histology cohort is based on 1) 12-week 
histologic response data from the 3-mg cohort and 2) estimated placebo histologic response 
rates from controlled Phase 2 studies in NASH. Preliminary 12-week histologic response 
data (n=16) demonstrated that 50% of subjects had a 1-stage improvement in fibrosis with no 
worsening of NASH or resolution of NASH with no worsening of fibrosis. The placebo 
histologic response rates from recent Phase 2b trials of obeticholic acid, cenicriviroc, 
liraglutide, and selonsertib were 14%–20% at timepoints ranging from 24 to 72 weeks. Based 
on these data, the assumptions of calculated sample-size estimates for 24-week efficacy used 
an NGM282 response of 50% versus 15% for placebo utilizing 80% power and alpha=0.05 
with a 2:1 randomization scheme. Assuming a 15% drop-out rate, the planned sample size of 
50 NGM282-treated subjects and 25 placebo subjects is sufficient to evaluate efficacy and 
support powering estimates for a late-stage clinical trial. 
12.2 
Randomization and Enrollment 
For the double-blind cohort, at Day 1 all eligible subjects will be randomized via IWRS to 
one of the three treatment arms (NGM282 3 mg, NGM282 6 mg, or placebo) in a 1:1:1 ratio. 
The proportion of subjects with diabetes (categorized on a dichotomous scale) will be 
balanced across the three groups to ensure an even distribution across the three groups. 

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Diabetes status for balancing (“no diabetes” or “diabetes”), will be based on medical history, 
Screening labs, current medications, and clinical assessments.  
The single-blind cohort is not randomized. Subjects will initially be enrolled sequentially into 
dosing Group 1 and enrollment will be continuous within and between each dosing groups. 
Sequencing of the dosing Groups 2 and 3 will be based on PD and safety parameters from 
dosing Group 1 and may run in parallel to each other. A fourth optional dosing group may be 
conducted based on the safety/tolerability, imaging data and histology (dosing Group 3 only) 
data from the prior 3 dosing groups. Dosing Group 4 will be initiated only after all subjects in 
Cohort 3 have been enrolled and a minimum of 10 subjects have completed 12 weeks of 
treatment in order to do a preliminary review of key data. Dosing group sequence and 
individual subject treatment assignment will be blinded only study subjects throughout the 
study period. 
For the placebo-controlled 24-week histology cohort, at Day 1 all eligible subjects will be 
randomized via IWRS to one of the two treatment arms (NGM282 1 mg or placebo) in a 
2:1 ratio. The Sponsor, study sites, and subjects will be blinded to treatment assignment. The 
randomization schedule will be stratified by subject’s fibrosis stage 2 or 3 based on the 
screening qualification liver biopsy.   
12.3 
Test of Hypothesis and Significance Levels 
The null hypothesis being tested for this study will be that there is no difference in the 
absolute change in liver fat content from Baseline between the NGM282 and the Placebo 
treatment groups at EOT for the double-blind cohort. The alternative hypothesis being tested 
will be that there is at least a 5% difference in the absolute change in liver fat content from 
Baseline between the NGM282 and the Placebo treatment arms at Week 12 for the 
double-blind cohort. A two-sided analysis will be conducted at a 5% significance level. 
Comparisons across the cohorts will be exploratory and further outlined in the SAP. 
12.4 
Study Populations 
The study populations are detailed below. Details of any other populations for analysis will 
be described in the SAP. 
12.4.1 
Intent-to-Treat Population 
All randomized subjects in the double-blind and placebo-controlled 24-week histology 
cohorts) will be included in the Intent-to-Treat (ITT) population. All Baseline characteristics 
and demographic data will be summarized using the ITT population. The ITT population will 
be based on randomized treatment if this differs from actual treatment received. 

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12.4.2 
All Patients Population 
For the open-label single-blind cohort, all enrolled subjects will be included in the All 
Patients population. All Baseline characteristics and demographic data for the open-label 
single-blind cohort will be summarized using the All Patients population. The All Patients 
population will be based on enrolled treatment if this differs from actual treatment received. 
12.4.3 
Safety Population 
All randomized/enrolled subjects who receive at least one dose (full or partial) of study drug 
and have at least one post-dose safety evaluation will be included in the Safety population. 
All safety endpoints will be summarized using the Safety population and will be based on 
actual treatment received if this differs from the randomized/enrolled treatment. 
12.4.4 
Efficacy Population 
All randomized/enrolled subjects who receive at least one dose (full or partial) of study drug 
and have at least one valid, non-missing post-dose efficacy/PD parameter value will be 
included in the Efficacy population. All efficacy and PD endpoints will be summarized and 
analyzed using the Efficacy population. This will be the main population for the analysis of 
efficacy and PD endpoints. The Efficacy population will be based on randomized/enrolled 
treatment if this differs from actual treatment received.  
12.4.5 
Per Protocol Population 
The Per Protocol (PP) population will constitute a subset of the Efficacy population and will 
include subjects that have at least one valid, non-missing post-dose liver fat content 
measurement. Subjects in the Efficacy population who deviate from the conduct of the study 
or have an AE deemed by the Medical Monitor to be impactful on the primary endpoint will 
be excluded from the PP population. This will be the secondary population for the analysis of 
efficacy and PD endpoints. The PP population will be based on actual treatment received if it 
differs from that to which the patient was randomized/enrolled. 
12.4.6 
Liver Histology Population 
The liver histology population will constitute a subset of patients in the Efficacy population 
and will include patients who have at least one valid, non-missing Baseline and EOT liver 
biopsy. Subjects in the Efficacy population who deviate from the conduct of the study or 
have an AE deemed by the Medical Monitor to be impactful on the primary endpoint will be 
excluded from the PP population. This will be the secondary population for the analysis of 
efficacy and PD endpoints. The PP population will be based on actual treatment received if it 
differs from that to which the patient was randomized/enrolled. 

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12.4.7 
Pharmacokinetic Population 
All randomized/enrolled subjects who receive at least one dose (full or partial) of drug, with 
a pre-dose (Baseline) blood draw, and at least one qualified (above the limit of 
quantification) post-dose sample will be included in the PK population. Subjects with 
protocol violations will be assessed by the medical monitor for inclusion in the 
PK population. PK summaries and analyses will be conducted using the PK population. 
The PK population will be based on actual treatment received if it differs from that to which 
the patient was randomized/enrolled. 
12.5 
Treatment Exposure 
Individual data listings for treatment exposure will be presented for each subject. Treatment 
exposure will be summarized as extent of exposure to the study drug. Measures of extent of 
exposure include the total number of doses per subject and compliance. Treatment 
compliance is defined as the number doses administered per protocol/number of doses 
prescribed per protocol. Treatment exposure will be summarized using the Safety population 
by actual treatment. 
12.6 
Patient Disposition 
Individual data listings for patient disposition will be presented for each patient, including 
enrollment date, treatment start date, treatment discontinuation date, discontinuation reason, 
and population flags. The number and percentage of patients entering and discontinuing the 
study will be presented by randomized treatment group for the double-blind and 
placebo-controlled 24-week histology cohorts and by enrolled treatment group for the 
open-label single-blind cohort. The reasons for discontinuation will also be summarized. 
Patient disposition will be summarized using the ITT population for the double-blind and 
placebo-controlled 24-week histology cohorts and the All Patients population for the 
open-label single-blind cohort. 
12.7 
Protocol Deviations 
Individual data listings for protocol deviations will be presented for each patient. Protocol 
deviations will be summarized using the ITT population for the double-blind and placebo-
controlled 24-week histology cohorts and the All Patients population for the open-label 
single-blind cohort. 
12.8 
Demographic Analysis 
Individual data listings for demographic and Baseline characteristics will be presented for 
each patient. Demographic and Baseline characteristics will be descriptively summarized by 
randomized treatment group for the double-blind and placebo-controlled 24-week histology 

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cohorts and by enrolled treatment group for the open-label single-blind cohort. Quantitative 
and/or categorical summaries will be presented for demographics, medical history, and other 
Baseline characteristics. Demographic and Baseline characteristics will be summarized using 
the ITT population for the double-blind and placebo-controlled 24-week histology cohorts 
and the All Patients population for the open-label single-blind cohort. 
12.9 
Efficacy and Pharmacodynamics 
Individual data listings for efficacy and PD variables will be presented for each patient. 
Efficacy and PD summaries and analyses will use the Efficacy population.  
12.9.1 
Efficacy and Pharmacodynamic Endpoints 
The primary efficacy endpoint for this study will be the absolute change in liver fat content 
as measured by MRI-PDFF in patients subjects with histologically confirmed NASH after 
12 or 24 weeks of treatment. 
Secondary Objectives: 
• Evaluate the percentage change in absolute liver fat content at EOT. 
o In the open-label single-blind cohort, additional evaluations will be performed at 
Weeks 6 and 18. 
o In the placebo-controlled 24-week histology cohort, additional evaluations will be 
performed at Weeks 6, 24, and 30. 
• Evaluate the percentage of normalization for liver fat content at EOT. 
• Evaluate the change in liver fat content response rate as defined by a ≥ 5% decrease in 
absolute liver fat content. 
• Evaluate the absolute and percentage changes from Baseline to EOT as well as the 
percentage of normalization of the following parameters: ALT, AST, triglycerides, 
bilirubin (total and direct), and GGT. Percentage of normalization will also be 
investigated for a clinically meaningful threshold for triglycerides. 
• Evaluate the absolute and percentage changes from Baseline to EOT of the following: 
o Total cholesterol, HDL-C, LDL-C, triglycerides, and lipoprotein particles  
o FFAs 
o Fasting blood glucose, insulin levels, 
, and HOMA-IR 
o Pro-C3 and ELF scores (Placebo Controlled 24 Week Histology Cohorts) 
o Body weight, BMI, and waist circumference 
o C4 and serum bile acids 
o Bile-mediated absorption as measured by vitamin D, INR, and fecal fat content 
• Evaluate the liver histologic response in Placebo Controlled 24 Week Histology Cohorts 
o Improvement in liver fibrosis by ≥ 1 stage by NASH Clinical Research Network 
(CRN) criteria with no worsening of steatohepatitis 

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o Resolution of NASH (defined as an NAS score of 0 or 1 for inflammation and 0 for 
ballooning) with no worsening of fibrosis as determined by the NASH CRN 
criteria.   
• Evaluate the exposure of NGM282 in patients with NASH. 
• In the double-blind and placebo-controlled 24-week histology cohorts, NGM282 
exposure will be compared to placebo at 2 hours post-dose at Day 1 and EOT and 
pre-dose at all on-treatment study visits. 
• In the open-label single-blind cohort, NGM282 exposure will be compared across the 
dosing groups at 2 hours post-dose at Day 1 and Week 12 and pre-dose at all 
on-treatment study visits. Additional PK samples will be collected at Baseline and 1, 
2, 4, 8, and 12 hours post-dose on Day 1 and Week 6 in a subset of subjects in each 
dosing group. 
Exposure of all doses from both double-blind and open-label single-blind cohorts will be 
compared to each other as well as to exposure in other study populations treated with 
NGM282 (Studies 12-0101, 13-0102, 13-0103, 14-0104, and 15-0106). 
The impact of rosuvastatin administered in response to increases in total cholesterol and 
LDL-C from NGM282 treatment will be evaluated. 
Exploratory Parameters: 
• 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12.9.2 
Analysis of Primary Endpoint 
The analysis of the primary endpoint will be based on the Efficacy population. 

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The absolute change in liver fat content from Baseline to EOT will be compared between 
treatment groups using an analysis of covariance (ANCOVA) model with treatment group 
and diabetic status (double-blind cohort only) as cofactors and Baseline endpoint as a 
covariate. Least square means with standard errors (SEs), differences in least square means 
with SE, 95% CIs for the difference in least square means, and corresponding p-values will 
be presented. Further covariates/cofactors may be included in the modeling depending on the 
relevance to the endpoint analyzed and will be further described in the SAP. 
In cases where the parameters do not follow a normal distribution, a non-parametric approach 
will be followed to analyze the difference between treatment groups.  
The primary analysis for the primary endpoint will be repeated for the Per Protocol 
population. 
12.9.3 
Analysis of Secondary Endpoints 
The analysis of secondary PD endpoints will be based on the Efficacy population, for all 
three cohorts separately. 
For continuous secondary endpoints the same method of analysis as for the primary endpoint 
will be followed. Further covariates/cofactors may be included in the modeling depending on 
the relevance to the endpoint analyzed and will be further described in the SAP. 
Categorical secondary endpoints (percentage of normalization) will be analyzed through a 
chi-square test. The difference between proportions along with 95% CIs for the difference 
between proportions will be presented by treatment-group comparisons. 
The analyses in the open-label single-blind cohorts will be stratified by statin use at Baseline 
whereas they will be stratified by fibrosis stage in the placebo-controlled 24-week histology 
cohort. The effect of statin use on lowering LDL cholesterol will also be explored both the 
open-label single-blind and placebo-controlled 24-week histology cohorts. In addition, 
sensitivity analyses will be performed to investigate the effect on the efficacy endpoints of 
statin use in the open-label single-blind cohorts and fibrosis stage on the placebo-controlled 
24-week histology cohort.  
Comparisons between the 3 cohorts will be performed and further detailed in the SAP. 
12.9.4 
Analysis of Exploratory Endpoints 
The analysis of exploratory endpoints will be based on the Efficacy population. 
For continuous exploratory endpoints the same method of analysis as for the primary 
endpoint will be followed. Further covariates/cofactors may be included in the modeling 
depending on the relevance to the endpoint analyzed and will be further described in the 
SAP. 

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12.10 
Safety 
Safety and tolerability will be assessed by clinical review of the following parameters: AEs, 
clinical laboratory tests, physical examination, and vital signs. All safety analyses will be 
conducted using the safety population. 
12.10.1 
Adverse Events 
AEs, including serious AEs, will be coded using the MedDRA. The number and percentage 
of subjects experiencing an AE will be summarized for each system organ class (SOC) and 
preferred term (PT) by treatment group. In addition, AEs will be tabulated according to 
intensity, causality, and relation to the study drug. Individual data listings for AEs will be 
presented for each subject. 
All AE summaries will be restricted to TEAEs only. TEAEs are defined as AEs that 
commence on or after the time of start of first study-drug administration. AEs without an 
onset date or time will be defined as treatment emergent, except if an incomplete date (e.g., 
month and year) clearly indicates that the event started prior to the start of first 
administration of study drug or if the AE stop date indicates that the event started or stopped 
prior to the start of first administration of study drug. 
For the summaries of AEs, subjects who experience the same AE (in terms of the MedDRA 
preferred term) more than once will be counted only once for that event. Separate summaries 
will be provided for AEs by intensity, causality, and relationship to study drug.  
All AEs will be listed. SAEs will be summarized and listed. 
12.10.2 
Clinical Laboratory Evaluations 
The absolute and percentage changes from Baseline to EOT and EOS of total cholesterol, 
HDL-C, LDL-C, and lipoprotein particles will be analyzed through inferential statistics and 
will be based on the Safety population. 
Observed values and absolute changes from Baseline to EOT and EOS for routine chemical 
laboratory values will be summarized descriptively at each time point for each treatment 
group and overall. Shift tables may also be presented for select chemistry and hematology 
laboratory parameters, as defined in the SAP.  
Individual data listings of laboratory results will be presented for each subject. Laboratory 
values will be compared to normal ranges; out-of-range and clinically significant laboratory 
values will be identified in the listings. 
12.10.3 
Physical Examinations 
Individual data listings for physical examination results will be presented for each subject. 

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12.10.4 
Vital Signs 
Observed values as well as absolute changes from Baseline will be summarized descriptively 
for all vital-sign parameters, by time point and treatment group. Individual data listings will 
be presented for each subject. 
12.10.5 
Pregnancy Test 
Individual listings for urine and serum pregnancy test data will be presented for each subject. 
12.10.6 
Electrocardiogram 
Observed values as well as absolute changes from Baseline will be summarized descriptively 
for all ECG parameters, by time point and treatment group. Individual data listings will be 
presented for each subject. 
12.10.7 
Injection-Site Reactions 
Frequency tabulations of ISR results will be presented at each time point by treatment group.  
12.10.8 
Concomitant Medications 
Concomitant medications will be classified using the current version of the World Health 
Organization Drug Dictionary Enhanced (2012). Concomitant medications are medications 
taken at least once from 28 days prior to Screening through the End of Study visit. 
Medications stopped on the 28 days prior to Screening time point will not be considered a 
concomitant medication. 
Individual data listings will be presented for each subject, with separate listings for prior 
medications and concomitant medications. In addition, concomitant medications will be 
summarized by Anatomical Therapeutic Chemical (ATC) classes and PT using frequency 
counts and percentages. For the summaries of concomitant medications, subjects who take 
the same medication (in terms of the preferred term) more than once will be counted only 
once for that medication. 
12.11 
Pharmacokinetics  
12.11.1 
Trough Serum Concentrations (All Subjects) 
The following PK parameters will be calculated using validated PK software, WinNonlin, 
Version 5.3 (or higher; Pharsight Corporation; Cary, NC, U.S.): 
• Day 1; Weeks 1, 2, 4, 8, 12, 18, and 24: trough concentration (Ctrough) 
• Day 1 and Week 12 or Week 24: Ctrough; concentration at 2 hours post-dose (C2h post-dose) 

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PK data will be used to evaluate the accumulation of NGM282 in the plasma of NASH 
patients following multiple-dose administration at 3 and 6 mg per day. This will be done by 
comparing the steady-state trough NGM282 levels in NASH patients to results obtained on 
Day 1 in the same subject and, more generally, in the dosing cohort. In addition, 
determination of NGM282 concentrations 2 hours post-dose on Day 1 and EOT will enhance 
information obtained on accumulation and provide an indication of expected maximum drug 
concentration (Cmax) in patients. This information will be directly compared to Phase 1 
results obtained in healthy volunteers as well as those obtained in patients with T2D, PBC, 
and primary sclerosing cholangitis. In addition, PK data will be used to explore PK/PD 
correlations in terms of drug efficacy and toxicity, where data allow. Actual sample times 
will be used in the data analysis. 
12.11.2 
Single-Dose Pharmacokinetics (Open-Label Single-Blind Subjects) 
The Day 1 PK data will be used to evaluate the single-dose PK of NGM282 in PBC patients 
at 0.3, 1, and 3 mg per day, using the PK population. For each subject, the following PK 
parameters will be calculated, whenever possible, based on the serum concentrations of 
NGM282 collected at pre-dose and 1, 2, 4, 8, and 12 hours after dosing on Day 1. 
• Cmax - maximum observed concentration 
• Tmax - time to maximum concentration 
• AUC0–t - area under the concentration–time curve from Hour 0 to the last measurable 
concentration, calculated using the linear trapezoidal rule  
• AUC0–∞ - area under the concentration–time curve extrapolated to infinity, calculated 
using the formula: 
AUC0–∞ = AUC0–t + 
z
t
λ
C
 
where Ct is the last measurable concentration and λZ is the apparent terminal elimination 
rate constant 
• t1/2 - apparent terminal elimination half-life, where t1/2 = (ln2)/λZ 
• CL/F - clearance divided by the bioavailable fraction calculated using this formula: 
Dose/AUC0–∞ 
• Vz/F - volume of distribution based on the terminal portion of the concentration–time 
curve divided by the bioavailable fraction, Dose / (AUC0–∞ × λz) 
The effect of dose level on NGM282 exposure will be assessed by evaluating Cmax and 
AUC0–t. Any substantial change in t1/2, CL/F, or Vz/F with dose will also be noted. 

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Further details will be specified in the SAP. 
12.11.3 
Multiple-Dose Pharmacokinetics (Open-label Single-blind Subjects) 
Week 6 PK data will be used to evaluate the effect of repeat dosing and potential 
accumulation of NGM282 following administration at 0.3, 1, and 3 mg per day, using the PK 
population. For each subject, the same PK parameters as listed in Section 12.11.2 will be 
calculated whenever possible, based on the serum concentrations of NGM282 collected at 
pre-dose and 1, 2, 4, 8, and 12 hours after dosing on Week 6. Where possible, AUC0–∞, t1/2, 
CL/F, and Vz/F will be used for the evaluation of time invariance in PK characteristics. 
Accumulation will be assessed by calculating Cmax, Week 4/Cmax, Day 1 and AUC0–t, Week 4/AUC0–t, 
Day 1 for each subject. 
In addition to the Week 6 versus Day 1 comparison, accumulation will also be assessed by 
comparing the trough and 2-hour post-dose NGM282 levels collected over the course of the 
study.  
PK parameters will be estimated, where appropriate, using validated commercial software. 
Additional software, if required, will be detailed in the SAP. Other parameters may be added 
as appropriate. PK analysis will use actual times as recorded on the CRF. 
12.12 
Interim Analysis  
A single interim analysis (IA) is planned to be conducted in the double-blind cohort after 
approximately 12 subjects per arm have completed 12 weeks of treatment. The final analysis 
of the double-blind cohort is planned to be conducted after all double-blind subjects have 
completed Week 16. The IA will include review of all safety and selected efficacy endpoints. 
The final analysis of the double-blind cohort will review all endpoints (safety, efficacy, and 
exploratory).  
The double blind will be maintained for the IA as the results in the summary listings and 
tables will be presented only by treatment group. The data will be fully unblinded at the final 
analysis of the double-blind cohort as the database will include all randomized and 
completed have undergone a soft-lock at that time.  
There will be no formal IAs performed in the open-label single-blind cohort. 
A single IA is planned to be conducted in the placebo-controlled 24-week cohort after at least 
50% subjects (2:1 randomization) have completed 24 weeks of treatment. The IA will 
include review of safety and selected efficacy endpoints by treatment group. The IA is being 
conducted only for internal planning purposes and the study will not be stopped early based 
on the results of the IA. Therefore, no formal hypothesis testing will occur with no effect on 
available alpha for the final planned analyses.  The final analysis is planned to be conducted 

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after all subjects have completed Week 30.  Results for individual subjects will not be shared 
with study investigators.  
Further details of the IA and final analyses, including statistical considerations and analyses, 
will be included in the SAP. 
 
13 
Administrative Aspects 
13.1 
Protocol Adherence 
The PI must adhere to the protocol as detailed in this document and agree that the Sponsor 
must approve any changes to the protocol prior to seeking approval from the EC. No 
alterations in the protocol will occur without agreement between the Sponsor and the PI. No 
alterations in the protocol affecting patient safety will occur without the express written 
approvals of the Sponsor, PI, and EC. 
13.2 
Disclosure 
All information provided regarding the study as well as all information collected/documented 
during the course of the study will be regarded as confidential. The PI agrees not to disclose 
such information in any way without prior written permission from the Sponsor. 
Any publication of the results either in part or in total (articles in journals or newspapers, oral 
presentations, abstracts, etc.) by the PI or their representative(s) shall require prior 
notification and review within a reasonable time frame by the Sponsor and cannot be made in 
violation of the Sponsor’s confidentiality restrictions or to the detriment of the Sponsor’s 
intellectual property rights. 
13.3 
Monitoring 
The Sponsor’s or designee’s Clinical Research Associate (CRA) will be responsible for 
monitoring this clinical trial. The CRA will monitor the study conduct, proper CRF and 
source documentation completion and retention, and accurate study-drug accountability. 
To this end, the CRA will visit the study site at suitable intervals and be in frequent contact 
through verbal and written communication. The PI will grant access to all documents (related 
to the study and the individual subjects) at any time these are requested. In turn, the CRA 
will adhere to all requirements for patient confidentiality as outlined in the ICF. The PI and 
PI’s staff will be expected to cooperate with the CRA, to be available during a portion of the 
monitoring visit to answer questions, and to provide any missing information. 

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13.4 
Ethics Committee 
This protocol, the informed consent document, and all relevant supporting data must be 
submitted to the EC for approval. EC approval of the protocol, informed consent document, 
and any advertisement used to recruit study patients must be obtained before the study may 
be initiated. 
The PI is responsible for keeping the EC advised of the progress of the study and of any 
changes made to the protocol as deemed appropriate, but in any case, at least once a year. 
The PI is also responsible for notifying the EC of any reportable AEs that occur during the 
study. 
13.5 
Informed Consent 
This study will be conducted in compliance with International Conference on Harmonisation 
(ICH) E6 Good Clinical Practice: Consolidated Guidelines pertaining to informed consent. 
At the first visit, prior to initiation of any study-related procedures, patients must give their 
written consent to participate in the study after having been informed about the nature and 
purpose of the study, participation/termination conditions, and risks and benefits. 
The informed consent document must be signed and dated by the patient and PI, or designee, 
prior to study participation. A copy of the informed consent document must be provided to 
the patient. Signed consent forms must remain in the patient’s study file and be available for 
verification by Sponsor or its representative at any time. 
13.6 
Records 
The results from Screening and data collected during the study will be recorded in the 
patient’s CRF. To maintain confidentiality, the patients will be identified only by numbers 
and initials. 
The completed CRFs will be transferred to the Sponsor or designee. Copies of each CRF will 
be retained by the PI. All source documents, records, and reports will be retained by the 
clinic. 
All primary source data or copies thereof (e.g., laboratory records, CRFs, data sheets, 
correspondence, photographs, and computer records) that are a result of the original 
observations and activities of the study and are necessary for the reconstruction and 
evaluation of any study report will be retained in the clinic archives. 
Sponsor will inform the PI of the time period for retaining these records to comply with all 
applicable regulatory requirements. The minimum retention time will meet the strictest 
(longest) standard applicable to that site for the study, as dictated by any institutional 
requirements or local laws or regulations, or Sponsor standards/procedures; otherwise, the 

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retention period will default to the retention period of 15 years following completion of the 
clinical trial.  
13.7 
Financing and Insurance 
The financing and insurance for this study are outlined in the Clinical Trial Research 
Agreement.  

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Investigator Protocol Review and Signature Form 
Protocol Number: 
15-0105 
 
Protocol Title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group 
Multiple-Center Study with Additional Open-Label Single-Blind and Placebo-Controlled 
24-Week Histology Cohorts to Evaluate the Safety, Tolerability, and Efficacy of NGM282 
Administered for Up to 24 Weeks in Patients with Histologically Confirmed Nonalcoholic 
Steatohepatitis (NASH) 
 
I have read the above-mentioned Protocol Amendment 9 dated 29 March 2019 
I agree to conduct the study as detailed herein and in compliance with ICH Guidelines for 
Good Clinical Practice and applicable regulatory requirements, and to inform all who assist 
me in the conduct of this study of their responsibilities and obligations.  
 
 
 
 
 
__________________________________________ 
Principal Investigator (Please PRINT) 
 
 
 
__________________________________________ 
__________________ 
Principal Investigator (Signature) 
 Date 
 
 
__________________________________________ 
Name of Institution (Please PRINT) 
 

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14 
References 
14.1 
Clinical Study References 
Study No. 
Phase 
Study Title 
Study Population 
12-0101 
1 
A Phase 1 Randomized, Double Blind, Placebo Controlled, 
Single Ascending Dose and Multiple Ascending Dose Study to 
Evaluate the Safety, Tolerability, and Pharmacokinetics of 
NGM282 in Healthy Adult Participants 
Normal 
volunteers 
13-0102 
2a 
A Randomized, Double Blind, Placebo Controlled, Parallel 
Group, Multiple Center Study to Evaluate the Safety, 
Tolerability, and Activity of NGM282 Administered for 28 Days 
to Participants with Type 2 Diabetes Mellitus 
T2D 
13-0103 
2a 
A Phase 2, Randomized, Double Blind, Placebo Controlled, 
Parallel Group, Multiple Center Study to Evaluate the Safety, 
Tolerability, and Pharmacodynamic Activity of NGM282 in 
Combination with Ursodeoxycholic Acid (UDCA) Administered 
for 28 Days in Patients with Primary Biliary Cirrhosis (PBC) 
PBC 
14-0104 
2b 
A Phase 2, Multicenter Study to Evaluate Four Doses of 
NGM282 Administered For 52 Weeks in Patients with Primary 
Biliary Cirrhosis (PBC) 
PBC 
15-0106 
2 
A Phase 2, Randomized, Double Blind, Placebo Controlled, 
Parallel Group, Multiple Center Study to Evaluate the Safety, 
Tolerability, and Efficacy of NGM282 Administered for 
12 Weeks in Patients with Primary Sclerosing Cholangitis (PSC) 
PSC 
 
14.2 
Nonclinical Study References 
Study No 
Study Title 
Study 11-MP-NGM282-1001 
Direct Effects of NGM282 on Mouse and Human Adipocytes 
Study 11-MP-NGM282-1002 
Analysis of NGM282 Binding to Fibroblast Growth Factor Receptors 
Study 11-PD-NGM282-1001 
A 24-week Study of Ectopic NGM282 Expression following Intravenous 
Adeno-Associated Viral Delivery to db/db Mice 
Study 11-PD-NGM282-1003 
A Single or 14-Day Efficacy Study of NGM282 Following Subcutaneous 
Administration in ob/ob Mice 
Study 11-PD-NGM282-1004 
Effects of NGM282 on Glucose Metabolism and Body Weight Following 
14-Day Daily Subcutaneous Administration in Diet-Induced Obese (DIO) 
Mice 
Study 11-TX-NGM282-1002 
A 28-Day Subcutaneous Toxicity and Toxicokinetic Study with NGM282 in 
Cynomolgus Monkeys with a 14-Day Recovery Phase 
Study 12-MP-NGM282-1006 
Effects of NGM282 Treatment on CYP7a1 Expression in Primary Mouse, 
Rat, and Human Hepatocytes 
Study 13-MP-NGM282-1004 
NGM282 Activation of Elk-1 in L6 Cells Expressing Mouse, Rat, Rabbit, 
Cynomolgus, or Human FGFR1c-βklotho Co-Receptors 
Study 13-MP-NGM282-1005 
Activation of FGFR4-β-klotho-Mediated Signaling by NGM282 in a Rat 
Myoblast Cell Line 
Study 13-PD-NGM282-1007 
A 24-Week Study of Ectopic NGM282 Expression following Intravenous 
Adeno-Associated Viral Delivery in FXR-deficient Mice 
Study 13-TX-NGM282-1004 
A 13/26-Week Subcutaneous Toxicity and Toxicokinetic Study of NGM282 
in Cynomolgus Monkey 
 
 
 

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15 
Appendices 
Appendix A. NASH Clinical Research Network (CRN) NAFLD Activity Score and 
Fibrosis Score 
Steatosis 
S 
Score 
Lobular 
Inflammation 
L 
Score 
Hepatocyte 
Ballooning 
B 
Score 
< 5% 
0 
None 
0 
None 
0 
5%–33% 
1 
< 2 
1 
Few ballooned cells 
1 
34%–66% 
2 
2–4 
2 
Many ballooned cells 
2 
> 66% 
3 
> 4 
3 
— 
— 
NAFLD = nonalcoholic fatty liver disease. 
Note: NAFLD activity grade score = total score: S + L + B (range 0–8). 
 
Fibrosis Stage 
Score 
0 
No Fibrosis 
1a 
Zone 3, Mild 
1b 
Zone 3, Moderate 
1c 
Periportal Only 
2 
Zone 3 and Periportal 
3 
Bridging 
4 
Cirrhosis 
 
 
 

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Appendix B. Food and Drug Administration Toxicity Grading Scale: 
Clinical Abnormalities in Local Injection-Site Symptom Assessments 
Local Reaction to 
Injection Product 
Mild 
(Grade 1) 
Moderate 
(Grade 2 ) 
Severe 
(Grade 3) 
Potentially  
Life-Threatening 
(Grade 4) 
Pain 
Does not 
interfere with 
activity 
Repeated use of 
non-narcotic 
pain reliever 
more than 
24 hours or 
interferes with 
activity 
Any use of 
narcotic pain 
reliever or 
prevents daily 
activity 
Emergency room 
(ER) visit or 
hospitalization 
 
 
 
 
 
Tenderness 
Mild discomfort 
to touch 
Discomfort with 
movement 
Significant 
discomfort at rest 
ER visit or 
hospitalization 
 
 
 
 
 
Erythema/Redness a 
2.5–5 cm 
5.1–10 cm 
> 10 cm 
Necrosis or 
exfoliative 
dermatitis 
 
 
 
 
 
Induration/Swelling b 
2.5–5 cm and 
does not 
interfere with 
activity 
5.1–10 cm or 
interferes with 
activity 
> 10 cm or 
prevents daily 
activity 
Necrosis 
ER = emergency room. 
Note: The FDA Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers enrolled in 
Preventive Vaccine Clinical Trials can be found at  
http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/
Vaccines/ucm074775.htm. 
a. In addition to grading the measured local reaction at the greatest single diameter, the measurements 
should be recorded as a continuous variable. 
b Induration or Swelling should be evaluated and graded using the functional scale as well as the actual 
measurement. 
 
 
 

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Appendix C. Rosuvastatin Package Insert 
The package insert for rosuvastatin currently being used in the open-label single-blind cohort 
can be found at the following web link: 
 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/079167Orig1s000lbl.pdf  
 
The package insert for rosuvastatin currently being used in the placebo-controlled 24-week 
histology cohort can be found at the following web link: 
 
http://www.torrentian.com/pisheet/Upload/PI_Sheet_US/181_2.pdf 
 
 

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Appendix D. Ezetimibe Package Insert 
 
The package insert for ezetimibe related to the placebo-controlled 24-week histology cohort 
can be found at the following web link: 
 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/021445s019lbl.pdf