Evaluation of Efficacy, Safety and Tolerability of NGM282 (Aldafermin) in a Phase 2b, Randomized, Double-blind, Placebo-controlled, Multi-center Study in Subjects With Compensated Cirrhosis Due to Nonalcoholic Steatohepatitis (ALPINE 4)
Phase: PHASE2
Conditions: Compensated Cirrhosis, Nonalcoholic Steatohepatitis
Sponsor: NGM Biopharmaceuticals, Inc



Aldafermin (NGM282) 
Study 282-CC-207 (ALPINE 4) Protocol v6.0, 11 Nov 2021 
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INVESTIGATOR PROTOCOL APPROVAL AND SIGNATURE PAGE 
Protocol Title 
Evaluation of Efficacy, Safety and Tolerability of NGM282 
(Aldafermin) in a Phase 2b, Randomized, Double-blind, Placebo-
controlled, Multi-center Study in Subjects with Compensated 
Cirrhosis Due to Nonalcoholic Steatohepatitis (ALPINE 4) 
Protocol Number 
282-CC-207 
Name of Investigational 
Product 
Aldafermin (NGM282)  
Date of Issue/Version # 
11 November 2021, Version 6.0  
 
INVESTIGATOR STATEMENT 
 
I have read the protocol, including all appendices, and I agree that it contains all necessary 
details for me and my staff to conduct this study as described. I will conduct this study as 
outlined herein and will make a reasonable effort to complete the study within the time 
designated. 
I will provide all study personnel under my supervision copies of the protocol and access to 
all information provided by NGM Biopharmaceuticals, Inc. I will discuss this material with 
them to ensure that they are fully informed about the drugs and the study. 
 
 
 
Principal Investigator Name (Printed) 
 
Signature  
 
 
 
Date (DD MMM YYYY) 
 
Site Number 

Aldafermin (NGM282) 
Study 282-CC-207 (ALPINE 4) Protocol v6.0, 11 Nov 2021 
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TABLE OF CONTENTS 
TITLE PAGE ............................................................................................................... 1 
SPONSOR PROTOCOL APPROVAL AND SIGNATURE PAGE .......................... 2 
INVESTIGATOR PROTOCOL APPROVAL AND SIGNATURE PAGE ............... 3 
PROTOCOL CHANGE HISTORY ............................................................................ 4 
TABLE OF CONTENTS ............................................................................................. 8 
List of Tables ............................................................................................................. 12 
List of Figures ............................................................................................................ 12 
List of Abbreviations ................................................................................................. 13 
1. 
SYNOPSIS ............................................................................................. 16 
2. 
INTRODUCTION .................................................................................. 34 
2.1. 
Background ............................................................................................. 34 
2.2. 
Cirrhosis Pathophysiology ...................................................................... 35 
2.3. 
Current Treatments for NASH Cirrhosis ................................................ 36 
2.4. 
Mechanism of Action of Aldafermin ...................................................... 37 
2.5. 
Therapeutic Rationale for Aldafermin in NASH .................................... 37 
2.6. 
Nonclinical Studies ................................................................................. 38 
2.7. 
Clinical Experience ................................................................................. 39 
2.8. 
Rationale for Dose Selection .................................................................. 43 
3. 
STUDY OBJECTIVES AND ENDPOINTS .......................................... 45 
3.1. 
Primary Objective and Endpoints ........................................................... 45 
3.2. 
Secondary Efficacy Objectives and Endpoints ....................................... 45 
3.3. 
Exploratory Endpoints ............................................................................ 46 
4. 
STUDY DESIGN ................................................................................... 48 
4.1. 
Methodology/Study Design: ................................................................... 48 
4.2. 
Study Stop Criteria ................................................................................. 52 
5. 
SUBJECT SELECTION ......................................................................... 53 
5.1. 
Inclusion Criteria .................................................................................... 53 
5.2. 
Exclusion Criteria ................................................................................... 56 
6. 
STUDY TREATMENT .......................................................................... 60 
6.1. 
Clinical Supplies ..................................................................................... 60 
6.1.1. 
Aldafermin .............................................................................................. 60 

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6.1.2. 
Aldafermin-matched Placebo ................................................................. 60 
6.1.3. 
Rosuvastatin / Placebo ............................................................................ 60 
6.1.3.1. 
Rosuvastatin Supply ............................................................................... 60 
6.2. 
Preparation / Handling / Storage / Accountability .................................. 61 
6.2.1. 
Preparation .............................................................................................. 61 
6.2.1.1. 
Aldafermin .............................................................................................. 61 
6.2.1.2. 
Rosuvastatin / Placebo ............................................................................ 61 
6.2.2. 
Storage .................................................................................................... 61 
6.2.3. 
Accountability ......................................................................................... 61 
6.3. 
Randomization and Blinding .................................................................. 62 
6.3.1. 
Removal of Study Blind (if applicable) .................................................. 62 
6.4. 
Concomitant Medications ....................................................................... 62 
6.4.1. 
Prohibited Medications: .......................................................................... 62 
6.4.2. 
Restricted Concomitant Medications / Treatments: ............................... 63 
7. 
STUDY TREATMENT DISCONTINUATION AND SUBJECT 
DISCONTINUATION / WITHDRAWAL FROM THE STUDY ......... 65 
7.1. 
Discontinuation of Study Treatment for an Individual Subject .............. 65 
7.1.1. 
Specific Actions Taken Will Be As Follows: ......................................... 65 
7.2. 
Discontinuation of Subjects from Study Participation ........................... 68 
8. 
STUDY PROCEDURES ........................................................................ 69 
8.1. 
Schedule of Study Procedures ................................................................ 69 
8.2. 
Study Visit Procedures ........................................................................... 74 
8.2.1. 
Screening - Day -56 (Screening) Procedures .......................................... 74 
8.2.2. 
Day –42 to Day -1 (Screening) Procedures ............................................ 75 
8.2.3. 
Day 1 Procedures .................................................................................... 75 
8.2.4. 
Week 2 Procedures ................................................................................. 77 
8.2.5. 
Week 6 Procedures ................................................................................. 78 
8.2.6. 
Week 12 Procedures ............................................................................... 79 
8.2.7. 
Week 18 Procedures ............................................................................... 81 
8.2.8. 
Week 24 Procedures ............................................................................... 82 
8.2.9. 
Week 30 Procedures ............................................................................... 84 
8.2.10. 
Week 36 Procedures ............................................................................... 85 
8.2.11. 
Week 42 Procedures ............................................................................... 86 

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8.2.12. 
Week 48 / Early Withdrawal (End of Treatment) Procedures ................ 87 
8.2.13. 
Week 49 Procedures ............................................................................... 90 
8.2.14. 
Week 54 (End of Study) Procedures ...................................................... 90 
8.2.15. 
Week 58 (Lipid Monitoring Assessment 4 Week Follow-up Visit 
Procedures) ............................................................................................. 92 
8.2.16. 
Monitoring of Anti-Drug Antibody Response ........................................ 92 
8.3. 
Clinical Evaluations ................................................................................ 92 
8.3.1. 
Alcohol Consumption ............................................................................. 92 
8.3.1.1. 
AUDIT-C ................................................................................................ 92 
8.3.1.2. 
PEth Screening ........................................................................................ 93 
8.3.1.3. 
History of Alcohol Consumption ............................................................ 93 
8.3.2. 
Liver Biopsy ........................................................................................... 93 
8.3.3. 
CPA and SHG ......................................................................................... 93 
8.3.4. 
CLDQ NASH.......................................................................................... 94 
8.3.5. 
Transient Elastography and Ultrasound Attenuation Rate (Steatosis) 
using (FibroScan®) Device ..................................................................... 94 
8.3.6. 
Esophagogastroduodenoscopy (EGD) .................................................... 94 
8.3.7. 
Pharmacokinetic Blood Sample Collection and Processing ................... 95 
8.3.8. 
Clinical Laboratory Evaluations ............................................................. 95 
8.3.9. 
C4 Testing ............................................................................................... 95 
8.3.10. 
Serum Bile Testing ................................................................................. 95 
8.3.11. 
12 -Lead Electrocardiograms .................................................................. 96 
8.3.12. 
Vital Signs .............................................................................................. 96 
8.3.13. 
Physical Examinations and RUQ Pain Assessment ................................ 96 
8.3.14. 
Weight, Body Mass Index, and Waist Circumference Measurements ... 96 
8.3.15. 
Local Injection-Site Symptom Assessments (LISSA) ............................ 96 
8.3.16. 
Evaluation of Biomarkers ....................................................................... 97 
8.3.17. 
Lipid Lowering Therapy Assessment ..................................................... 97 
8.3.18. 
Diet and Activity Control ....................................................................... 98 
8.3.19. 
MRI, CT, and Ultrasound for HCC Testing ........................................... 98 
8.3.20. 
Evaluation of Biomarkers ....................................................................... 99 
8.4. 
Safety and Other Assessments ................................................................ 99 
8.4.1. 
Definition of Adverse Events ................................................................. 99 

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8.4.2. 
Definition of Serious Adverse Events and SAE Reporting .................. 100 
8.4.3. 
Classification of Severity of Adverse Event ......................................... 100 
8.4.3.1. 
Relationship to Study Drug .................................................................. 101 
8.5. 
Safety Monitoring ................................................................................. 101 
8.5.1. 
Data Safety Monitoring Board .............................................................. 101 
8.5.2. 
Independent Adjudication ..................................................................... 102 
9. 
STATISTICAL CONSIDERATIONS ................................................. 103 
9.1. 
Sample Size Determination .................................................................. 103 
9.2. 
Analysis Populations ............................................................................ 104 
9.3. 
Demographics and Other Baseline Characteristics ............................... 104 
9.4. 
Efficacy Analyses ................................................................................. 104 
9.4.1. 
Primary Efficacy Analysis .................................................................... 104 
9.4.2. 
Secondary Efficacy Analyses ............................................................... 105 
9.4.3. 
Other Efficacy Analyses ....................................................................... 105 
9.4.4. 
Subgroup Analyses ............................................................................... 105 
9.5. 
Safety Analyses .................................................................................... 105 
9.6. 
Interim Analysis .................................................................................... 106 
9.7. 
Pharmacokinetics .................................................................................. 106 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................ 107 
10.1. 
Regulatory, Ethical, and Study Oversight Considerations ................... 107 
10.1.1. 
Informed Consent Process .................................................................... 107 
10.1.2. 
Ethics Committee .................................................................................. 107 
10.1.3. 
Data Safety Monitoring Board (DSMB) ............................................... 107 
10.1.4. 
Protocol Adherence .............................................................................. 107 
10.1.5. 
Confidentiality and Privacy .................................................................. 108 
10.1.6. 
Clinical Monitoring .............................................................................. 108 
10.1.7. 
Quality Assurance and Quality Control ................................................ 108 
10.1.8. 
Records ................................................................................................. 108 
10.1.9. 
Financing and Insurance ....................................................................... 109 
10.1.10. 
Publication Policy ................................................................................. 109 
11. 
REFERENCES ..................................................................................... 110 
11.1. 
Clinical Studies Referenced in this Protocol ........................................ 110 

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11.2. 
Nonclinical Studies Referenced in this Protocol .................................. 110 
11.3. 
Literature References ............................................................................ 111 
12. 
APPENDICES ...................................................................................... 117 
Appendix 1. NASH Clinical Research Network NAFLD Activity Score and 
Fibrosis Score ....................................................................................... 117 
Appendix 2. Food and Drug Administration Toxicity Grading Scale: Clinical 
Abnormalities in Local Injection Site Symptom Assessments ............. 118 
Appendix 3. AUDIT-C Alcohol Consumption Questionnaire .............................. 119 
Appendix 4. Lipid Lowering Algorithm: Statin Naïve and Stain Experienced 
Subjects ................................................................................................. 121 
Appendix 5. Rosuvastatin Package Insert ............................................................. 122 
Appendix 6. Prohibited Hepatotoxic Agents ......................................................... 123 
 
List of Tables 
Table 1. 
Summary of Aldafermin Efficacy in Mouse NASH Models .................. 38 
Table 2. 
Change from Baseline to Week 12 in MRI-PDFF in NASH Subjects ... 40 
Table 3. 
Changes in Noninvasive Imaging and Biomarkers from Baseline to 
Week 12 in the Single-Blind Cohort in Study 15-0105 .......................... 41 
Table 4. 
Histologic Measures in the 1 mg and 3 mg Single-blind Histology 
Cohorts in Study 15-0105 ....................................................................... 42 
Table 5. 
Change from Baseline to Week 24 in Key Parameters: Interim Analysis 
of a 24-week, Double-blind, Placebo-controlled Study of Aldafermin 
(15-0105, Part 3) in Patients with NASH ............................................... 43 
Table 6. 
Study Design 282-CC-207 (Versions 1.0-4.0) ....................................... 49 
Table 7. 
Study Design 282-CC-207 (Version 5.0) ............................................... 49 
Table 8. 
Schedule of Assessments ........................................................................ 70 
Table 9. 
Categorization of Severity of Adverse Events ...................................... 101 
Table 10. 
Categorization for Determining Relationship of AEs to Study 
Treatment .............................................................................................. 101 
Table 11. 
Power Simulations for the Primary Efficacy Analysis ......................... 103 
 
List of Figures 
Figure 1. 
Absolute ALT and AST Values by Study Visit during and after 
Aldafermin Treatment ............................................................................ 40 
Figure 2. 
Schematic Overview of the Study Design .............................................. 49 
 

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List of Abbreviations 
Abbreviation 
Definition/Explanation 
AAV 
Adeno-associated virus 
ADA 
Anti-drug antibody 
ADL 
Activities of daily living 
AE 
Adverse event 
AFP 
Alpha fetoprotein 
 
  
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
ASCVD 
Atherosclerotic Cardiovascular Disease  
ASK1 
Apoptosis signal-regulating kinase 1 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
AUC 
Area under the concentration–time curve 
BA 
Bile acid 
BLM 
Baseline measurements 
BMI 
Body mass index 
C4h post-dose 
Concentration at 4 hours post-dose 
C4 
7-alpha-hydroxy-4-cholesten-3-one 
CBC 
Complete blood count (hematology clinical laboratory evaluations) 
CCR2 / CCR5 
C-C chemokine receptor type 2 / C-C chemokine receptor type 5 
CHMP 
Committee for Medicinal Products for Human Use (European Medicines Agency) 
CI 
Confidence interval 
CK 
Creatine kinase 
CL/F 
Clearance divided by the bioavailable fraction 
CLDQ-NASH 
Chronic Liver Disease Questionnaire for NASH 
Cmax 
Maximum drug concentration 
CMH 
Cochran-Mantel-Haenszel 
CPA 
Collagen proportional area 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
CRN 
Clinical Research Network 
cT1 
Corrected T1 
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctrough 
Trough concentration 
CV 
Cardiovascular 
CYP7A1 
Cholesterol 7α hydroxylase 
D 
Day 
DBC 
Double blind cohort 
DILI 
Drug-Induced Liver Injury 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
EGD 
Esophagogastroduodenoscopy, aka upper endoscopy 
ELF 
Enhanced liver fibrosis 
EOS 
End of Study 
EOT 
End of Treatment 
ER 
Emergency room 
F4 
Fibrosis stage 4 cirrhosis 
FDA 
Food and Drug Administration 
FGF19 
Fibroblast growth factor 19 
FXR 
Farnesoid X receptor 
GGT 
Gamma-glutamyl transpeptidase 
GI 
Gastrointestinal 

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Abbreviation 
Definition/Explanation 
GLP 
Good Laboratory Practice 
GLP1 
Glucagon-like peptide-1 
GRE 
Gradient recalled echo 
HbA1C 
Hemoglobin A1C 
HBsAg 
Hepatitis B virus surface antigen 
HCC 
Hepatocellular carcinoma 
HCV 
Hepatitis C virus 
HDL 
High-density lipoprotein 
HDL-C 
High-density lipoprotein-cholesterol 
HIV 
Human immunodeficiency virus 
h 
Hour(s) 
HOMA-IR 
Homeostasis model assessment–estimated insulin resistance 
 
 
HVPG 
Hepatic venous pressure gradient measurement 
IA 
Interim analysis 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonisation 
INR 
International Normalized Ratio 
ISR 
Injection-site reaction 
ITT 
Intent-to-treat 
 
 
LDL 
Low-density lipoprotein 
LDL-C 
Low-density lipoprotein-cholesterol 
LFC 
Liver fat content 
LI-RADS 
Liver Imaging and Reporting Data System 
LISSA 
Local injection-site symptom assessment 
LLT 
Lowest Level Term (MedDRA) 
MAD 
Multiple ascending dose 
MAR 
Missing at random 
MCP-Mod 
Multiple Comparison Procedure – Modelling 
MedDRA 
Medical Dictionary for Regulatory Activities 
MELD 
Model for end-stage liver disease 
MI 
Multiple imputation 
mITT 
Modified intent to treat 
MMRM 
Mixed model for repeated measures 
MRI 
Magnetic resonance imaging 
MRI-PDFF 
Magnetic resonance imaging–proton density fat fraction 
n 
Number 
NAb 
Neutralizing antibody 
NAFLD 
Nonalcoholic fatty liver disease 
NAS 
NAFLD Activity Score 
NASH 
Nonalcoholic steatohepatitis 
NGM 
NGM Biopharmaceuticals, Inc. 
NIH 
National Institutes of Health 
No. 
Number 
NOAEL 
No-observed-adverse-effect level 
NPO 
Nothing by mouth  
NRS 
Numeric Rating Scale 
NZW 
New Zealand White 
OCA 
Obeticholic acid 
PBC 
Primary biliary cholangitis 
PD 
Pharmacodynamics; pharmacodynamic 
PDFF 
Proton density fat fraction 
PEth 
Phosphatidylethanol 

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Abbreviation 
Definition/Explanation 
PI 
Principal investigator 
PIIINP 
Propeptide of type III procollagen 
PK 
Pharmacokinetics; pharmacokinetic 
PNPLA3 
Patatin-like phospholipase domain-containing protein 3 
PP 
Per protocol 
Pro-C3 
Novel serum marker deriving exclusively from collagen III synthesis and deposition 
PSC 
Primary sclerosing cholangitis 
PT 
Preferred term 
REML 
Restricted maximum likelihood 
RUQ 
Right upper-quadrant 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SBC 
Single blind cohort 
SC 
Subcutaneous 
SD 
Standard deviation 
SHG 
Second Harmonic Generation  
SHP 
Small heterodimer partner 
SNP 
Single nucleotide polymorphism 
SOC 
System organ class OR Standard of care 
SOP 
Standard Operating Procedure 
t1/2 
Apparent terminal elimination half-life 
T2D 
Type 2 Diabetes 
TBL 
Total bilirubin 
TEAE 
Treatment-emergent adverse event 
TIA 
Transient ischemic attack 
TIMP-1 
Tissue inhibitor of metalloproteinase 1 
TNF 
Tissue necrosis factor 
Tmax 
Time to maximum concentration 
UA 
Urinalysis 
ULN 
Upper limit of the normal range 
 

Aldafermin (NGM282) 
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1. 
SYNOPSIS 
Synopsis 
Study 282-CC-207 
Protocol Title:  
Evaluation of Efficacy, Safety and Tolerability of NGM282 
(Aldafermin) in a Phase 2b, Randomized, Double-blind, 
Placebo-controlled, Multi-center Study in Subjects with Compensated 
Cirrhosis Due to Nonalcoholic Steatohepatitis (ALPINE 4) 
Protocol 
Number: 
282-CC-207 
Phase: 
2b 
Investigational 
Product: 
NGM282 
International nonproprietary name (INN): aldafermin 
Primary 
Objective and 
Endpoints  
The primary objective of this study is to evaluate the efficacy and 
safety of aldafermin compared to placebo.  
1. The primary efficacy endpoint is the change in Enhanced Liver 
Fibrosis (ELF) score from baseline to Week 48 with aldafermin or 
matched placebo. 
2. The primary safety endpoint is frequency, severity, and timing of 
adverse events (AEs) and serious adverse events (SAEs).  
Secondary 
Objectives and 
Endpoints 
The secondary objectives of this study are to evaluate the efficacy of 
aldafermin and the effect of aldafermin on pharmacokinetics and on 
biomarkers of target engagement, fibrogenesis, and imaging. 
The following will be measured:  
1. Improvement in liver fibrosis greater than or equal to one stage 
(NASH CRN fibrosis score) and no worsening of steatohepatitis 
(defined as no increase in NAFLD Activity Score [NAS] for 
ballooning, inflammation, or steatohepatitis), after 48 weeks of 
treatment with aldafermin or matched placebo, in subjects who had 
a minimum 1 point in each category (hepatocellular ballooning, 
steatohepatitis, and lobular inflammation) of NAS at baseline as 
determined by the central pathologist evaluation. 
2. Improvement in liver fibrosis greater than or equal to one stage 
(NASH CRN fibrosis score) after 48 weeks of treatment with 
aldafermin or matched placebo. 
3. Changes from baseline in fibrosis as measured by Collagen 
Proportionate Area (CPA) and/or Second Harmonic Generation 
(SHG) methodologies at Week 48. 
4. Aldafermin concentrations pre-dose at all treatment visits and 
4-hours post-dose at Day 1, Week 24, and Week 48 in all subjects. 

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Synopsis 
Study 282-CC-207 
b. Previous biopsy showed steatohepatitis, but now with cirrhosis 
either by clinical history or current features, imaging, 
noninvasive tests, or biopsy. If there is a current biopsy, it does 
not show evidence of steatosis or steatohepatitis, as these 
histological findings may have disappeared (burn-out). There is 
no evidence for a competing etiology. There is at least 1 
coexisting or history of metabolic comorbidity to corroborate a 
diagnosis of NAFLD. 
c. Current biopsy shows cirrhosis with steatosis. There is no 
evidence for competing etiology. There are at least 2 coexisting 
or history of metabolic comorbidities, including obesity and/or 
T2DM to corroborate a diagnosis of NAFLD. 
Have AFP ≤20 ng/mL at Screening.  
Negative for hepatic lesions/nodules indicating HCC risk: 
a. MRI is the preferred imaging modality. There must be no 
nodules with a Liver Imaging and Reporting Data System 
(LI-RADS) score of ≥2 by central radiologist evaluation. 
b. If MRI is not available or not possible to be performed, a 
multi-phasic CT scan may be used to assess HCC risk. There 
must be no nodules with a LI-RADS score ≥2 by central 
radiologist evaluation. 
c. If MRI and CT are not available or not possible to be performed 
for screening a potential subject, then ultrasonography of the 
liver may be performed: 
i. If no hepatic lesions or nodules (local radiologist evaluation) 
and AFP ≤20 ng/mL, the potential subject may be 
considered further for enrollment. 
ii. For any findings of hepatic lesions or nodules (local 
radiologist evaluation) that are not clearly benign cysts and 
have not been shown clearly benign by prior CT or MRI, 
follow-up MRI must be performed and meet criteria (no 
nodules with LI-RADS score of ≥2 evaluated centrally) in 
order for the potential subject to be considered further for 
enrollment. 
7. Subjects with T2D or insulin resistance are permitted as long as 
diabetic medications are reasonably “stable” within 3 months prior 
to Screening, as outlined in Section 6.4. 
8. Other concomitant medications/therapies used for the treatment of 
coexisting conditions are acceptable (Section 6.4), if on a stable 

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Synopsis 
Study 282-CC-207 
regimen for at least 3 months prior to the Screening, except for 
non-statin lipid lowering agents, which can be used until Day 1 of 
Screening. 
9. Statin use is acceptable based on the following criteria, as assessed 
by the investigator at Screening: 
a. Statin-naïve is defined as no administration of statins within 
3 months prior to Screening 
b. Statin-Experienced is defined as currently receiving ≤50% of 
the maximal approved dose of statin therapy  
i. Requires a reasonably stable statin dose at least 3 months 
prior to Screening. 
Note: The following are the acceptable daily doses of approved 
statin therapies, and other lipid lowering agents. Also listed under 
Section 6.4: 
i. 
Atorvastatin: ≤40 mg/day 
ii. 
Fluvastatin: ≤40 mg/day 
iii. 
Lovastatin: ≤40 mg/day (for both immediate and 
extended release) 
iv. 
Pitavastatin: ≤2 mg/day 
v. 
Pravastatin: ≤40 mg/day 
vi. 
Simvastatin: ≤40 mg/day 
vii. 
Rosuvastatin: ≤20 mg/day  
10. The following additional laboratory parameters must be met at 
Screening  
a. Total bilirubin ≤1.3 mg/dL 
i. if Gilbert’s Syndrome, with direct bilirubin within ULN.  
b. HbA1c ≤9.5%  
c. Platelet count ≥120,000/mm3  
Subjects who meet the Baveno VI criteria with a platelet count 
>110,000/mm3 and <120,000/mm3 may be enrolled if they meet 
the expanded Baveno VI criteria (Note: No more than 30% of 
the remaining population will be enrolled using the Baveno VI 
criteria). 

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Synopsis 
Study 282-CC-207 
d. Creatinine clearance ≥60 mL/min as calculated by 
Cockcroft-Gault equation  
e. Serum alanine amino transferase (ALT) levels ≤5 x ULN 
f. Serum aspartate amino transferase (AST) levels ≤5 x ULN 
g. Alkaline phosphatase ≤1.5 x ULN 
h. Serum albumin ≥3.5 g/dL 
i. International normalized ratio (INR) ≤1.7. 
Note: A 10% laboratory variability is allowed on platelets and 
bilirubin values. Platelet variability does not apply to Baveno VI. 
11. Female subjects must be either of a) non-childbearing potential, 
defined as women who have had a hysterectomy, bilateral 
oophorectomy, medically documented ovarian failure, documented 
postmenopausal, or a follicle stimulating hormone ≥40 mIU/mL, 
OR b) if of childbearing potential, defined as including women 
<55 years of age with ≤2 years of amenorrhea (absence of 
menstruation and not due to any reversible medical cause or any 
current medication use), then have a negative serum pregnancy test 
at Screening and urine pregnancy test at the Day 1 visit prior to first 
dose of study drug, and must be non-lactating and non-
breastfeeding. Note: Females who do not meet this criterion can be 
included if they meet Inclusion Criterion 12.  
12. Female subjects of childbearing potential and male subjects with a 
female partner of childbearing potential must agree to consistent 
and adequate birth control from Screening to End of Study 
(Week 54): 
• Recommended forms of contraception for males: condom, 
vasectomy, and sexual abstinence 
i. 
Vasectomized partner is a highly effective birth control 
method provided that the partner is the sole sexual partner 
of the female subject of childbearing potential trial 
participant and that the vasectomized partner has received 
medical assessment of the surgical success. 
ii. 
Condom use is not considered as a highly effective form 
of contraception alone and may be used effectively with a 
second method of contraception. 
iii. 
Sexual abstinence is considered a highly effective method 
only if defined as abstaining from heterosexual 
intercourse during the entire period of risk associated with 

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Synopsis 
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the study treatments. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the trial 
and the preferred and usual lifestyle of the subject. 
• Recommended forms of contraception for females: hormone 
containing contraceptive medication, Intrauterine device with 
failure rate <1% per year, cervical cap or diaphragm with 
spermicidal agent, bilateral tubal occlusion (tubal sterilization), 
sexual abstinence 
i. 
Combined (estrogen and progestogen containing) 
hormonal contraception (oral, intravaginal, transdermal) 
associated with inhibition of ovulation 
ii. 
Progestogen-only hormonal contraception (oral, 
injectable, implantable) associated with inhibition of 
ovulation  
iii. 
Cervical cap or diaphragm with spermicidal agent is not 
considered as a highly effective form of contraception 
alone and may be used effectively with a second method 
of contraception 
Sexual abstinence is considered a highly effective method only 
if defined as abstaining from heterosexual intercourse during 
the entire period of risk associated with the study treatments. 
The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the trial and the preferred and usual 
lifestyle of the subject. 
13. Able and willing to comply with the dosing instructions for study 
drug administration and able to complete the study schedule of 
assessments.  
Exclusion 
Criteria: 
The following will exclude subjects from the study: 
1. Other causes of liver disease that are primary, secondary, or 
otherwise causes of cirrhosis or which may confound the 
intended patient population according to the investigator, 
including but not limited to alcoholic liver disease, hepatitis B, 
hepatitis C, autoimmune disorders, primary biliary cirrhosis, 
drug-induced hepatotoxicity, Wilson’s disease, 
hemochromatosis, and alpha-1-anti-trypsin deficiency based on 
medical history and/or centralized read of liver histology.  

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Synopsis 
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2. Evidence of drug induced steatohepatitis secondary to 
amiodarone, corticosteroids, estrogens, methotrexate, 
tetracycline, or other medications known to cause hepatic 
steatosis. 
3. History of hepatic decompensation, including variceal bleeding, 
ascites, or hepatic encephalopathy. 
4. Prior or pending liver transplantation. 
5. Child Pugh class B and C status. 
6. Model of end stage liver disease (MELD) score >12. 
7. Evidence of worsening liver disease (defined below) between 
screening visits (i.e., Day -56 and Day -42) including measures 
of AST, ALT, alkaline phosphatase (ALP) or total bilirubin 
(TBL): 
a. For subjects with TBL, AST, ALT, or ALP baseline 
levels >ULN, the second assessment should not exceed 
an increase of 35% over the first assessment.  
Note: An unscheduled visit may be necessary to confirm eligibility 
if the difference exceeds the allowable percent difference. If 
performed, unscheduled visit results will be compared to the 
average of Day -56 and Day -42 results to determine eligibility. If 
liver function tests are repeated to verify eligibility criteria have 
been met, there must be a minimum of 14 days (2 weeks) between 
the Day -42 visit and any unscheduled visit. 
8. History of porto-systemic shunt procedure 
9. No evidence of gastroesophageal varices as documented by one 
of the following assessments: 
a. A historical and locally evaluated EGD obtained within 
365 days of screening or 
b. A locally evaluated EGD conducted during the screening 
period 
*If no EGD is available, the latest EGD assessment guidelines 
during a global pandemic† for patients with compensated 
cirrhosis (i.e., the expanded Baveno VI criteria, Petta 2018) as 
follows can be used as a replacement for the EGD to determine 
eligibility: 

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Synopsis 
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c. Platelet count >110,000/mm3, and a FibroScan® <30 kPa on a 
M probe or <25 kPa on a XL probe  
Note: No more than 30% of the remaining population will be 
enrolled with the expanded Baveno VI criteria 
†EGD waived in patients with compensated cirrhosis during a 
global pandemic per AASLD/ASGE guidelines. 
10. Clinically significant cardiovascular or cerebrovascular event or 
new diagnosis within 6 months of Screening, including but not 
limited to congestive heart failure, myocardial infarction, acute 
coronary syndrome, revascularization, stroke (hemorrhagic or 
ischemic), transient ischemic attack (TIA), or implanted 
defibrillator or pacemaker (for uncomplicated elective, 
non-biventricular pacemaker procedure, 3 months post 
procedure will be allowed).  
11. Gastric bypass or bariatric surgery in the past 5 years or 
planned procedure during the study period. 
12. History of clinically significant unstable or untreated illness or 
any other major medical disorder that may interfere with 
subject treatment, assessment, or compliance with the protocol. 
13. Documented significant weight change (± 5%) <3 months prior 
to Screening. 
14. Screening ECG with clinically significant abnormalities that in 
the investigator's opinion, require evaluation and possible 
treatment.  
15. Positive for HBsAg, antiHIV Ab, or antiHCV Ab plus 
HCV-RNA. Subjects who are antiHCV Ab- positive but HCV-
RNA negative (secondary to treatment or viral clearance) are 
eligible with at least a 1-year period since documented 
sustained viral response at Week 12 post-treatment. 
16. 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 or 
breast ductular carcinoma in situ is allowed if appropriately 
treated within 2 years prior to Screening); subjects under 
evaluation for suspected malignancy are not eligible. History of 
hepatocellular carcinoma at any point regardless of treatment or 
treatment success will be excluded. 

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Synopsis 
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17. A positive drug screen (e.g., morphine, heroin, cocaine) will 
exclude subjects unless it can be clearly explained by a 
prescribed medication. The diagnosis and prescription must be 
approved by the investigator and the Medical Monitor.  
18. Significant alcohol intake as measured by a 
phosphatidylethanol (PEth) level ≥200 ng/mL AND significant 
alcohol use, as determined by the Alcohol Use Disorders 
Identification Test (AUDIT-C) alcohol consumption 
questionnaire (Appendix 3). 
19. Criterion deleted per protocol Version 3.0.  
20. Consumption of ≥21 units of alcohol per week in males and 
≥14 units of alcohol per week in females for two years prior to 
screening, where a “unit” of alcohol is equivalent to a 12-ounce 
beer, 4-ounce glass of wine, or 1-ounce shot of hard liquor. 
21. Use of any prohibited concomitant medications as described in 
Section 6.4 within 3 months prior to screening; 
a. 
Weight loss medications. 
b. 
Any medication that is contraindicated according to the 
rosuvastatin package insert (Appendix 5) or if subject has 
a known hypersensitivity to rosuvastatin product 
components (Section 6.1.3). 
c. 
Hepatotoxic medications (Appendix 6); allopurinol 
allowed.  
d. 
Anabolic steroids. 
22. History of statin intolerance, as defined by presence of 
significant side effects while on statins and/or inability to take 
or use statins for treatment. 
23. Prior participation in a clinical trial of aldafermin unless 
previously enrolled into a placebo arm of the trial.  
24. History of severe allergic or anaphylactic reactions to 
recombinant therapeutic proteins, fusion proteins, or chimeric, 
human, or humanized antibodies. 
25. 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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Synopsis 
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26. Any acute or chronic condition that, in the opinion of the 
investigator, would limit the subject’s ability to participate, 
complete, and/or would confound data interpretation in this 
clinical study. 
Study Design/ 
Methodology: 
This study is a double-blind, randomized, placebo-controlled, 
multi-center study of aldafermin in subjects with histologically 
confirmed compensated cirrhosis due to NASH. 
The study consists of a screening period, a double-blind treatment 
period of 48 weeks, and a safety follow-up period of 6-10 weeks. 
Subjects will be treated with either aldafermin or matched placebo 
given as a subcutaneous injection daily for 48 weeks.  
Eligible subjects will have histologically confirmed cirrhosis (NASH 
CRN fibrosis Stage 4, with a limited number of subjects with fibrosis 
Stage 3 with a clinical diagnosis of cirrhosis) due to NASH. Historical 
biopsy may be used for inclusion into the study. Otherwise, a liver 
biopsy must be obtained for eligibility assessment. Liver biopsy results 
of either historical or screening biopsy must be confirmed by a central 
pathologist reading.  
At Screening, all subjects will undergo evaluation for risk of HCC. 
A gadolinium-enhanced MRI or multi-phasic CT scan showing no 
evidence of nodules with a Liver Imaging and Reporting Data System 
(LI-RADS) score of ≥2 on central read will be required at Screening to 
rule out HCC risk. For potential subjects unable to obtain an MRI or 
CT scan, ultrasound that is negative for hepatic lesions/nodules (local 
read) at Screening may be used. In all cases, AFP must be ≤20 ng/mL. 
Subjects with suspicious lesions/nodules at ultrasound followed by 
observation of nodules that are LI-RADS ≥2 by central read of 
gadolinium-enhanced MRI or multi-phasic CT scan at Screening will 
be excluded from enrollment and will be referred for further evaluation 
for HCC per the standard of care (SOC). Subjects will also be excluded 
if EGD documented any signs of esophageal or gastric varices.  
Up to approximately 150 eligible subjects will be randomized into 1 of 
4 treatment groups in a 3:2:2:3 ratio to receive either subcutaneous 
placebo, 0.3 mg aldafermin, 1 mg aldafermin, or 3 mg aldafermin, 
respectively. Under protocol Version 5.0 and subsequent versions, 
eligible subjects will no longer be randomized into the 0.3 mg 
aldafermin treatment group. Instead, subjects will be randomized into 
1 of 3 treatment groups in a 4:3:4 ratio to receive either subcutaneous 
placebo, 1 mg aldafermin, or 3 mg aldafermin, respectively. Subjects 
randomized to the 0.3 mg aldafermin treatment group prior to protocol 
Version 5.0 will continue to receive the same dose until treatment 
completion. No more than 30% of the remaining population will be 

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Synopsis 
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enrolled with the expanded Baveno VI criteria. 
Randomization will be stratified by clinical diagnosis of T2D versus no 
T2D to ensure planned allocation ratio of treatment groups within each 
stratum. 
Study drug self-administration instructions and training will be 
provided to the subjects and study drug kits will be dispensed.  
In the clinic, subjects will self-administer the first dose of 
aldafermin/placebo (Day 1) and doses at Weeks 2, 6, 12, 18, 24, 30, 36, 
42, and 48 study visits. Subjects will self-administer all other doses 
through Week 48 at home. Self-administration should occur at a similar 
time for every dose in both the clinic and at home. 
Subjects will return to the clinic on Weeks 2, 6, 12, 18, 24, 30, 36, 42, 
and 48 for on treatment assessments.  
Subject cholesterol levels will be followed during the course of the 
study, and treatment with over-encapsulated rosuvastatin/matched 
placebo will start at Week 2 according to a lipid management algorithm 
(Appendix 4).  
LDL-C levels and related safety data will be evaluated at Weeks 2, 6, 
12, 18, 24, 30, 36, and 42 in all subjects by an independent third-party 
Medical Monitor who will determine the need for initiation/titration of 
rosuvastatin according to the protocol. Rosuvastatin will be used to 
manage cholesterol levels according to the established lipid 
management algorithm described in Appendix 4.  
Rosuvastatin and matched placebo are over-encapsulated to maintain 
the treatment blind. Initiation and ongoing dose adjustments of 
rosuvastatin/matched placebo will be managed through the 
 
 by a third-party Medical Monitor 
who is unblinded to subject lipid levels but blinded to the treatment 
assignment (aldafermin or matched placebo). The sponsor and study 
sites will be blinded to subject lipid levels, rosuvastatin/placebo 
allocation, and the specific rosuvastatin dosing decisions. A kit 
containing rosuvastatin or matched placebo bottles will be assigned 
based on assessment by the unblinded Medical Monitor, at each study 
visit from Week 2 through Week 42 (statin-naïve) or Week 48 
(statin-experienced), according to the lipid management algorithm and 
will be delivered to subjects via a courier service vendor 
(Section 6.1.3.1) or to the study site for subjects to collect, depending 
on subject preference. Reference Appendix 4 for specific dosing 
algorithm for statin-naïve and statin experienced subjects. 
Over-encapsulated rosuvastatin will be initiated at Week 2, starting at 
5 mg QD in statin-naïve subjects whose ASCVD 10-year risk score is 

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Synopsis 
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≥7.5% (US) or ≥ moderate level risk (European), Appendix 4. 
In subjects who are statin-naïve with diabetes or a history of 
myocardial infarction or stroke, or other ASCVD risk-enhancing 
diagnoses, rosuvastatin will be initiated at 5 mg at Week 2 if LDL-C is 
not already at the goal of ≤70 mg/dL (1.8 mmol/L). Though there is 
incremental cardiovascular benefit to additional LDL-C lowering 
(Sabatine 2018), other reports, including the meta-analysis by Ma, et 
al. suggest an association between low LDL-C levels and hemorrhagic 
stroke (Ma 2019), and overall, controversy remains regarding the 
long-term safety of medications that can help achieve low LDL-C 
levels such as PCSK9 inhibitors (Pasta 2020, Bandyopadhyay 2018). 
Thus, for safety considerations, statin-naïve subjects with risk-
enhancing diagnoses who are already at an LDL-C treatment goal of 
≤70 mg/dL (1.8 mmol/L) will be initiated on over-encapsulated 
rosuvastatin placebo. At subsequent clinic visits, lipid levels will be 
evaluated and treatment with over-encapsulated rosuvastatin may be 
initiated or placebo may be continued. 
Subjects who are statin-experienced (i.e., on statin concomitant 
medication), will be switched to an equivalent intensity rosuvastatin 
dose at Week 2. For self-identified Asians, 10 mg is considered a high 
intensity dose, and 5 mg is considered a moderate intensity dose. 
Matched placebo will be given to statin-naive study subjects who do 
not meet initiation criteria at Week 2 or subsequent visits.  
LDL-C values will be further evaluated at study visit Week 6, 12, 18, 
24, 30, 36, and 42, in order to identify subjects who require 
rosuvastatin initiation or dose-escalation. Specific LDL goal or 
treatment success criteria are described in detail in Section 8.3.17. 
Subjects who do not meet rosuvastatin increase criteria will continue 
on their prior assigned dose of over-encapsulated rosuvastatin/ matched 
placebo. Subjects on the maximum dose of rosuvastatin 40 mg whose 
LDL-C levels are still not at goal will continue on the study with 
rosuvastatin 40 mg unless the subject experiences a 
cardiovascular-related SAE (e.g., myocardial infarction, CVA). 
Subjects experiencing a CV-related SAE on rosuvastatin 40 mg will 
discontinue both aldafermin and rosuvastatin for the remainder of the 
trial, and cardiovascular care will continue per the subject’s regular 
physician and as per local standard of care practices. Subjects who 
experience rosuvastatin-related intolerance (by evaluation of muscular 
symptoms and creatine kinase (CK) levels) will be evaluated by 
follow-up laboratory testing after the over-encapsulated 
rosuvastatin/placebo has been held. Depending on the CK levels and 
clinical status, subjects may be allowed to restart over-encapsulated 
rosuvastatin/placebo at a reduced dose. Algorithm details are found in 
Section 7.1.1, part ii. 

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Synopsis 
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All subjects will be assessed at Weeks 49 and 54 to confirm their 
LDL-C levels have either decreased to near baseline, at which point no 
additional follow-up is needed. Subjects who do not meet LDL-C 
decrease criteria at Week 54 will have an additional 4-week follow-up 
visit at Week 58 to confirm that their LDL-C level returned to near 
baseline. Subjects may remain on statin through Week 58.  
As part of safety monitoring, subjects will undergo ultrasound and 
alpha fetoprotein (AFP) testing at Weeks 24 and 48 to screen for HCC. 
Subjects with new lesions ≥10 mm with AFP >20 ng/mL will be 
treated according to local guidelines. If new lesions ≥10 mm with AFP 
>20 ng/mL occur at Week 24, subjects may continue on study drug at 
the discretion of the investigator unless or until a clinical diagnosis of 
HCC is made (defined as LI-RADS 4 or 5 on MRI, or histological 
confirmation of HCC). For subjects with suspected HCC by ultrasound 
and AFP screening, additional imaging may be obtained, and data will 
be gathered for adjudication. 
Safety will be monitored by a data safety monitoring board (DSMB).  
All subjects will return to the clinic for the End-of-Treatment (EOT) 
visit at Week 48. Subjects will return to the clinic at Weeks 49 and 54 
(or at 1 and 6 weeks after last dose of aldafermin) for a post-treatment 
response and End-of-Study (EOS) follow-up visits.  
Subjects may be contacted to participate in additional optional 
follow-up visits, if necessary, to monitor anti-drug antibody (ADA) 
response.  
Number of 
Subjects:  
Up to approximately 150 eligible subjects will be randomized 
Number of 
Study Sites:  
This is a global study planned in approximately 80 sites 
Test Product, 
Dose, and Mode 
of 
Administration:  
The investigational product is aldafermin, which will be administered 
once daily by subcutaneous injection. Subjects will receive 0.3 mg 
aldafermin, 1 mg aldafermin, 3 mg aldafermin, or matched placebo. 
Under protocol Version 5.0 and subsequent versions, randomization to 
the 0.3 mg aldafermin dose was discontinued. 
Rosuvastatin will be administered for subjects meeting pre-specified 
criteria at Week 2 with dose optimization opportunities at Weeks 6, 12, 
18, 24, 30, 36, and 42. Subjects who do not meet dose escalation 
criteria will continue on their prior assigned dose of 
rosuvastatin/placebo. Study-labeled rosuvastatin/matched placebo is 
over-encapsulated and will be supplied in either 5 mg, 10 mg, 20 mg, 
or 40 mg total daily doses as outlined in Section 6.2.1.2 of the protocol 
to manage possible LDL-C increase during aldafermin treatment.  

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Synopsis 
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Duration of 
Treatment and 
Study:  
Total study-drug treatment: 48 weeks.  
Total study duration: up to 74 weeks. 
Subjects will review and sign the Informed Consent Form at the 
Day 56 Screening Visit and will undergo screening assessments to 
verify eligibility for the study for up to 8 weeks (up to 16 weeks with 
Medical Monitor approval) from the date of consent. All subjects will 
be treated with aldafermin or matched placebo for 48 weeks and will 
be monitored for additional 6-10 weeks after completing their final 
dose of aldafermin or matched placebo.  
The total duration of individual subject participation, including 
screening (up to 8 weeks [up to 16 weeks with Medical Monitor 
approval]), the treatment period (48 weeks) and the safety follow-up 
(6-10 weeks) will be up to 74 weeks. 
Statistical 
Considerations  
Analysis Populations: 
• Intent to treat (ITT) population: all randomized subjects  
• Modified ITT (mITT) population: all subjects who receive at least 
2 weeks of study drug and have at least one valid, post-dose, on-
treatment ELF score 
• Safety population: all subjects who receive at least one dose (full or 
partial) of study drug 
• Full-Analysis population: all randomized 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 
• Per-Protocol (PP) population: a subset of subjects in the Full 
Analysis population; will include subjects who have valid, 
non-missing baseline and post-dose liver biopsy results and do not 
have protocol deviations that impact the liver biopsy assessments 
• PK population: all randomized subjects who receive at least one 
dose (full or partial) of drug, and have a qualified (i.e., above the 
lower limit of quantification) pre-dose and post-dose (at least one) 
PK assessment.  
General Approach: 
Descriptive statistics including the number of non-missing observations 
(n), arithmetic mean (mean), standard deviation (SD), median, 
minimum, and maximum will be presented for continuous variables, 
frequency and percentage distribution for categorical variables, 
Kaplan-Meier estimates for time-to-event variables. 

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2. 
INTRODUCTION 
2.1. 
Background 
Aldafermin is an engineered analog of human fibroblast growth factor 19 (FGF19) that is 
currently being developed as a potential treatment for Nonalcoholic Steatohepatitis (NASH). 
Although the natural history of NASH is not fully elucidated, the risk of progression to 
end-stage liver disease is characterized by an increased fibrosis stage and cirrhosis, with 
increased risk for outcomes of hepatic decompensation, need for liver transplant, and 
mortality (Angulo 2015, Younossi 2018). Decompensation events include ascites, sepsis, 
variceal bleeding, encephalopathy, and nonobstructive jaundice. 
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 initial dysfunction is likely followed by oxidative injury resulting in the 
necroinflammatory component of NASH (Cusi 2012). Hepatic iron, antioxidant deficiency, 
and intestinal 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 non-alcoholic fatty 
liver disease (NAFLD) activity score (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 2015). 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). 
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 

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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 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 development of cirrhosis over the 
lifetime of patients with NASH is estimated to be at least 20%, with decompensation 
occurring in about 45% of patients with NASH related cirrhosis over a 10-year period 
(Rinella 2015, McCullough 2004, Sanyal 2006). In a recent study that evaluated the 
prevalence of NASH cirrhosis and NAFLD-associated fibrosis by the National Health and 
Nutrition Examination Survey (NHANES) (7,034 participants), the prevalence of NASH 
cirrhosis and NAFLD-associated fibrosis increased by 2.5 fold and 2-fold in 2009-2012 
compared to 1999-2002. Significant increases in obesity, diabetes, and insulin resistance also 
increased significantly (p < .005 for all). Thus, regression or prevention of the progression of 
NASH-related cirrhosis represents an important unmet need.  
2.2. 
Cirrhosis Pathophysiology 
Cirrhosis is an advanced stage of liver fibrosis defined as the histological development of 
regenerative nodules surrounded by fibrous bands in response to chronic liver injury, which 
leads to portal hypertension and end-stage liver disease. Liver fibrosis results from 
interference in the normal wound-healing response, thus preventing tissues from disassembly 
during inflammation, apoptosis, necrosis, and proteolysis (Schuppan 2008). With chronic 
liver disease and the development of cirrhosis, activated myofibroblasts deriving from 
proliferating hepatic stellate cells and portal fibroblasts result in fibrogenesis, angiogenesis, 
and parenchymal extinction lesions caused by vascular exclusions (Tsochatzis 2014). 
This process leads to sinusoidal remodeling and extracellular matrix (ECM) deposition with 
cross-linking of fibrillary collagen (Friedman 2010). The vascular distortion that occurs with 
cirrhosis leads to shunting of the portal and arterial blood supply directly into the hepatic 
outflow (central veins), compromising exchange between hepatic sinusoids and the adjacent 
liver parenchyma. The hepatic sinusoids are lined by fenestrated endothelia that rest on a 
sheet of permeable connective tissue in the space of Disse, which also contains hepatic 
stellate cells and some mononuclear cells. The other side of the space of Disse is lined by 
hepatocytes that execute most of the known liver functions. In cirrhosis, the space of Disse is 
filled with scar tissue and endothelial fenestrations are lost. The general circulatory 
abnormalities in cirrhosis (splanchnic vasodilation, vasoconstriction, and hypoperfusion of 
kidneys, water and salt retention, increased cardiac output) are intimately linked to the 
hepatic vascular alterations and resulting portal hypertension. Cirrhosis and its associated 
vascular distortion are traditionally regarded as irreversible, but recent data suggest that 
cirrhosis regression or even reversal may be possible (Schuppan 2008). 

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2.3. 
Current Treatments for NASH Cirrhosis 
There are currently no approved therapies for affecting progression or regression of cirrhosis, 
though a variety of targets are being pursued with potential anti-fibrotic therapies. Many of 
these potential therapies are also being studied for earlier stages of NASH in a population of 
patients with F2/F3 fibrosis stage. (Friedman 2018). 
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. Anti-fibrotic agents have targeted the advanced 
fibrosis and cirrhotic populations but have little activity on the underlying disease causing the 
chronic hepatic injury (Harrison 2018). 
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 
require other interventions. In cases of morbid obesity, bariatric surgery has been successful 
in reversing the metabolic and hepatic injury associated with NASH. 
Many agents are currently being studied in clinical trials. In current clinical practice, 
vitamin E is the most commonly used medication, though evidence of efficacy is limited in 
those with diabetes and cirrhosis and current American Association for the Study of Liver 
Diseases (AASLD) and the European Association for the Study of the Liver (EASL) 
guidelines recommend its use be restricted to nondiabetic, non-cirrhotic patients with NASH 
(Chalasani 2017, EASL 2016). This recommendation has been largely generated by data 
from the PIVENS trial, in which subjects randomized to receive 800 IU/day of vitamin E for 
96 weeks demonstrated improvement in steatosis, lobular inflammation and ballooning, as 
well as resolution of NASH, but no improvement in fibrosis (Sanyal 2010). There have also 
been subsequent safety concerns regarding the use of vitamin E as data suggest a possible 
increased risk of overall mortality and higher rates of prostate cancer, though this remains 
controversial. Of the insulin sensitizers, pioglitazone has been extensively evaluated in 
clinical trials with fairly consistent improvements in various features of NASH and less 
consistently fibrosis. The primary downside to the use of pioglitazone is fluid retention, 
weight gain, and bone fracture, limiting both patient and provider acceptance. Given the 
increasing disease burden and no approved treatment options, the development of 
pharmacologic therapies to treat NASH is critical.  
There are several drugs in Phase 2 and Phase 3 development for the treatment of noncirrhotic 
and compensated cirrhotic patients with NASH. These drugs are targeting either modification 
of the underlying disease-related injury, fibrosis, or both. Despite the presence of numerous 
agents in clinical development, none have demonstrated a rapid or potent effect on liver 

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histology, and a significant medical need for new effective therapies with favorable safety 
and tolerability profiles remains. 
The management of liver cirrhosis secondary to NASH currently focuses on reducing the 
complications of cirrhosis and preventing progression to decompensated hepatic events or 
death/liver transplant. This includes assessment and treatment of renal complications, 
treatment of ascites (low sodium diet, paracentesis, diuretics, or shunt) and screening for 
hepatocellular carcinoma with imaging techniques (e.g., MRI , CT scan, or ultrasonography) 
and screening for gastroesophageal varices with assessment of risk for bleeding to guide 
testing frequency (Rinella 2015). Prevention of bleeding in patients with varices includes 
variceal band ligation or a nonselective β-blocker to reduce hepatic venous pressure gradient 
(HVPG). Statins such as simvastatin have also been used to lower HVPG and improve liver 
hemodynamics, in patients with cirrhosis and varices. Statins have also demonstrated 
reduction in the incidence of HCC in patients with T2DM (Tsochatzis 2014). 
2.4. 
Mechanism of Action of Aldafermin 
Aldafermin is 95.4% identical to FGF19. FGF19 and its murine homologue FGF15 have 
been implicated in the regulation of hepatic bile acid (BA) metabolism. FGF19 interacts with 
the FGFR4/β-klotho receptor complex located in the liver to induce the expression of small 
heterodimer partner (SHP), an orphan nuclear receptor, in the liver to suppress the expression 
of CYP7A1, the gene encoding cholesterol 7α-hydroxylase. In catalyzing the first, and 
rate-limiting step in the conversion of cholesterol into BAs, cholesterol 7α-hydroxylase 
represents the key regulatory checkpoint in the control of BA synthesis, and changes in the 
level of this enzyme have been shown to have a significant effect on both the size and 
composition of the BA pool (Russell 2003). Additionally, FGF19 interacts with the 
FGFR1c/β-klotho receptor complex located in the adipose tissue and the brain to regulate 
insulin sensitivity, glucose metabolism, and energy homeostasis (Kliewer 2015). 
Aldafermin differs from wild-type FGF19 in the amino terminus, a key region of the protein 
involved in receptor interactions and signaling modulation (Zhou 2014, DePaoli 2019, 
Luo 2014). In aldafermin, a 5-amino acid deletion (P24-S28) coupled with the substitution of 
three amino acids at critical positions (A30S, G31S, H33L) enable biased FGFR4 signaling 
so that aldafermin retains the ability to potently repress CYP7A1 expression but no longer 
triggers activation of signal transducer and activator of transcription 3, a signaling pathway 
essential for FGF19-mediated hepatocarcinogenesis (Zhou 2017). By engaging both FGFR4 
and FGFR1c pathways to reduce bile acid toxicity and lipotoxicity, and to improve insulin 
sensitivity, aldafermin has demonstrated robust anti-steatotic, anti-inflammatory, and 
anti-fibrotic activities in multiple animal models of NASH (Zhou 2017, Zhou 2019). 
2.5. 
Therapeutic Rationale for Aldafermin in NASH 
The potential role of reduced FGF19 activity in the pathogenesis of NASH is not fully 
elucidated but may, in part, be due to accumulation of hepatic bile acids. For example, 
increased bile acid synthesis as well as serum bile acid 7-alpha-hydroxy-4-cholesten-3-one 
(C4) concentrations, a key marker of cholesterol 7α-hydroxylase 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 

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CYP7A1-mediated classic pathway (toxic bile acids) to the less toxic alternative pathway 
(Lake 2013). Increased hepatic concentrations of bile acids are also associated with increased 
apoptosis, Fas, and tissue necrosis factor (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). FGF19 levels are also decreased in subjects with Type 2 diabetes (T2D) or 
metabolic syndrome and return to normal levels after bariatric surgery in diabetic subjects 
(Mingrone 2012). 
2.6. 
Nonclinical Studies 
Aldafermin has been evaluated in various mouse animal models of NASH, and has 
demonstrated significant reduction in steatosis, inflammation, ballooning and fibrosis in 
mouse models of NASH (Table 1).  
Table 1. 
Summary of Aldafermin Efficacy in Mouse NASH Models 
Mouse Model 
(Study No.) 
Treatment 
Duration 
(weeks) 
NAS Score a Fibrosis Score b 
STAM 
(14-PD-NGM282-1001) 
GFP-AAV 
aldafermin-AAV 
3 
5.33 + 1.5 
1.5 + 1.0*** 
1.09 
1.06 
FXR Knockout on chow 
(13-PD- NGM282-1007) 
GFP-AAV 
aldafermin-AAV 
24 
4.0 ± 1.73 
2.0± 1.73 
1.8 + 0.4 
1.4 + 0.6 
HFFCh/C57BL6 
(15-PD- NGM282-1001; data on file) 
GFP-AAV 
aldafermin-AAV 
34 
7.3 ± 0.3 
3.0 ± 0.4*** 
3.9 + 0.5 
0.8 + 0.1*** 
HFFCh/FXR Knockout 
(15-PD- NGM282-1002; data on file) 
GFP-AAV 
aldafermin-AAV 
34 
7.5 ± 0.5 
6.4 ± 0.7 
3.8 + 0.2 
1.4 + 0.2*** 
HFFCh/C57BL6 
(data on file) 
GFP-AAV 
V97c-AAV 
24 
5.4 
2.2*** 
1.8  
1.2 
AAV=adeno-associated virus; FXR=farnesoid X receptor; HFFCh=high-fat, fructose, cholesterol diet; 
SC=subcutaneous. 
a  
NAS score represents sum of steatosis, inflammation, and ballooning degeneration scores 
b  
Fibrosis score estimated using Kleiner criteria 
c  
V97 is a surrogate molecule for aldafermin 
*** P < 0.001 vs. GFP-AAV 
 
Importantly, aldafermin is devoid of proliferative activity based on chronic evaluation in 
rodents and non-human primates that is a potential limitation of FGF19 as a therapeutic. 
Aldafermin was selected from more than 160 variants of human FGF19 that were screened to 
retain robust efficacy, while lacking evidence of proliferative activity in db/db mice 
(Luo 2014, Zhou 2014, DePaoli 2019). 
The nonclinical safety program for aldafermin includes general toxicity and pharmacokinetic 
(PK) studies in the mouse, rat and cynomolgus monkey for up to 26 weeks of treatment and 
embryofetal and developmental toxicity studies in the mouse and rabbit. Based on the 
cumulative nonclinical safety profile of aldafermin for up to 26 weeks of treatment, the no 
observed adverse effect levels (NOAELs) in the mouse, rat and monkey were determined to 
be 1, 1, and 3 mg/kg, respectively. A sufficient safety margin exists for aldafermin at the 
proposed maximal clinical dose of 3 mg (0.033 mg/kg based on a 90 kg subject). 

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Please refer to Appendix 1 and Appendix 2 of the Investigator’s Brochure (IB) for 
Pharmacological and Toxicology studies supporting the development of aldafermin in 
NASH.  
2.7. 
Clinical Experience 
The clinical testing of aldafermin includes a completed first in human Phase 1 study 
(Study 12-0101) in healthy subjects in Australia; a completed Phase 1b study in subjects with 
functional constipation (Study 15-0107); a completed single-dose Phase 1 study in subjects 
with varying degrees of impaired renal function (Study 282-RI-103); a completed 28-day 
Phase 2a study in subjects with type 2 diabetes (T2D) (Study 13-0102) in Australia and 
New Zealand; a completed 28-day Phase 2a (Study 13-0103) in subjects with Primary Biliary 
Cholangitis (PBC) in the United States, Australia and New Zealand; a completed 52-week 
Phase 2b (Study 14-0104) study in subjects with PBC in the United States, Australia, and 
New Zealand; and a completed 12-week Phase 2 study in subjects with Primary Sclerosing 
Cholangitis (PSC) (Study 15-0106) in the United States, France, Netherlands and United 
Kingdom. Additionally, a Phase 2 study in subjects with NASH (Study 15-0105) has 
evaluated 3 mg and 6 mg doses of aldafermin in a double-blind cohort (DBC) for 12 weeks 
(completed [Part 1]), 0.3 mg, 1 mg, and 3 mg doses for 12 weeks in an open-label 
single-blind cohort (SBC) (completed [Part 2]), and 1 mg for 24 weeks in an ongoing 
placebo-controlled histology cohort (Part 3; new results from interim analysis included). 
In the randomized, placebo-controlled, double-blind cohort of Study 15-0105 (Part 1), 
patients with biopsy-confirmed non-cirrhotic NASH had decreased absolute liver fat content 
(LFC) by -9.7% and -11.9% upon treatment with aldafermin doses of 3 mg and 6 mg 
(p<0.001), respectively, versus -0.9% with placebo (Table 2). 74% (20/27) of patients 
receiving aldafermin at 3 mg and 85% (22/26) of patients receiving aldafermin at 6 mg met 
the primary endpoint of decrease in absolute LFC of ≥5%, while only 7% (2/27) of patients 
in the placebo group met this criteria (Table 2). There were no significant differences 
between the two aldafermin doses in either absolute or relative LFC reductions. 
Patients receiving aldafermin had a mean relative change in LFC from Baseline to Week 12 
of -47% and -61% with the 3 mg and 6 mg doses, respectively, versus -1% with placebo 
(p < 0.001) (Table 2). Overall, 89% (47/53) of patients receiving aldafermin for 12 weeks 
achieved a clinically meaningful change (≥30% relative change) in LFC, with normalization 
(below a threshold of <5% absolute LFC) observed in 34% of patients of aldafermin-treated 
subjects versus none in the placebo group.  

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Table 2. 
Change from Baseline to Week 12 in MRI-PDFF in NASH Subjects  
 
Aldafermin 
Placebo 
(N=27) 
3 mg 
(N=27) 
6 mg 
(N=26) 
MRI-PDFF, Absolute % (Wk 12) 
-0.9% 
-9.7% 
-11.9% 
Absolute ≥5% (% pts.) 
7% 
74% 
85% 
MRI-PDFF, Relative % (Wk 12) 
-1% 
-47% 
-61% 
Relative ≥30% (% pts.) 
7% 
85% 
92% 
ALT, Absolute IU (Wk 12) 
-2 
-35 
-32 
ALT Normalization 
(female <19 IU, male <30 IU) 
3.8% 
37.0% 
35.7% 
ALT, Relative % (Wk 12) 
1% 
-43% 
-44% 
ALT=alanine aminotransferase; MRI-PDFF=magnetic resonance imaging-proton density fat fraction; 
pts=patients; Wk=week 
Greater reductions from Baseline in mean absolute ALT levels were observed for both 
aldafermin 3 mg (−35 IU, p<0.0001) and 6 mg (−33 IU, p<0.0001) at Week 12 compared to 
placebo. The reductions achieved statistical significance as early as 1 week with a sustained 
reduction throughout the entire 12-week study treatment period. The mean relative 
percentage decreases in ALT levels from Baseline to Week 12 were also significant in both 
doses, ranging from -45% to -47% (p<0.001). ALT levels achieved normalization (defined as 
<19 IU in females and <30 IU in males) in 24% of aldafermin-treated patients by Week 2 and 
36% of treated subjects by Week 12 (Figure 1). Similarly, treatment with aldafermin resulted 
in significant mean absolute reductions in AST levels from Baseline to Week 12 compared 
with placebo with the majority of subjects decreasing below the clinically meaningful 
threshold of 40 IU as soon as 2 weeks after starting treatment (Figure 1). 
Figure 1. 
Absolute ALT and AST Values by Study Visit during and after 
Aldafermin Treatment  
 
In the single-blind cohort of Study 15-0105 (Part 2) evaluating 3 doses aldafermin (0.3 mg, 
1 mg, 3 mg) in patients with biopsy-confirmed non-cirrhotic NASH, the primary endpoint 
(≥ 5% decrease in absolute LFC) was met in 57%, 90% and 100% of the 0.3 mg, 1 mg and 
3 mg doses, respectively, at week 12. LFC normalization was achieved in 17%, 24% and 

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Table 5. 
Change from Baseline to Week 24 in Key Parameters: Interim Analysis 
of a 24-week, Double-blind, Placebo-controlled Study of Aldafermin 
(15-0105, Part 3) in Patients with NASH 
PBO (n=13) 
Aldafermin 1 mg (n=25) 
Imaging Parameters 
Δ Absolute MRI-PDFF, % 
−2.0 (2.0) 
−7.9 (1.4)**** Ϯ 
% subjects with ↓5% absolute
17% 
72% Ϯ Ϯ 
Δ Relative MRI-PDFF 
−5.9% 
−39.6%**** Ϯ 
% subjects with ↓30% relative
17% 
72% Ϯ Ϯ 
Serum Parameters 
Δ Absolute ALT, U/L 
−18.6 (5.6)** 
−38.0 (4.1)**** Ϯ Ϯ 
Δ Relative ALT 
−2.0%  
−38.7%**** Ϯ Ϯ 
Δ Absolute AST, U/L 
−9.4 (6.4) 
−18.5 (4.8)*** 
Δ Relative AST 
−4.1% 
−23.4%** 
Δ Pro-C3, ng/mL 
0.3 (1.5) 
−4.3 (1.0)*** Ϯ 
Δ Relative Pro-C3 
5.4% 
−24.3%** Ϯ 
Δ Absolute ELF  
0.06 (0.18) 
−0.21 (0.14) 
Shown are least squares mean (SE). 
****p<0.0001, ***p<0.001, **p<0.01, *p<0.05 vs baseline,  
ϮϮp<0.01, Ϯp<0.05 vs PBO 
 
Overall, aldafermin has demonstrated robust activity in reducing LFC, transaminases, and 
serum markers of fibrogenesis, leading to improvement in liver fibrosis and histology in 
patients with biopsy-confirmed, non-cirrhotic NASH. 
2.8. 
Rationale for Dose Selection  
The planned aldafermin dose levels for Phase 2b Study 282-CC-207 in F4 subjects are 0.3, 1, 
or 3 mg. These doses are proposed based on assessment of safety, tolerability, and efficacy 
data from a total of 326 subjects obtained from the following studies: 
• Phase 1 Study 12-0101 in healthy subjects: placebo, aldafermin dose range for single-
ascending dose (SAD) from 0.1 mg to 30 mg and dose range for multiple-ascending dose 
(MAD) from 0.1 mg to 20 mg; 
• Phase 2 Study 13-0102 in T2D (presumptive NASH subjects): placebo, aldafermin dose 
range from 2 mg to 10 mg; and 
• Phase 2 Study 15-0105 in noncirrhotic NASH  
o Double-blind cohort (completed): placebo, aldafermin doses (3 and 6 mg), 
o Single-blind cohort (completed): aldafermin doses (0.3, 1 and 3 mg), and  
o Placebo-controlled cohort (ongoing): placebo and 1 mg aldafermin dose.  
In the Phase 1 Study 12-0101, aldafermin demonstrated a favorable tolerability profile up to 
30 mg in the SAD portion of the study and 10 mg in the MAD portion of the study. 
Significant rapid and dose-dependent biological action on BA synthesis and reduction in C4 
(80 to 90%) was observed at doses of 0.3, 1, and 3 mg of aldafermin in healthy subjects. 
The 0.1 mg dose did not demonstrate any reduction in C4, suggesting it to be a “no effect” 
dose. This established the lowest dose for evaluation of aldafermin in other subject 
populations as 0.3 mg, and a dose range for evaluation of 0.3 to 10 mg. 

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In the Phase 2 Study 13-0102, data from the T2D study subjects (presumptive NASH 
patients) indicated that aldafermin demonstrated an increased frequency and severity of 
gastrointestinal (GI) symptoms and injection-site reactions (ISRs) in patients treated with 
10 mg. Therefore, the dose range of 0.3 to 6 mg was selected for the Phase 2 Study 15-0105. 
In addition, aldafermin at doses >2 mg demonstrated greater decreases in body weight, 
fasting blood glucose, triglycerides, high-density lipoprotein (HDL), and ALT and C4 were 
suppressed by >95% in T2D patients treated with the 2 and 5 mg doses of aldafermin. 
Therefore, a dose range of 0.3 to 6 mg was evaluated in the NASH patients. 
In the Phase 2 Study 15-0105, the integrated safety data from the noncirrhotic NASH 
subjects double-blind and single-blind cohorts demonstrated a dose-dependent increase in the 
incidence of most commonly-occurring treatment-emergent adverse events (TEAEs), 
i.e., ≥10%, comprising gastrointestinal symptoms, headache, fatigue, and injection site 
erythema, with incidence plateauing from 1 mg (90%), 3 mg (86%), to 6 mg (86%). 
The 6 mg dose of aldafermin was associated with more drug-related treatment 
discontinuations and study withdrawals compared to the 3 mg dose, and hence was not 
further evaluated. 
In addition, data from the double-blind cohort suggest that both the 3 and 6 mg doses of 
aldafermin have equivalent efficacy in terms of reductions in LFC, liver transaminases, and 
anti-fibrotic markers. The primary endpoint of ≥5% decrease in absolute LFC was met in 
57%, 90%, and 100% of the 0.3 mg, 1 mg, and 3 mg doses, respectively. Noninvasive marker 
analyses demonstrated a dose dependent and significant decrease in Pro-C3 and enhanced 
liver fibrosis (ELF) scores at these doses. ALT decreased rapidly and was similar for the 
1 mg and 3 mg doses. The decrease in ALT levels was lesser in magnitude and plateaued 
above the ULN for most of the subjects in the 0.3 mg group. A total of 43 subjects were 
enrolled in the 1 and 3 mg single-blind dose cohorts and completed 12 weeks of treatment 
with paired biopsies. At Week 12, a greater proportion of subjects in the 3 mg arm (i.e., 68%) 
than 1 mg arm (i.e., 50%) met the histologic responder criteria. 
These studies also showed that repeat dosing of aldafermin does not cause accumulation of 
aldafermin systemically due to the short (~5 hour) half-life. Additionally, NGM does not 
expect an increased risk of liver injury in well-compensated cirrhotic NASH subjects as 
aldafermin is not metabolized in the liver.  
Therefore, based on the totality of the safety, tolerability, and efficacy data from these 
studies, NGM has selected aldafermin doses of 0.3, 1, and 3 mg for evaluation in this 
Phase 2b study. These selected doses are within the safety margins determined from the 
chronic toxicology studies in mice, rats, and monkeys. 

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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Primary Objective and Endpoints  
The primary objective of this study is to evaluate the efficacy and safety of aldafermin 
compared to placebo.  
1. The primary efficacy endpoint is the change in Enhanced Liver Fibrosis (ELF) score 
from baseline to Week 48 with aldafermin or matched placebo.  
2. The primary safety endpoint is frequency, severity, and timing of adverse events (AEs) 
and serious adverse events (SAEs).  
3.2. 
Secondary Efficacy Objectives and Endpoints  
The secondary objectives are to evaluate the efficacy of aldafermin and the effect of 
aldafermin on pharmacokinetics and on biomarkers of target engagement, fibrogenesis, and 
imaging.  
The following endpoints will be measured:  
1. Improvement in liver fibrosis greater than or equal to one stage (NASH CRN fibrosis 
score) and no worsening of steatohepatitis (defined as no increase in NAS for ballooning, 
inflammation, or steatosis), after 48 weeks of treatment with aldafermin or matched 
placebo, in subjects who had a minimum 1 point in each category (hepatocellular 
ballooning, steatosis, and lobular inflammation) of NAFLD Activity Score (NAS) at 
baseline as determined by central pathologist evaluation. 
2. Improvement in liver fibrosis greater than or equal to one stage (NASH CRN fibrosis 
score) after 48 weeks of treatment with aldafermin or matched placebo. 
3. Changes from baseline in fibrosis as measured by Collagen Proportional Area (CPA) 
and/or Second Harmonic Generation (SHG) methodologies at Week 48. 
4. Aldafermin concentrations pre-dose at all treatment visits and 4-hours post-dose at Day 1, 
Week 24, and Week 48 in all subjects. In a subset of subjects participating in an optional 
PK study, full PK profiles up to 24 hours will be assessed at Day 1 and steady state at end 
of treatment (EOT), i.e., 48 weeks.  
5. Changes from baseline over time in C4 and serum bile acids and compared to placebo. 
6. Changes from baseline over time in Pro-C3 compared to placebo. 
7. Changes from baseline over time in alanine transaminase (ALT) and aspartate 
transaminase (AST) and compared to placebo in subjects with elevated transaminases at 
baseline. 

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8. Changes from baseline over time in liver stiffness measure (LSM by FibroScan®) and 
compared to placebo.  
3.3. 
Exploratory Endpoints  
The following exploratory endpoints will be evaluated to understand change from baseline 
with aldafermin and compared to placebo:  
 
 
 
 
 
 
  
  
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 

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4. 
STUDY DESIGN 
4.1. 
Methodology/Study Design:  
This study is a double-blind, randomized, placebo-controlled, multi-center study of 
aldafermin in subjects with histologically confirmed cirrhosis with NASH.  
The study consists of a screening period, a double-blind treatment period of 48 weeks and a 
safety follow-up period of 6-10 weeks. Subjects will be treated with either aldafermin or 
matched placebo given as a subcutaneous injection daily for 48 weeks.  
Eligible subjects will have histologically confirmed cirrhosis (NASH CRN fibrosis Stage 4, 
with a limited number of subjects with fibrosis Stage 3 with a clinical diagnosis of cirrhosis) 
due to NASH. Historical biopsy may be used for inclusion into the study. Otherwise, a liver 
biopsy must be obtained for eligibility assessment. Liver biopsy results of either historical or 
screening biopsy must be confirmed by a central pathologist reading.  
At Screening, all subjects will undergo evaluation for risk of HCC. A gadolinium-enhanced 
MRI or multiphasic CT scan without any nodules evaluated as Liver Imaging and Reporting 
Data System (LI-RADS) score of ≥2 on central read will be required at Screening to rule out 
HCC risk. For potential subjects unable to obtain an MRI or CT scan, ultrasound that is 
negative for hepatic lesions/nodules (local read) at Screening may be used. In all cases, AFP 
must be ≤20 ng/mL. 
Subjects with suspicious lesions/nodules at ultrasound followed by observation of nodules 
that are LI-RADS ≥2 by central read of gadolinium-enhanced MRI or multiphasic CT scan at 
Screening will be excluded from enrollment and will be referred for further evaluation for 
HCC per the standard of care (SOC). Subjects will also be excluded if EGD documented any 
signs of esophageal or gastric varices.  
Up to approximately 150 eligible subjects will be randomized into 1 of 4 treatment groups in 
a 3:2:2:3 ratio to receive either subcutaneous placebo, 0.3 mg aldafermin, 1 mg aldafermin, 
or 3 mg aldafermin, respectively. Under protocol Version 5.0 and subsequent versions, 
eligible subjects will no longer be randomized into the 0.3 mg aldafermin treatment group. 
Instead, subjects will be randomized into 1 of 3 treatment groups in a 4:3:4 ratio to receive 
either subcutaneous placebo, 1 mg aldafermin or 3 mg aldafermin, respectively. Subjects 
randomized to the 0.3 mg aldafermin treatment group prior to protocol Version 5.0 will 
continue to receive the same dose until treatment completion. No more than 30% of the 
remaining population will be enrolled with the expanded Baveno VI criteria. 
Randomization will be stratified by clinical diagnosis of T2D versus no T2D to ensure 
planned allocation ratio of treatment groups within each stratum (see Table 6 
[Version 1.0-4.0], Table 7 [Version 5.0], and Figure 2). 

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Table 6. 
Study Design 282-CC-207 (Versions 1.0-4.0) 
Treatment 
Group 
Dose of aldafermin 
(mg) 
Mode of 
Treatment 
Regimen 
Number of 
Subjects 
Planned 
1 
0 (Placebo) 
Subcutaneous 
Daily 
45 
2 
0.3 
30 
3 
1 
30 
4 
3 
45 
Total Subjects Planned 
150 
 
Table 7. 
Study Design 282-CC-207 (Version 5.0) 
Treatment 
Group 
Dose of aldafermin 
(mg) 
Mode of 
Treatment 
Regimen 
Number of 
Subjects 
Planned 
1 
0 (Placebo) 
Subcutaneous 
Daily 
52 
2 
0.3 
8 
3 
1 
38 
4 
3 
52 
Total Subjects Planned 
150 
 
Figure 2. 
Schematic Overview of the Study Design 
 

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Study drug self-administration instructions and training will be provided to the subjects and 
study drug kits will be dispensed. Subjects will self-administer in the clinic the first dose of 
aldafermin/ placebo (Day 1) and doses at Weeks 2, 6, 12, 18, 24, 30, 36, 42, and 48 study 
visits. Subjects will self-administer all other doses through Week 48 at home. 
Self-administration should occur at a similar time for every dose in both the clinic and at 
home. 
Subjects will return to the clinic on Weeks 2, 6, 12, 18, 24, 30, 36, 42, and 48 for on 
treatment assessments.  
Subject cholesterol levels will be followed during the course of the study, and treatment with 
over-encapsulated rosuvastatin/matched placebo will start at Week 2 according to the lipid 
management algorithm (Appendix 4).  
LDL-C levels and related safety data will be evaluated at Weeks 2, 6, 12, 18, 24, 30, 36, and 
42 in all subjects by an independent third-party Medical Monitor who will determine the 
need for initiation/titration of rosuvastatin according to the protocol. Rosuvastatin will be 
used to manage cholesterol levels according to the established lipid management algorithm 
described in Appendix 4.  
Rosuvastatin and matched placebo are over-encapsulated to maintain the treatment blind. 
Initiation and ongoing dose adjustments of rosuvastatin/matched placebo will be managed 
through the 
 
who is unblinded to subject lipid levels but blinded to the treatment assignment (aldafermin 
or matched placebo). The sponsor and study sites will be blinded to subject lipid levels, 
rosuvastatin/placebo allocation, and the specific rosuvastatin dosing decisions. A kit 
containing rosuvastatin or matched placebo bottles will be assigned based on assessment by 
the unblinded Medical Monitor, at each study visit from Week 2 through Week 42 
(statin-naïve) or Week 48 (statin-experienced), according to the lipid management algorithm 
and will be delivered to subjects via a courier service vendor (Section 6.1.3.1) or to the study 
site for subjects to collect, depending on subject preference. Reference Appendix 4 for 
specific dosing algorithm for statin-naïve and statin experienced subjects. 
Over-encapsulated rosuvastatin will be initiated at Week 2, starting at 5 mg QD in 
statin-naïve subjects whose ASCVD 10-year risk score is ≥7.5% (US) or ≥ moderate level 
risk (European), Appendix 4. In subjects who are statin-naïve with diabetes or a history of 
myocardial infarction or stroke, or other ASCVD risk-enhancing diagnoses, rosuvastatin will 
be initiated at 5 mg at Week 2 if LDL-C is not already at the goal of ≤70 mg/dL 
(1.8 mmol/L). Though there is incremental cardiovascular benefit to additional LDL-C 
lowering (Sabatine 2018), other reports, including the meta-analysis by Ma, et al. suggest an 
association between low LDL-C levels and hemorrhagic stroke (Ma 2019), and overall, 
controversy remains regarding the long-term safety of medications that can help achieve low 
LDL-C levels such as PCSK9 inhibitors (Pasta 2020, Bandyopadhyay 2018). Thus, for safety 
considerations, statin-naïve subjects with risk-enhancing diagnoses who are already at an 
LDL-C treatment goal of ≤ 70 mg/dL (1.8 mmol/L) will be initiated on over-encapsulated 
rosuvastatin placebo. At subsequent clinic visits, lipid levels will be evaluated and treatment 
with over-encapsulated rosuvastatin may be initiated or placebo may be continued. 
Subjects who are statin-experienced (i.e., on statin concomitant medication), will be switched 
to an equivalent intensity rosuvastatin dose at Week 2. For self-identified Asians, 10 mg is 

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considered a high intensity dose, and 5 mg is considered a moderate intensity dose. 
Matched placebo will be given to statin-naive study subjects who do not meet initiation 
criteria at Week 2 or subsequent visits.  
LDL-C values will be further evaluated at study visit Week 6, 12, 18, 24, 30, 36, and 42, in 
order to identify subjects who require rosuvastatin initiation or dose-escalation. Specific LDL 
goal or treatment success criteria are described in detail in Section 8.3.17. Subjects who do 
not meet rosuvastatin increase criteria will continue on their prior assigned dose of over-
encapsulated rosuvastatin/ matched placebo. Subjects on the maximum dose of rosuvastatin 
40 mg whose LDL-C levels are still not at goal will continue on the study with rosuvastatin 
40 mg unless the subject experiences a cardiovascular-related SAE (e.g., myocardial 
infarction, CVA). Subjects experiencing a CV-related SAE on rosuvastatin 40 mg will 
discontinue both aldafermin and rosuvastatin for the remainder of the trial, and 
cardiovascular care will continue per the subject’s regular physician and as per local standard 
of care practices. Subjects who experience rosuvastatin-related intolerance (by evaluation of 
muscular symptoms and creatine kinase (CK) levels) will be evaluated by follow-up 
laboratory testing after the over-encapsulated rosuvastatin/placebo has been held. Depending 
on the CK levels and clinical status, subjects may be allowed to restart over-encapsulated 
rosuvastatin/placebo at a reduced dose. Algorithm details are found in Section 7.1.1, part ii. 
All subjects will be assessed at Weeks 49 and 54 to confirm their LDL-C levels have 
decreased to near baseline, at which point no additional follow-up is needed. 
Subjects who do not meet LDL-C decrease criteria at Week 54 will have an additional 
4-week follow-up visit at Week 58 to confirm that their LDL-C level returned to near 
baseline. Subjects may remain on statin through Week 58. 
As part of safety monitoring, subjects will undergo ultrasound and alpha fetoprotein (AFP) 
testing at Weeks 24 and 48 to screen for HCC. Subjects with new lesions ≥10 mm with AFP 
>20 ng/mL will be treated according to local guidelines. If new lesions ≥10 mm with AFP 
>20 ng/mL occur at Week 24, subjects may continue on study drug at the discretion of the 
investigator unless or until a clinical diagnosis of HCC is made (defined as LI-RADS 4 or 5 
on MRI, or histological confirmation of HCC). For subjects with suspected HCC by 
ultrasound and AFP screening, additional imaging may be obtained, and data will be 
gathered for adjudication. 
Overall safety will be monitored by a data safety monitoring board (DSMB).  
All subjects will return to the clinic for the End-of-Treatment (EOT) visit at Week 48. 
Subjects will return to the clinic at Weeks 49 and 54 (or at 1 and 6 weeks after last dose of 
aldafermin) for a post-treatment response and End-of-Study (EOS) follow-up visits. 
Subjects may be contacted to participate in additional optional follow-up visits, if necessary, 
to monitor anti-drug antibody (ADA) response.  

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4.2. 
Study Stop Criteria 
The entire study may be discontinued at the discretion of the sponsor based on the occurrence 
of the following: 
• AEs with respect to their nature, frequency, severity, and/or duration (reference 
Section 7.1 for details) 
• Medical or ethical reasons affecting the continued performance of the study 
• Difficulties in the recruitment of subjects 
• Cancellation of drug development 

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Negative for hepatic lesions/nodules indicating HCC risk: 
a. MRI is the preferred imaging modality. There must be no nodules with a Liver 
Imaging and Reporting Data System (LI-RADS) score of ≥2 by central radiologist 
evaluation. 
b. If MRI is not available or not possible to be performed, a multi-phasic CT scan may 
be used to assess HCC risk. There must be no nodules with a LI-RADS score ≥2 by 
central radiologist evaluation. 
c. If MRI and CT are not available or not possible to be performed for screening a 
potential subject, then ultrasonography of the liver may be performed: 
1) If no hepatic lesions or nodules (local radiologist evaluation) and AFP ≤20 ng/mL, 
the potential subject may be considered further for enrollment. 
2) For any findings of hepatic lesions or nodules (local radiologist evaluation) that are 
not clearly benign cysts and have not been shown clearly benign by prior CT or MRI, 
follow-up MRI must be performed and meet criteria (no nodules with LI-RADS score 
of ≥2 evaluated centrally) in order for the potential subject to be considered further 
for enrollment. 
7. Subjects with T2D or insulin resistance are permitted as long as diabetic medications are 
reasonably “stable” within 3 months prior to Screening, as outlined in Section 6.4. 
8. Other concomitant medications/therapies used for the treatment of coexisting conditions 
are acceptable (Section 6.4), if on a stable regimen for at least 3 months prior to the 
Screening, except for non-statin lipid lowering agents, which can be used until Day 1 of 
Screening. 
9. Statin use is acceptable based on the following criteria, as assessed by the investigator at 
Screening: 
a. Statin-naïve is defined as no administration of statins within 3 months prior to 
Screening 
b. Statin-Experienced is defined as currently receiving ≤50% of the maximal approved 
dose of statin therapy  
Requires a reasonably stable statin dose at least 3 months prior to Screening 
Note: The following are the acceptable daily doses of approved statin therapies, and other 
lipid lowering agents. Also listed under Section 6.4: 
i. 
Atorvastatin: ≤40 mg/day 
ii. 
Fluvastatin: ≤40 mg/day 
iii. 
Lovastatin: ≤40 mg/day (for both immediate and extended release) 
iv. 
Pitavastatin: ≤2 mg/day 
v. 
Pravastatin: ≤40 mg/day 

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vi. 
Simvastatin: ≤40 mg/day 
vii. 
Rosuvastatin: ≤20 mg/day  
10. The following additional laboratory parameters must be met at Screening  
a. Total bilirubin ≤1.3 mg/dL 
i. if Gilbert’s Syndrome, with direct bilirubin within ULN.  
b. HbA1c ≤9.5%  
c. Platelet count ≥120,000/mm3  
Subjects who meet the Baveno VI criteria with a platelet count >110,000/mm3 and 
<120,000/mm3 may be enrolled if they meet the expanded Baveno VI criteria. (Note: 
No more than 30% of the remaining population will be enrolled using the Baveno VI 
criteria.) 
d. Creatinine clearance ≥60 mL/min as calculated by Cockcroft-Gault equation  
e. Serum alanine amino transferase (ALT) levels ≤5 x ULN 
f. Serum aspartate amino transferase (AST) levels ≤5 x ULN 
g. Alkaline phosphatase ≤1.5 x ULN 
h. Serum albumin ≥3.5 g/dL 
i. International normalized ratio (INR) ≤1.7. 
Note: A 10% laboratory variability is allowed on platelets and bilirubin values. 
Platelet variability does not apply to Baveno VI. 
11. Female subjects must be either of a) non-childbearing potential, defined as women who 
have had a hysterectomy, bilateral oophorectomy, medically documented ovarian failure, 
documented postmenopausal, or a follicle stimulating hormone ≥40 mIU/mL, OR b) if of 
childbearing potential, defined as including women <55 years of age with ≤2 years of 
amenorrhea (absence of menstruation and not due to any reversible medical cause or any 
current medication use), then have a negative serum pregnancy test at Screening and urine 
pregnancy test at the Day 1 visit prior to first dose of study drug, and must be 
non-lactating and non-breastfeeding. Note: Females who do not meet this criterion can be 
included if they meet Inclusion Criterion 12.  
12. Female subjects of childbearing potential and male subjects with a female partner of 
childbearing potential must agree to consistent and adequate birth control from Screening 
to EOS (Week 54): 
• Recommended forms of contraception for males: condom, vasectomy, and sexual 
abstinence 
i.  Vasectomized partner is a highly effective birth control method provided that the 
partner is the sole sexual partner of the female subject of childbearing potential 
trial participant and that the vasectomized partner has received medical 
assessment of the surgical success. 

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ii.  Condom use is not considered as a highly effective form of contraception alone 
and may be used effectively with a second method of contraception. 
iii.  Sexual abstinence is considered a highly effective method only if defined as 
abstaining from heterosexual intercourse during the entire period of risk 
associated with the study treatments. The reliability of sexual abstinence needs to 
be evaluated in relation to the duration of the trial and the preferred and usual 
lifestyle of the subject. 
• Recommended forms of contraception for females: hormone containing contraceptive 
medication, Intrauterine device with failure rate <1% per year, cervical cap or 
diaphragm with spermicidal agent, bilateral tubal occlusion (tubal sterilization), 
sexual abstinence 
i.  Combined (estrogen and progestogen containing) hormonal contraception (oral, 
intravaginal, transdermal) associated with inhibition of ovulation 
ii.  Progestogen-only hormonal contraception (oral, injectable, implantable) 
associated with inhibition of ovulation  
iii.  Cervical cap or diaphragm with spermicidal agent is not considered as a highly 
effective form of contraception alone and may be used effectively with a second 
method of contraception 
Sexual abstinence is considered a highly effective method only if defined as 
abstaining from heterosexual intercourse during the entire period of risk associated 
with the study treatments. The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the trial and the preferred and usual lifestyle of the subject. 
13. Able and willing to comply with the dosing instructions for study drug administration and 
able to complete the study schedule of assessments.  
5.2. 
Exclusion Criteria 
The following will exclude potential subjects from participating the study: 
1. Other causes of liver disease that are primary, secondary, or otherwise causes of cirrhosis 
or which may confound the intended patient population according to the investigator, 
including but not limited to alcoholic liver disease, hepatitis B, hepatitis C, autoimmune 
disorders, primary biliary cirrhosis, drug-induced hepatotoxicity, Wilson’s disease, 
hemochromatosis, and alpha-1-anti-trypsin deficiency based on medical history and/or 
centralized read of liver histology.  
2. Evidence of drug induced steatohepatitis secondary to amiodarone, corticosteroids, 
estrogens, methotrexate, tetracycline, or other medications known to cause hepatic 
steatosis. 
3. History of hepatic decompensation, including variceal bleeding, ascites, or hepatic 
encephalopathy. 
4. Prior or pending liver transplantation. 
5. Child Pugh class B and C status. 

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6. Model of end stage liver disease (MELD) score >12. 
7. Evidence of worsening liver disease (defined below) between screening visits 
(i.e., Day -56 and Day -42) including measures of AST, ALT, alkaline phosphatase 
(ALP) or total bilirubin (TBL): 
a. For subjects with TBL, AST, ALT, or ALP baseline levels >ULN, the second 
assessment should not exceed an increase of 35% over the first assessment.  
Note: An unscheduled visit may be necessary to confirm eligibility if the difference 
exceeds the allowable percent difference. If performed, unscheduled visit results will be 
compared to the average of Day -56 and Day -42 results to determine eligibility. If liver 
function tests are repeated to verify eligibility criteria have been met, there must be a 
minimum of 14 days (2 weeks) between the Day -42 visit and any unscheduled visit. 
8. History of porto-systemic shunt procedure. 
9. No evidence of gastroesophageal varices as documented by one of the following 
assessments: 
a. A historical and locally evaluated EGD obtained within 365 days of screening or 
b. A locally evaluated EGD conducted during the screening period 
* If no EGD is available, the latest EGD assessment guidelines during a global 
pandemic† for patients with compensated cirrhosis (i.e., the expanded Baveno VI 
criteria, Petta 2018) as follows can be used as a replacement for the EGD to determine 
eligibility: 
c. Platelet count >110,000/mm3, and a FibroScan® <30 kPa on a M probe or <25 kPa 
on a XL probe  
Note: No more than 30% of the remaining population will be enrolled with the 
expanded Baveno VI criteria. 
† EGD waived in patients with compensated cirrhosis during a global pandemic per 
AASLD/ASGE guidelines. 
10. Clinically significant cardiovascular or cerebrovascular event or new diagnosis within 
6 months of Screening, including but not limited to congestive heart failure, myocardial 
infarction, acute coronary syndrome, revascularization, stroke (hemorrhagic or 
ischemic), transient ischemic attack (TIA), or implanted defibrillator or pacemaker (for 
uncomplicated elective, non-biventricular pacemaker procedure, 3 months post 
procedure will be allowed).  
11. Gastric bypass or bariatric surgery in the past 5 years or planned procedure during the 
study period. 
12. History of clinically significant unstable or untreated illness or any other major medical 
disorder that may interfere with subject treatment, assessment, or compliance with the 
protocol. 
13. Documented significant weight change (±5%) <3 months prior to Screening. 

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14. Screening ECG with clinically significant abnormalities that in the investigator's opinion, 
require evaluation and possible treatment.  
15. Positive for HBsAg, antiHIV Ab, or antiHCV Ab plus HCV-RNA. Subjects who are 
antiHCV Ab- positive but HCV-RNA negative (secondary to treatment or viral 
clearance) are eligible with at least a 1-year period since documented sustained viral 
response at Week 12 post-treatment. 
16. 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 
or breast ductular carcinoma in situ is allowed if appropriately treated within 2 years 
prior to Screening); subjects under evaluation for suspected malignancy are not eligible. 
History of hepatocellular carcinoma at any point regardless of treatment or treatment 
success will be excluded. 
17. A positive drug screen (e.g., morphine, heroin, cocaine) will exclude subjects unless it 
can be clearly explained by a prescribed medication. The diagnosis and prescription 
must be approved by the investigator and the Medical Monitor.  
18. Significant alcohol intake as measured by a phosphatidylethanol (PEth) level 
≥200 ng/mL AND significant alcohol use, as determined by the Alcohol Use Disorders 
Identification Test (AUDIT-C) alcohol consumption questionnaire (Appendix 3). 
19. Criterion deleted per protocol Version 3.0.  
20. Consumption of ≥21 units of alcohol per week in males and ≥14 units of alcohol per 
week in females for two years prior to screening, where a “unit” of alcohol is equivalent 
to a 12-ounce beer, 4-ounce glass of wine, or 1-ounce shot of hard liquor. 
21. Use of any prohibited concomitant medications as described in Section 6.4 within 
3 months prior to screening; 
a. Weight loss medications. 
b. Any medication that is contraindicated according to the rosuvastatin package insert 
(Appendix 5) or if subject has a known hypersensitivity to rosuvastatin product 
components (Section 6.1.3). 
c. Hepatotoxic medications (Appendix 6); allopurinol allowed.  
d. Anabolic steroids. 
22. History of statin intolerance, as defined by presence of significant side effects while on 
statins and/or inability to take or use statins for treatment. 
23. Prior participation in a clinical trial of aldafermin unless previously enrolled into a 
placebo arm of the trial.  
24. History of severe allergic or anaphylactic reactions to recombinant therapeutic proteins, 
fusion proteins, or chimeric, human, or humanized antibodies. 

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25. Participation in a study of another investigational agent within 28 days or five half-lives 
of the drug (whichever is longer) prior to Screening. 
26. Any acute or chronic condition that, in the opinion of the investigator, would limit the 
subject’s ability to participate, complete, and/or would confound data interpretation in 
this clinical study. 

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6. 
STUDY TREATMENT 
6.1. 
Clinical Supplies 
6.1.1. 
Aldafermin 
Aldafermin 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. 
Aldafermin is provided as a sterile solution for injection in a single use prefilled syringe for 
SC administration at doses of 0.3 mg, 1 mg, and 3 mg (note: under protocol Version 5.0 and 
subsequent versions, randomization to the 0.3 mg aldafermin dose was discontinued). The 
drug product is manufactured for NGM under current Good Manufacturing Practice (cGMP) 
regulations 
 
, a contract manufacturing facility that has undergone FDA inspection. 
6.1.2. 
Aldafermin-matched Placebo 
Aldafermin placebo 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. 
Aldafermin placebo is provided as a sterile solution for injection in a single use- pre-filled 
syringe for SC administration. The drug product is manufactured for NGM under cGMP 
regulations 
 
, an FDA-inspected contract manufacturing facility. 
6.1.3. 
Rosuvastatin / Placebo 
Commercial rosuvastatin tablets will be over-encapsulated and will be supplied as 5 mg, 
10 mg, 20 mg, or 40 mg strengths in multi-count bottles. Inactive ingredient microcrystalline 
cellulose will be used to backfill over-encapsulated rosuvastatin calcium tablets. 
Placebo capsules for rosuvastatin calcium contains only microcrystalline cellulose and will 
be supplied in multi-count bottles. The capsules used for the active and placebo are opaque, 
Swedish Orange, size A, hard gelatin capsules containing gelatin, titanium oxide, and 
FDA/E172 red iron oxide. Refer to Appendix 5 for the rosuvastatin package inserts. 
6.1.3.1. 
Rosuvastatin Supply 
Upon subject consent, over-encapsulated rosuvastatin/placebo bottles will be delivered to 
his/her designated location (e.g., home, office) via a courier service vendor. Delivery can be 
done through either a depot or central pharmacy. In compliance with data privacy 
regulations, the vendor has a data privacy system in place to cover any local obligations. 
If subjects do not agree to use this courier service, they have the option to pick up the 
rosuvastatin/placebo bottles at the study site. 

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6.2. 
Preparation / Handling / Storage / Accountability  
6.2.1. 
Preparation  
6.2.1.1. 
Aldafermin 
Subjects will be instructed to self-administer aldafermin/placebo at relatively the same time 
each day. Study drug/placebo syringes will be equilibrated to room temperature prior to use 
and will be administered as a SC injection in the abdomen. On Day 1, subjects will be trained 
on self-administering a SC injection. During the treatment visits, self-administration 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/placebo administration diary. 
6.2.1.2. 
Rosuvastatin / Placebo 
Subjects will be instructed to take one capsule of rosuvastatin/placebo once a day by mouth 
at approximately the same time each day. All bottles will be blinded. The subject will be 
contacted by the site a few days after study visits and instructed as to which bottle to dose 
from. During the on-treatment visits, subjects will take their study drug to clinic visits and 
dose from the dosing bottle dispensed at the last visit in the clinic under observation by clinic 
staff. The subject will be required to complete a daily study drug/placebo dosing diary. 
6.2.2. 
Storage 
Aldafermin/placebo 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, aldafermin/placebo syringes are to be stored in the 
provided packaging and refrigerated at 2°C–8°C (36°F–46°F) in a location protected from 
light (e.g., refrigerator). 
Rosuvastatin /placebo bottles should be stored at room temperature, at 68°F–77°F 
(20°C-25°C) and in a dry place. 
Subjects will be instructed to keep both study drugs out of the reach of children and other 
family members who may have access to the storage location. 
6.2.3. 
Accountability 
The principal investigator (PI) is responsible for ensuring that a current record of 
inventory/drug accountability (aldafermin/placebo and rosuvastatin/placebo) 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.  
Upon receipt of the investigational drug/placebo, 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, 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. 

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6.3. 
Randomization and Blinding 
Subjects will be randomized to a treatment group using 
 
. Treatment assignment will be blinded to the sites, study subjects, sponsor 
study team, and sponsor Medical Monitor throughout the study period.  
Rosuvastatin and matched placebo will be over-encapsulated to maintain the blind at the sites 
and with the sponsor study teams. Initiation and ongoing dose adjustments of 
rosuvastatin/matched placebo will be managed through the 
 
 but blinded to the treatment assignment (aldafermin or 
matched placebo). The sponsor and study sites will be blinded to LDL-C values and the 
specific rosuvastatin dosing decisions. 
6.3.1. 
Removal of Study Blind (if applicable) 
Breaking of any blind will be available to the PI 
 The subject’s treatment 
assignment will be available to the PI in the event of a medical emergency or an AE that 
necessitates identification of the study drug for the welfare of that subject. Except in the case 
of a medical emergency, the PI and clinic staff will remain blinded during the conduct of the 
study and until such time that all discrepancies in the clinical database are resolved (i.e., at 
the time of the database lock). The date and time when the PI removed the study blind for an 
individual subject will be documented by 
 
 to the sponsor. 
6.4. 
Concomitant Medications 
Any medication taken at least once within 90 days prior to Screening Visit and during the 
study period as well as the reason for use will be recorded in the source documents and the 
CRFs. Subjects should refrain from the use of any new prescription medications or products 
or changes in the dose or frequency of existing therapies from Screening to Day 1 until EOS.  
The sponsor Medical Monitor or designee should be informed of any changes or addition of 
prohibited medications during this time. 
6.4.1. 
Prohibited Medications: 
• Investigational agents, other than aldafermin, or devices for any indication, within 28 
days or 5 half-lives of the drug (whichever is longer) prior to Screening through the end 
of the study.  
• Non-statin lipid lowering agents, from Day 1 of Screening through the end of the study  
o Example medications to avoid include: Cholestyramine, colesevelam, PCSK9 
inhibitors (evolocumab or alirocumab), colestid, fibrates, fenofibrates, pharmacologic 
(dose of >1 g daily) fish oil  
• Statins other than the study provided rosuvastatin from Week 2 through the end of the 
study: 
o 
Prior statin use must be at a reasonably stable dose for 3 months prior to 
Screening and will continue as a concomitant medication until Week 2.  

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• Agents used for the treatment of any condition listed in the exclusionary enrollment 
criteria (see Section 5.1). 
• Weight loss medications including orlistat, phentermine, qsymia, lorcaserin 
hydrochloride, naltrexone hydrochloride, benzphentamine, diethylpropion, 
phendimetrazine, from 3 months prior to Screening through the end of the study. 
• 
Contraindicated medications according to the rosuvastatin package insert 
(Appendix 5), including; cyclosporine, gemfibrozil, protease inhibitors (atazanavir, 
ritonavir, lopinavir, simeprevir), coumarin anticoagulants, fenofibrates, niacin, 
colchicine, from randomization through the end of the study.  
• Known hepatotoxic agents (refer to Appendix 6). 
• Anabolic steroids.  
This list of prohibited medications along with Appendix 6, are not an inclusive list. 
investigator judgement must be used to avoid prohibited medications and to justify initiating 
any other medication during the study. 
6.4.2. 
Restricted Concomitant Medications / Treatments:  
• Statin Therapies:  
For statin experienced subjects only, the following daily dose of approved statin therapies 
will allow for enrollment consideration if dosing is stable at least 3 months with reasonable 
dose adjustment (as per Medical Monitor’s judgment) prior to Screening through Week 2. 
All subjects will transition to study rosuvastatin treatment at Week 2 according to the 
protocol. From Week 2 onward, over-encapsulated rosuvastatin or matched placebo will be 
dispensed according to the Lipid Lowering Algorithm (Appendix 4). 
o Atorvastatin: ≤40 mg/day 
o Fluvastatin: ≤40 mg/day 
o Lovastatin: ≤40 mg/day (for immediate and extended release) 
o Pitavastatin: ≤2 mg/day 
o Pravastatin: ≤40 mg/day 
o Simvastatin: ≤40 mg/day 
o Rosuvastatin: ≤20 mg/day  
• Other therapies for coexisting conditions require a stable regimen for at least 3 months 
prior to the Screening and throughout the study including: 
o Standard vitamin supplements 
o Vitamin E (>400 IU) 
o Milk thistle 
o Pentoxifylline 

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• Diabetic medications: 
o GLP1 agonists and pioglitazone: require a stable regimen for at least 3 months prior 
to Screening and throughout the study.  
o Insulin: require stable dosing, defined as reasonable dose adjustments (as per 
Investigator’s judgment) to maintain glucose control, for at least 3 months prior to 
Screening.  
o All other diabetic medications: require a stable dose with reasonable dose adjustment 
(as per Investigator’s judgment) for at least 3 months prior to Screening. 
• Antibiotics (not listed in Appendix 6): Antibiotics for short-term use (<10 days) are 
allowed; however, chronic, continuous use is not allowed. Use will be at the discretion of 
the PI. 
• Procedural medications (e.g., anti-anxiety medication for MRI scan, anesthetic for liver 
biopsy) use will be at the discretion of the PI. 

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7. 
STUDY TREATMENT DISCONTINUATION AND SUBJECT 
DISCONTINUATION / WITHDRAWAL FROM THE STUDY 
7.1. 
Discontinuation of Study Treatment for an Individual Subject  
Study treatment discontinuation, interruption or dose reduction will be considered if subjects 
experience the following: 
• TEAE of Grade 3 or 4 (per CTCAE V5.0) with severity and relationship noted below 
• Any suspected statin-related AE, as determined by the investigator (see below) 
• Laboratory result(s) indicative of drug induced liver disease (DILI), based on assessment 
by the Medical Monitor and by the independent DILI adjudication 
• Confirmed diagnosis of HCC 
• Progression from Child-Pugh A to Child-Pugh B or C status 
• Liver decompensation events 
• Subjects with MELD score ≥15. 
7.1.1. 
Specific Actions Taken Will Be As Follows: 
i)  TEAE of Grade 3 or 4 (per CTCAE V5.0): 
• Any possibly or probably related Grade 3 TEAE, aldafermin and/or statin may be 
discontinued or interrupted; evaluation and determination by the PI or the unblinded 
Medical Monitor in the case of TEAEs possibly related to statin use. 
• Any Grade 4 or higher TEAE, aldafermin and statin will be discontinued 
ii)  Any suspected statin-related AE: 
Subjects will be allowed a rosuvastatin dose adjustment if the subject experiences a 
statin-related AE (as determined by the PI). The third-party Medical Monitor will be 
contacted by the study site to report a possible statin-related AE requiring intervention. 
Information will be collected on the AE including the specific description, history, and 
severity based on CTCAE grading. The study team should instruct the subject to refrain from 
administering the rosuvastatin/placebo therapy and to repeat safety laboratory examinations 
as indicated by the specific AE within 72 hours. If the subject is <2 weeks from their next 
visit, they should not dose the rosuvastatin/placebo therapy until the next scheduled visit. 
If they are >2 weeks from their next study visit, an unscheduled visit should be made to 
repeat laboratory examinations.  
If the AE resolves, subjects will be restarted on a lower dose of over encapsulated 
rosuvastatin. Subjects on rosuvastatin 20 mg or 40 mg will be restarted on rosuvastatin 
10 mg, and subjects on 5 mg or 10 mg will be restarted on rosuvastatin 5 mg. Subjects taking 
over-encapsulated placebo will be restarted on placebo. In the event that the AE re-occurs 
upon re-initiation at the lower dose, over encapsulated rosuvastatin/placebo should be 
discontinued. If the AE does not re-occur with the lower dose, an increase in the over 
encapsulated rosuvastatin dose may be considered at the subsequent clinic visits according to 
the protocol algorithm. If the AE re-occurs following administration of this new dose of 

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rosuvastatin, over encapsulated rosuvastatin/placebo may be reverted to the last tolerated 
dose. Aldafermin dosing will not be interrupted.  
If a subject experiences a statin-related AE of myalgia or rhabdomyolysis (as determined by 
the PI), information will be collected on the AE including the specific description, history, 
and severity based on CTCAE grading and forwarded to the designated third-party Medical 
Monitor who is blinded to treatment assignment but unblinded to laboratory data and statin 
assignment and dose. The clinical study team will collect a blood sample for safety 
laboratory evaluations within 48-72 hours. For subjects that have signs or symptoms 
suggestive of rhabdomyolysis from either muscle symptoms (such as myalgia, pain, 
weakness, dark urine) or elevated creatine kinase (CK), the origin of the symptoms/CK 
elevation will be investigated. To this end, the subject will be interviewed about recent heavy 
exercise, trauma, convulsions, surgery, use of excessive alcohol, morphine, cocaine, or other 
contributing factors. Additional laboratory tests (creatinine, AST/ALT, total and conjugated 
bilirubin, potassium, calcium, and/or myoglobin (serum and urine)) will also be performed.  
If the subject experienced statin-related increased CK>3 x ULN with clinical symptoms, 
administration of over-encapsulated rosuvastatin/placebo should be held and may be 
re-initiated at half the prior dose if follow-up CK is <3 x ULN. If CK rises to >3 x ULN 
again, the administration of over-encapsulated rosuvastatin/placebo should be held until CK 
<3 x ULN and can be re-initiated at 5 mg. For subjects experiencing symptoms and CK 
elevation on 5 mg, over-encapsulated rosuvastatin/placebo should be discontinued. 
Aldafermin dosing will continue.  
For subjects with suspicion of statin-related myalgia or rhabdomyolysis AND CK 
3-5 x ULN, administration of over-encapsulated rosuvastatin/placebo should be held until 
CK<3 x ULN and may be reinitiated at half the original dose. If symptoms persist and if CK 
increases >3 x ULN, rosuvastatin should be discontinued. For CK>5 x ULN with clinical 
suspicion of rhabdomyolysis (ruling out other causes, e.g., recent heavy exercise, trauma, 
convulsions, surgery, use of excessive alcohol, morphine, cocaine, or other contributing 
factors), rosuvastatin will be discontinued. Throughout, aldafermin dosing should continue. 
iii)  
Laboratory value(s) suggestive of DILI:  
a) Elevation of AST or ALT >2 x above subject-specific baseline value (calculated 
using the average of the Day -56 and the Day 1 values) and total bilirubin 
>1.5 x subject specific baseline value, repeat testing of ALT, AST, and bilirubin must 
be performed within 48-72 hours. If there are persistent elevations (AST or ALT 
>2 x baseline or TBL >1.5 x baseline values) upon repeat testing, then close 
observation (testing and physical examination 2-3 times per week) should be 
implemented and discontinuation of aldafermin and rosuvastatin should be considered 
(see below). Note: the unblinded study Medical Monitor will be notified of acute 
suspected cases and upon identification of suspected DILI cases, the Liver Events 
Adjudication Committee chair will be notified. 
b) A decision to discontinue or temporarily interrupt the study drug will be considered 
based on factors that include how much higher than baseline ALT and AST were 
relative to the ULN and how much the on-study ALT and AST levels have increased 

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relative to baseline, in addition to whether there is concomitant elevation of bilirubin 
or INR. aldafermin and rosuvastatin will be discontinued or temporarily interrupted as 
follows: 
• 
If baseline measurements (BLM) were <2 x ULN, discontinue if ALT or AST 
increases to >5 x BLM 
• 
If BLM ≥2 x ULN but <5 x ULN, discontinue if ALT or AST increases to 
>3 x BLM 
• 
Discontinue if ALT or AST increase >2 x BLM AND the increase is 
accompanied by a concomitant increase in TBL to >2 x BLM OR the INR 
concomitantly increases by >0.2 
• 
Discontinue if total bilirubin >3.0 mg/dL 
• 
In any subjects with signs and symptoms of fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
c) If a subject resides in a remote area, laboratory testing can be performed locally, and 
the results should be promptly communicated to the investigator site. 
d) Close observation for suspected DILI will include: 
• Repeating liver enzyme and serum bilirubin tests two or three times weekly. 
Frequency of repeat testing can decrease to once a week or less if abnormalities 
stabilize or the study drug has been discontinued and the subject is 
asymptomatic. 
• Obtaining or re-confirming a detailed history of symptoms and prior or 
concurrent diseases. 
• Obtaining or re-confirming the history of concomitant drug use (including 
nonprescription medications and herbal and dietary supplement preparations), 
alcohol use, recreational drug use, and special diets. 
• Ruling out acute viral hepatitis types A, B, C, D, and E; autoimmune or alcoholic 
hepatitis; NASH hypoxic/ischemic hepatopathy; and biliary tract disease. 
• Obtaining a history of exposure to environmental chemical agents. 
Outside of situations listed above, no aldafermin/matched placebo dose reductions will be 
allowed. Temporary drug holidays from aldafermin dosing <5 days will be allowed on a 
case-by-case basis for subjects for safety or tolerability but must be approved by the sponsor 
Medical Monitor or designee. If drug is restarted and is still not tolerated, the subject should 
stop the medication as multiple drug holidays will not be allowed.  

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7.2. 
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 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 administration of 
non-permitted concomitant medication that might affect subject safety or study 
assessments/objectives. In addition, for any AEs noted, the PI will determine whether there is 
impact, or a potential for impact, on subject safety or study assessments/objectives, and will 
remove such subjects. Subjects will be discontinued due to clinically relevant changes in a 
subject’s status related to Inclusion and Exclusion criteria that significantly affect subject 
safety or study integrity, development of pregnancy, or necessary administration of 
non-permitted concomitant medications that might affect subject safety or study 
assessments/objectives. Notification of discontinuation will be made immediately to the 
sponsor Medical Monitor or designee. 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. 

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8. 
STUDY PROCEDURES  
8.1. 
Schedule of Study Procedures  
The Schedule of Study Procedures is shown in Table 8. The visits should occur as close to 
the intended dates as possible. However, there is an acceptable ±3-day window from Week 2 
through Week 6, and Week 54 (Week 58 if needed). Visit window from Weeks 12 through 
48 is ±7 days. Visit window for Week 49 is +3 days. 
Subjects attending any visits out of windows from Day 1 to Week 48/Early Withdrawal 
(EOT) visit should be brought back into compliance with the overall study visit schedule as 
soon as possible thereafter. 
The PI has discretion to repeat assessments if he/she believes the results are erroneous or to 
rule out worsening of liver disease (Exclusion #7) for Day -56 and Day -42 visits. Repeat 
assessments must be conducted within the 8-week Screening Period. The screening window 
may be increased up to 16 weeks (112 days) to obtain all screening assessments, with 
Medical Monitor approval. Only assessments that need to be repeated should be done rather 
than a full re-screening of the subject. The results of the repeat testing will be used for 
evaluation. 
All subjects will be assessed at Weeks 49 and 54 to confirm their LDL-C levels have 
returned to near baseline. At that point, no additional follow-up will be performed. 
Subjects who do not meet criteria at Week 54 (Day 1 levels within 15 mg/dL or at the 
protocol-defined LDL-C goal) will have an additional 4-week follow-up visit at Week 58 to 
confirm that their LDL-C level returned to near baseline or at the protocol-defined LDL-C 
goal. Subjects may remain on over-encapsulated rosuvastatin through Week 58.  
All subjects will have pre-dose PK blood collection on all treatment visits as well as 4-hours 
post-dose on Day 1, Week 24, and Week 48. 
All subjects will be offered the opportunity to participate in a PK sub-study, which will 
involve a few additional procedures, including blood draws (i.e., on Day 1 and Week 48 at 
pre-dose, and post-dose at 0.5, 1, 2, 4, 6, 8, 12, and 24 hours). Reference Table 8 for more 
details.  
 

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[k] Creatine kinase will be collected at all time points as serum chemistry. 
[l] Per Exclusion #7, total bilirubin, AST, ALT, ALP 
[m] A serum pregnancy test will be performed on all female subjects of childbearing potential at Day -56 Screening visit, Week 24, and Week 48. A urine pregnancy test will be 
performed on all female subjects of childbearing potential at all study visits through EOS. 
[n] Urine drug and alcohol tests may be repeated during treatment for subjects suspected of excessive alcohol intake or to rule out association with a safety event.  
[o] Serum bile acids will be collected pre-dose Day 1 and Week 48/early withdrawal.  
[p] C4 will be collected pre-dose on Day 1 and Weeks 2, 6, 12, 18, 24, 30, 36, 42, 48 and 4-h post dose on Days 1, Weeks 24, and 48. In addition, for subjects participating in the 
optional PK sub-study, additional C4 will be tested at the same time points as the PK blood sample collections: Day 1 and Week 48 at pre-dose, and post-dose at 0.5, 1, 2, 4, 6, 8, 
12, and 24 hours. The window for sample collection for the pre-dose through 4 hours is ±5 minutes, 6-12-hour time points is ±30 minutes. The window for sample collection for 
the 24-hour time points is -2 hours. 
[q] PK blood samples will be collected in all subjects before dosing themselves in the clinic (pre-dose) on Day 1, Weeks 2, 6, 12,18, 24, 30, 36, 42, and 48 and 4-hours post-dose on 
Day 1, Week 24 and Week 48 .  
[r] For subjects participating in the optional PK sub-study, blood samples will be collected when the subjects dose themselves in the clinic on Day 1 and Week 48 at pre-dose, and 
post-dose at 0.5, 1, 2, 4, 6, 8, 12, and 24 hours. The window for sample collection for the pre-dose through 4 hours is ±5 minutes, 6-12-hour time points is ±30 minutes. The 
window for sample collection for the 24-hour time points is -2 hours.  
[s] A single buccal swab sample for PNPLA3/other genetic biomarkers will be collected pre-dose on Day 1. 
[t] Subjects will be instructed to self-inject aldafermin/placebo in the abdomen at a similar time each day. Subjects will not self-inject aldafermin/placebo at home on clinic visit 
day. 
[u] Rosuvastatin will be dispensed at Weeks 2, 6, 12, 18, 24, 30, 36, and 42 visits and subjects will be provided further dosing instruction based on their ASCVD risk assessment, 
prior statin history (statin naïve or statin experienced), and LDL-C levels or LDL reduction levels. Subjects on a statin at Screening will switch from their current statin to an 
equivalent intensity dose of rosuvastatin at Week 2 and will be dispensed additional rosuvastatin at Week 48 and continue through Week 54 (or Week 58 if LDL-C follow-up is 
needed). 
[v] For subjects who were statin experienced at Baseline, medication compliance will be assessed at Week 54 only. 
[w] All subjects will be assessed at Weeks 49 and 54 to confirm their LDL-C levels are decreasing to near baseline, at which point, no additional follow-up is needed. Subjects who 
do not meet LDL-C decrease criteria at Week 54 will have an additional 4-week follow-up visit at Week 58 to confirm their LDL-C has returned to near baseline.  
[x] ONLY for subjects who were identified at Week 49 as needing re-assessment of LDL-C at Week 54, the third-party Medical Monitor will evaluate LDL-C results to assess the 
need to schedule a 4-week LDL-C safety follow-up visit (Study Week 58) to confirm their LDL-C value has returned to near baseline.  
[y] For EW patients only, the last, on-treatment ELF values at the visit prior to the EW visit will also be measured, in addition to the EW visit. This measurement will be done using 
the banked serum samples for the Exploratory Biomarker. 
 

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8.2. 
Study Visit Procedures 
8.2.1. 
Screening - Day -56 (Screening) Procedures 
Subjects will report to clinic fasted. The Screening procedures must be completed within 
56 days from consent in order to randomize the subject.  
• Obtain informed consent 
• Collect demographic data 
• Ascertain medical history and smoking status  
• Assess inclusion/exclusion criteria 
• Measure height 
• Measure body weight, BMI, waist circumference 
• Conduct physical examination and right upper quadrant (RUQ) pain assessment with 
numeric rating scale (NRS) 
• 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) 
• Complete AUDIT-C alcohol consumption questionnaire 
• Record prior and concomitant medications 
• Record AEs (starting from the when the subject signs informed consent) 
• Obtain FibroScan® scores (transient elastography, VCTE™ and in steatosis by ultrasound 
attenuation rate CAP™), where available 
• Obtain blood for 10-hour fasted laboratory sample collection for: 
o Chemistry, including creatine kinase 
o CBC 
o HbA1c 
o Insulin level 
o HOMA-IR calculation 
o INR 
o Alpha fetoprotein (AFP)  
o Serum pregnancy test (all female subjects of childbearing potential) 
o Hepatitis and HIV Ab screen 
o PEth alcohol screen  
o Lipid panel 

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• Obtain urine sample for: 
o Urinalysis 
o Urine drug screen 
8.2.2. 
Day –42 to Day -1 (Screening) Procedures 
Subjects will report to clinic fasted. Day -42 Screening procedures must be completed no 
sooner than 14 days (2 weeks) days after the Day -56 Screening visit to allow for adequate 
separation of liver function tests.  
• Conduct Chronic Liver Disease Questionnaire for NASH (CLDQ-NASH) 
• Obtain imaging (MRI, CT, or ultrasound) for HCC screening (preferably prior to any 
histologic evaluation unless a historical biopsy is available) 
• Gadolinium-enhanced MRI (if necessary, based on ultrasound screening result)  
• Obtain an EGD (see Section 8.3.6 for additional details regarding EGD requirement) 
• Obtain viable tissue slides from eligible historical liver biopsy or undergo a liver biopsy 
procedure to obtain new tissue 
• Record concomitant medications 
• Record AEs  
• Obtain blood for 10-hour fasted laboratory sample collection for: 
o Laboratory assessments for worsening liver disease per Exclusion #7, total bilirubin, 
AST, ALT, ALP 
o INR 
• Obtain urine for pre-dose urine pregnancy in all female subjects of childbearing potential  
8.2.3. 
Day 1 Procedures 
Subjects will report to clinic fasted. 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 and RUQ pain assessment with NRS 
• 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 10-hour fasted clinical laboratory samples for the following:  

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o Chemistry, including creatine kinase.  
o CBC 
o HbA1c 
o 
 
o Insulin level 
o HOMA-IR calculation 
o INR 
o Lipid panel  
o Lipoprotein particles 
o Lipase 
o C4  
o Serum bile acids 
o PK 
o Anti-drug antibodies (ADAs)  
o Neutralizing antibodies (NAbs)  
o ELF panel 
o Pro-C3 
o Pro-C3X 
o CTX-III 
o C3M 
o Exploratory Plasma biomarker #1 
o Exploratory Plasma biomarker #2 
o Exploratory Serum biomarker #3 
o Single exploratory buccal swab sample for PNPLA3/other genetic biomarkers 
• Obtain urine sample for: 
o Pre-dose urine pregnancy in all female subjects of childbearing potential 
o Urinalysis 
o Urine drug screen 
• Randomize subject 
  
In-clinic dosing and post-dose assessments/activities: 
• Dispense initial aldafermin study drug kit and home diary  
• Provide aldafermin study drug self-administration training 
• Oversee subject’s aldafermin study drug self-administration 

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o Exploratory Plasma biomarker #2 
o Exploratory Serum biomarker #3 
Results for ALT, AST, Total Cholesterol, LDL, HDL, and triglycerides are blinded to the 
site and sponsor. 
• Obtain urine sample for: 
Pre-dose urine pregnancy in all female subjects of childbearing potential  
In-clinic dosing and dispensing: 
• Collect old aldafermin study drug kit and diary and conduct reconciliation 
• Dispense new aldafermin study drug kit and diary 
• Rosuvastatin/ matched placebo diary. Inform Subjects that they will be contacted in a few 
days regarding the delivery or pick up of their rosuvastatin/placebo drug bottles.  
• Oversee subject’s aldafermin study drug self-administration (from new kit) 
• Perform LISSA evaluation 
Before clinic discharge: 
• Remind subject to bring study drug kit and diary at the next visit and not to 
self-administer aldafermin/placebo at home on clinic visit days 
• Schedule Week 6 visit 
Lipid Lowering Therapy Assessment: 
The third-party Medical Monitor will evaluate LDL-C results to assess the need for lipid 
lowering therapy (refer to Section 8.3.17). 
8.2.5. 
Week 6 Procedures 
Subjects will report to clinic fasted and not dosed with aldafermin. The following procedures 
will be performed: 
Pre-dose: 
• 
Conduct physical examination and RUQ pain assessment with NRS 
• 
Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse) 
• 
Record concomitant medications 
• Record AEs  
• Obtain blood for 10-hour fasted clinical laboratory samples:  
o Chemistry, including creatine kinase 
o CBC 
o INR 
o Lipid panel  
o Lipoprotein particles 

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o Lipase 
o C4  
o PK  
o ADAs 
o NAbs 
o Exploratory Plasma biomarker #1 
o Exploratory Plasma biomarker #2 
o Exploratory Serum biomarker #3 
Results for ALT, AST, Total Cholesterol, LDL, HDL, and triglycerides are blinded to the 
site and sponsor. 
• Obtain urine sample for: 
Pre-dose urine pregnancy in all female subjects of childbearing potential  
In-clinic dosing and dispensing: 
• Collect old aldafermin study drug kit and diary and conduct reconciliation 
• Collect old rosuvastatin or matched placebo bottles and diary and conduct reconciliation 
• Dispense new aldafermin study drug kit and diary 
• Re-dispense rosuvastatin or matched placebo bottles and diary. Remind subjects that they 
will be contacted in a few days regarding the delivery or pick up of their 
rosuvastatin/placebo drug bottles. 
• Oversee subject’s aldafermin study drug self-administration (from new kit) 
• Perform LISSA evaluation  
Before clinic discharge: 
• 
Remind subject to bring study drug kit and diary at the next visit and not to 
self-administer aldafermin/placebo at home on clinic visit days 
• Schedule Week 12 visit 
Lipid Lowering Therapy Assessment: 
The third-party Medical Monitor will evaluate LDL-C results to assess the need for lipid 
lowering therapy (refer to Section 8.3.17). 
8.2.6. 
Week 12 Procedures 
Subjects will report clinic fasted and not dosed with aldafermin. The following procedures 
will be performed: 
Pre-dose: 
• Conduct physical examination and RUQ pain assessment with NRS  
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse) 

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• Record prior and concomitant medications 
• Record AEs  
• Obtain blood for 10-hour fasted laboratory sample collection for: 
o Chemistry, including creatine kinase 
o CBC 
o INR 
o Lipid panel 
o Lipoprotein particles 
o Lipase 
o C4  
o PK  
o ADAs 
o NAbs 
o Exploratory Plasma biomarker #1 
o Exploratory Plasma biomarker #2 
o Exploratory Serum biomarker #3 
Results for ALT, AST, Total Cholesterol, LDL, HDL, and triglycerides are blinded to the 
site and sponsor. 
• Obtain urine sample for: 
Pre-dose urine pregnancy in all female subjects of childbearing potential  
In-clinic dosing and dispensing: 
• Collect old aldafermin study drug kit and diary and conduct reconciliation 
• Collect old rosuvastatin or matched placebo bottles and diary and conduct reconciliation 
• Dispense new aldafermin study drug kit and diary 
• Re-dispense rosuvastatin medication or matched placebo bottles and diary. 
Remind Subjects that they will be contacted in a few days regarding the delivery or pick 
up of their rosuvastatin/placebo drug bottles. 
• Oversee subject’s aldafermin study drug self-administration (from new kit) 
• Perform LISSA evaluation  
Before clinic discharge: 
• 
Remind subject to bring study drug kit and diary at the next visit and not to 
self-administer aldafermin/placebo at home on clinic visit days 
• Schedule Week 18 visit 

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Lipid Lowering Therapy Assessment: 
The third-party Medical Monitor will evaluate LDL-C results to assess the need for lipid 
lowering therapy (refer to Section 8.3.17). 
8.2.7. 
Week 18 Procedures 
Subjects will report to clinic fasted and not dosed with aldafermin. The following procedures 
will be performed: 
Pre-dose: 
• Measure body weight, BMI, and waist circumference 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes) 
• Conduct physical examination and RUQ pain assessment with NRS  
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse) 
• Record concomitant medications 
• Record AEs 
• Obtain blood for 10-hour fasted laboratory sample collection for: 
o Chemistry, including creatine kinase.  
o CBC 
o INR 
o Lipid panel 
o Lipoproteins 
o C4  
o PK  
o Exploratory Plasma biomarker #1 
o Exploratory Plasma biomarker #2 
o Exploratory Serum biomarker #3 
Results for ALT, AST, Total Cholesterol, LDL, HDL, and triglycerides are blinded to the 
site and sponsor. 
• Obtain urine sample for: 
Pre-dose urine pregnancy in all female subjects of childbearing potential  
In-clinic dosing and dispensing: 
• Collect old aldafermin study drug kit and diary and conduct reconciliation 
• Collect old rosuvastatin medication or matched placebo bottles and diary and conduct 
reconciliation 
• Dispense new aldafermin study drug kit and diary 

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• Re-dispense rosuvastatin or matched placebo bottles and diary. Remind Subjects that they 
will be contacted in a few days regarding the delivery or pick up of their 
rosuvastatin/placebo drug bottles. 
• Oversee subject’s aldafermin study drug self-administration (from new kit) 
• Perform LISSA evaluation  
Before clinic discharge: 
• Remind subject to bring study drug kit and diary at the next visit and to not 
self-administer aldafermin/placebo at home on clinic visit days 
• Schedule Week 24 visit 
Lipid Lowering Therapy Assessment: 
The third-party Medical Monitor will evaluate LDL-C results to assess the need for lipid 
lowering therapy (refer to Section 8.3.17). 
8.2.8. 
Week 24 Procedures 
Subjects will report clinic fasted and not dosed with aldafermin. The following procedures 
will be performed: 
Pre-dose: 
• Conduct physical examination and RUQ pain assessment with NRS  
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse) 
• Conduct Chronic Liver Disease Questionnaire for NASH (CLDQ-NASH) 
• Obtain an ultrasound of the liver for HCC surveillance 
• Obtain FibroScan® scores (for transient elastography, VCTE™ and steatosis by ultrasound 
attenuation rate CAP™), where available  
• Record prior and concomitant medications 
• Record AEs (starting from the when the subject signs informed consent) 
• Obtain blood for 10-hour fasted laboratory sample collection for: 
o Chemistry, including creatine kinase.  
o CBC 
o INR 
o AFP 
o Insulin level 
o HOMA-IR calculation 
o Lipid panel 
o Lipoprotein particles 

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o Lipase 
o C4  
o PK  
o ADAs 
o NAbs 
o ELF panel 
o Pro-C3 
o Pro-C3X 
o CTX-III 
o C3M 
o Exploratory Plasma biomarker #1 
o Exploratory Plasma biomarker #2 
o Exploratory Serum biomarker #3 
o Serum pregnancy test (all female subjects of childbearing potential) 
Results for ALT, AST, Total Cholesterol, LDL, HDL, and triglycerides are blinded to the 
site and sponsor. 
• Obtain urine sample for: 
o Urinalysis 
o Urine drug screen 
In-clinic dosing and dispensing: 
• Collect old aldafermin study drug kit and diary and conduct reconciliation 
• Collect old rosuvastatin or matched placebo bottles and diary and conduct reconciliation 
• Dispense new aldafermin study drug kit and diary 
• Re-dispense rosuvastatin or matched placebo bottles and diary. Remind Subjects that they 
will be contacted in a few days regarding the delivery or pick up of their 
rosuvastatin/placebo drug bottles. 
• Oversee subject’s aldafermin study drug self-administration (from new kit) 
• Perform LISSA evaluation  
• Obtain PK blood sample 4-hours post dose. 
• Obtain C4 blood sample 4-hours post dose.  
Before clinic discharge: 
• Remind subject to bring study drug kit and diary at the next visit and to not 
self-administer aldafermin/placebo at home on clinic visit days 
• Schedule Week 30 visit 

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Lipid Lowering Therapy Assessment: 
The third-party Medical Monitor will evaluate LDL-C results to assess the need for lipid 
lowering therapy (refer to Section 8.3.17). 
8.2.9. 
Week 30 Procedures 
Subjects will report to clinic fasted and not dosed with aldafermin. The following procedures 
will be performed: 
Pre-dose: 
• Measure body weight, BMI, and waist circumference 
• Conduct physical examination and RUQ pain assessment with NRS 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse) 
• Record concomitant medications 
• Record AEs 
• Obtain blood for 10-hour fasted laboratory sample collection for: 
o Chemistry 
o CBC 
o INR 
o Lipid panel 
o Lipoproteins 
o C4  
o PK  
o Exploratory Plasma biomarker #1 
o Exploratory Plasma biomarker #2 
o Exploratory Serum biomarker #3 
Results for ALT, AST, Total Cholesterol, LDL, HDL, and triglycerides are blinded to the 
site and sponsor. 
• Obtain urine sample for: 
Pre-dose urine pregnancy in all female subjects of childbearing potential  
In-clinic dosing and dispensing: 
• Collect old aldafermin study drug kit and diary and conduct reconciliation 
• Collect old rosuvastatin or matched placebo bottles and diary and conduct reconciliation 
• Dispense new aldafermin study drug kit and diary 

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• Re-dispense rosuvastatin or matched placebo bottles and diary. Remind Subjects that they 
will be contacted in a few days regarding the delivery or pick up of their 
rosuvastatin/placebo drug bottles. 
• Oversee subject’s aldafermin study drug self-administration (from new kit) 
• Perform LISSA evaluation  
Before clinic discharge: 
• Remind subject to bring study drug kit and diary at the next visit and to not 
self-administer aldafermin/placebo at home on clinic visit days 
• Schedule Week 36 visit 
Lipid Lowering Therapy Assessment: 
The third-party Medical Monitor will evaluate LDL-C results to assess the need for lipid 
lowering therapy (refer to Section 8.3.17). 
8.2.10. 
Week 36 Procedures 
Subjects will report to clinic fasted and not dosed with aldafermin. The following procedures 
will be performed: 
Pre-dose: 
• Measure body weight, BMI, and waist circumference 
• Conduct physical examination and RUQ pain assessment with NRS  
• 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 blood for 10-hour fasted laboratory sample collection for: 
o Chemistry 
o CBC 
o INR 
o Lipid panel 
o Lipoproteins 
o Lipase 
o C4  
o PK  
o ADAs 
o NAbs 

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o Exploratory Plasma biomarker #1 
o Exploratory Plasma biomarker #2 
o Exploratory Serum biomarker #3 
Results for ALT, AST, Total Cholesterol, LDL, HDL, and triglycerides are blinded to the 
site and sponsor. 
• Obtain urine sample for: 
Pre-dose urine pregnancy in all female subjects of childbearing potential  
In-clinic dosing and dispensing: 
• Collect old aldafermin study drug kit and diary and conduct reconciliation 
• Collect old rosuvastatin or matched placebo bottles and diary and conduct reconciliation 
• Dispense new aldafermin study drug kit and diary 
• Re-dispense rosuvastatin or matched placebo bottles and diary. Remind Subjects that they 
will be contacted in a few days regarding the delivery or pick up of their 
rosuvastatin/placebo drug bottles. 
• Oversee subject’s aldafermin study drug self-administration (from new kit) 
• Perform LISSA evaluation  
Before clinic discharge: 
• Remind subject to bring study drug kit and diary at the next visit and to not 
self-administer aldafermin/placebo at home on clinic visit days 
• Schedule Week 42 visit 
Lipid Lowering Therapy Assessment: 
The third-party Medical Monitor will evaluate LDL-C results to assess the need for lipid 
lowering therapy (refer to Section 8.3.17) 
8.2.11. 
Week 42 Procedures 
Subjects will report to clinic fasted and not dosed with aldafermin. The following procedures 
will be performed: 
Pre-dose: 
• Conduct physical examination and RUQ pain assessment with NRS  
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse) 
• Record concomitant medications 
• Record AEs 
• Obtain blood for 10-hour fasted laboratory sample collection for: 
o Chemistry 
o CBC 
o INR 

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o Lipid panel 
o Lipoproteins 
o C4  
o PK  
o Exploratory Plasma biomarker #1 
o Exploratory Plasma biomarker #2 
o Exploratory Serum biomarker #3 
Results for ALT, AST, Total Cholesterol, LDL, HDL, and triglycerides are blinded to the 
site and sponsor. 
• Obtain urine sample for: 
Pre-dose urine pregnancy in all female subjects of childbearing potential  
In-clinic dosing and dispensing: 
• Collect old aldafermin study drug kit and diary and conduct reconciliation 
• Collect old rosuvastatin or matched placebo bottles and diary and conduct reconciliation 
• Dispense new aldafermin study drug kit and diary 
• Re-dispense rosuvastatin or matched placebo bottles and diary. Remind Subjects that they 
will be contacted in a few days regarding the delivery or pick up of their 
rosuvastatin/placebo drug bottles. 
• Oversee subject’s aldafermin study drug self-administration (from new kit) 
• Perform LISSA evaluation  
Before clinic discharge: 
• Remind subject to bring study drug kit and diary at the next visit and to not 
self-administer aldafermin/placebo at home on clinic visit days 
• Schedule Week 48 visit 
Lipid Lowering Therapy Assessment: 
The third-party Medical Monitor will evaluate LDL-C results to assess the need for lipid 
lowering therapy (refer to Section 8.3.17). 
8.2.12. 
Week 48 / Early Withdrawal (End of Treatment) Procedures 
Subjects will report to this visit fasted and not dosed with aldafermin.  
The following procedures will be performed at the Week 48/Early Withdrawal visit: 
Pre-dose: 
• Measure body weight, BMI, and waist circumference 
• Conduct physical examination and RUQ pain assessment with NRS 
• Obtain 12-lead ECG (after subject has been supine for at least 5 minutes) 

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• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse) 
• Conduct Chronic Liver Disease Questionnaire for NASH (CLDQ-NASH) 
• Obtain FibroScan® scores (for transient elastography, VCTE™ and steatosis by ultrasound 
attenuation rate CAP™), where available  
• Obtain an ultrasound liver for routine HCC surveillance  
• Undergo a liver biopsy procedure to obtain new tissue  
• Record concomitant medications 
• Record AEs 
• Obtain 10-hour fasted clinical laboratory samples for the following:  
o Chemistry 
o CBC 
o HbA1c 
o 
 
o Insulin level 
o HOMA-IR calculation 
o INR 
o AFP 
o Serum pregnancy test (all female subjects of childbearing potential) 
o Lipid panel  
o Lipoprotein particles 
o Lipase 
o C4  
o Serum bile acids 
o PK  
o ADAs 
o NAbs 
o ELF panel 
o Pro-C3 
o Pro-C3X 
o CTX-III 
o C3M 
o Exploratory Plasma biomarker #1 

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8.2.13. 
Week 49 Procedures  
Subjects will report to this visit fasted. The following procedures will be performed at the 
Week 49 visit: 
• Conduct physical examination and RUQ pain assessment with NRS 
• Measure vital signs (including temperature, respiratory rate, and seated blood pressure 
and pulse) 
• Record concomitant medications 
• Record new and/or changes to AEs 
• Obtain 10-hour fasted clinical laboratory samples for the following:  
o Chemistry 
o CBC 
o INR 
o AFP 
o Lipid panel 
o Exploratory Plasma biomarker #1 
o Exploratory Plasma biomarker #2 
o Exploratory Serum biomarker #3 
Obtain urine sample for: 
• Urine pregnancy in all female subjects of childbearing potential 
Before clinic discharge: 
• Schedule Week 54 (EOS) visit 
Lipid Lowering Therapy Assessment: 
The third-party Medical Monitor will evaluate LDL-C (refer to Section 8.3.17).  
All subjects will be assessed at Weeks 49 and 54 to confirm their LDL-C levels are 
decreasing to near baseline, at which point, no additional follow-up is needed.  
Subjects who do not meet LDL-C decrease criteria at Week 54 will have an additional 
4-week follow-up visit at Week 58 to confirm their LDL-C change has returned to near 
baseline. 
8.2.14. 
Week 54 (End of Study) Procedures 
This visit will be performed 6 weeks after the EOT visit. Subjects will report to this visit 
fasted. 
• Measure body weight, BMI, and waist circumference 
• Conduct physical examination and RUQ pain assessment with NRS 
• 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) 

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• Conduct Chronic Liver Disease Questionnaire for NASH (CLDQ-NASH) 
• Record concomitant medications 
• Record new and/or changes to AEs 
• Obtain 10 hour fasted clinical laboratory samples for the following:  
o Chemistry 
o CBC 
o HbA1c 
o Insulin level 
o HOMA-IR calculation 
o 
 
o INR 
o Lipid panel  
o Lipoprotein particles 
o Lipase 
o ADAs 
o NAbs 
o ELF panel 
o Pro-C3 
o Pro-C3X 
o CTX-III 
o C3M 
o Exploratory Plasma biomarker #1 
o Exploratory Plasma biomarker #2 
o Exploratory Serum biomarker #3 
• Obtain urine sample for urinalysis and urine pregnancy in all female subjects of 
childbearing potential 
• Collect old rosuvastatin bottles/diary and conduct reconciliation (only for subjects who 
were on statin therapy at Baseline and continued on rosuvastatin after EOT visit). 
• Invite consent for ADA follow-up study (reference Section 8.2.16). 
• For subjects who do not require additional lipid monitoring (Section 8.2.15), this 
Week 54 visit will mark their end of participation in this clinical trial. For subjects who 
do need the additional 4-week lipid monitoring follow-up visit, the end of their trial 
participation will occur at Week 58 (Section 8.2.15).  

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Lipid Lowering Therapy Assessment: 
For subjects who were identified at Week 49 as needing re-assessment of LDL-C at 
Week 54, the third-party- Medical Monitor will evaluate LDL-C results to assess the need to 
schedule a 4-week LDL-C safety follow-up visit (Study Week 58, Section 8.2.15) to confirm 
their LDL-C value has returned to near baseline (refer to Section 8.3.17). Based on this lipid 
assessment, the third-party Medical Monitor may recommend specific follow-up with the 
subject’s regular physician. Otherwise, all subjects should be advised to follow-up with their 
regular physician regarding any lipid management needs going forward. 
8.2.15. 
Week 58 (Lipid Monitoring Assessment 4 Week Follow-up Visit Procedures) 
This visit will be performed only for those subjects who are determined to require additional 
lipid monitoring at the Week 54 visit. The following procedures will be performed at this 
visit: 
• Record concomitant medications 
• Record AEs  
• Obtain blood for 10-hour fasted laboratory sample collection for: 
o Lipid panel 
Based on this lipid assessment, the third-party Medical Monitor may recommend specific 
follow-up with the subject’s regular physician. Otherwise, all subjects should be advised to 
follow-up with their regular physician regarding any lipid management needs going forward. 
8.2.16. 
Monitoring of Anti-Drug Antibody Response 
Subjects may be contacted to participate in additional optional follow-up visits, if necessary, 
to monitor anti-drug antibody (ADA) responses.  
8.3. 
Clinical Evaluations 
8.3.1. 
Alcohol Consumption 
8.3.1.1. 
AUDIT-C 
During Screening, clinical sites will implement the AUDIT-C, a 3-item alcohol screen that 
can help identify persons who are hazardous drinkers or have active alcohol use disorders 
(Appendix 3). The AUDIT-C is scored on a scale of 0-12. Each AUDIT-C question has 
5 answer choices. Points allotted are: a=0 points, b=1 point, c=2 points, d=3 points, e=4 
points. For men, a score of 4 or more is considered positive, optimal for identifying 
hazardous drinking or active alcohol use disorders. For women, a score of 3 or more is 
considered positive. 
However, when the points are all from Question #1 alone (#2 & #3 are zero), it can be 
assumed that the patient is drinking below recommended limits and it is suggested that the 
provider review the patient’s alcohol intake over the past few months to confirm accuracy. 

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8.3.1.2. 
PEth Screening  
Subjects with PEth levels ≥200 ng/mL AND a positive AUDIT-C at Screening will be 
excluded from the study.  
8.3.1.3. 
History of Alcohol Consumption 
Subjects will also be asked to report their history of alcohol consumption and will be 
excluded from study participation if they consume ≥21 units per week (males) or ≥14 units 
per week (females) for two years prior to Screening and where a unit of alcohol is equivalent 
to a 12-ounce beer, 4-ounce glass of wine, or a 1-ounce shot of hard liquor. 
8.3.2. 
Liver Biopsy 
Subjects who meet the Screening criteria of having a historical liver biopsy if tissue slides are 
available from within 12 months prior to Screening and are acceptable for central pathologist 
evaluation will not be required to undergo a liver biopsy. All other subjects will be required 
to undergo a liver biopsy during the Screening period and prior to randomization according 
to the study site’s local standard of care. Liver biopsy procedures have inherent risks and 
benefits, and qualified study personnel will discuss these risks and benefits with each 
potential participant prior to enrollment.  
The common procedure for obtaining a liver biopsy sample involves a percutaneous 
approach using an appropriate gauge needle for sample collection. Other means of obtaining 
liver biopsy may be used if found appropriate by the study investigator. The primary risks 
involved include bleeding, pain, and infection at the incision site. Premedication (for 
example, midazolam can be used, if consistent with local procedures) and post-biopsy care 
will be according to the study site’s standard of care. Adverse events will be collected, and 
subjects followed as appropriate. 
Sites should not perform a local reporting of the NAS or fibrosis score at either Screening or 
Week 48 in order to maintain the blinding of the primary endpoint. Tissue from all subjects 
will be collected, prepared, and sent to the Central Study Pathologist for review and 
determination of NASH. Liver biopsies with histologically confirmed NASH will be further 
assessed using the NAS established and validated by the NASH CRN (see Appendix 1), and 
liver biopsies will also be assessed for fibrosis stage for primary endpoint analysis. 
The Week 48 biopsy should be obtained before the last dose of aldafermin with a visit 
window of -7 days. 
Sites will collect a liver biopsy sample for subjects who received at least 24 weeks of 
aldafermin dose and terminate early from the study. 
8.3.3. 
CPA and SHG 
CPA (collagen proportional area, with staining) and SHG (Second Harmonic Generation, 
stain-free) technologies for assessment of fibrosis involve digital pathology system to 
characterize and accurately quantify collagen fibers area in the liver biopsies. For SHG, when 
a scan begins with an unstained liver tissue sample, the laser produces two photons (tiny light 

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particles), which – upon interaction with the collagen fibers – results in the combination of 
both photons into a single new photon, with twice the energy and therefore twice the 
frequency and half the wavelength of the initial photons. This is known as SHG, and the 
detection of SHG signals lead to a high-resolution imaging of collagen fibers within the 
tissue. Subjects will be assessed using this methodology at baseline and following 48 weeks 
of treatment with study drug. All testing will be through a central read.  
8.3.4. 
CLDQ NASH  
A chronic liver disease questionnaire will be conducted at Screening and on Weeks 24, 48, 
and 54.  
8.3.5. 
Transient Elastography and Ultrasound Attenuation Rate (Steatosis) using 
(FibroScan®) Device  
A noninvasive device (FibroScan®), where available, will be used for assessing liver stiffness 
as a measure of fibrosis via elastography (VCTE™) at the Screening Day -56, Weeks 24 and 
48. Currently, there are no 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 2018). The rationale for using “stiffness” or “elasticity” is that 
the collagen deposition associated with fibrosis imparts parenchymal rigidity, which on 
imaging tests is considered as assessing “stiffness” or “elastography.” In addition, the 
FibroScan® device will provide steatosis information using an ultrasound attenuation rate 
method (CAP™). For individual subjects, the same FibroScan® device and the same probe 
(medium [M] or extra large [XL]) must be used for all assessments. Where available, the 
median Controlled Attenuation Parameter (CAP) value will be recorded from FibroScan® 
examinations. 
8.3.6. 
Esophagogastroduodenoscopy (EGD) 
No evidence of gastroesophageal varices as documented by one of the following 
assessments: 
a. A historical and locally evaluated EGD obtained within 365 days of screening or 
b. A locally evaluated EGD conducted during the screening period 
*If no EGD is available, the latest EGD assessment guidelines during a global 
pandemic† for patients with compensated cirrhosis (i.e., the expanded Baveno VI 
criteria, Petta 2018) as follows can be used as a replacement for the EGD to determine 
eligibility: 
c. Platelet count >110,000/mm3, and a FibroScan® <30 kPa on a M probe or <25 kPa 
on a XL probe  
Note: No more than 30% of the remaining population will be enrolled with the 
expanded Baveno VI criteria. 
† EGD waived in patients with compensated cirrhosis during a global pandemic per 
AASLD/ASGE guidelines. 

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8.3.7. 
Pharmacokinetic Blood Sample Collection and Processing 
In all subjects, blood samples for PK analysis of aldafermin levels will be collected pre-dose 
on all treatment visits and 4-hours post dose on Day 1, Week 24, and Week 48. The window 
for sample collection for the pre-dose time points is ± 5 minutes. 
Subjects participating in the optional PK sub-study will have blood samples collected at the 
Day 1 and Week 48 visits at the following time points: pre-dose, 0.5, 1, 2, 4, 6, 8, 12, and 
24 hours post-dose. The window for sample collection for the pre-dose through 4 hours is 
±5 minutes, 6-12-hour time points is ±30 minutes. The window for sample collection for the 
24-hour time points is -2 hours.  
Processing, storage, and shipping instructions for these PK blood samples will be presented 
in the study Lab Manual. 
8.3.8. 
Clinical Laboratory Evaluations 
Clinical laboratory evaluations will be collected as outlined in Section 8. 
Serum chemistry will include ALT, AST, ALP, bilirubin (direct and total), creatinine, CK, 
GGT, glucose, HDL, LDL, lipase, total cholesterol, TG, bicarbonate, calcium, BUN, 
chloride, phosphate, potassium, proteins (albumin, total protein), and sodium. Samples for 
analysis of ADAs, NAbs will be collected. All NAb samples will be collected as scheduled, 
and analyzed only if necessary, based on ADA results.  
Liver function tests, including AST, ALT, TBL, and ALP, will be compared between 
Day -56 and Day -42 to assess whether there is worsening of liver disease during screening 
according to Exclusion #7. An unscheduled visit may be necessary to confirm eligibility if 
the difference exceeds the allowable percent difference. If performed, unscheduled visit 
results will be compared to the average of Day -56 and Day -42 results to determine 
eligibility. If liver function tests are repeated to verify eligibility criteria have been met, there 
must be a minimum of 14 days (2 weeks) between the Day -42 visit and any unscheduled 
visit. 
Processing, storage, and shipping instructions for the above will be presented in a separate 
Lab Manual. 
8.3.9. 
C4 Testing  
C4 testing will be collected at pre-dose at all treatment visits as well as 4-hours post-dose on 
Day 1, Week 24, and Week 48.  
Subjects participating in the optional PK study will undergo additional C4 testing at the same 
time points as their PK blood sample collections: Day 1 and Week 48 at pre-dose, and 
post-dose at 0.5, 1, 2, 4, 6, 8, 12, and 24 hours. The window for sample collection for the 
pre-dose through 4 hours is ±5 minutes, 6-12-hour time points is ±30 minutes. The window 
for sample collection for the 24-hour time points is -2 hours. 
8.3.10. 
Serum Bile Testing  
Serum bile acids samples will be collected pre-dose Day 1 and Week 48/early withdrawal. 

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8.3.11. 
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 Schedule of Study Procedures. 
8.3.12. 
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 Section 8. Seated blood pressure 
and pulse will be measured after the subject has been seated for at least 5 minutes. 
8.3.13. 
Physical Examinations and RUQ Pain Assessment 
A routine physical examination will be performed at Screening Day -56, Day 1, and 
Weeks 6, 12, 18, 24, 30, 36, 42, 48, 49 and 54. A specific assessment of RUQ pain will be 
collected and scored based on 10-point NRS. During the physical examination, the PI 
directly palpitates the RUQ region and asks the subject to provide a number between 0, equal 
to no pain and 10, being equal to worst pain.  
8.3.14. 
Weight, Body Mass Index, and Waist Circumference Measurements 
Subjects will be weighed, BMI calculated, and waist circumference measured at Screening 
Day -56, Day 1, and Weeks 18, 30, 36, 48 and 54. Formal instructions for recording weight 
and measuring waist circumference will be provided to sites. 
8.3.15. 
Local Injection-Site Symptom Assessments (LISSA) 
Injection site evaluation will be made and documented by the PI or clinic staff using a 
LISSA. 
LISSA evaluations are to be performed at each clinic visit from Day 1 through Week 48. 
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 FDA Toxicity Grading Scale 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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8.3.16. 
Evaluation of Biomarkers  
A single buccal swab sample for evaluation of PNPLA3/other genetic biomarkers will be 
collected pre-dose on Day 1.  
8.3.17. 
Lipid Lowering Therapy Assessment 
LDL-C will be evaluated at all study visits beginning at Week 2 for possible increases in 
lipid levels associated with aldafermin administration. Rosuvastatin will be used to manage 
cholesterol levels and initiated if protocol-defined lipid management criteria are met. 
Rosuvastatin and matched placebo are over-encapsulated and provided in multi-capsule 
bottles (Section 6.2.1.2). Initiation and ongoing dose adjustments of rosuvastatin will be 
managed by a third-party Medical Monitor who is blinded to treatment assignment but 
unblinded to LDL-C values and related safety laboratory results. Rosuvastatin dose changes 
will be managed through the IxRS. Lipid levels and titration recommendations will be 
blinded to the sponsor, sponsor’s Medical Monitor, investigators, subjects, and site. Initiation 
and dose adjustments will be determined by the lipid levels collected at Week 2 through 
Week 54, with lipid levels at Day 1 serving as baseline. LDL-C samples will be analyzed and 
reported to the third-party Medical Monitor. A kit containing rosuvastatin or matched 
placebo bottles will be assigned as instructed through the IxRS system and based on subjects 
LDL-C level assessment at each study visit from Week 2 through Week 42 (statin-naïve) or 
Week 48 (statin-experienced), and will be delivered to subjects via a courier service vendor 
(Section 6.1.3.1). The site will communicate to the subject the assigned bottle(s) and dosing 
should be immediately initiated.  
  
Group A 
Statin-experienced subjects (definition from Exclusion Criteria 9b) will be switched to an 
equivalent intensity rosuvastatin dose (high intensity dose – 20 mg rosuvastatin, moderate 
intensity dose – 10 mg rosuvastatin, low intensity dose – 5 mg rosuvastatin). For subjects 
who are self-identified Asians, the high intensity rosuvastatin dose is 10 mg, and the 
moderate intensity rosuvastatin dose is 5 mg. The treatment goal for this group of 
statin-experienced subjects is LDL-C level of ≤70 mg/dL (1.8 mmol/L) or ≥50% LDL-C 
reduction from the Week 2 level, starting at Week 6. 
Group B 
Subjects who are statin-naïve (definition from Exclusion Criteria 9a) AND who have 
risk-enhanced diagnoses (e.g., clinical ASCVD, CVA) AND LDL-C level of >70 mg/dL 
(1.8 mmol/L) will initiate over-encapsulated rosuvastatin at 5 mg daily with a treatment goal 
of LDL-C level of ≤70 mg/dL (1.8 mmol/L) or ≥50% LDL-C reduction from the Week 2 
level. Those subjects who are already at LDL-C level of ≤70 mg/dL (1.8 mmol/L) will 
initiate over-encapsulated rosuvastatin placebo, and LDL-C initiation criteria will be 
re-evaluated at subsequent clinic visits (i.e., Week 6, 12, 18, 24, 30, 36, 42).  
Group C 
Statin-naïve subjects without risk-enhanced diagnoses AND with a 10-year ASCVD risk 
≥7.5% (US) >1% (Europe) will initiate over-encapsulated rosuvastatin at 5 mg daily. 

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The treatment goal is LDL-C level of ≤70 mg/dL (1.8 mmol/L) or ≥ 50% LDL-C reduction 
from the Week 2 level. 
Statin-naïve subjects without risk-enhanced diagnoses AND with a 10-year ASCVD risk 
<7.5% will initiate over-encapsulated rosuvastatin placebo. ASCVD risk and LDL-C 
laboratory assessment will be evaluated at subsequent clinic visits (i.e., Week 6, 12, 18, 24, 
30, 36, 42) in order to determine whether rosuvastatin should be initiated at 5 mg daily. 
All Subjects 
At subsequent clinic visits, subjects who have achieved the protocol-defined LDL-C 
treatment goal will continue on their most recent assigned dose of rosuvastatin/placebo. If a 
subject fails to achieve the determined LDL-C goal despite increasing the rosuvastatin dose, 
those subjects will be reassigned to the lowest dose used to achieve the current LDL-C level. 
Subjects on the maximum dose of rosuvastatin 40 mg whose LDL-C levels are still not at the 
protocol-defined LDL-C goal will continue on the study with rosuvastatin 40 mg unless the 
subject experiences a cardiovascular-related SAE(e.g., myocardial infarction, CVA).  
All subjects will be assessed at Weeks 49 and 54 to confirm their LDL-C levels have either 
decreased to near baseline or at the protocol-defined LDL-C goal. At that point, no additional 
follow-up will be performed. 
Subjects who do not meet criteria at Week 54 (Day 1 levels within 15 mg/dL or at the 
protocol-defined LDL-C goal) will have an additional 4-week follow-up visit at Week 58 to 
confirm that their LDL-C level returned to near baseline. At this point, the third-party 
Medical Monitor may recommend specific follow-up with the subject’s regular physician. 
Otherwise, all subjects should be advised to follow-up with their regular physician regarding 
any lipid management needs going forward. 
8.3.18. 
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). For subjects enrolled in the optional PK sub-study, participants 
may be domiciled during dosing and 24-hour sampling and receive a standardized diet at 
scheduled times that do not conflict with other study-related activities. 
8.3.19. 
MRI, CT, and Ultrasound for HCC Testing 
As part of safety monitoring, subjects will undergo liver imaging and AFP testing to screen 
for HCC, followed by liver ultrasound and AFP testing at Weeks 24 and 48 for surveillance. 
Lesions detected on ultrasound at 24 weeks or 48 weeks, without significant change in AFP 
levels, will be managed according to the SOC at the clinical site. Subjects with an AFP level 
>20 ng/mL at either Week 24 or 48, without detectable lesions on ultrasound, will be 
managed according to the SOC at the clinical site. Subjects with a lesion ≥10 mm detected on 
ultrasound at 24 weeks with an AFP level >20 ng/mL at 24 weeks may continue on study 
drug at the discretion of the investigator unless or until a clinical diagnosis of HCC is made 
(defined as LI-RADS 4 or 5 at MRI, or histological confirmation of HCC). Abnormal 
readings with an AFP test results or suspicious ultrasound lesions will have follow-up and 
adjudication as defined by the Hepatocellular Carcinoma Adjudication Charter 
(see Section 8.5.2). 

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8.3.20. 
Evaluation of Biomarkers  
Blood samples will be collected for evaluation of exploratory biomarkers 1, 2, and 3, as 
outlined in Table 8.  
8.4. 
Safety and Other Assessments  
8.4.1. 
Definition of Adverse Events 
An AE is defined as any untoward medical occurrence in a patient or clinical investigational 
subject who has been administered a pharmaceutical product that does not necessarily have a 
causal relationship with this treatment. A TEAE is an AE that is reported after a dose of 
study drug. 
AEs are all: 
• unfavorable changes in general condition 
• subjective or objective signs/symptoms 
• concomitant diseases or accidents 
• clinically relevant adverse changes in laboratory parameters observed in a participant 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, whether volunteered, elicited, or noted on physical examination, will be recorded 
throughout the study (i.e., from screening until EOS). 
Subjects will be queried for resolution of ongoing AEs 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 in the subject’s CRF. 
Any pregnancy diagnosed during the study must be reported immediately to the investigator 
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 treatment may have 
interfered with the effectiveness of a contraceptive medication or method. 

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8.4.2. 
Definition of Serious Adverse Events and SAE 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., puts the subject, in the view of the PI, at immediate risk of 
death) 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant disability/incapacity 
• A congenital anomaly/birth defect 
• Important medical event that may require medical or surgical intervention to prevent one 
of the above outcomes 
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 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 aldafermin 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 or designee of all reported SAEs. 
Suspected statin-related AEs requiring either dose reduction or discontinuation should be 
reported to the third-party Medical Monitor by the PI. These subjects will be managed as 
outlined in Section 8.3.17. 
8.4.3. 
Classification of Severity of Adverse Event  
The severity of AEs will be categorized as shown below, based on common terminology 
criteria for adverse events (CTCAE) Version 5.0 criteria.  

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Table 9. 
Categorization of Severity of Adverse Events  
Mild 
The event is minor and does not cause significant discomfort to subject or 
change in activities of daily living (ADL); participant is aware of symptoms, 
but symptoms are easily tolerated. 
Moderate The event is an inconvenience or concern to the subject and causes 
interference with ADL, but the participant is able to continue with ADL. 
Severe 
The event significantly interferes with ADL and the subject is incapacitated 
and/or unable to continue with ADL. 
Potentially 
life 
threatening 
An event/reaction in which the subject was at risk of death at the time of the 
event/reaction; it does not refer to an event/reaction, which hypothetically 
might have caused death if it were more severe. 
 
8.4.3.1. 
Relationship to Study Drug 
The investigator will make a determination of the relationship of the AE to the study drug 
using a 4-category system (not related, possible, probable, definite), as shown below, based 
on common terminology criteria for adverse events (CTCAE) Version 5.0 criteria.  
Table 10. 
Categorization for Determining Relationship of AEs to Study Treatment  
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 
 
8.5. 
Safety Monitoring  
8.5.1. 
Data Safety Monitoring Board  
The study will be performed under review by an external independent Data Safety and 
Monitoring Board (DSMB) to closely monitor the safety and welfare of the study subjects. 
The DSMB will be comprised of experienced hepatologists and other relevant specialists. 
The DSMB will review study data at regular intervals and determine whether it is safe to 

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continue the study according to the protocol. The DSMB members will be independent of the 
sponsor, the clinical study sites, and investigators. The event definitions information relevant 
to the operation of the committee will be described in a DSMB Charter.  
8.5.2. 
Independent Adjudication  
In addition to the DSMB, NGM will incorporate a formal Adjudication process for: 
a) drug-induced liver injury (DILI) monitoring as part of the Liver Events Adjudication 
Committee, b) hepatocellular carcinoma (HCC), and c) cardiovascular events. Adjudication 
of possible/suspected cases will be conducted by independent clinicians with relevant clinical 
expertise. A cardiovascular adjudication committee is already in place across all aldafermin 
studies and performs blinded review of known and suspected cardiovascular events with 
focus on CV death, MI and hospitalization for heart failure and cerebrovascular accident 
(stroke). The Cardiovascular adjudication also reviews off-target effects of the potential 
investigational products on parameters potentially influencing the overall cardiovascular risk, 
such as: plasma lipids, glucose homeostasis, and (systemic) inflammatory (and fibrosis) 
parameters. 

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9. 
STATISTICAL CONSIDERATIONS 
A detailed statistical analysis plan (SAP) will be provided and finalized prior to the study 
database lock or unblinding. No discrepancies are expected between the SAP and the 
protocol. However, if there are discrepancies between this section of the protocol and the 
final SAP, the SAP will override the protocol. 
In general, descriptive statistics including the number of non-missing observations (n), 
arithmetic mean (mean), standard deviation (SD), median, minimum, and maximum will be 
presented for continuous variables, frequency and percentage distribution for categorical 
variables, and Kaplan–Meier estimates for time-to-event variables. 
9.1. 
Sample Size Determination 
The sample size for this study is determined based on power simulations for the modified 
primary efficacy endpoint (the change in ELF at Week 48) and using the analysis method 
described in Klingenberg (2009). Based on the ALPINE 2/3 study, the change from baseline 
in ELF at Month 6 (24 weeks) are 0.066, 0.083, -0.013, and 0.224 for placebo and aldafermin 
0.3 mg, 1.0 mg, and 3.0 mg, respectively. Assuming a change in ELF of 0.1 for subjects 
treated with placebo, and a change in ELF of -0.4 at Month 12 (48 weeks) for subjects treated 
with aldafermin 3 mg, and a 15% subject drop-out rate at Week 48, a sample size of 
150 subjects will provide at least 92% power to detect an upward dose-response trend at the 
5% significance level (two-sided) (Table 11). Under protocol Version 5.0 and subsequent 
versions, eligible subjects will no longer be randomized into the 0.3 mg aldafermin treatment 
group. Instead, subjects will be randomized into 1 of 3 treatment groups in a 4:3:4 ratio to 
receive either subcutaneous placebo, 1 mg aldafermin or 3 mg aldafermin, respectively. 
Subjects randomized to the 0.3 mg aldafermin treatment group prior to protocol Version 5.0 
will continue to receive the same dose until treatment completion. No more than 30% of the 
remaining population will be enrolled with the expanded Baveno VI criteria. The power 
under the new randomization is expected to be higher than that under the original 
randomization (3:2:2:3). More details of the power simulations will be provided in the SAP.  
Based on the modified primary endpoint of the change from baseline in ELF at Week 48 and 
the analysis results from ALPINE 2/3, the following table presents the change from baseline 
needed for different powers. 
Table 11. 
Power Simulations for the Primary Efficacy Analysis 
Assumed Change from Baseline in ELF at Week 48 
Power 
Aldafermin 3 mg 
Placebo 
-0.224 
0.066 
51.00% 
-0.3 
0.066 
69.83% 
-0.3 
0.1 
77.33% 
-0.4 
0.066 
88.35% 
-0.4 
0.1 
92.33% 
-0.5 
0.1 
99.25% 
 

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9.2. 
Analysis Populations 
Subjects will be analyzed using the following analysis populations:  
• Intent to treat (ITT) population: all randomized subjects  
• Modified ITT (mITT) population: all subjects who receive at least 2 weeks of study drug 
and have at least one valid, post-dose, on-treatment ELF score 
• Safety population: all subjects who receive at least one dose (full or partial) of study drug 
• Full-Analysis population: all randomized 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 
• Per-Protocol (PP) population: a subset of subjects in the Full Analysis population who 
have valid, non-missing baseline and post-dose liver biopsy results and do not have 
protocol deviations that impact the liver biopsy assessments 
• PK population: all randomized subjects who receive at least one dose (full or partial) of 
drug and have a qualified (i.e., above the lower limit of quantification) pre-dose and 
post-dose (at least one) PK assessment 
9.3. 
Demographics and Other Baseline Characteristics  
Demographics (e.g., age, sex, race, body weight, height, etc.) and other baseline 
characteristics will be summarized with descriptive statistics by treatment group for each 
analysis population. 
9.4. 
Efficacy Analyses 
9.4.1. 
Primary Efficacy Analysis 
The primary efficacy endpoint is the change from baseline in ELF at Week 48. Missing 
change from baseline in ELF will be imputed using a multiple imputation (MI) method under 
the assumption of missing at random (MAR).  
Sensitivity analysis under the assumption of missing not at random (e.g., pattern mixture 
model) will be performed. In addition, another sensitivity approach to impute the missing 
ELF measurement at Week 48 using the last observation carried forward (LOCF) method 
will be performed.  
The primary efficacy endpoint will be analyzed using the Multiple Comparison Procedure – 
Modeling (MCP-Mod) approach to assess the dose-response relationship. Within the 
framework of the MCP-Mod procedure, the null hypothesis of no dose-response will be 
tested at the 5% significance level (two-sided) against the alternative hypothesis that there is 
a dose-response.  
The primary efficacy analysis will be performed using the ITT population. The mITT, 
Full-Analysis and PP populations will be used as sensitivity analyses. Both MI approaches 
and LOCF approaches will be applied to the missing change from baseline ELF as sensitivity 
analysis for ITT, mITT, Full-Analysis, and PP populations. 

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9.4.2. 
Secondary Efficacy Analyses 
The between-group comparisons (aldafermin doses vs placebo) of the change from baseline 
in ELF at Week 48 will be performed using an analysis of covariance (ANCOVA) model 
with effects for treatment, baseline T2D status (Yes/No) and the baseline outcome value as a 
covariate. 
Between-group comparisons (aldafermin doses vs placebo) of the histologic response at 
Week 48 (by NASH CRN criteria) will be performed using the Cochran-Mantel-Haenszel 
(CMH) test stratified by baseline T2D status (Yes/No). 
In addition, analyses will be performed for the following secondary efficacy endpoints: 
• Changes from baseline in C4 and serum bile acids  
• Changes from baseline in Pro-C3 
• Changes from baseline in ALT, AST  
• Changes from baseline in liver stiffness measure (LSM by FibroScan®)  
All secondary efficacy endpoints will be analyzed using an analysis of covariance 
(ANCOVA) model with effects for treatment, baseline T2D status (Yes/No) and the baseline 
outcome value as a covariate.  
All secondary efficacy endpoints will be performed using the ITT population. Full-Analysis, 
and PP populations will be used as sensitivity analyses. 
No multiplicity adjustment will be made between the primary and secondary efficacy 
analyses to control the experiment-wise type I error rate, and thus all secondary efficacy 
analyses are exploratory in nature. 
9.4.3. 
Other Efficacy Analyses 
The details of other efficacy analyses will be provided in the SAP. 
9.4.4. 
Subgroup Analyses 
 
 
9.5. 
Safety Analyses 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). TEAEs will be summarized by primary system organ class and preferred term. 
Actual values and change from baseline values for vital signs, ECGs, clinical laboratory 
(hematology and chemistry) tests, and other continuous safety variables will be summarized 
with descriptive statistics. Concomitant medications, injection site reactions, and other 
categorical safety variables will be summarized with frequency and percentage distribution.  

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Regulatory, Ethical, and Study Oversight Considerations  
This study will be conducted in accordance with the protocol and with the following: 
• Ethical principles for medical subjects involving human subjects derived from the 
Declaration of Helsinki 
• Applicable ICH Good Clinical Practice Guidelines 
• Applicable laws and regulations 
10.1.1. 
Informed Consent Process  
This study will be conducted in compliance with International Conference on Harmonisation 
(ICH) E6 Good Clinical Practice: Consolidated Guidance pertaining to informed consent. 
At the first visit, prior to initiation of any study-related procedures, subjects 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 subject prior to study 
participation. A copy of the informed consent document must be provided to the subject. 
Signed consent forms must remain in the subject’s study file and be available for verification 
by sponsor or its representative at any time. 
10.1.2. 
Ethics Committee 
This protocol, the informed consent document, and all relevant supporting data must be 
submitted to the IRB/EC for approval. IRB/EC approval of the protocol, informed consent 
document, and any advertisement used to recruit study subjects must be obtained before the 
study may be initiated. 
The PI is responsible for keeping the IRB/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 IRB/EC of any reportable AEs that occur during 
the study. 
10.1.3. 
Data Safety Monitoring Board (DSMB)  
Please refer to Section 8.5.  
10.1.4. 
Protocol Adherence 
The investigator 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 
institutional review board (IRB). There will be no alterations in the protocol without 
agreement between the sponsor and the investigator. There will be no alterations in the 
protocol affecting subject safety without the express written approval of the sponsor, 
investigator, and the IRB. 

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10.1.5. 
Confidentiality and Privacy  
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 investigator 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 investigator 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. 
10.1.6. 
Clinical Monitoring 
The sponsor or designee (e.g., 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 investigator will grant access to all 
documents (related to the study and the individual participants) at any time these are 
requested. In turn, the CRA will adhere to all requirements for participant confidentiality as 
outlined in the informed consent form (ICF). The investigator and investigator’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. 
10.1.7. 
Quality Assurance and Quality Control 
Each clinical site will perform internal quality management of study conduct, data and 
biological specimen collection, documentation, and completion. An individualized quality 
management plan may be developed to describe a site’s quality management. 
10.1.8. 
Records 
The results from Screening and data collected during the study will be recorded in the 
subject’s CRF. To maintain confidentiality, the subjects 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. 
The 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 

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requirements or local laws or regulations, or sponsor standards/procedures; otherwise, the 
retention period will default to the retention period of 15 years following completion of the 
clinical trial. 
Blood and tissue samples will be collected and any remaining or back-up study samples may 
be used for future exploratory and biomarker analysis related to aldafermin treatment or 
metabolic diseases. The samples will be stored for up to 15 years. 
10.1.9. 
Financing and Insurance 
The financing and insurance for this study are outlined in the Clinical Trial Agreement. 
10.1.10. 
Publication Policy 
NGM will retain ownership of all data. All proposed publications based on this study will be 
subject to sponsor’s approval requirements. 

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11. 
REFERENCES 
11.1. 
Clinical Studies Referenced in this Protocol 
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 
282-RI-103 
1 
A Phase 1, Single-center, Open label, Parallel group Study to 
Evaluate the Pharmacokinetics, Safety & Tolerability of a Single 
Dose of Aldafermin (NGM282) in Subjects with Impaired Renal 
Function 
Renally 
impaired 
and 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 
15-0105 
2a 
A Phase 2, Randomized, Double-Blind, Placebo Controlled, 
Parallel Group and An Open-Label Single-Blind Cohort 
Multiple Center Study to Evaluate the Safety, Tolerability, and 
Efficacy of NGM282 Administered for 12 Weeks in Patients 
with Histologically Confirmed Nonalcoholic Steatohepatitis 
(NASH) 
NASH 
15-0106 
2 
A Phase 2, Randomized, Double Blind, Placebo Controlled, 
Parallel Group, Multiple Center Study to Evaluate the Safety, 
Tolerability, and Efficacy of NGM282Administered for 12 
Weeks in Patients with Primary Sclerosing Cholangitis (PSC) 
PSC 
15-0107 
1b 
A Phase 1b, Double-Blind, Placebo-controlled, Parallel-Group 
Multidose Study of the Pharmacodynamics of NGM282 on 
Colonic Transit, Bile acid Homeostasis, and Fecal Fat in 
Subjects with Functional Constipation Individuals 
Functionally 
Constipated 
and Healthy 
Volunteers 
 
11.2. 
Nonclinical Studies Referenced in this Protocol 
Study No. 
Study Title 
13-PD-NGM282-1007 
A 24-Week Study of Ectopic NGM282 Expression following 
Intravenous Adeno-Associated Viral Delivery in FXR-deficient Mice 
14-PD-NGM282-1001 
Effects of NGM282 administration on disease progression 
in the STAM mouse model of NASH 
15-PD-NGM282-1001 
Effect of Human FGF-19 and NGM282 in a High Fat/Fructose/Cholesterol Diet-
Induced Animal Model of NASH (data on file) 
15-PD-NGM282-1002 
Effect of Human FGF-19 and NGM282 in FXR-null mice fed a High 
Fat/Fructose/Cholesterol Diet-Induced Animal Model of NASH (data on file) 

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11.3. 
Literature References 
Afzali A, Berry K, Ioannou GN. Excellent posttransplant survival for patients with nonalcoholic steatohepatitis 
in the United States. Liver Transpl 2012;18:29–37. 
Alisi A, Ceccarelli S, Panera N, et al. Association between serum atypical fibroblast growth factors 21 and 19 
and pediatric nonalcoholic fatty liver disease. PLoS One 2013;8:e67160. 
Angulo P, Kleiner DE, Dam-Larsen S, et al. Liver Fibrosis, but No Other Histologic Features, Is Associated 
With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease. Gastroenterology. 2015 
Aug;149(2):389-97.e10. 
Aranha MM, Cortez-Pinto H, Costa A, et al. Bile acid levels are increased in the liver of patients with 
steatohepatitis. Eur J Gastroenterol Hepatol 2008;20:519–25. 
Argo CK, Caldwell SH. Epidemiology and natural history of non-alcoholic steatohepatitis. Clin Liver Dis 
2009;13:511–31. 
Bandyopadhyay D, Qureshi A, Ghosh S, et al. Safety and Efficacy of Extremely Low LDL-Cholesterol Levels 
and Its Prospects in Hyperlipidemia Management. J. Lipids. 2018 Apr 23; 2018:1-8. 
Bannerjee R, Pavlides M, Tunnicliffe EM, et al. Multiparametric magnetic resonance for the non-invasive 
diagnosis of liver disease. J Hepatol 2014 Jan;60:69–77. 
Bechmann LP, Kocabayoglu P, Sowa JP, et al. Free fatty acids repress small heterodimer partner (SHP) 
activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic 
steatohepatitis. Hepatology 2013;57:1394–1406.  
Bhala N, Jouness RI, Bugianesi E. Epidemiology and natural history of patients with NAFLD. Curr Pharm Des 
2013;19:5169–76.  
Bircher J, Benhamou JP, McIntyre N, et al., eds. Oxford Textbook of Clinical Hepatology. 2nd ed. Oxford; 
New York: Oxford University Press, 1999. 
Boursier J, Roux M, Costentin C, et al. Independent validation of Agile 4: novel FibroScan based score for the 
diagnosis of cirrhosis in patients with non-alcoholic fatty liver disease. J Hepatol 2021;75(2):S565. 
Brunt EM, Kleiner DE, Wilson LA, et al. Portal chronic inflammation in nonalcoholic fatty liver disease 
(NAFLD): a histologic marker of advanced NAFLD-clinicopathologic correlations from the nonalcoholic 
steatohepatitis clinical research network. Hepatology 2009;49:809–20.  
Caldwell SH, Chang CY, Nakamoto RK, et al. Mitochondria in nonalcoholic fatty liver disease. Clin Liver Dis 
2004;8:595–17.  
Centers for Disease Control US Obesity Trends http://www.cdc.gov/obesity/data/index.html (Accessed 12 
December 2014).  
Chalasani N, Younossi Z, Lavine JE, et al. The diagnosis and management of nonalcoholic fatty liver disease: 
Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018 
Jan;67(1):328-357. doi: 10.1002/hep.29367. Epub 2017 Sep 29. Review. 
Charlton MR, Burns JM, Pedersen RA, et al. Frequency and outcomes of liver transplantation for nonalcoholic 
steatohepatitis in the United States. Gastroenterology 2011;141:1249–53.  
Corey KE, Vuppalanchi R, Wilson LA, et al. NASH resolution is associated with improvements in HDL and 
triglyceride levels but not improvement in LDL or non-HDL-C levels. Aliment Pharmacol Ther. 2015 Feb;41(3 

Aldafermin (NGM282) 
Study 282-CC-207 (ALPINE 4) Protocol v6.0, 11 Nov 2021 
NGM Biopharmaceuticals, Inc. 
Confidential 
Page 112 of 124 
Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology 
and clinical implications. Gastroenterology 2012;142:711–25.  
DePaoli AM, Zhou M, Kaplan DD, et al. FGF19 Analog as a Surgical Factor Mimetic That Contributes to 
Metabolic Effects Beyond Glucose Homeostasis. Diabetes 2019 Jun; 68(6): 1315-1328. 
Desmet VJ, Roskams T. Cirrhosis reversal: a duel between dogma and myth. J Hepatol. 2004 May;40(5):860-7. 
Review. 
Eddowes PJ, Sasso M, Allison M, et al. Accuracy of FibroScan controlled attenuation parameter and liver 
stiffness measurement in assessing steatosis and fibrosis in patients with nonalcoholic fatty liver disease. 
Gastroenterology 2019;156(6):1717-30. 
European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes 
(EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice 
Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016 Jun;64(6):1388-402. 
Elsayes KM, Kielar AZ, Agrons MM, et al. Liver Imaging Reporting and Data System: an expert consensus 
statement. J Hepatocell Carcinoma. 2017 Feb 17;4:29-39. 
Eren F, Kurt R, Ermis F, et al. Preliminary evidence of a reduced serum level of fibroblast growth factor 19 in 
patients with biopsy-proven nonalcoholic fatty liver disease. Clin Biochem 2012;45:655–8. 
Elsayes KM, Kielar AZ, Agrons MM, et al. Liver Imaging Reporting and Data System: an expert consensus 
statement. J Hepatocell Carcinoma. 2017 Feb 17;4:29-39. 
Faubion WA, Guicciardi ME, Miyoshi H, et al. Toxic bile salts induce rodent hepatocyte apoptosis via direct 
activation of Fas. Clin Invest 1999;103:137–45. 
FDA 2019. Nonalcoholic steatohepatitis with compensated cirrhosis: developing drugs for treatment guidance 
for industry. June 2019. https://www.fda.gov/regulatory-information/search-fda-guidance-
documents/nonalcoholic-steatohepatitis-compensated-cirrhosis-developing-drugs-treatment-guidance-industry 
Friedman SL. Evolving challenges in hepatic fibrosis. Nat Rev Gastroenterol Hepatol. 2010 Aug;7(8):425-36. 
Friedman SL, Ratziu V, Harrison SA, et al. A randomized, placebo-controlled trial of cenicriviroc for treatment 
of nonalcoholic steatohepatitis with fibrosis. Hepatology. 2018 May;67(5):1754-1767. 
Fu L, John LM, Adams SH, et al. Fibroblast growth factor 19 increases metabolic rate and reverses dietary and 
leptin deficient diabetes. Endocrinology 2004;145:2594–603. 
Glass LM, Dickson RC, Anderson JC, et al. Total body weight loss of ≥10 % is associated with improved 
hepatic fibrosis in patients with nonalcoholic steatohepatitis. Dig Dis Sci. 2015 Apr;60(4):1024-30. 
Harrison SA, Abdelmalek MF, Caldwell S, et al. Simtuzumab Is Ineffective for Patients With Bridging Fibrosis 
or Compensated Cirrhosis Caused by Nonalcoholic Steatohepatitis. Gastroenterology 2018;155(4):1140-1153 
Higuchi H, Gores GJ. Bile acid regulation of hepatic physiology: IV. Bile acids and death receptors. Am J 
Physiol Gastrointest Liver Physiol 2003;284:G734–8.  
Jia X, Naito H, Yetti H, et al. Dysregulated bile acid synthesis, metabolism and excretion in a high 
fat-cholesterol diet-induced fibrotic steatohepatitis in rats. Dig Dis Sci 2013;58:2212–22.  
Kabbany MN, Conjeevaram Selvakumar PK, Watt K, et al. Prevalence of Nonalcoholic Steatohepatitis-
Associated Cirrhosis in the United States: An Analysis of National Health and Nutrition Examination Survey 
Data. Am J Gastroenterol. 2017 Apr;112(4):581-587. 

Aldafermin (NGM282) 
Study 282-CC-207 (ALPINE 4) Protocol v6.0, 11 Nov 2021 
NGM Biopharmaceuticals, Inc. 
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Page 113 of 124 
Kim D, Kim WR, Kim HJ, T et al. Association between noninvasive fibrosis markers and mortality among 
adults with nonalcoholic fatty liver disease in the United States. Hepatology 2013;57:1357–65. 
Kir S, Beddow SA, Samuel VT, et al. FGF19 as a postprandial, insulin independent activator of hepatic protein 
and glycogen synthesis. Science 2011;331:1621–4.  
Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for 
nonalcoholic fatty liver disease. Hepatology 2005;41:1313–21.  
Kliewer SA, Mangelsdorf DJ. Bile acids as hormones. The FXR-FGF15 pathway. Dig Dis 2015; 33:327-331. 
Klingenberg B. Proof of concept and dose estimation with binary responses under model uncertainty. Stat Med. 
2009 Jan 30;28(2):274-92. 
Lake AD, Novak P, Shipkova P, et al. Decreased hepatotoxic bile acid composition and altered synthesis in 
progressive human nonalcoholic fatty liver disease. Toxicol Appl Pharmacol 2013;268:132–40.  
Loomba R, Lawitz E, Mantry PS, et al. The ASK1 inhibitor selonsertib in patients with nonalcoholic 
steatohepatitis: A randomized, phase 2 trial. Hepatology. 2017e Sep 11. doi: 10.1002/hep.29514. 
Lundasen T, Gälman C, Angelin B, et al. Circulating intestinal fibroblast growth factor 19 has a pronounced 
diurnal variation and modulates hepatic bile acid synthesis in man. J Intern Med 2006;260:530–6. 
Luo J, Ko B, To C, et al. Hepatoprotective effects of NGM282 compared to obeticholic acid and bezafibrate in 
mouse models of cholestasis. International Liver Congress 49th Annual Meeting, Late Breaker Poster No. 1308. 
April 10th 2014, London UK. 
Luo J, Ko B, Elliott M, et al. A nontumorigenic variant of FGF19 treats cholestatic liver diseases. Sci Transl 
Med. 2014 Jul 30;6(247):247ra100. 
Luo J, Ko B, Ding X, et al. Serum cholesterol changes associated with NGM282 treatment in obese insulin 
resistant cynomolgus monkeys are reversed with either a statin or a PCSK9 inhibitor. J Hepatol. 
2017;66(1):S430 
Ma C, Na M, Neumann S, Gao X. Low-Density Lipoprotein Cholesterol and Risk of Hemorrhagic Stroke: a 
Systematic Review and Dose-Response Meta-analysis of Prospective Studies. Curr Atheroscler Rep. 2019 Nov 
20;21(12):52. 
McCullough AJ. The clinical features, diagnosis and natural history of nonalcoholic fatty liver disease. Clin 
Liver Dis. 2004 Aug;8(3):521-33, viii. Review. 
Mehta R, Birerdinc A, Younossi ZM. Host genetic variants in obesity-related nonalcoholic fatty liver disease. 
Clin Liver Dis 2014;18:249–67.  
Mingrone G, Panunzi S, De Gaetano A, et al. Bariatric surgery versus conventional medical therapy for type 2 
diabetes. N Engl J Med 2012;366:1577–85. 
Neuschwander-Tetri BA, Loomba R, Sanyal AJ, et al. Farnesoid X nuclear receptor ligand obeticholic acid for 
noncirrhotic, nonalcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo controlled trial. Lancet 
2014 Nov 7. pii: S0140 6736(14)61933–4. 
Noureddin M, Chan JL, Barradas K, et al. Attribution of nonalcoholic steatohepatitis as an etiology of cirrhosis 
for clinical trials eligibility: recommendations from the multi-stakeholder liver form. Gastroenterol 2020; 
159(2);422-7. 
Paradis V, Zalinski S, Chelbi E, et al. Hepatocellular carcinomas in patients with metabolic syndrome often 
develop without significant liver fibrosis: a pathological analysis. Hepatology 2009;49:851–9.  

Aldafermin (NGM282) 
Study 282-CC-207 (ALPINE 4) Protocol v6.0, 11 Nov 2021 
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Page 114 of 124 
Pasta A, Cremonini AL, Pisciotta L, et al. PCSK9 inhibitors for treating hypercholesterolemia. Expert Opin 
Pharmacother. 2020 Feb;21(3):353-363. 
Pavlides M, Banerjee R, Sellwood J, et al. Multiparametric magnetic resonance imaging predicts clinical 
outcomes in patients with chronic liver disease. J Hepatol. 2016 Feb;64(2):308-315. 
Permutt Z, Le TA, Peterson MR, et al. Correlation between liver histology and novel magnetic resonance 
imaging in adult patients with non-alcoholic fatty liver disease—MRI accurately quantifies hepatic steatosis in 
NAFLD. Aliment Pharmacol Ther 2012;36:22–9.  
Petta S, Sebastiani G, Bugianesi E, et al. Non-invasive prediction of esophageal varices by stiffness and platelet 
in non-alcoholic fatty liver disease cirrhosis. J Hepatol 2018;69:878-85. 
Potthoff MJ, Boney-Montoya J, Choi M, et al. FGF15/19 regulates hepatic glucose metabolism by inhibiting the 
CREB PGC 1 alpha pathway. Cell Metab 2011;13:729–38.  
Promrat K, Kleiner DE, Niemeier HM, et al. Randomized controlled trial testing the effects of weight loss on 
nonalcoholic steatohepatitis. Hepatology 2010;51:121–9. 
Qamar AA, Grace ND, Groszmann JD, et al. Platelet count is not a predictor of the presence or development of 
gastroesophageal varices in in cirrhosis. Hepatology 2008;47(1):153-9. 
Ratziu V, Harrison SA, Francque S, et al. Elafibranor, an Agonist of the Peroxisome Proliferator-Activated 
Receptor-α and -δ, Induces Resolution of Nonalcoholic Steatohepatitis Without Fibrosis Worsening. 
Gastroenterology. 2016 May;150(5):1147-1159.e5. 
Rinella ME. Nonalcoholic fatty liver disease: a systematic review. JAMA. 2015 Jun 9;313(22):2263-73. 
Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 2003;72:137-74. 
Sabatine MS, Wiviott SD, Im K, et al. Efficacy and Safety of Further Lowering of Low-Density Lipoprotein 
Cholesterol in Patients Starting With Very Low Levels: A Meta-analysis. JAMA Cardiol. 2018 Sep 1;3(9):823-
828. 
Sanyal AJ, Banas C, Sargeant C, et al. Similarities and differences in outcomes of cirrhosis due to nonalcoholic 
steatohepatitis and hepatitis C. Hepatology. 2006 Apr;43(4):682-9. 
Sanyal AJ, Chalasani N, Kowdley KV, et al. Pioglitazone, vitamin E, or placebo for nonalcoholic 
steatohepatitis. N Engl J Med 2010;362:1675–85. 
Sanyal AJ, Ling L, Beuers U, et al. Potent suppression of hydrophobic bile acids by aldafermin, an FGF19 
analogue, across metabolic and cholestatic liver diseases. JHEP Reports (2021), doi: 
https://doi.org/10.1016/j.jhepr.2021.100255. 
Schaffner H, Poper H. Capillarization of hepatic sinusoids in man. Gastroenterology. 1963 Mar;44:239-42. 
Schiff ER, Sorrell MF, Maddrey EC, eds. Schiff ’s diseases of the liver. 9th ed. Philadelphia, PA: Lippincott, 
Williams & Wilkins, 2003. 
Schreuder TC, Marsman HA, Lenicek M, et al. The hepatic response to FGF19 is impaired in patients with 
nonalcoholic fatty liver disease and insulin resistance. Am J Physiol Gastrointest Liver Physiol. 2010 
Mar;298(3):G440-5. 
Schuppan D, Afdhal NH. Liver cirrhosis. Lancet. 2008 Mar 8;371(9615):838-51. 
Schuppan D, Kim YO. Evolving therapies for liver fibrosis. J Clin Invest. 2013 May;123(5):1887-901. 

Aldafermin (NGM282) 
Study 282-CC-207 (ALPINE 4) Protocol v6.0, 11 Nov 2021 
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Page 115 of 124 
Sherlock S, Dooley J, eds. Diseases of the liver and biliary system. 11th ed. Oxford, UK, and Malden, MA, 
USA: Blackwell Science, 2002. 
Singh S, Allen AM, Wang Z, et al. Fibrosis progression in nonalcoholic fatty liver vs nonalcoholic 
steatohepatitis: a systematic review and meta-analysis of paired-biopsy studies. Clin Gastroenterol Hepatol. 
2015 Apr;13:643–54.e1-9; quiz e39–40. 
Stejskal D, Karpísek M, Hanulová Z, et al. Fibroblast growth factor-19: development, analytical 
characterization and clinical evaluation of a new ELISA test. Scand J Clin Lab Invest 2008;68:501–7. 
Swinburn BA, Sacks G, Hall KD, et al. The global obesity pandemic: shaped by global drivers and local 
environments. Lancet 2011;378:804–14. 
Tanaka N, Matsubara T, Krausz KW, et al. Disruption of phospholipid and bile acid homeostasis in mice with 
nonalcoholic steatohepatitis. Hepatology 2012;56:118–29. 
Tomlinson E, Fu L, John L, et al. Transgenic mice expressing human fibroblast growth factor 19 display 
increased metabolic rate and decreased adiposity. Endocrinology 2002;143:1741–7. 
Torres DM, Williams CD, Harrison SA. Features, diagnosis, and treatment of nonalcoholic fatty liver disease. 
Clin Gastroenterol Hepatol 2012;10:837–58. 
Triantos C, Kalafateli M. Endoscopic treatment of esophageal varices in patients with liver cirrhosis. World J. 
Gastroenterol. 2014; 20(36): 13015-13026. 
Tsochatzis EA, Papatheodoridis GV, Archimandritis AJ. Adipokines in nonalcoholic steatohepatitis: from 
pathogenesis to implications in diagnosis and therapy. Mediators Inflamm. 2009;2009:831670. 
Tsochatzis EA, Bosch J, Burroughs AK. Liver cirrhosis. Lancet. 2014 May 17;383(9930):1749-61. 
U.S. of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and 
Research. Guidance for industry: toxicity grading scale for healthy adult and adolescent volunteers enrolled in 
preventive vaccine clinical trials. September 2007. 
Williams CD, Stengel J, Asike MI, et al. Prevalence of nonalcoholic fatty liver disease and nonalcoholic 
steatohepatitis among a largely middle aged population utilizing ultrasound and liver biopsy: a prospective 
study. Gastroenterology 2011;140:124–31. 
Wojcik M, Janus D, Dolezal Oltarzewska K, et al. A decrease in fasting FGF19 levels is associated with the 
development of nonalcoholic fatty liver disease in obese adolescents. J Pediatr Endocrinol Metab 
2012;25:1089–93.  
World Gastroenterology Organisation Global Guidelines. Nonalcoholic Fatty Liver Disease and Nonalcoholic 
Steatohepatitis [Internet]. 2019 [cited 2019 11 Mar]. Available from: 
http://www.worldgastroenterology.org/guidelines/global-guidelines/nafld-nash/nafld-nash-english 
World Health Organization Uppsala Monitoring Centre. WHODrug Global [Internet]. 2019 [cited 
2019 11 Mar]. Available from: https://www.who-umc.org/whodrug/whodrug-portfolio/whodrug-global/ 
Younossi Z, Anstee QM, Marietti M, et al. Global burden of NAFLD and NASH: trends, predictions, risk 
factors and prevention. Nat Rev Gastroenterol Hepatol 2018 Jan;15:11–20. 
Younossi ZM, Harrison SA, Newsome PN, et al. Improving diagnosis of cirrhosis in patients with NAFLD by 
combining liver stiffness measurement by vibration-controlled transient elastography and routing biomarkers: a 
global derivation and validation study. AASLD 2020; abstract LP12. 

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Zhou M, Wang X, Phung V, et al. Separating tumorigenicity from bile acid regulatory activity for endocrine 
hormone FGF19. Cancer Res 2014 Jun 15;74:3306–16. 
Zhou M, Yang H, Learned RM, et al. Non-cell-autonomous activation of IL-6/STAT3 signaling mediates 
FGF19-driven hepatocarcinogenesis. Nat Commun. 2017 May 16;8:15433.  
Zhou M, Learned RM, Rossi SJ, et al. Engineered FGF19 eliminates bile acid toxicity and lipotoxicity leading 
to resolution of steatohepatitis and fibrosis in mice. Hepatol Commun. 2017 Oct 16;1(10):1024-1042.  
Zhou M, Learned RM, Rossi SJ, et al. Therapeutic FGF19 promotes HDL biogenesis and transhepatic 
cholesterol efflux to prevent atherosclerosis. J Lipid Res. 2019 Mar;60(3):550-565.  

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12. 
APPENDICES 
Appendix 1. NASH Clinical Research Network 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 2. 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 
2.5–5cm 
5.1–10cm 
>10cm 
Necrosis or exfoliative 
dermatitis 
 
 
 
 
 
Induration/ 
Swelling b 
2.5–5cm and does 
not interfere with 
activity 
5.1–10cm or interferes 
with activity 
>10cm 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 3. AUDIT-C Alcohol Consumption Questionnaire 
 

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Appendix 4. Lipid Lowering Algorithm: Statin Naïve and Stain Experienced Subjects  
 
 

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Appendix 5. Rosuvastatin Package Insert 
The package insert for rosuvastatin being used in the study can be found at the following web 
link: 
https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021366s016lbl.pdf  

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Appendix 6. Prohibited Hepatotoxic Agents 
All other hepatotoxic agents will be left to the discretion of the PI.  
If a patient is on stable therapy for an appropriate period of time (e.g., 3 months) or received 
short-term therapy without hepatotoxicity, continuation of a listed agent may be appropriate 
per PI discretion and Medical Monitor approval without exclusion from the study. 
There should be clear documentation in the subject’s study records of investigator assessment 
of safety and approval of use of the listed medication to support the eligibility and/or 
continued use during the study. 
Generic Name 
Drug Class/Common Use 
Acetaminophen >3000 mg/day 
Analgesic 
Albendazole 
Anthelmintics (parasitic infections) 
Amiodarone 
Antiarrhythmic  
Amodiaquine,  
Antimalarial 
Azathioprine/6-Mercaptopurine 
Antineoplastic/Antirheumatic, autoimmune 
Buspirone 
Sedatives, hypnotics, Psychoactive drug – for anxiety 
Busulfan 
Antineoplastic/Alkylating, cancer 
Carbamazepine 
Anticonvulsant 
Chemotherapies 
 
Chlorpromazine 
GI, antipsychotic 
Dantrolene 
Muscle relaxant 
Didanosine 
Antiviral 
Dimethyl Fumarate 
For MS 
Disufiram 
Alcohol Deterrents 
Dronedarone 
Antiarrhythmic (AFib/flutter) 
Efavirenz 
Antiviral 
Fenofibrate 
Anti-lipemic Hypertriglyceridemia, hypercholesterolemia 
Floxuridine 
Antineoplastic, cancer 
Flutamide 
Antineoplastic, nonsteroidal antiandrogen (NSAA) 
Glatiramer acetate 
For MS 
Gold Salts  
Antirheumatic, RA 
Halothane 
Anesthetics for surgery 
Hydralazine 
Antihypertensive 
Infliximab 
Antirheumatic, Dermatologic, GI 
Interferon alpha 
Antiviral 
Interferon beta 
MS 
Isoniazid 
Anti TB 
Methotrexate 
Antineoplastic, Antirheumatic, Dermatologic 
Methyldopa 
Antihypertensive 
Nefazodone, 
antidepressant 
Nevirapine 
Anti-viral (HIV/AIDS therapy) 
Nimesulide,  
NSAID – COX-2 
Norethisterone 
For menstrual issues 
Phenytoin 
anticonvulsant 
Pirfenidone 
Pulmonary fibrosis 
Propylthiouracil 
Antithyroid 
Pyrazinamide 
Anti TB 
Quinidine 
Antiarrhythmic 
Rifampin 
Anti TB 
Sulfasalazine 
Anti-infective (DMARD, anti-inflammatory) 
Suramin 
Injectable – antiprotozoal agent  

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Thioguanine 
Antineoplastic/Antirheumatic, 
Ticlopidine 
Antithrombotic, platelet inhibitor 
Valproate 
Anticonvulsant (epilepsy), mood stabilizer (Bipolar)