A Phase 2 Study to Evaluate the Safety and Biologic Activity of APL- 2 in Patients With IgA Nephropathy, Lupus Nephritis, Primary Membranous Nephropathy, or C3 Glomerulopathy (C3 Glomerulonephritis and Dense Deposit Disease)
Phase: PHASE2
Conditions: IgA Nephropathy, Lupus Nephritis, Membranous Nephropathy, C3 Glomerulonephritis, Dense Deposit Disease
Sponsor: Apellis Pharmaceuticals, Inc.

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Protocol No.: APL2‑201 
A PHASE 2 STUDY TO EVALUATE THE SAFETY AND 
BIOLOGIC ACTIVITY OF PEGCETACOPLAN IN 
PATIENTS WITH IGA NEPHROPATHY, LUPUS 
NEPHRITIS, PRIMARY MEMBRANOUS 
NEPHROPATHY, OR C3 GLOMERULOPATHY (C3 
GLOMERULONEPHRITIS AND DENSE DEPOSIT 
DISEASE)
Phase: 2 
Protocol Amendment 7
Approval Date: 07 July 2022 
Confidentiality Statement
This document is confidential. It contains proprietary information of Apellis Pharmaceuticals, Inc. Any viewing or 
disclosure of such information that is not authorized in writing by Apellis Pharmaceuticals, Inc, is strictly prohibited. 
Such information may be used solely for the purpose of reviewing or performing this study.

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INVESTIGATOR AGREEMENT  
 
Long Title:  
A Phase 2 Study to Evaluate the Safety and Biologic 
Activity of Pegcetacoplan in Patients With IgA 
Nephropathy, Lupus Nephritis, Primary Membranous 
Nephropathy, or C3 Glomerulopathy (C3 
Glomerulonephritis and Dense Deposit Disease) 
Protocol Number/Version/Date 
APL2-201/Amendment 7/07 July 2022 
Study Phase:  
Phase 2 
Sponsor Name and Address:  
Apellis Pharmaceuticals, Inc 
100 5th Avenue 
Waltham, MA 02451 
Investigational Test Article:  
Pegcetacoplan Subcutaneous Infusion 
US IND#: 
136409 
Indication Studied:  
IgA Nephropathy, Lupus Nephritis, Primary Membranous 
Nephropathy, C3 Glomerulopathy 
Investigator Agreement:  
I have read the clinical study protocol described herein, 
recognize its confidentiality, and agree to conduct the 
described trial in compliance with Good Clinical Practices 
(GCP), the ethical principles contained within the 
Declaration of Helsinki, this protocol, and all applicable 
regulatory requirements.  
 
Principal Investigator:  
 
Name: _________________________________________  
 
 
Signature: ______________________________________  
 
 
Date: ______/______/______ (DD/MMM/YYYY)  

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TABLE OF CONTENTS 
TITLE PAGE ...................................................................................................................................1 
INVESTIGATOR AGREEMENT...................................................................................................2 
TABLE OF CONTENTS .................................................................................................................3 
LIST OF TABLES ...........................................................................................................................8 
PROTOCOL AMENDMENT SUMMARY OF CHANGES ..........................................................9 
1. 
SPONSOR INFORMATION .....................................................................................10 
2. 
ABBREVIATIONS ....................................................................................................11 
3. 
SYNOPSIS .................................................................................................................13 
4. 
SCHEDULE OF EVENTS .........................................................................................20 
5. 
INTRODUCTION ......................................................................................................25 
5.1. 
Background .................................................................................................................25 
5.2. 
Complement-Mediated Glomerulopathy Disease Overview ......................................25 
5.2.1. 
IgA Nephropathy ..................................................................................................25 
5.2.2. 
Lupus Nephritis ....................................................................................................25 
5.2.3. 
Primary Membranous Nephropathy .....................................................................26 
5.2.4. 
C3 Glomerulopathy ..............................................................................................26 
5.3. 
Pegcetacoplan .............................................................................................................27 
5.4. 
Rationale for Treatment with Pegcetacoplan ..............................................................27 
6. 
NONCLINICAL DATA .............................................................................................28 
6.1. 
Pharmacology .............................................................................................................28 
6.2. 
Safety Pharmacology ..................................................................................................28 
6.3. 
Pharmacokinetics and Drug Metabolism ....................................................................28 
6.4. 
Toxicology ..................................................................................................................28 
7. 
CLINICAL DATA ......................................................................................................30 
7.1. 
Pegcetacoplan Pharmacokinetic Effects in Humans ...................................................30 
7.2. 
Pegcetacoplan Pharmacodynamics and Efficacy in Humans .....................................30 
7.3. 
Pegcetacoplan Safety in Humans ................................................................................31 
8. 
RATIONALE .............................................................................................................32 
8.1. 
Purpose of the Study ...................................................................................................32 
8.2. 
Dose Selection ............................................................................................................32 
8.2.1. 
Transition to Twice-Weekly Dosing ....................................................................32 

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8.3. 
Risk/Benefit ................................................................................................................33 
8.3.1. 
COVID-19 Risk Mitigation Measures ..................................................................33 
9. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................35 
9.1. 
Study Objectives .........................................................................................................35 
9.2. 
Study Endpoints ..........................................................................................................35 
9.2.1. 
Primary Efficacy Endpoints ..................................................................................35 
9.2.2. 
Secondary Efficacy Endpoints ..............................................................................35 
9.2.3. 
Exploratory Endpoints ..........................................................................................35 
9.2.4. 
Pharmacokinetic Endpoints ..................................................................................35 
9.2.5. 
Pharmacodynamic Endpoints ...............................................................................35 
9.2.6. 
Safety Endpoints ...................................................................................................36 
10. 
STUDY DESIGN .......................................................................................................37 
10.1. 
Transition to Twice-Weekly Dosing ..........................................................................38 
11. 
SUBJECT SELECTION .............................................................................................40 
11.1. 
Inclusion Criteria ........................................................................................................40 
11.1.1. 
Approved Methods of Contraception .............................................................41 
11.2. 
Exclusion Criteria .......................................................................................................41 
12. 
STUDY TREATMENTS............................................................................................43 
12.1. 
Identity of Investigational Product .............................................................................43 
12.2. 
Administration of Investigational Product ..................................................................43 
12.2.1. 
Allocation to Treatment ..................................................................................43 
12.2.2. 
Dosing .............................................................................................................43 
12.2.3. 
Investigational Product Administration ..........................................................43 
12.3. 
Labeling, Packaging, Storage, and Handling ..............................................................44 
12.3.1. 
Labeling ..........................................................................................................44 
12.3.2. 
Packaging ........................................................................................................44 
12.3.3. 
Infusion Supplies ............................................................................................44 
12.3.4. 
Storage and Handling .....................................................................................44 
12.4. 
Investigational Product Accountability ......................................................................45 
12.5. 
Subject Compliance ....................................................................................................46 
12.6. 
Concomitant Medications ...........................................................................................46 
12.6.1. 
Rescue Antibiotics ..........................................................................................46 
13. 
STUDY PROCEDURES ............................................................................................47 

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13.1. 
Screening (Week –4 to Week –2) ...............................................................................47 
13.1.1. 
Vaccinations ...................................................................................................48 
13.2. 
Treatment Period (Week 1 to Week 48) .....................................................................48 
13.2.1. 
Day 1 (Visit 4) ................................................................................................48 
13.2.2. 
Week 2 to Week 48 (Visits 5-15) ...................................................................49 
13.3. 
Part B: Long-Term Extension Phase (Week 48 and Beyond) ....................................50 
13.4. 
Follow-up (Visits 16-20) ............................................................................................51 
13.4.1. 
Exit Visit (Visit 21) ........................................................................................51 
13.4.2. 
Unscheduled Follow-up Visits .......................................................................52 
13.4.3. 
Safety Monitoring Committee ........................................................................52 
13.5. 
Treatment Discontinuation and Study Withdrawal ....................................................52 
13.5.1. 
Liver Toxicity .................................................................................................53 
13.5.2. 
Lost to Follow-up ...........................................................................................54 
14. 
ASSESSMENTS.........................................................................................................55 
14.1. 
Assessments ................................................................................................................55 
14.1.1. 
Medical History ..............................................................................................55 
14.1.2. 
Prior and Concomitant Medications ...............................................................55 
14.1.3. 
Body Height and Weight ................................................................................55 
14.1.4. 
Physical Examination .....................................................................................55 
14.1.5. 
Vital Signs ......................................................................................................56 
14.1.6. 
Electrocardiogram Monitoring .......................................................................56 
14.1.7. 
24 Hour Urine Collection ...............................................................................56 
14.1.8. 
Consecutive Spot uPCR ..................................................................................57 
14.1.9. 
Clinical Laboratory Tests ...............................................................................57 
14.1.9.1. 
Hematology ...............................................................................................57 
14.1.9.2. 
Coagulation* .............................................................................................57 
14.1.9.3. 
Serum Chemistry ......................................................................................58 
14.1.9.4. 
Urinalysis ..................................................................................................58 
14.1.9.5. 
Serum Pregnancy Test and Screening Assays ..........................................58 
14.1.9.6. 
Vaccination Antibody Titer ......................................................................58 
14.1.10. 
Injection/Infusion Site and Pump Safety Assessment ....................................59 
14.2. 
Pharmacokinetic Assessments ....................................................................................59 
14.2.1. 
Blood Sampling and Processing .....................................................................59 

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14.2.2. 
Analytical Method ..........................................................................................59 
14.3. 
Pharmacodynamic Assessments .................................................................................59 
14.4. 
Antidrug Antibody Assessment ..................................................................................59 
14.5. 
Blood Volume for Study Assessments .......................................................................60 
14.6. 
Pregnancy Tests ..........................................................................................................60 
14.7. 
COVID-19 Assessments .............................................................................................61 
15. 
ADVERSE EVENTS..................................................................................................62 
15.1. 
Definitions ..................................................................................................................62 
15.1.1. 
Adverse Events ...............................................................................................62 
15.1.2. 
Serious Adverse Events ..................................................................................62 
15.1.3. 
Unexpected Adverse Events ...........................................................................62 
15.2. 
Recording and Reporting Adverse Events ..................................................................63 
15.2.1. 
Relationship to Study Drug ............................................................................63 
15.2.2. 
Severity of Events ...........................................................................................64 
15.2.3. 
Reporting Adverse Events to Health Authorities, Institutional Review 
Boards, and Ethics Committees ......................................................................64 
15.3. 
Pregnancy ...................................................................................................................64 
15.4. 
Abuse, Misuse, Overdose, and Medication Error .......................................................65 
16. 
STATISTICS ..............................................................................................................66 
16.1. 
Sample Size Justification ............................................................................................66 
16.2. 
Statistical Analysis Methodology ...............................................................................66 
16.2.1. 
Analysis Populations ......................................................................................66 
16.2.1.1. 
Screened Population .................................................................................66 
16.2.1.2. 
Safety Population/ Intent-to-Treat (ITT) Population ................................66 
16.2.1.3. 
Per Protocol Population ............................................................................66 
16.2.1.4. 
Pharmacokinetic (PK) Population ............................................................67 
16.2.1.5. 
Pharmacodynamic Population ..................................................................67 
16.2.1.6. 
Data Review for Analysis Populations .....................................................67 
16.2.2. 
Efficacy Analyses ...........................................................................................67 
16.2.2.1. 
Primary Endpoint ......................................................................................67 
16.2.2.2. 
Secondary Endpoints ................................................................................67 
16.2.2.3. 
Exploratory Endpoints ..............................................................................67 
16.2.3. 
Safety Analyses ..............................................................................................67 

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16.2.3.1. 
Adverse Events .........................................................................................68 
16.2.3.2. 
Clinical Laboratory Tests .........................................................................68 
16.2.3.3. 
Vital Signs and ECGs ...............................................................................68 
16.2.4. 
Pharmacokinetic Analyses ..............................................................................68 
16.2.5. 
Pharmacodynamic Analyses ...........................................................................68 
16.2.6. 
Other Data Analyses .......................................................................................69 
16.3. 
Interim Analyses .........................................................................................................69 
17. 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS ..................................................................................................70 
17.1. 
Direct Access to Source Data/Documents ..................................................................70 
17.2. 
Quality Control and Quality Assurance ......................................................................70 
17.2.1. 
Monitoring ......................................................................................................70 
17.3. 
Ethics ..........................................................................................................................71 
17.3.1. 
Ethical Conduct of the Study ..........................................................................71 
17.3.2. 
Institutional Review Board or Independent Ethics Committee Review .........71 
17.3.3. 
Subject Information and Consent ...................................................................71 
17.3.4. 
Confidentiality ................................................................................................72 
17.3.5. 
ClinicalTrials.gov ...........................................................................................72 
17.3.6. 
Termination of Study ......................................................................................72 
17.4. 
Data Handling and Record Keeping ...........................................................................72 
17.5. 
Protocol Amendments ................................................................................................73 
17.6. 
Report Format .............................................................................................................73 
17.7. 
Finance and Insurance ................................................................................................73 
17.8. 
Publication Policy .......................................................................................................73 
18. 
REFERENCES ...........................................................................................................75 
19. 
APPENDICES ............................................................................................................78 
 
 
 
 

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LIST OF TABLES 
Table 1: 
Schedule of Events, Part A, Core Study Phase ...........................................................20 
Table 2: 
Part A, Dose Transition Visits ....................................................................................39 
Table 3: 
Blood Volume During Part A, the Core Study Phase .................................................60 
Table 4: 
Definitions of Adverse Event Relatedness .................................................................64 
Table 5: 
Severity of Events .......................................................................................................64 
 
 
 
 
 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Protocol Amendment 7 (Approval date 07 July 2022) 
Overall Rationale for the Amendment: 
The protocol was amended to permit the shipping of investigational product and/or ancillary 
supplies from the study site to a subject’s home or other designated location in situations other 
than COVID-19-related disruptions to study conduct. Additional revisions were made to align 
the endpoints and analyses with the Statistical Analysis Plan and to align study procedures with 
current company practices.  
Minor formatting and stylistic revisions were made to align with current templates, and any 
identified typographical errors were corrected; these are not identified individually in the 
descriptions below. 
Description of change 
Section(s) affected  
Rationale for Change 
Adding the option to ship 
investigational product and/or ancillary 
supplies from the study site to a 
subject’s home or other designated 
location in situations other than 
COVID-19-related disruptions to study 
conduct. 
Section 12.3.4, 
Section A1.1.5.4 
Align with current company practice 
permitting direct-to-subject shipments, 
where permitted. 
Remove measurement of C3Nef after 
Part A of the study. 
Synopsis, Section 9.2.3, 
Section 16.2.2.3, 
Table A1, Table A3 
Recommended to remove C3NF testing 
post-dose as pegcetacoplan interferes with 
the assay performance. Testing in Part A is 
already completed and reported so is 
retained. 
Add CH50 to the list of 
pharmacodynamic assays. 
Synopsis, Section 9.2.5, 
Section 14.3 
Previously omitted from list of 
complement assays to be evaluated. 
Updated description of the analyses of 
pharmacokinetic parameters. 
Synopsis 
Align with description in Section 16.2.4.  
Updated procedures for reporting 
SAEs. 
Section 15.2 
Align with current company practices. 
Update procedures for reporting 
changes in severity of AEs. 
Section 15.2.2 
Align with current company practices. 
Updated procedures for reporting 
pregnancies. 
Section 15.3 
Align with current company practices. 
Updated definition of TEAEs to 
include events up to 8 weeks after the 
last dose of study medication. 
Section 16.2.3.1 
Align with current understanding of 
pegcetacoplan pharmacology and with 
company reporting practices. 
Reduce frequency of collection of 
ADA samples in the long-term 
extension portion of the study to 
approximately every 24 weeks. 
Table A1, Table A3 
Minimize unnecessary blood collections; 
reduced frequency should be sufficient to 
effectively monitor immunogenic 
responses. 
Add recommendations regarding 
vaccination against COVID-19. 
Section A2.1.5 
Align with current company practices. 
Abbreviations: ADA = antidrug antibody; AE = adverse event; C3Nef = C3 nephritic factor; CH50 = total hemolytic complement 
activity assay; COVID-19 = coronavirus disease 2019; SAE = serious adverse event.  

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2. 
ABBREVIATIONS 
Abbreviation 
Definition 
ACIP 
Advisory Committee on Immunization Practices 
ACR 
albumin-to-creatinine ratio 
ADA 
antidrug antibody 
AE 
adverse event 
AH50 
complement alternative pathway assay 
ALT 
alanine aminotransferase 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC 
area under the serum concentration versus time curve 
AUC0-∞ 
area under the serum concentration versus time curve, from time 0 to infinity 
AUCtau 
area under the serum concentration versus time curve, over the dosing interval 
β-HCG 
beta human chorionic gonadotropin 
C3G 
C3 glomerulopathy 
C3GN 
C3 glomerulonephritis 
C3NeF 
C3 nephritic factor 
CH50 
total hemolytic complement activity assay 
Cmax 
maximum observed serum concentration 
CKD/EPI 
Chronic Kidney Disease Epidemiology Collaboration 
CL 
clearance 
CL/F 
apparent total body clearance after extravascular administration 
CRF 
case report form 
DDD 
dense deposit disease 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eGFR 
estimated glomerular filtration rate 
ESRD 
end-stage renal disease 
Gd-IgA1 
galactose-deficient IgA 
GGT 
gamma-glutamyl transferase 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practice 
Hb 
hemoglobin 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C  

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Abbreviation 
Definition 
hERG 
human ether-à-go-go-related gene 
HIV 
human immunodeficiency virus 
IB 
investigator’s brochure 
ICH 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use 
IEC 
independent ethics committee 
IgAN 
immunoglobulin A nephropathy 
IND 
investigative new drug 
INR 
international normalized ratio (for coagulation) 
IRB 
institutional review board 
ITT 
intent-to-treat  
IV 
intravenous 
LDH 
lactate dehydrogenase 
LN 
lupus nephritis 
MBL 
mannose-binding lectin 
MedDRA 
Medical Dictionary for Regulatory Activities 
NOAEL 
no-observed-adverse-effect level 
NOEL 
no observed effect level 
PCR 
protein-to-creatinine ratio 
PD 
pharmacodynamic(s) 
PI 
primary investigator 
PLA2R 
phospholipase A2 receptors  
PK 
pharmacokinetic(s) 
PNH 
paroxysmal nocturnal hemoglobinuria 
primary MN 
primary membranous nephropathy  
RBC 
red blood cell 
SAP 
statistical analysis plan 
SC 
subcutaneous 
t½ 
terminal elimination half-life 
Tmax 
time at which maximum serum concentration is observed 
ULN 
upper limit of normal 
uPCR 
urine protein-to-creatinine ratio 
Vz/F 
apparent volume of distribution after extravascular administration 
WBC 
white blood cell 
WOCBP 
women of childbearing potential 

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3. 
SYNOPSIS 
Protocol Number: 
APL2‑201 
Protocol Title: 
A Phase 2 Study to Evaluate the Safety and Biologic Activity of Pegcetacoplan in Patients With 
IgA Nephropathy, Lupus Nephritis, Primary Membranous Nephropathy, or C3 Glomerulopathy 
(C3 Glomerulonephritis and Dense Deposit Disease) 
Version Number: 
Amendment 7 
Investigational Product, Dose, and Route of Administration: 
1. Pegcetacoplan (APL-2) 
2. 360 mg daily; may transition to 1080 mg twice weekly 
3. Subcutaneous infusion 
Study Phase and Type: 
Phase 2 study consisting of an open-label, nonrandomized group of patients with complement-
mediated nephropathies.  
Number of Planned Subjects: 
Up to approximately 48 patients (pegcetacoplan treatment naive) with clinical diagnosis 
(confirmed by renal biopsy) of IgA nephropathy (IgAN), lupus nephritis (LN), primary 
membranous nephropathy (primary MN), or C3 glomerulopathy (C3G), with 6-12 patients per 
disease.  
Treatment Groups: 
1. Pegcetacoplan in patients with IgAN, LN, primary MN, or C3G 
Duration of Study Participation:  
The planned length of participation in the study for each subject is 76 weeks, including an 
approximate 4-week screening period, 48-week treatment period and 24-week follow-up period 
(Part A, Core Study Phase). Any subject who, in the opinion of the investigator, is experiencing 
clinical benefit from pegcetacoplan administration will be invited to participate in Part B, a 
Long-Term Extension Phase in order to continue to receive treatment with pegcetacoplan until it 
is commercially available for the disease under treatment. If invited to participate in Part B, the 
subject can enter the Long-Term Extension Phase as soon as they complete the 48-week 
treatment period and do not need to participate in the 24-week follow-up period. 
Study Population: 
Patients, at least 18 years of age with either IgAN, LN, primary MN, or patients at least 16 years 
of age with C3G. 

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Rationale for the Study: 
The 4 diseases of IgAN, LN, primary membranous nephropathy (primary MN) and C3 
glomerulopathy (C3G) have a shared pathogenesis of activation of the central complement 
component, C3. These diseases all involve activation of either 2 or 3 of the pathways to C3 
activation (classical, lectin, or alternative complement activation). Complement activation in 
glomeruli induces the inflammatory cascade, which results in renal injury and loss of function. 
Both decreased circulating C3 levels and mesangial C3 deposition are independently associated 
with poor renal outcome in patients with complement-mediated glomerulopathies, which 
suggests that systemic and local activation of complement play a role in the disease progression. 
Genetic mutation also supports the importance of the complement alternative pathway in 
complement-mediated glomerulopathies. By targeting therapy directly to the key junction of the 
classical, lectin, and alternative complement activation pathways, pegcetacoplan documented C3 
inhibitory activity may control the C3-mediated inflammatory response and the downstream 
inflammatory events responsible for the renal manifestations of injury common to all these 
diseases. To date, no safety signals have emerged from ongoing studies in paroxysmal nocturnal 
hemoglobinuria (PNH) or age-related macular degeneration that preclude further development 
with pegcetacoplan in other indications. Thus, this proposed Phase 2 study’s aim is to explore 
treatment efficacy and safety of pegcetacoplan for the treatment of IgAN, LN, primary MN, and 
C3G. 
Study Objectives and Endpoints: 
Objectives 
The primary objectives of this study are to establish preliminary efficacy and safety of 
pegcetacoplan in patients with IgAN, LN, primary MN, and C3G. 
Endpoints 
Primary efficacy endpoint: 
• Proteinuria reduction from baseline to Week 48, based on urinary protein-to-
creatinine ratio (uPCR) 
Secondary efficacy endpoints: 
• All disease groups: changes of disease-specific biomarkers:  
− Serum C3 levels 
− AH50 and C3a concentrations 
− Serum albumin levels  
• All disease groups: complete clinical remission defined as normalization of 
proteinuria as defined by <200 mg/g uPCR at Week 48 
• All disease groups: stabilization or improvement in estimated glomerular filtration 
rate (eGFR) from baseline to Week 48 
Exploratory endpoints: 
• Complete renal response: defined as <200 mg/g uPCR and stabilization or 
improvement in eGFR from baseline to Week 48 

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• Changes of disease-specific biomarkers:  
− LN: autoantibodies to double-stranded DNA, C3, and C1q  
− Primary MN: autoantibodies to phospholipase A2 receptors (PLA2R) 
− C3G: C3 nephritic factor (Part A only) 
Pharmacokinetic endpoint: 
• Pegcetacoplan pharmacokinetic concentrations 
Pharmacodynamic endpoints: 
• Pegcetacoplan activity: Absolute levels, change from baseline, and % change from 
baseline in CH50, C3, C3a, C4, C5a, and soluble C5b9 complex (sC5b9) 
• Immunogenicity: Presence of autoantibodies to polyethylene glycol and 
pegcetacoplan throughout treatment and follow-up periods 
Safety endpoints: 
• Physical examination; incidence and severity of adverse events (AEs) 
• Changes from baseline in laboratory parameters 
• Changes from baseline in electrocardiogram parameters 
 
Study Design: 
This is a prospective Phase 2 study, consisting of a single cohort with a total of approximately 
48 patients among the 4 indications. This is an open-label study, with 48 patients clinically 
diagnosed with IgAN, LN, primary MN, or C3G (with 6-12 patients per disease). Each clinical 
diagnosis must be confirmed by renal biopsy prior to dosing with pegcetacoplan. Subject 
participation will include a Part A Core Study Phase that consists of an approximate 4-week 
screening period, 48-week treatment period, and 24-week safety follow-up. During the treatment 
period, patients will receive subcutaneous (SC) once daily infusions of 360 mg pegcetacoplan. 
Following the completion of 48-week treatment period in Part A Core Study Phase, if invited, 
subjects may participate in Part B, the Long-Term Extension Phase, in order to continue to 
receive treatment with pegcetacoplan until it is commercially available for the disease under 
treatment. If they are invited to participate in Part B, they do not need to complete the 24-week 
follow-up period.  
For each indication, patients whose underlying renal disease is stable for at least 2 months prior 
to the first dose may enter the study. In this trial, stable renal disease should include stable eGFR, 
proteinuria, and blood pressure, as well as a stable and optimized treatment regimen for their 
renal disease, in the opinion of the primary investigator (PI) (see Section 10.1 for the complete 
detailed eligibility information). Upon completion of the screening period, patients who meet all 
of the inclusion and none of the exclusion criteria will begin the treatment phase of the study. 
The treatment phase will consist of once daily, self-administered, SC dosing of 360 mg 
pegcetacoplan at home, with the exception of all scheduled clinic visits. During scheduled Visit 4 
only, the site staff will assist in administering the first SC dose of pegcetacoplan. At Visits 5-

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15 subjects will self-administer pegcetacoplan in the presence of the site staff and undergo 
various safety and efficacy assessments by qualified site staff. Subjects may be switched over to 
twice-weekly dosing as early as Week 24. Any subject who is invited to participate in Part B 
who has not already switched over to twice-weekly dosing, must do so at the beginning of Part 
B. If a subject transitions to the twice-weekly dosing, they need to follow the dose transition 
visits (T1, T2, and T3) as outlined in Section 10.1, Table 2 (during Part A) or Appendix 1, 
Table A1 (for Part B). The change in proteinuria from baseline through the end of treatment will 
be assessed as the primary endpoint. Urinary protein-to-creatinine ratio (PCR) will be used to 
measure changes in proteinuria for the primary endpoint. 
After completion of the 48-week treatment period, each subject will have the opportunity to enter 
Part B, the Long-Term Extension Phase (see Appendix 1), at the discretion of the investigator. If 
the subject does not enter Part B, he or she will enter into a 24 week follow-up period, consisting 
of 6 clinic visits at weeks 50, 52, 54, 60, 66, and 72 (Exit Visit). Various safety assessments will 
be undertaken during these clinic visits, and follow-up phone calls will be performed to gain 
relevant safety information. Patients will be maintained on their baseline treatment regimen 
during treatment and the follow-up period, as determined by the PI in consultation with the 
medical monitor. During the study, changes to the baseline treatment regimen should be avoided 
to the extent possible and made only when required for the well-being of the patient, in the 
opinion of the PI.  
Safety summaries will be presented over the screening period, 48 weeks of treatment and 
24 weeks of follow-up, as well as the overall duration of the study. 
An external, independent safety monitoring committee will assess the safety/tolerability data of 
the study. 
Subject level discontinuation will occur for any subject who develops a serious adverse event 
(SAE) due to infection confirmed to be caused by encapsulated organisms (see Section 8.3 for 
further information) or any subject with a sustained and significant reduction in renal function, as 
defined by one of the following: initiation of chronic dialysis, a confirmed and sustained eGFR 
≤15 mL/min/1.73 m2 or a confirmed and sustained reduction in eGFR of at least 30% which is 
drug related in the opinion of the PI. A reduction in eGFR would be considered confirmed if 
present on 2 separate consecutive measurements and considered sustained if the 2 measurements 
are at least 1 week apart. Subject level discontinuation can also occur for any individual for 
whom the PI deems it in the best interest of the patient to not continue in the study. Indication 
level discontinuation will occur if 2 or more subjects in a particular indication are discontinued 
by these criteria.  
Subjects who do not meet the criteria for participation in the study (screen failure) may be 
rescreened. The timeframe and scope of eligibility reassessment will be determined by the 
sponsor. Any requests to rescreen an individual more than one time must be approved by the 
sponsor. For each rescreening, the individual must sign a new informed consent form and will be 
assigned a new identification number. Record of the subject’s prior identification number and 
screening should be maintained with the source documents. Subjects who received vaccinations 
per protocol within 2 years of their rescreening date do not need to have the respective 
vaccination repeated but may do so at the discretion of the investigator. 

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Study Outline 
The following study outline is for Part A, the Core Study Phase. Appendix 1 (Section A1.1) 
presents the information for Part B, the Long-Term Extension Phase. 
 
 
 
 
Inclusion Criteria: 
At specified screening visit(s) all subjects must fulfill all of the following inclusion criteria to be 
eligible for participation in the study: 
1. Patients of at least 18 years of age at screening (16 years of age for C3G), able to provide 
written informed consent, and able to understand and comply with all scheduled 
procedures and other requirements of the study by the opinion of PI 
2. Patients must have a diagnosis of IgAN, LN, primary MN, or C3G confirmed by renal 
biopsy and required measurements performed prior to study participation  
− IgAN: Prior biopsy results for C3 and C4d staining should be made available 
− LN: Diagnostic biopsy showing proliferative focal, diffuse, or membranous 
lesions (Class III, IV, or V, respectively) by renal biopsy. Subject should have 
either a biopsy in the last 6 months, or evidence of disease activity (nephritic 
changes on urinalysis or nephrotic changes)  
− Primary MN: PLA2R positive titer plus nephrotic range proteinuria (defined as 
uPCR >2350 mg/g) 
− C3G plus one of the following: Low serum C3 level or historical renal biopsy 
within the last 3 years 
3. Have proteinuria >750 mg/g (calculated by uPCR on 24-hour urine collection) collected 
during the first screening visit (Visit 3a) 
4. eGFR ≥30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) creatinine equation at Screening Visit 3a and currently not on 
dialysis 
5. Must have stable or worsening renal disease, on stable and optimized treatment, in the 
opinion of the PI, for at least 2 months prior to the first dose of pegcetacoplan (Visit 4); 
treatments may include, but are not limited to, immunosuppressive agents, 
antihypertensives and/or antiproteinurics 
 
 
 
 
 
 
 
 
 
 
 
 

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6. Willing to receive vaccinations against Neisseria meningitidis at least 2 weeks prior to 
dosing on Day 1 with a booster on Day 56 (for both vaccinations) and Pneumococcal and 
Hib vaccines at least 2 weeks prior to dosing on Day 1 
7. Women of childbearing potential (WOCBP) must have a negative blood pregnancy test at 
screening (and negative urine pregnancy at Visit 4) and must agree to use protocol 
defined methods of contraception from screening through 3 months after last dose of 
pegcetacoplan 
8. Males must agree to use protocol defined methods of contraception and agree to refrain 
from donating sperm from screening through 3 months after receiving last dose of 
pegcetacoplan 
9. Willing and able to give informed consent 
10. Willing and able to self-administer pegcetacoplan (administration by caregiver will be 
allowed) 
 
Exclusion Criteria: 
1. Absolute neutrophil count <1000 cells/mm3 at screening Visits 3a and 3b 
2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3.0× the upper 
limit of normal at screening Visits 3a and 3b 
3. Previous treatment with pegcetacoplan  
4. History of solid organ transplant 
5. Diagnosis of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection, 
or positive serology at screening Visits 3a and 3b (previous hepatitis B or hepatitis C 
diagnosis cleared by treatment is allowed) 
6. Malignancy except for cured basal or squamous cell skin cancer, curatively treated in situ 
disease, or have been disease-free for ≥5 years or more from cancer, and off ongoing 
treatment 
7. Renal disease secondary to another condition (eg, infection, malignancy, monoclonal 
gammopathy, or a medication) 
8. Presence or suspicion of active bacterial or viral infection or severe recurrent bacterial 
infections 
9. Participation in any other investigational drug trial or exposure to other investigational 
agent, device, or procedure within 30 days prior to screening period 
10. Pregnant, breastfeeding, or intending to conceive during the course of the study 
11. Inability to cooperate or any condition that, in the opinion of the investigator, could 
increase the patient’s risk by participating in the study or confound the outcome of the 
study 
12. Unwillingness to receive or intolerant of SC infusions of study medication or known 
allergy to ingredients in pegcetacoplan 

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13. Positive results for drug abuse (upon urinary drug screen) or alcohol dependence at 
screening (Visit 3a). Documented evidence of prescribed marijuana use is not 
exclusionary 
Sample Size: 
A sample size of 6-12 subjects will be recruited from each of the 4 disease types. As these 
complement-mediated glomerulopathies are rare diseases it may be difficult to recruit subjects 
from 1 or more of the disease types; hence the range of 6-12 subjects per type. The intention is to 
obtain safety, pharmacokinetic (PK), pharmacodymanic (PD), and efficacy data to support the 
progress of pegcetacoplan into further clinical studies. 
With 6 subjects treated with pegcetacoplan in each disease type there is a 95% chance of an AE 
being reported if its true incidence is over 40%. Similarly, there is a 47%, 74% and 88% chance 
if the true incidence is 10%, 20% or 30% respectively. With 12 subjects treated in each disease 
type the chance increases to >93% for true incidences over 20% and 72% if the true incidence is 
10%. 
Statistical Methods: 
Given the exploratory nature of the study no formal statistical hypothesis testing will be 
performed. Data will be presented by disease type (IgAN, LN, primary MN, or C3G), study day, 
and nominal time postdose (if appropriate).  
Continuous variables will be summarized using descriptive statistics (eg, median and mean) 
whilst for categorical variables the frequency and percentage in each category will be displayed. 
Summaries may also be presented pooling data from the different disease types. 
Treatment-emergent AEs will be summarized by System Organ Class and Preferred Term, 
according to the current version of the Medical Dictionary for Regulatory Activities (MedDRA) 
at the time of analysis. The number of patients reporting each AE Preferred Term will be 
tabulated for all treatment-emergent adverse events and separately for those considered as 
possibly related to study treatment by the investigator. Number of patients reporting SAEs will 
also be tabulated. 
The number and percentage of patients achieving partial clinical remission of proteinuria will be 
tabulated. Similarly the number and percentage of patients will be tabulated for secondary 
responder endpoints. 
Changes from baseline in continuous efficacy and pharmacodynamics endpoints will be 
summarized and plotted (individual and mean) over time. 
PK concentrations will be summarized and concentration profiles over time (individual and 
median) will be plotted. 
 

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pressure; BUN = blood urea nitrogen; CDC = Centers for Disease Control and Prevention; Chem = serum chemistry; CKD-EPI = Chronic Kidney Disease Epidemiology 
Collaboration; Coag = coagulation; ECG = electrocardiogram; FSH = follicle-stimulating hormone; GGT = gamma-glutamyl transferase; HBsAg = hepatitis B surface antigen; 
HCV = hepatitis C; Hem = hematology; HIV = human immunodeficiency virus; HR = heart rate; INR = international normalized ratio; LDH = lactate dehydrogenase; 
PCR = protein-to-creatinine ratio; PD = pharmacodynamic; PI = primary investigator; PK = pharmacokinetics; RBC = red blood cell(s); RR = respiration rate; T = temperature; 
UA = urinalysis; uPCR = urine protein-to-creatinine ratio; WBC = white blood cell(s); WOCBP = women of childbearing potential. 
Note: When multiple assessments occur at the same time, order of collection will be: vital signs, ECGs, and blood collection/sampling. Further information can be found in 
schedule section. 
 
a 
Patients who meet the medical history requirements will enter the screening period at Visit 3a and return for Visit 3b. 
b 
Specific inclusion/exclusion criteria will be measured during screening, and some of them require confirmation on Visit 4 (Day 1) prior to performing any activities of Day 1 
procedures. See the inclusion/exclusion criteria in Section 11 for further detail. 
c 
Neisseria meningitidis vaccine(s) will be administered during screening (Day –14); a booster for Neisseria vaccination(s) should be administered at Visit 7. Additionally, 
pneumococcal vaccine PCV13 will be administered at least 2 weeks prior to Day 1, and a dose of PPSV23 will be administered at least 8 weeks later unless documented 
evidence exists that patients are nonresponders to vaccination as evidenced by titers or display titer levels within acceptable local limits. Haemophilus influenzae Type B 
(Hib) vaccinations will be administered at Day –14. Subjects who withdraw from the study prior to any vaccine booster will be offered the opportunity to return to the site as 
recommended by current CDC Adult Immunization schedule to receive the booster shot. Subjects who are being rescreened for the trial will not require repeat vaccination for 
those vaccines documented as given during a previous screening visit.  
d 
Full physical examination will be performed at Visits 4 and 15. Brief physical examinations will be conducted at all other clinic visits as noted above in the schedule of 
events. A symptom-driven physical examination may be performed at other times, at the PI’s discretion. (Body height [cm] and weight [kg] will be measured at Visit 3a, and 
body weight will be measured throughout study, during brief and full physical examinations.) 
e 
Triplicate 12-lead ECGs (which have a ±5-minute start window) are to be performed: D1 (V4) and Week 48 (V15): –45, –30, –15 minutes predose and before dosing at all 
other treatment visits. Once each triplicate ECG begins, subsequent ECGs should be at least one minute and no more than 2 minutes apart. During screening and follow-up 
periods, triplicate ECGs will be collected immediately after vital measurements. 
f 
Patients will self-administer SC pegcetacoplan after receiving appropriate training and sign-off by a research nurse or other personnel in their first treatment week. During site 
visits patients will self-administer pegcetacoplan at the site, with the exception of the very first dose.  
g 
Between site visits, patients will be instructed to report any injection site reaction to the study staff. Pump use safety assessment will be performed by licensed health care 
professional (ie, investigator or nurse) within 30 min following study drug administration at all clinic visits and during at-home qualification (Days 2-7). 
h 
Vital signs will be measured before venipuncture and ECG; vital signs measured post dose will be timed from the completion of the study drug administration. Additional 
monitoring of vital signs will occur on D1 and Visit 15 (predose and 30 minutes, 2 hours, and 4 hours post dose), Days 2 to 7 (at home, predose and 30 minutes post dose) by 
the health care professional conducting the self-administration qualification (ie, in-home nurse). At all other visits where pegcetacoplan is administered at the study site, vital 
signs will be measured predose and 30 minutes post dose. Blood pressure and heart rate should be evaluated after the subject has been resting in a seated, recumbent, or supine 
position for at least 5 minutes. All of these vital sign measurements have a ±15-minute start window. 
i 
24-hour urine collected for ACR and PCR, defined as collection for a 24-hour period in a urine pooling container following the first urinary output on that day (first urinary 
output is discarded). Courier arrangements will be made by site personnel to pick up urine containers from patient’s home. Urine ACR and PCR will be calculated on 24-hour 
urine collections for accuracy in estimating 24-hour proteinuria.  
j 
Urinary PCR samples (first urinary output for the day) should be collected on 3 consecutive days, biweekly, for both uACR/uPCR analysis with a ±3-day window. On weeks 
of scheduled clinic visit, samples will be brought with patient during the site visit.  
k 
On weeks when no clinic visit is scheduled, courier service will be arranged for urine sample pickup and delivery to the site.  
l 
Urinalysis—routine dipstick for protein, glucose, hemoglobin, blood, ketones, ACR, pH, bilirubin, urobilinogen, leukocyte esterase, specific gravity.  
m 
All blood samples will be taken predose. 
n 
Hematology consists of hemoglobin, hematocrit, RBC count, platelet count, WBC count with differential (basophils, eosinophils, monocytes, lymphocytes, neutrophils), 
aPTT, INR. The use of silica reagents in coagulation panels should be avoided in subjects treated with pegcetacoplan. 
o 
Chemistry consists of BUN, creatinine (b), bilirubin (total and conjugated), uric acid, albumin, ALP, LDH, creatine kinase, AST, ALT, GGT, glucose, sodium, potassium, 
chloride, bicarbonate. 
p 
Vaccination serum samples (for antibody titer) will be collected prior to patient receiving vaccinations on that study visit. 

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q 
All PK collections will be taken predose for treatment visits and following ECGs at all other visits. Predose PK collections to occur within 1 hour before dose. 
r 
Patients who discontinue dosing will need to have ADA samples collected at 6 and 12 weeks after the last treatment. Patients who test positive for ADAs at any time will be 
followed up with ADA samples being collected every 6 months until the antibody levels revert to baseline.  
s 
Biomarkers for primary MN (PLA2R) and C3G (serum C3) should be collected for screening, while all secondary/exploratory disease-specific biomarkers should be collected 
throughout the treatment and follow-up period. 
t 
CKD-EPI creatinine equation (see https://www.niddk.nih.gov/); the CKD-EPI creatinine-cystatin C equation (if confirmation required). 
u 
Serum FSH to be performed on females only. Blood HIV, HCV, and HBsAg to be performed on all patients. 

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5. 
INTRODUCTION 
5.1. 
Background 
This study is being conducted as part of a series of studies for the clinical development of 
pegcetacoplan (APL-2). The study will be conducted in compliance with the protocol, Good 
Clinical Practice (GCP), and applicable regulatory requirements. The subject population will be 
comprised of adult male and female subjects with either of 4 different complement-mediated 
dependent glomerulopathies: IgA nephropathy (IgAN), lupus nephritis (LN), primary 
membranous nephropathy, and C3 glomerulopathy (C3 glomerulonephritis and dense deposit 
disease). 
5.2. 
Complement-Mediated Glomerulopathy Disease Overview 
5.2.1. 
IgA Nephropathy 
IgAN, also known as Berger’s disease, is a rare autoimmune disease and is the most common 
cause of chronic glomerulonephritis (GN). It is characterized by a predominant deposition of IgA 
and complement C3 alone or with IgG or IgM in the glomerular mesangium (Rauen and Floege 
2017). In the United States, IgAN incidence is estimated at 2.1 per 100,000 (Swaminathan et al. 
2006). The clinical and pathological manifestations are highly variable and may include 
asymptomatic hematuria, proteinuria, hypertension, interstitial fibrosis, glomerulosclerosis, and a 
slow progression to chronic kidney disease (Haas 1997). Within 10-20 years of diagnosis, 10% 
to 40% of patients with IgAN progress in kidney failure or end-stage renal disease (Wyatt and 
Julian 2013; Hastings et al. 2007). 
In IgAN, B cells synthesize antibodies to galactose-deficient IgA (Gd-IgA1) and these 
Gd-IgA1-containing immune complexes are deposited in the glomerular mesangium, which 
causes local inflammation and kidney damage (Wyatt and Julian 2013; Rauen and Floege 2017; 
Nasri et al. 2013). Consistent with IgA’s ability to activate lectin (Roos et al. 2001) and 
alternative complement pathways (Hiemstra et al. 1987), it contributes to C3 activation. 
Mesangial co-deposits of properdin, a natural activator of C3 through the alternative pathway, 
are observed in about 60% of patient biopsies (Segarra-Medrano et al. 2017) while the deposition 
of mannose-binding lectins (MBL), activators of the complement lectin pathway, is observed in 
20% to 25% of cases (Roos et al. 2006; Wyatt et al. 1987).  
5.2.2. 
Lupus Nephritis 
LN is one of the most serious manifestations of systemic lupus erythematosus (SLE). LN is 
caused by complement-mediated inflammation and damage of the kidney. Approximately 44% 
of patients with diffuse proliferative LN will progress to end-stage renal disease (ESRD) within 
15 years of diagnosis (Tektonidou et al. 2016). In SLE autoantibodies are generated against 
various nuclear self-antigens such as histones and double-stranded DNA, and against proteins of 
the classical and alternative complement pathways (Vasilev et al. 2015; Nozal et al. 2015; 
Kenyon et al. 2011; Pang et al. 2014; Chen et al. 2012). Autoantibodies and self-antigens form 
immune complexes that deposit at the glomerular basement membrane, the mesangium, and the 
endothelium and within the proximal tubular epithelial cell membrane (Weening et al. 2004). 

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Deposited immune complexes initiate local inflammation through activation of the complement 
cascade which causes a chronic inflammatory response. Patients with LN have low levels of C3 
proteins as all 3 pathways (classical, lectin, and alternative pathways) play a role in disease 
progression and damage (Sato et al. 2011). In the United States, LN prevalence is estimated at 
30.9 per 100,000, or 76,000 persons, and LN incidence is estimated at 6.9 per 100,000, or 17,000 
persons (Feldman et al. 2013). Approximately 18% to 22% overall and 44% patients with diffuse 
proliferative glomerulonephritis (Class IV) lupus will progress to ESRD within 15 years of 
diagnosis (Tektonidou et al. 2016). 
All 3 pathways of complement activation have been implicated in LN pathogenesis, disease 
progression, and damage (Sato et al. 2011). Renal biopsies display IgG, IgA, and IgM deposition 
associated with C3 and C1q, and MBL deposition as well as high levels of glomerular C3aR 
(Nisihara et al. 2013; Mizuno et al. 2007).  
5.2.3. 
Primary Membranous Nephropathy 
Primary MN is the second most common nephrotic syndrome in adults worldwide. Primary MN 
is a slow progressive, chronic, autoimmune disease of the kidney. It is predominantly mediated 
by autoantibodies directed against phospholipase A2 (PLA2) receptors on podocytes that play an 
important role in kidney filtration. Though mediated by autoantibodies directed to antigens on 
the podocytes the immune complex induced complement activation may occur by several 
pathways. The lectin pathway activated by anti-PLA2R (most common autoantibodies) and IgG4 
immune complexes binding to MBL leading to complement activation (Ma et al. 2013; Bally 
et al. 2016). Patients with high urinary C3dg levels and/or C5b-9 have a poor clinical prognosis 
(Brenchley et al. 1992).  
Direct evidence shows the implication of the lectin and alternative pathways in primary MN 
pathogenesis while the classical pathway is typically absent in primary MN (Ma et al. 2013). 
High urinary C3dg levels in patients with primary MN correlate with the presence of proteinuria 
and a poor clinical prognosis (Brenchley et al. 1992). 
In the United States, incidence of primary MN is estimated at 1.2 per 100,000; it accounts for 
about 3,000 persons. Current data indicate that after 5 years of treatment, approximately 20% of 
patients achieve remission, 40% of patients have stable to slowly decreasing renal function, and 
40% have persistent nephrotic leading to ESRD (Ruggenenti et al. 2012; Glassock 2003). 
Approximately 40% to 50% of patients with primary MN progress to ESRD and renal failure 
within 15 years (Glassock 2003). Mortality for primary MN is estimated at approximately 9.8% 
per 100 person years (O'Shaughnessy et al. 2015). 
5.2.4. 
C3 Glomerulopathy 
C3G includes C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). Both types of 
C3G are characterized by dense or isolated deposits of C3, and either the presence of 
autoantibodies called C3 nephritic factors or genetic mutations of complement inhibitory 
proteins that sustain complement activation (Servais et al. 2012). The key abnormality in both 
C3GN and DDD is an uncontrolled amplification of fragment C3b in the circulation and/or along 
the glomerular basement membrane (Servais et al. 2012). C3b and its breakdown fragments, and 
the terminal component of the complement system lead to impairment of kidney function 
(Bomback et al. 2012). Although there is no formal US registry for C3G, the National 

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Organization for Rare Disorders estimates C3G prevalence at 2-3 per 1,000,000 persons; it 
accounts for over 850 persons in the United States with a median diagnosis at 12 years of age for 
DDD and 26 years of age for C3GN (Lu et al. 2012). 
Patients with C3G have either C3 nephritic factor (C3NeF), complement factor H (CFH), or 
complement factor I(CFI) autoantibodies and/or mutations in complement inhibitory proteins and 
regulatory factors (CFH, CFI, and membrane cofactor protein) that inhibit the regulation of 
convertases and lead to C3b-mediated activation of the amplification loop (Servais et al. 2012). 
In the absence of tight regulation, the amplification loop will consume all C3 available and 
maintain an ongoing activation of C3. Production of C3b and its breakdown fragments, and 
membrane attack complex leads to impairment of kidney function. 
5.3. 
Pegcetacoplan 
Pegcetacoplan is a PEGylated cyclic peptide inhibitor of complement C3. Pegcetacoplan is 
formed by 2 identical pentadecapeptides (combining a cyclic tridecapeptide active C3-inhibiting 
moiety and a 2-amino acid linker) covalently coupled to each end of a linear 40 kDa 
polyethylene glycol (PEG) chain. The bioactive tridecapeptide moiety binds to C3 to effect broad 
inhibition of the complement cascade. The PEGylation greatly improves solubility of the peptide 
and slows elimination in vivo following administration.  
Pegcetacoplan solution for injection or infusion, 40 mg/mL (drug product) will be supplied as a 
sterile presentation of pegcetacoplan in acetate-buffered sorbitol or acetate-buffered mannitol 
solution, pH 5.0, contained in individual vials. It is designed for administration by subcutaneous 
administration.  
5.4. 
Rationale for Treatment with Pegcetacoplan 
Activation of the complement pathway through C3 appears to be a common pathogenic 
mechanism for the complement-mediated glomerulopathies IgAN, LN, primary membranous 
nephropathy, and C3 glomerulopathy (C3 glomerulonephritis and DDD). Pegcetacoplan 
therefore has potential in the treatment of these complement-mediated glomerulopathies. 
Complement-mediated glomerulopathies include inflammatory kidney disorders that represent a 
significant unmet medical need. Based on the key role of complement activation in these renal 
diseases pegcetacoplan has the potential to prevent the C3-mediated inflammatory response 
associated with kidney injuries. 

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6. 
NONCLINICAL DATA 
The nonclinical effects of pegcetacoplan are summarized below; further details can be found in 
the pegcetacoplan Investigator’s Brochure (IB). 
6.1. 
Pharmacology 
Pegcetacoplan binds to C3 and C3b and retains the human and nonhuman primate-specific 
inhibition of classical and alternative pathway activation of compstatin derivatives, but with a 
longer half-life and greater aqueous solubility than that of nonPEGylated peptides. 
Pegcetacoplan inhibits alternative and classical complement pathway activation, resulting in a 
decrease of the complement activation protein C3a, indicative of reduced C3 cleavage, and an 
increase in C3, indicative of target engagement resulting in decreased clearance of C3. On the 
basis of the absence of signals suggestive of off-target pharmacological effects in toxicology and 
safety pharmacology studies, it can be concluded that pegcetacoplan is a selective complement 
inhibitor.  
6.2. 
Safety Pharmacology 
Safety pharmacology studies indicate that pegcetacoplan does not inhibit the hERG (fast 
potassium [IKr]) channel or pose an acute cardiovascular or respiratory functional risk. 
6.3. 
Pharmacokinetics and Drug Metabolism 
In monkeys (the pharmacologically human-relevant test species), pegcetacoplan is readily and 
extensively absorbed following SC injection with an estimated bioavailability >85%. 
Pegcetacoplan distributes widely in tissues at concentrations lower than circulating drug but not 
to the brain and minimally to the eye. The pharmacokinetic (PK) behavior of pegcetacoplan is 
typical of a PEGylated peptide and is characterized by a prolonged systemic half-life (t½) and 
slower clearance in vivo than that of the unPEGylated peptide. The main route of elimination is 
urinary excretion. Minimal, non–pharmacologically significant pegcetacoplan placental transfer 
and excretion in milk (<1% of maternal serum concentrations) were demonstrated in monkeys. 
Results of in vitro absorption, distribution, metabolism, and excretion testing (hepatic 
cytochrome P450 enzymes and transporter proteins) suggest minimal potential for clinical drug-
drug interactions.  
6.4. 
Toxicology  
In toxicology studies, repeated daily SC doses up to 140 mg/kg/day to rabbits and monkeys were 
well tolerated and did not induce injection site reactions. After 28-day and chronic dosing, the 
principal findings were nonreversible renal tubular degeneration (considered adverse) and 
nonreversible multitissue microscopic vacuolation (considered an adaptative change related to 
the PEG40 moiety and not adverse). The no-observed-adverse-effect level (NOAEL) for renal 
degeneration in monkeys was 7 mg/kg/day (maximum concentration [Cmax] and area under the 
concentration-time curve [AUC] margins over clinical exposure were approximately 1.4-fold, 
according to data from PNH patients). Renal tubular degeneration at 28 mg/kg/day was minimal 
and nonprogressive (a >5-fold margin over clinical exposures for monthly PEG load). 
Significance to humans of the minimal renal degeneration observed in the animal studies is not 

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known. No signal to suggest disturbed renal function has been detected in the current cumulative 
clinical safety database for pegcetacoplan. Population PK analysis demonstrated that renal 
function had no statistically significant impact on the PK parameters of pegcetacoplan among 
healthy adults and adult patients with PNH. 
Pegcetacoplan was weakly to moderately antigenic in rabbits but minimally antigenic in 
monkeys. Negative results of in vitro and in vivo assays indicate that pegcetacoplan is not 
genotoxic. 
Pegcetacoplan had no effect on embryofetal development in rats, rabbits, or monkeys, but SC 
doses of 28 mg/kg/day were associated with an increase in abortions and stillbirths in monkeys 
dosed during gestation. This is not considered a predicted on-target pharmacological effect of 
pegcetacoplan because complement-cascade regulation is recognized as potentially beneficial to 
pregnancy maintenance. The no-effect dose for abortions and stillbirths was 7 mg/kg/day 
(representing AUC and Cmax margins over clinical exposure of approximately 1.3-fold, according 
to data from PNH patients). Clinical relevance of the increase in abortions and stillbirths 
observed in monkeys is not known. 

Pe gcetac o pla n ( A P L‑ 2)  
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C o nfi de ntial  
7.  
C LI NI C A L D A T A  
T he eff ects of p e gcet ac o pla n i n h u ma ns are s u m marize d bel o w; f urt her d etails ca n be f o u n d i n 
t he pe gcet ac o pla n I B. 
7. 1.  
Pe gcet ac o pl a n P h ar m ac o ki netic  Effects i n H u m a ns  
F oll o wi n g si n gle asce n di n g d oses of S C pe gcetac o pla n fr o m 4 5 t o 1 4 4 0 m g i n healt h y s u bjects 
( St u d y  
), a bs or pti o n was sl o w ( me dia n ti me t o reac h ma xi m u m c o nce ntrati o n [ Tma x ] 
ra n ge d fr o m 1 0 8 t o 1 4 4 h o urs [ 4. 5 t o 6. 0 da ys]), e x p os ure metrics i ncreas e d wit h d ose i n a 
pr o p orti o nal ma n ner, g e o metric mea n f or a p pare nt cleara nce ( C L/ F) ra n ge d fr o m 1 1. 1 t o 
1 7. 2 m L/ h, a p pare nt v ol u me of distri b uti o n ( V z/ F) ra n ge d fr o m 3. 6 t o 4. 8 L, a n d ge o metric mea n 
of t he ter mi nal eli mi nati o n half -life (t½ ) ra n g e d fr o m 1 9 4 t o 2 3 5 h o urs ( 8. 1 t o 9. 8 da ys). 
S C pe gcetac o pla n li q ui d f or m ulati o ns ha ve bee n d e m o nstrate d t o be w ell a bs or be d. 
Bi oa vaila bilit y of t he S C d ose was esti mate d at a p pr o xi matel y 8 7 % b y c o m pari n g t he d ose-
n or malize d A U C fr o m zer o t o i nfi nit y ( A U C 0- ∞) fr o m an S C st u d y ( St u d y  
) a n d a n I V 
st u d y ( St u d y 
) i n healt h y s u bjects. 
I n a m ulti ple asce n di n g d ose st u d y of dail y S C d oses of pe gcetac o pl a n fr o m 3 0 t o 2 7 0 m g f or 
2 8 da ys i n healt h y s u bjects ( St u d y  
), ge o metric mea ns f or e x p os ure metrics, t he area 
u n der t he c o n ce ntr ati o n-ti me c ur ve o ver t he d osi n g i nter val ( A U C ta u) a n d Cma x , i ncrease d i n a 
ge nerall y pr o p orti o nal ma n ner, a n d n o ti me- de pe n de nt P K was e vi de nt , as dis pla ye d b y t he 
si milar C L/ F a n d Vz/ F val ues bei n g si milar t o t h ose of si n gle d osi n g. T he g e o metric mea n of 
C L/ F ra n ge d fr o m 1 5. 7 t o 2 0. 7 m L/ h, V z/ F ra n ge d fr o m 5. 2 t o 6. 1 L, a n d t he ge o metric mea n of 
t he t½  ra n ge d fr o m 1 9 7. 8 t o 2 3 7. 2 h o urs ( 8. 2 t o 9. 9 da ys). T he dis p ositi o n of pe gcetac o pla n after 
m ulti ple d oses was c o nfir me d i n a n ot her st u d y i n healt h y s u bjects ( St u d y  
), w hic h 
i ncl u de d a re gi me n of S C 1 0 8 0 m g t wice wee kl y.  
I n P N H s u bjects gi ve n S C pe gcetac o pl a n at 1 0 8 0 m g t wice wee kl y f or a 1 6 -wee k p eri o d 
( St u d y A P L 2 - 3 0 2), stea d y-state e x p os ure was reac he d aft er 4 t o 6 wee ks of d osi n g. Ge o metric 
mea n stea d y -stat e ser u m c o nce ntr ati o ns ra n ge d fr o m 6 5 5. 3 t o 7 0 6. 3 µ g/ m L. A p o p ulati o n P K 
a nal ysis was perf or me d o n t he basis of p o ole d data fr o m 1 0 cli nical st u dies i n healt h y a d ults, 
a d ults wit h re nal i m pair me nt, a n d a d ult patie nts wit h P N H . T he res ults de m o nstrate d t hat 
patie nts wit h P N H ha d l o wer pe g cetac o pla n e x p os ure t ha n healt h y v ol u nteers beca us e of 
i ncreas e d C L/ F wit h o ut mea ni n gf ul differe nces i n V z/ F. T he effecti ve h alf -life of pe g cetac o pla n 
at an S C d ose of 1 0 8 0 m g t wice wee kl y was esti mate d as  8. 0 da ys f or a d ult P N H patie nts  a n d 
1 0. 1 da ys f or healt h y a d ults. 
E val uati o ns of P K pr o perties of pe gcet ac o pla n i n ot her disease p o p ulati o ns are o n g oi n g.  
7. 2.  
Pe gcet ac o pl a n P h ar m ac o d y n a mics a n d Effic ac y i n H u m a ns  
C o nsiste nt c ha n ges i n c o m ple me nt p har mac o d y n a mic para meters were o bs er ve d after S C d osi n g 
of pe gcet ac o pla n i n b ot h healt h y s u bjects a n d P N H s u bjects. 
C o m ple me nt C 3 le vels i ncreas e d wit h i ncreasi n g p e gcetac o pla n d ose i n b ot h si n gle a n d m ulti ple-
d ose S C st u dies. A n i ncrease i n ser u m C 3 of m ore t ha n 1 5 0 % fr o m baseli ne le vels was o bs er ve d 
at S C d oses of 2 7 0 m g/ da y or hi g her, i n dicati n g t hat pe gcet ac o pla n i nteracts wit h c o m ple me nt 
C 3 a n d is li kel y t o sl o w d o w n its cleara n ce ( C L) fr o m circ ulati o n. 
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Mean alternative complement pathway hemolytic activity (as determined by the AH50 assay) 
decreased from baseline levels with increasing pegcetacoplan dose. A decrease of 50% or more 
from baseline level was generally observed at SC doses of 270 mg/day or higher doses, tested in 
healthy volunteers and patients with PNH, indicating that repeated dosing of pegcetacoplan can 
achieve significant inhibition of the hemolytic activity via the alternative pathway. 
No meaningful effect on classical complement pathway activity (as determined by the total 
hemolytic complement activity assay [CH50] assay) was noted during SC administration of 
pegcetacoplan at any of the doses evaluated using this assay. 
Evaluations of pharmacodynamic (PD) properties of pegcetacoplan in other disease populations 
are ongoing.  
Clinical data from studies with pegcetacoplan in subjects with PNH indicate that pegcetacoplan 
is effective in providing broad control of intravascular and extravascular hemolysis, as evidenced 
by increased and stable Hb levels and improvement in Functional Assessment of Chronic Illness 
Therapy (FACIT)–Fatigue Scale score, normalization of LDH, normalization of absolute 
reticulocyte count, and normalization of total bilirubin levels, along with reduction in C3 
fragment opsonization and increased numbers of PNH RBCs. 
7.3. 
Pegcetacoplan Safety in Humans 
Available safety data from nonclinical and clinical studies have not indicated any serious safety 
concern in subjects treated with pegcetacoplan. As with other complement-inhibiting drugs, there 
is a potential increased risk of infections with encapsulated pathogens, however, there have been 
no reports of serious infections due to encapsulated bacteria to date.  
Overall, SC administration of pegcetacoplan in clinical studies has been generally safe and well 
tolerated. 
 

Pe gcetac o pla n ( A P L‑ 2)  
A P L 2 -2 0 1 Pr ot oc ol A me n d me nt 7 
0 7 J ul y 2 0 2 2  
A pellis P har mace uticals, I nc  
Pa ge 3 2   
 
C o nfi de ntial  
8.  
R A TI O N A L E  
T he 4 diseases of I g A N , LN, pri mar y me m bra n o us ne p hr o pat h y ( pri mar y  M N) , a n d C 3 
gl o mer ul o pat h y ( C 3 G) h a ve a s hare d p at h o ge nesis of acti vati o n of t he ce ntral c o m ple me nt 
c o m p o ne nt, C 3. I n I g A N a nti b o dies t o galact ose- d eficie nt I g A ( G d -I g A 1) are de p osite d as 
i m m u ne c o m ple xes i n t he gl o mer ular mes a n gi u m. I n L N  a nti- D N A a n d a nti hist o ne 
a ut oa nti b o dies f or m i m m u ne c o m ple xes t hat are d e p osite d i n t he gl o mer ular base me nt 
me m bra ne . I n pri mar y m e m bra n o us ne p hr o pat h y a ut oa nti b o dies t o self-a nti ge ns o n t he p o d oc yte 
s uc h as P L A 2 rece pt ors f or m i n-sit u i m m u ne c o m ple xes. I n C 3 gl o mer ul o p at h y acti vate d C 3 is 
directl y de p osite d i n re n al gl o mer ul us. All t hese diseases i n v ol ve acti vati o n of eit her all 3 or 2 of 
t he 3 pat h wa ys t o C 3 acti vati o n (classical, lecti n , or alter nati ve c o m ple me nt pat h wa y). B y 
tar geti n g C 3 at t he p oi nt of c o n ver g e nce of all 3 p at h wa ys, pe gcetac o pl a n  has t he p ote ntial t o 
pre ve nt C 3 acti vati o n a n d C 3- me diate d i nfla m mat or y effects res p o nsi ble f or t he re n al 
ma nifestati o ns of i nj ur y c o m m o n t o a ll t hese diseases. T o date, n o s afet y si g nals ha ve e mer ge d 
fr o m o n g oi n g st u dies t hat precl u de f urt her d e vel o p me nt. T h us, t his pr o p ose d P hase 2 st u d y’s ai m 
is t o e x pl ore treat me nt efficac y a n d safet y of pe g cetac o pla n f or t he treat me nt of I g A N, L N, 
pri mar y  M N, a n d C 3 G. 
8. 1.  
P ur p ose of t he St u d y  
T he p ur p ose of t his st u d y is t o esta blis h t he preli mi nar y effi cac y a n d safet y of pe gcet ac o pla n  as a 
p ote ntial treat me nt f or p atie nts wit h I g A N, L N, pri mar y me m bra n o us ne p hr o pat h y ( pri mar y 
M N), a n d C 3 gl o mer ul o p at h y ( C 3 G), w hic h are all c o m ple me nt - me diate d gl o mer ul o pat hies. 
8. 2.  
D ose Selecti o n  
T he t o xic ol o gical data acc u m ulate d fr o m t he a ni mal st u dies were us e d t o g ui de d ose selecti o n 
d uri n g t he P hase 1 si n gle asce n di n g d ose a n d m ulti ple asce n di n g d ose st u di es i n healt h y 
v ol u nteers ( Pr ot oc ols 
 res pecti vel y). I n 
partic ular, t he hi g h est d oses wer e select e d base d o n e x p os ure pre dicte d b y a P K m o del a n d 
c o m pare d wit h t he e x p os ures o bser v e d at t he N O A E L i n c y n o m ol g us m o n ke ys.  
T he pla n ne d d ose of pe g cetac o pl a n  is s u bc uta ne o us 3 6 0 m g/ d a y. D ose sel ecti o n was bas e d o n 
past cli nical e x peri e nce wit h S C pe gcetac o pla n  c o u ple d wit h n o ncli nical t o xic ol o gical st u dies. 
Dail y d oses u p t o 3 6 0 m g/ d a y ha ve bee n teste d i n past a n d o n g oi n g cli nical trials a n d ha ve bee n 
f o u n d t o be well t olerat e d, wit h e x p os ures t hat are well bel o w t he p e gcet ac o pla n  le vels 
ass ociate d wit h t he N O A E L i n m o n ke ys. D oses of 1 8 0 m g/ d a y a n d a b o ve h a ve bee n s h o w n t o be 
p har mac ol o gicall y acti ve i n b ot h healt h y v ol u nteers a n d P N H patie nts, wit h cli nical a n d 
bi o mar ker r es p o nses i ncr easi n g i n a d ose de p e n de nt ma n ner. T heref ore w hile n o safet y c o n cer n 
has bee n ass o ciate d wit h a d ose of 3 6 0 m g/ d a y i n t he cli nical testi n g c o n d ucte d t o date, t hat d ose 
is e x pecte d t o ma xi mize a n y p ote ntial cli nical res p o nse i n t hese patie nts a n d pr o vi de a n o pti mal 
ris k/ be nefit pr ofile. 
8. 2. 1.  
Tr a nsiti o n t o T wice- Wee kl y D osi n g 
Patie nts ma y tra nsiti o n t o t wice - wee kl y d osi n g as earl y as Wee k 2 4, at t he discreti o n of t he 
s p o ns or. S uc h a d ose tra nsiti o n fr o m dail y t o t wice-wee kl y pe g cetac o pla n  h as bee n safel y 
i m ple me nte d i n P N H patie nts, a n d t his st u d y ai ms t o f oll o w a si milar pr ocess w he n tra nsiti o ni n g 
patie nts. I n P N H p atie nts tra nsiti o ni n g fr o m dail y t o t wice - wee kl y d osi n g, t he starti n g d ose was 
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1 0 8 0 m g t wice wee kl y, wit h t he o pti o n t o a dj ust t he d ose, t o a ma xi m u m d ose of 1 0 8 0 m g e ver y 
3 da ys. As ill ustrate d i n Fi g ure A 1 , t h e P K e x p os ure ( Cma x ) wit h 1 0 8 0 m g e ver y 3  da ys will still 
be l o wer t ha n t hat o bs er v e d i n St u d y  
 ( 1 3 0 0 m g t wice wee kl y ) a n d will be safel y 
bel o w t hat o bser ve d at t he N O A E L d os e ( 7 m g/ k g/ da y) i n c y n o m ol g us m o n ke ys.  
A d diti o nal i nf or mati o n o n t he selecti o n of t he 1 0 8 0 m g d ose ca n be f o u n d i n A p pe n di x 1  
(Secti o n  A 1. 1. 3. 2 ), a n d a d diti o nal details ar o u n d t he d ose tra nsiti o n pr ocess ca n be f o u n d i n 
Secti o n  1 0. 1 .  
8. 3.  
Ris k/ Be nefit  
A n u m ber of safet y m o nit ori n g practices are b ei n g e m pl o ye d b y t his pr ot oc ol (i ncl u di n g, b ut n ot 
li mite d t o, p h ysical e xa mi nati o n, vital si g ns m o nit ori n g at s pecifie d i nter vals, tri plicate 1 2- lea d 
electr ocar di o gr a m ( E C G ), he mat ol o g y (i ncl u di n g c oa g ulati o n), ser u m c he mistr y, uri nal ysis, 
pr o m pt re p orti n g of pre d efi ne d  a d v erse e ve nts ( A Es ) of s pecial i nterest , a n d A E c ollecti o n) i n 
or der t o e ns ur e t he s u bjects’ safet y.  
I njecti o n/i nf usi o n site a n d p u m p use safet y will be assesse d d uri n g cli nical visits, a n d a n y 
si g nifica nt fi n di n g fr o m t he assessme nt will be re p orte d as  a n A E (see  Secti o n  1 4. 1. 1 0 ). 
T he v ol u me of bl o o d pla n ne d f or c ollecti o n fr o m eac h s u bject o ver t he c o urse of t he st u d y ( see 
Secti o n  1 4. 1. 6 ) will be mi ni mize d i n or der t o li mit t he i m pact o n t he o verall healt h of t hese 
a ne mic s u bjects . 
S yste mic c o m ple me nt i n hi biti o n mi g ht pre dis p ose i n di vi d uals t o i nfecti o ns ca use d b y 
e nca ps ulate d or ga nis ms, i ncl u di n g Stre pt oc occ us p ne u m o ni ae , Neisseri a m e ni n giti d is, 
a n d H ae m o p hil us i nfl ue nz ae . Vacci nati o ns a gai nst t hese or ga nis ms will be ta ke n t o mi ni mize 
p ote ntial ris k of i nfecti o n. B o d y te m perat ure a n d vital si g ns will be m o nit ore d peri o dicall y, a n d 
rele va nt bl o o d para meters m o nit ore d re g ularl y t hr o u g h o ut t he st u d y t o assess f or si g ns of 
i nfecti o n. T he p ri mar y i n vesti gat or ( PI) s h o ul d be c o ntacte d i m me diatel y i n t he e ve nt of a 
s us pecte d i nfecti o n f or g ui da nce o n a p pr o priate acti o n t o be ta ke n. 
W hile n o car di ac safet y si g nal has e mer g e d fr o m precli nical or cli nical e x perie nce t o dat e, t he 
c urre nt cli nical e x perie nce is n ot s ufficie nt t o ne gate a n y p ote ntial u na ntici p ate d ris ks. T heref ore, 
car diac ris k will be e val u ate d as part of t his st u d y  a n d car di ac m o nit ori n g h as bee n i m ple me nte d.  
8. 3. 1.  
C O VI D - 1 9 Ris k Miti g ati o n Me as ures 
A pellis is n ot c urre ntl y a wa re of a n y e vi d e nce ass ociati n g pe gcetac o pla n use wit h s pecific ris ks 
or c o m plicati o ns of c or o na vir us disease 2 0 1 9 ( C O VI D - 1 9). A pellis rec o g nizes t he nee d t o 
c o nsi der t he p u blic healt h ris ks of t he C O VI D- 1 9 pa n de mic wit hi n t he c o nt e xt of c o n d ucti n g a 
cli nical trial. Beca us e  t hese ris ks ma y c ha n g e as t h e pa n de mic e v ol ves a n d ma y var y b y 
ge o gra p hic l ocati o n, A pellis will c o nti n ue t o e val uate t he ris k/ be nefit ar o u n d st u d y c o n d uct o n a n 
o n g oi n g a n d patie nt- b y- p atie nt basis.  
I n t he e ve nt t hat a n i n v esti gati ve site is cl ose d or a s u bject is u na ble or u n willi n g t o tra vel 
beca use of t he C O VI D -1 9  pa n de mic, a n d, if i n t he o pi ni o n of t he i nvesti gat or it is i n t he 
s u bject’s best i nterest t o c o nti n ue i n t he st u d y, ris k miti gati o n meas ures ma y be i m ple me nte d f or 
t he st u d y a n d utilize d if dee me d necessar y a n d a ut h orize d b y t he s p o ns or, i ncl u di n g b ut n ot 
li mite d t o:  
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• Collection of AEs or SAEs should be done over the phone and documented in the 
source documents and in the applicable case report form (CRF) page.  
• A minimized schedule of events is presented in Table A2 of Appendix 2, including 
identification of laboratory tests that can be performed at a certified local laboratory.  
• Any activities not performed because of COVID-19–related restrictions will be 
identified in the electronic data capture (EDC) system.  
• Any change in COVID-19 status (serology or antigen), if available, will be captured 
separately in the EDC system.  
• Where applicable, relevant study documentation will be updated and communicated 
to health authorities and/or institutional review boards (IRBs) or independent ethics 
committees (IECs) as required.  
These measures are described in more detail in Appendix 2.  

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9. 
STUDY OBJECTIVES AND ENDPOINTS 
9.1. 
Study Objectives 
The primary objectives of this study are to establish preliminary efficacy and safety of 
pegcetacoplan in patients with complement-mediated glomerulopathies (IgAN, LN, primary MN, 
and C3G). 
9.2. 
Study Endpoints 
9.2.1. 
Primary Efficacy Endpoints 
• Proteinuria reduction from baseline to Week 48, based on urinary protein-to-
creatinine ratio (uPCR) 
9.2.2. 
Secondary Efficacy Endpoints 
• All disease groups: changes of disease-specific biomarkers:  
− Serum C3 levels 
− AH50 and C3a concentrations 
− Serum albumin levels 
• All disease groups: complete clinical remission defined as normalization of 
proteinuria as defined by <200 mg/g uPCR at Week 48 
• All disease groups: stabilization or improvement in estimated glomerular filtration 
rate (eGFR) from baseline to Week 48 
9.2.3. 
Exploratory Endpoints 
• Complete renal response: defined as <200 mg/g uPCR and stabilization or 
improvement in eGFR from baseline to Week 48 
• Changes of disease-specific biomarkers:  
− LN: autoantibodies to double-stranded DNA, C3, and C1q  
− Primary MN: autoantibodies to PLA2R 
− C3G: C3NeF (Part A only) 
9.2.4. 
Pharmacokinetic Endpoints 
• Pegcetacoplan pharmacokinetic concentrations  
9.2.5. 
Pharmacodynamic Endpoints 
• Pegcetacoplan activity: Absolute levels, change from baseline, and % change from 
baseline in CH50, C3, C3a, C4, C5a, and soluble C5b9 complex (sC5b9)  
• Immunogenicity: Presence of autoantibodies to PEG and pegcetacoplan throughout 
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9.2.6. 
Safety Endpoints 
• Physical Examination; Incidence and severity of AEs 
• Changes from baseline in laboratory parameters 
• Changes from baseline in ECG parameters 

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10. 
STUDY DESIGN 
This is a prospective Phase 2 study, consisting a single cohort with a total of approximately 
48 patients (pegcetacoplan treatment native). This is an open-label study, with 48 patients 
clinically diagnosed with IgAN, LN, primary MN, or C3G (with 6-12 patients per disease). 
Subject participation will include a Part A, Core Study Phase which is an approximately 4-week 
screening period, 48-week treatment period, and 24-week safety follow-up. During the treatment 
period, patients will receive SC once daily dosing of 360 mg pegcetacoplan. Following the 
completion of the 48-week treatment period, any subject who, in the opinion of the investigator, 
is experiencing clinical benefit from pegcetacoplan administration will be invited to participate 
in Part B, the Long-Term Extension Phase in order to continue to receive treatment with 
pegcetacoplan until it is commercially available for the disease under treatment. If invited to 
participate in Part B, subjects do not need to complete the 24-week follow-up period of Part A.  
For each indication, patients who have sufficient medical history may enter the study. In this 
trial, sufficient medical history is defined as having stable proteinuria with a uPCR >750 mg/g, 
stable and optimized treatment regimen for their disease, stable eGFR or renal function, and 
stable blood pressure. Patients entering the 4-week screening period will begin screening at Visit 
3a and return for Visit 3b. Upon completion of the screening period, patients who meet all of the 
inclusion and exclusion criteria will begin the treatment phase of this study. The treatment phase 
will consist of once daily, self-administered, SC dosing of 360 mg pegcetacoplan at home, with 
the exception of all scheduled clinic visits. During scheduled Visit 4 only, the site staff will assist 
in administering the first SC dose of pegcetacoplan. At Visits 5-15 subjects will self-administer 
pegcetacoplan in the presence of the site staff and undergo various safety and efficacy 
assessments by qualified site staff. The change in proteinuria from baseline through the end of 
treatment will be assessed as the primary endpoint. Urinary protein-to-creatinine ratio (PCR) will 
be used to measure changes in proteinuria. 
After completion of the 48-week treatment period, any subject who, in the opinion of the 
investigator, is experiencing clinical benefit from pegcetacoplan treatment, will be invited to 
participate in Part B, the Long-Term Extension Phase (see Appendix 1 [Section A1.1]). If the 
subject does not enter Part B, he or she will enter the 24-week follow-up period, consisting of 6 
clinic visits at weeks 50, 52, 54, 60, 66, and 72 (Exit Visit). Various safety assessments will be 
undertaken during this visit clinics. Patients will be maintained on the standard of care during 
treatment and the follow-up period, as determined by the PI in consultation with the medical 
monitor.  
An external, independent safety monitoring committee (SMC) will assess the progress and 
cumulative safety/tolerability data of the study at specified times described in Section 13.4.3.  
Any subject with a sustained and significant reduction in renal function, as defined by one of the 
following: initiation of chronic dialysis, a confirmed and sustained eGFR ≤15 mL/min/1.73 m2 
or a confirmed and sustained reduction in eGFR of at least 30% which is drug related in the 
opinion in the PI. A reduction in eGFR would be considered confirmed if present on 2 separate 
consecutive measurements and sustained if the 2 measurements are at least 1 week or apart. 
Subject level discontinuation can also occur for any individual for whom the PI deems it in the 
best interest of the patient to not continue in the study. Indication level discontinuation will occur 
if 2 or more subjects in a particular indication are discontinued by these criteria. 

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Subjects who do not meet the criteria for participation in the study (screen failure) may be 
rescreened. The timeframe and scope of eligibility reassessment will be determined by the 
sponsor. Any requests to rescreen an individual more than one time must be approved by the 
sponsor. For each rescreening, the individual must sign a new informed consent form and will be 
assigned a new identification number. Record of the subject’s prior identification number and 
screening should be maintained with the source documents. Subjects who received vaccinations 
per protocol within 2 years of their rescreening date do not need to have the respective 
vaccination repeated but may do so at the discretion of the investigator. 
 
STUDY OUTLINE 
 
 
10.1. 
Transition to Twice-Weekly Dosing 
Patients are able, at the discretion of the sponsor, to transition to twice-weekly dosing with 
1080 mg pegcetacoplan prior to the Long-Term Extension Phase, but not earlier than Week 24. If 
a dose transition occurs during Part A, the subject will need to follow the dose transition visits, 
outlined in Table 2 below. Dose can be adjusted, as needed, to maintain clinical response.  
Transition Visits (T1, T2, and T3) should be scheduled for 1, 2, and 4 weeks after the first day on 
which their dose was adjusted. Additionally, subjects should be instructed to skip their Core 
Study Phase dose the day before the visit at which their dose will transition.  
 
 
 
 
 
 
 
 
 
 
 
 

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11. 
SUBJECT SELECTION 
The study plans to enroll approximately 48 subjects with IgAN, LN, primary MN, or C3G 
(6-12 subjects per disease)  
11.1. 
Inclusion Criteria 
At specified screening and/or treatment visit(s) subjects must fulfill all of the following inclusion 
criteria to be eligible for participation in the study: 
1. Patients of at least 18 years of age at screening (16 years of age for C3G), able to provide 
written informed consent, and able to understand and comply with all scheduled 
procedures and other requirements of the study by the opinion of PI 
2. Patients must have a diagnosis of IgAN, LN, primary MN, or C3G confirmed by renal 
biopsy and required measurements performed prior to study participation  
− IgAN: Prior biopsy results for C3 and C4d staining should be made available 
− LN: Diagnostic biopsy showing proliferative focal, diffuse, or membranous 
lesions (Class III, IV, or V, respectively) by renal biopsy. Subject should have 
either a biopsy in the last 6 months, or evidence of disease activity (nephritic 
changes on urinalysis or nephrotic changes)  
− Primary MN: PLA2R positive titer plus nephrotic range proteinuria (defined as 
uPCR >2350 mg/g) 
− C3G plus one of the following: Low serum C3 level or historical renal biopsy 
within the last 3 years 
3. Have proteinuria >750 mg/g uPCR (on 24-hour urine collection) collected during at the 
first screening visit (Visits 3a). 
4. eGFR ≥30 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology 
Collaboration (CKD-EPI) creatinine equation at Screening Visit 3a, currently not on 
dialysis. 
5. Must have stable or worsening renal disease, on stable and optimized treatment, in the 
opinion of the PI, for at least 2 months prior to the first dose of pegcetacoplan (Visit 4); 
treatments may include, but are not limited to, immunosuppressive agents, 
antihypertensives and/or antiproteinurics.  
6. Willing to receive vaccinations against Neisseria meningitidis at least 2 weeks prior to 
dosing on Day 1 with a booster on Day 56 (for both vaccinations) and pneumococcal and 
Hib vaccines at least 2 weeks prior to dosing on Day 1.  
7. Women of childbearing potential (WOCBP) must have a negative blood pregnancy test at 
screening (and negative urine pregnancy at Visit 4) and must agree to use protocol 
defined methods of contraception from screening through 3 months after last dose of 
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8. Males must agree to use protocol defined methods of contraception and agree to refrain 
from donating sperm from screening through 3 months after receiving last dose of 
pegcetacoplan. 
9. Willing and able to give informed consent 
10. Willing and able to self-administer pegcetacoplan (administration by caregiver will be 
allowed) 
11.1.1. 
Approved Methods of Contraception 
Approved methods of contraception include: oral contraceptives, intrauterine device, medically 
acceptable barrier methods (diaphragm or condom), implantable or injectable contraceptives 
(like Depo-Provera), or removable birth control device (like NuvaRing or Ortho Evra patches); 
and/or surgical sterilization (at least 6 months before dosing). Subjects practicing abstinence and 
coitus interruptus (pull out method) must agree to use an approved method of contraception 
during the study. 
11.2. 
Exclusion Criteria 
Subjects will be excluded from the study if there is evidence of any of the following criteria at 
specified screening and/or treatment visits as appropriate. 
1. Absolute neutrophil count <1000 cells/mm3 at screening Visits 3a and 3b 
2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3.0× the upper 
limit of normal at screening Visits 3a and 3b 
3. Previous treatment with pegcetacoplan 
4. History of solid organ transplant 
5. Diagnosis of human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C 
(HCV) infection, or positive serology at screening Visits 3a and 3b (previous HBV or 
HCV diagnosis cleared by treatment is allowed) 
6. Malignancy except for cured basal or squamous cell skin cancer, curatively treated in situ 
disease, or have been disease-free for ≥5 years or more from cancer, and off ongoing 
treatment. 
7. Renal disease secondary to another condition (eg, infection, malignancy, monoclonal 
gammopathy, or a medication) 
8. Presence or suspicion of active bacterial or viral infection or severe recurrent bacterial 
infections 
9. Participation in any other investigational drug trial or exposure to other investigational 
agent, device, or procedure within 30 days prior to screening period 
10. Pregnant, breastfeeding, or intending to conceive during the course of the study 
11. Inability to cooperate or any condition that, in the opinion of the investigator, could 
increase the patient’s risk by participating in the study or confound the outcome of the 
study 

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12. Unwillingness to receive or intolerant of SC infusions of study medication or known 
allergy to ingredients in pegcetacoplan. 
13. Positive results for drug abuse (upon urinary drug screen) or alcohol dependence at 
screening (Visit 3a). Documented evidence of prescribed marijuana use is not 
exclusionary. 

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12. 
STUDY TREATMENTS 
12.1. 
Identity of Investigational Product 
The test product is pegcetacoplan, which will be provided as a sterile solution of pegcetacoplan 
in acetate-buffered mannitol or sorbitol, supplied in stoppered glass vials. Additional information 
is provided in the pegcetacoplan IB. Investigational product will be administered as a 9-mL 
mannitol SC infusion (for 360-mg daily infusions) or as a 20-mL sorbitol SC infusion (for 
1080-mg twice-weekly infusions). 
12.2. 
Administration of Investigational Product 
12.2.1. 
Allocation to Treatment 
All subjects who meet all the inclusion criteria and none of the exclusion criteria will receive 
open-label daily SC infusions of pegcetacoplan. Following completion of the 48-week treatment 
period, each subject will have the opportunity to enter Part B, the Long-Term Extension Phase 
(see Appendix 1 [Section A1.1]), at the discretion of the investigator. Any subject who does not 
enter Part B will enter the follow-up period, consisting of 6 clinic visits at Weeks 50, 52, 54, 60, 
66, and 72 (Exit Visit). 
12.2.2. 
Dosing 
Starting on Day 1 (Visit 4), subjects will receive self-administered daily SC doses of 360 mg of 
pegcetacoplan until at least Week 24 (Visit 11) and then as directed based on the timing of 
transition to twice-weekly dosing, and whether they are following Part A (Follow-up) or Part B 
(Long-Term Extension). Of important note, patients may be switched over to twice-weekly 
dosing with 1080 mg, as early as Week 24, but no later than the entrance into the extension phase 
of the study; timing of the switch is at the discretion of the sponsor. If dose transition occurs, the 
subject will need to follow the dose transition visits (T1, T2, and T3), as outlined in Section 10.1, 
Table 2 (Part A) or Appendix 1, Table A1 (Part B). The dose can be adjusted, as needed, to 
maintain clinical response, but no more than 1080 mg every third day.  
12.2.3. 
Investigational Product Administration 
Investigational product will be administered as an SC infusion. For more details on infusion 
duration, pump specifications, and utilization, please see the instructions for use and pharmacy 
manual.  
The preferred site of injection will be the abdomen, however, if a subject does not tolerate 
administration into the abdomen, alternative appropriate sites may be considered. Research 
nurses or other appropriately qualified research personnel will administer the SC infusions at 
Visit 4 and will qualify and supervise the self-administration (or caregiver administration) for a 
minimum of 6 days until the subject has been qualified to conduct self-administration. During 
qualification the subject (or caregiver) must demonstrate to the research personnel their ability to 
safely and effectively administer study drug using the infusion pump. Following self-
administration qualification, subjects may self-administer the SC infusions without supervision. 
Once qualified, the patient will continue to self-administer infusions at the clinic on those days 
when a clinic visit occurs and at an off-site location convenient to the subject on all other days. 

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Self-administration conducted at the clinic will be supervised to ensure that the subject continues 
to remain compliant with the administration guidelines.  
Note: If the subject requires further training, the self-administration qualification period may be 
extended beyond 6 days. Self-administration may also be conducted by a member of the 
subject’s household or family member, etc. who will undergo the same qualification criteria by 
the in-home medical professional (qualification is not intended to be restricted to the patient). 
Please refer to the Study Operations Manual for further details regarding the self-administration 
qualification. 
12.3. 
Labeling, Packaging, Storage, and Handling 
12.3.1. 
Labeling 
Labels containing study information and pack identification are applied to the investigational 
product(s) container. 
All investigational product is labeled with a minimum of the following: dosage form (including 
product name and quantity in pack), route of administration, directions for use, storage 
conditions, batch number and/or packaging reference, the statements “For clinical trial use only” 
and/or “CAUTION: New Drug – Limited by Federal (or US) Law to Investigational Use,” and 
name and address of sponsor. 
Space is allocated on the label so that the site representative can record a unique subject 
identifier and date dispensed by the site to the subject. 
Additional labels may, on a case-by-case basis, be applied to the investigational product in order 
to satisfy national, local, or institutional requirements, but must not: 
• Contradict the clinical study label. 
• Obscure the clinical study label. 
• Identify the study subject by name. 
Additional labels may not be added without the sponsor’s prior full agreement. 
12.3.2. 
Packaging 
Investigational product is packaged in the following labeled containers: 
• 20-mL glass vials, 6 vials per carton.  
Changes to sponsor-supplied packaging prior to dosing may not occur without full agreement in 
advance by the sponsor. 
12.3.3. 
Infusion Supplies 
The sponsor will supply syringes, vial adapters, infusion sets, and ambulatory syringe infusion 
pumps as required. Refer to the Study Operations Manual for further details. 
12.3.4. 
Storage and Handling 
The investigational product should be stored refrigerated at 2-8 °C both at home and in the clinic.  

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The investigator has overall responsibility for ensuring that investigational product is stored in a 
secure, limited-access location at the site. Limited responsibility may be delegated to the 
pharmacy or member of the study team, but this delegation must be documented. 
A pharmacist or appropriately qualified designated person will be responsible for storing the 
investigational product appropriately and dispensing the vials of investigational product to the 
subject. The pharmacist/nominated team member will enter the unique subject identifier on the 
investigational product bottle/carton labels as they are distributed. 
Temperature monitoring is required at the investigator site (or documented storage location) to 
ensure that the investigational product is maintained within an established temperature range. 
The investigator is responsible for ensuring that the temperature in monitored throughout the 
duration of the study and that records are maintained.  
The investigational product should be transported from the clinic to the subject’s residence as 
described in the pharmacy manual, using the preconditioned phase change material plates and 
cooler bags. Temperature monitoring will not be required during transport or at the subject’s 
residence, but a log will be kept for every infusion to ensure that all investigational product was 
kept refrigerated.  
With sponsor prior approval, investigational product and/or ancillary supplies may be shipped 
from the study site to a subject’s designated location. Such shipments will only be implemented 
at sites where this activity is approved by the IRB/EC and health authority (if required). Subject 
consent will be required prior to any subject information being provided to a courier. The 
responsibility to return both empty vials and any unused investigational product shall remain 
unchanged, as described in Section 12.5.  
12.4. 
Investigational Product Accountability 
Accountability for the study drug at the study center is the responsibility of the investigator, who 
must ensure that the study drug is used only in accordance with this protocol. Where allowed, the 
investigator may choose to delegate drug accountability responsibilities to a pharmacist or other 
appropriate individual. 
Investigators will be provided with sufficient amounts of the investigational product to carry out 
this protocol for the agreed number of subjects. The investigator or designee will acknowledge 
receipt of the investigational product and document shipment content and condition. Accurate 
records of all investigational product dispensed, used, returned, and/or destroyed must be 
maintained. The investigator is responsible for ensuring the retrieval of all returnable study 
supplies from subjects. Study drug that has been dispensed to a subject and returned unused must 
not be re-dispensed to a different subject. 
All unused and used study drug vials should be retained at the center until they are inventoried 
by the study monitor. At the conclusion of the study, any unused investigational product will 
either be destroyed at the investigator site or be returned to the sponsor or designee for 
destruction, and destruction will be documented appropriately. If no supplies remain, this fact 
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12.5. 
Subject Compliance 
Subjects must be instructed to bring their unused investigational product and empty/used 
investigational product packaging to every visit. The pharmacist/nominated person will record 
details on the drug accountability form. 
12.6. 
Concomitant Medications 
12.6.1. 
Rescue Antibiotics 
Body temperature, vital signs, and relevant blood parameters will be monitored regularly 
throughout the study to assess for signs of infection. The PI should be contacted immediately in 
the event of a suspected infection for guidance on appropriate action to be taken. Action to be 
taken may include administration of a broad-spectrum antibiotic to cover possible resistant 
organisms such as resistant pneumococcus (eg, levofloxacin). 

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13. 
STUDY PROCEDURES 
Please see the Schedule of Events in Section 4 for Part A, the Core Study Phase, for a summary 
of the schedule of study participation and procedures. The schedule of visit dates should be 
established either prior to or at the time of screening, allowing subjects an opportunity to assess 
whether there are likely to be significant conflicts with other activities or planned absences. To 
the extent possible, subjects will be expected to adhere to the visit schedule and any 
re-scheduling of visits must be agreed, in advance, with the PI and sponsor.  
A summary of the schedule of study participation and procedures for the Part B Long-Term 
Extension Phase is provided in Appendix 1, Table A1. 
13.1. 
Screening (Week –4 to Week –2) 
The subject will be screened to confirm that the subject selection criteria for the study has been 
met. Informed consent will be obtained at screening prior to any study-related procedures being 
conducted (see Section 17.3.3). Patients with sufficient previous medical history (see Section 10 
for details) will begin the 4-week screening period. 
A screen failure is a subject who has given informed consent and failed to meet at least one of 
the inclusion and/or met at least 1 of the exclusion criteria and has not been randomized or 
administered investigational product(s).  
Screening procedures are listed in the Schedule of Events in Section 4. 
The following assessments will be performed at each visit: 
• Informed consent 
• Demographics 
• Medical history (including current angiotensin-converting enzyme 
inhibitor/angiotensin-receptor blocker therapy) (Visit 3a only) 
• Review of inclusion/exclusion criteria 
• Physical examination 
• Begin 24-hour urine collection during scheduled clinic visit (Visit 3a only) 
• Triplicate 12-lead ECG  
• Prior and concomitant medications 
• Vital sign measurements 
• Urinalysis assessment (see schedule of events for details) 
• Blood tests (see schedule of events for details) 
• β-HCG pregnancy test, if applicable 
• Follicle-stimulating hormone, HIV, HCV, HBsAg (see schedule of events for details) 
• AE collection  
• Vaccination Titer Serum Sample (Visit 3b only) 

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• Vaccination (see schedule of events for details) 
• Dispense 3 uPCR containers for consecutive collection (Visit 3b only) 
13.1.1. 
Vaccinations 
Subjects will be required to be vaccinated as follows, according to Advisory Committee on 
Immunization Practices (ACIP) recommendations for vaccination in patients with 
immunocompromising conditions (available at 
https://www.cdc.gov/vaccines/schedules/hcp/imz/adult-conditions.html).  
• Neisseria meningitidis types A, C, W, Y: Menactra®. First dose at least 2 weeks prior 
to dosing (Day –14) with a booster after 2 months (Day 56).  
• Neisseria meningitidis type B: Bexsero®. First dose at least 2 weeks prior to dosing 
(Day –14) with a booster after 2 months (Day 56).   
• Streptococcus pneumoniae: Prevnar 13®(PCV13) at least 2 weeks prior to dosing 
(Day –14) and Pneumovax® (PPSV23) after 2 months (Day 56).   
• Haemophilus influenzae type B: ActHIB® at least 2 weeks prior to dosing (Day –14). 
  
Vaccination is mandatory, unless documented evidence exists that subjects have received all 
recommended vaccines or are nonresponders to vaccination. All required vaccination(s) for 
which evidence is not available will be administered as needed to bring subjects up to date. The 
investigator should discuss with the medical monitor any individual patient circumstances that 
are relevant to the vaccination requirements or that would make the above schedule not possible 
or reasonable. On an ongoing basis, including upon entry into the long-term extension phase, 
subjects should be reevaluated for the need for any vaccinations based on ACIP 
recommendations. Subjects who withdraw from the study prior to any vaccine booster will be 
offered the opportunity to return to the site as recommended by current ACIP Adult 
Immunization schedule to receive the booster shot. 
13.2. 
Treatment Period (Week 1 to Week 48) 
13.2.1. 
Day 1 (Visit 4) 
Following completion of the 4-week screening period, subjects will enter the treatment period 
and will receive pegcetacoplan. The following assessments outlined in the schedule of events 
(Section 4) will be performed: 
Prior to treatment: 
• Procure 3 previously collected consecutive uPCR samples  
• Eligibility confirmation 
• Triplicate 12-lead ECG at –45, –30, and –15 minutes predose 
• Concomitant medications collection 
• Vital sign measurements 

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• Urinalysis (See schedule of events for details) 
• Blood tests (see schedule of events for details) 
• Pregnancy (β-HCG) 
• Urine pregnancy test, if applicable 
• Predose PK collection (within 1 hour before dose) 
• Dispense investigational product and infusion materials 
• Train subject to perform home infusion  
• Full physical examination 
Following Treatment:  
• Subjects will be contacted via phone by study staff 6 hours after the study treatment 
to collect safety information  
• Vital sign measurements at 30 minutes, 2 hours, and 4 hours post dose 
• Injection Site Assessment 
• Collect AEs 
• Dispense 3 uPCR containers for consecutive collection 
13.2.2. 
Week 2 to Week 48 (Visits 5-15) 
Subjects will self-administer once daily SC doses 360 mg of pegcetacoplan and will attend the 
investigator site at Visits 5-15 where the assessments outlined in the schedule of events 
(Section 4), will be performed. 
Visit window: ±2 days.  
Research nurses or other appropriately qualified research personnel will administer the SC 
infusions until the subject has been qualified to conduct self-administration. Following self-
administration qualification, subjects may self-administer the SC infusions. The subject will 
continue to self-administer infusions at the clinic on those days when a clinic visit occurs and at 
an off-site location convenient to the subject on all other days. Subjects have the opportunity to 
transition to a biweekly 1080 mg SC infusion of pegcetacoplan, as early as Week 24 of Part A of 
the study. If this occurs, the subject will need to have 3 transition visits (T1, T2, and T3), the 
details of which are provided in Table A1 of Appendix 1.  
The following assessments will be performed prior to investigational product administration:  
• Procure 3 previously collected consecutive uPCR samples (except Visit 15) 
− Arrange courier pickup for all biweekly triplicate uPCR samples during non-clinic 
visit weeks  
• Dispense 24-hour urine container at Visit 14 (for urine collection within 2 weeks 
prior to Visit 15) 
• Vital sign measurements (to be performed prior to ECG and venipuncture)  

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• Triplicate 12-lead ECG 15 minutes predose 
− Visit 15: Triplicate 12-lead ECG at –45, –30, and –15 minutes predose 
• PK sample predose (within 1 hour before dosing) to coincide with the 15 min predose 
ECG 
• Concomitant medications review 
• AE collection and review 
• Urinalysis collection (See schedule of events for details) 
• eGFR assessment 
• Pregnancy (β-HCG) (Visit 15 only), if applicable 
• Blood tests (see schedule of events for details) 
• Urine pregnancy test, if applicable  
• Physical examination (Full exam at Visit 15 only) 
• Vaccination Titer Serum Sample (Visit 7 only) 
• Vaccination(s) Booster (Visit 7 only) 
• Dispense investigational product and infusion materials 
• Observe Infusion of investigational product 
After investigational product administration:  
• Subjects will be contacted via phone by study staff 6 hours after the study treatment 
to collect safety information (Visit 15 only) 
• Vital sign measurements at 30 minutes post dose 
− Visit 15 only: Vital sign measurements to be measured at 30 minutes, 2 hours, and 
4 hours post dose 
• Injection Site Assessment 
• Collect AEs 
• Dispense uPCR containers for consecutive collection 
− 3 uPCR containers (Visit 5 and 15 [for subjects entering the follow-up period]), 6 
uPCR containers (Visits 6-10, Visit 14, and, for subjects entering Part B, 
Visit 15), 9 containers (Visits 11-13) 
13.3. 
Part B: Long-Term Extension Phase (Week 48 and Beyond) 
At Visit 15 (Day 336; Week 48) subjects will have the opportunity to enter Part B, the Long-
Term Extension Phase, at the discretion of the investigator, in order to continue to receive 
treatment with pegcetacoplan until it is commercially available for the disease under treatment. 
Subjects who enter the Long-Term Extension Phase will complete study procedures as outlined 
in Appendix 1 and Table A1.  

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13.4. 
Follow-up (Visits 16-20) 
All subjects who complete study treatment through Day 336/Week 48 but do not enter the Part B 
Long-Term Extension Phase will need to return to the clinical site for Follow-up Visits 16, 17, 
18, 19, and 20, where the assessments outlined in the schedule of events (Section 4) will be 
performed.  
Subjects who discontinue treatment early and do not continue their participation in the study 
should complete a follow-up visit 6 weeks after discontinuation of treatment and also the Exit 
Visit 6 weeks thereafter.  
Visit window: ±2 days (Visits 16-18) ±7 days (Visits 19 and 20) 
• Procure 3 previously collected consecutive uPCR samples to site (Visits 16-20)  
− Arrange courier pickup for all biweekly triplicate uPCR samples during non-clinic 
visit weeks  
• Physical examination (Visit 16 and 17 only) 
• Concomitant medications review (Visit 16 and 17 only) 
• Injection Site Assessment (Visit 16 only) 
• Antidrug Ab collection 
• eGFR assessment 
• Urinalysis collection (See schedule of events for details) 
• Urine pregnancy test (Visit 16-19 only) 
• AE review 
• PK Sample collection 
• Vital Signs 
• Blood tests (See schedule of events for details) 
• Triplicate 12-lead ECG 
• Dispense uPCR containers for consecutive collection (Visits 16-20): 
− 3 uPCR containers (Visits 16 and 17), 6 uPCR containers (Visit 20), 9 uPCR 
containers (Visits 18 and 19) 
• Dispense 24-hour urine container 
13.4.1. 
Exit Visit (Visit 21)  
If subjects are not participating in Part B the Long-Term Extension Phase, they will return to the 
clinical facility for the Exit Visit 24 weeks after the final dose of pegcetacoplan, on Day 504 (or 
sooner if the subject discontinues prior to the Week 48).  
Study participation for each subject will be concluded following completion of the Exit Visit. If a 
subject withdraws from the study prior to the scheduled Exit Visit, all Exit Visit evaluations 
should be performed at the subject’s final visit to the clinic, including the collection of blood 

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samples for PK and/or PD assessments, as well as a postdose antigenicity sample if not yet 
collected. 
The Exit Visit procedures are listed in the Schedule of Events in Section 4. 
Visit window: ±7 days.  
• Arrange courier service to pick up 24-hour urine collection to deliver to site 
• Procure 3 previously collected consecutive uPCR samples to site 
• Blood tests (see schedule of events for details) 
• Concomitant medications 
• AE review 
• Antidrug Ab assay 
• eGFR assessment 
• Urinalysis (See schedule of events for details) 
• PK Sample 
• Vital Signs 
• Triplicate 12-lead ECG 
13.4.2. 
Unscheduled Follow-up Visits 
All subjects will be asked to return to the clinical facility for additional follow-up visits if 
considered necessary by the PI. 
Unscheduled follow-up visits may include (but are not limited to) any of the procedures listed in 
the Schedule of Events in Section 4. 
13.4.3. 
Safety Monitoring Committee 
An SMC will review cumulative safety/tolerability data (eg, physical examinations, ECGs, vital 
signs, clinical laboratory tests, and AEs). The SMC will have the responsibility to conduct a 
thorough safety assessment at regular predefined intervals during the treatment period of the 
study. 
The first SMC meeting will be scheduled 3 months after the first subject is dosed, and at further 
3 monthly intervals until all subjects complete the Week 48 Visit. An ad hoc SMC data review 
may be recommended by the SMC or requested by the sponsor at any time during the study. 
The remit, roles, and responsibilities of the SMC will be specified in a separate SMC charter. 
13.5. 
Treatment Discontinuation and Study Withdrawal 
Subjects will be considered to have completed the study when they have completed the Week 72 
exit visit activities described in the Schedule of Assessments in Section 4, when they have 
enrolled in a subsequent study of pegcetacoplan, or when they have discontinued study treatment 
and completed any early termination activities. 

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A subject may withdraw from the study at any time, for any reason, without prejudice to his/her 
future medical care by the physician or at the institution. If a subject discontinues or is 
withdrawn from study treatment for any reason, the study site must immediately notify the 
medical monitor.  
Treatment may be discontinued and/or a subject’s participation in the study may be discontinued, 
for any of the following reasons: 
1. Any serious adverse event (SAE), clinically significant AE, severe laboratory 
abnormality, intercurrent illness, or other medical condition (including infections) that 
indicates to the PI that continued participation is not in the best interest of the subject. 
2. Subject's decision to withdraw. 
3. Subject’s failure to comply with protocol requirements (including pregnancy) or study-
related procedures. 
4. Termination of the study by the sponsor, US Food and Drug Administration, or other 
regulatory authorities. 
5. Liver Toxicity (please refer to Section 13.5.1 for further details). 
6. Sustained and significant reduction in renal function (see more details below).  
 
A sustained and significant reduction in renal function is defined by one of the following: 
initiation of chronic dialysis, a confirmed and sustained eGFR ≤15 mL/min/1.73 m2 or a 
confirmed and sustained reduction in eGFR of at least 30% which is drug related in the opinion 
in the PI. A reduction in eGFR would be considered confirmed if present on 2 separate 
consecutive measurements and sustained if the 2 measurements are at least 1 week or apart.  
The reason for treatment discontinuation and/or withdrawal from the study must be recorded in 
the subject’s source document.  
Subjects who discontinue study treatment prior to the end of the treatment period, should 
undergo all follow-up visits and procedures through study completion (Exit Visit), unless 
unwilling or unable, or consent has been withdrawn. Subjects who wish to fully withdraw from 
the study before Visit 15, should be encouraged to complete the Early Termination Exit Visit. 
Any subject withdrawn due to an AE (whether serious or nonserious) or clinically significant 
abnormal laboratory test values will be evaluated by the investigator and should be treated and/or 
followed at least up until the symptoms or values return to normal or acceptable levels, as judged 
by the PI. 
If consent is withdrawn, no further study evaluations are to be performed and no attempts are to 
be made to collect additional data. 
13.5.1. 
Liver Toxicity 
Drug treatment continuation will be evaluated in case of any signs of possible drug-induced 
hepatic injury as follows: 
Drug treatment will be discontinued immediately if either: 

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• ALT or AST is >3 × the upper limit of normal (ULN) and (total bilirubin is >2× ULN 
or international normalized ratio [INR] is >1.5)  
or 
• ALT or AST is >8× ULN 
Drug treatment will be withheld if either:  
• ALT or AST is >5× ULN  
or 
• ALT or AST is >3× ULN with the appearance of fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%).  
Drug treatment will be permanently discontinued and the subject withdrawn from the study if the 
condition persists for more than 2 weeks. 
If the subject is not withdrawn from the study, drug treatment may be resumed when both ALT 
and AST are less than 1.5× ULN.  
Any possible hepatic abnormalities will be monitored with repeat testing at a frequency of at 
least every 72 hours. Frequency of retesting will decrease to weekly or less once abnormalities 
stabilize. Repeat testing will discontinue once abnormalities are no longer detected.  
Causes for the significant liver test abnormalities will be investigated (eg, acute viral hepatitis, 
Epstein-Barr virus, cytomegalovirus, herpes simplex virus, toxoplasmosis, varicella, and 
parvovirus) and subjects will be followed up until all abnormalities return to normal or to the 
baseline state.  
Work-up will also include consideration of alcoholic and autoimmune hepatitis, hepatobiliary 
disorders (eg, gallstones), nonalcoholic steatohepatitis, cardiovascular causes (eg, right-sided 
heart failure), and concomitant medications or supplements. 
13.5.2. 
Lost to Follow-up 
A minimum of 3 documented attempts must be made to contact any subject lost to follow-up at 
any time point prior to the last scheduled contact (office visit or telephone contact). At least 1 of 
these documented attempts must include a written communication sent to the subject’s last 
known address via courier or mail (with an acknowledgment of receipt request) asking that 
he/she return to the site for final safety evaluations and to return any investigational product. 
Should the subject continue to be unreachable, he/she will be considered to have withdrawn from 
the study. 

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14. 
ASSESSMENTS 
14.1. 
Assessments 
For Part A, the Core Study Phase, assessments to be performed during the study are described 
below. Every effort should be made to ensure that the protocol-required assessments are 
completed as described. 
If deemed necessary, additional safety measurements will be performed at the discretion of the 
PI. 
14.1.1. 
Medical History 
Medical history, including changes to angiotensin-converting enzyme inhibitor/angiotensin-
receptor blocker therapies, will be collected at Screening Visit 3a. 
14.1.2. 
Prior and Concomitant Medications 
To be eligible for entry into the study, subjects must be on a stable optimized treatment regimen 
for their disease, in the opinion of the PI, for at least 2 months prior to the first dose of 
pegcetacoplan (Visit 4), which may include, but is not limited to, use of immunosuppressive 
agents, antihypertensives and/or antiproteinurics.  
All other prior medications administered within 12 Weeks of Screening Visit 3a will be 
collected. 
Use of rituximab, belimumab, and eculizumab during the study (and/or within 6 months prior to 
the first dose of pegcetacoplan) must be discussed with the sponsor for consideration and 
approval.  
All medications and procedures administered to subjects from the time of informed consent 
through the End of Study Visit are regarded as concomitant and will be documented. 
To the extent possible, baseline treatment regimens (including medications, dietary restrictions, 
and lifestyle modifications), should not be changed during the study, except as necessary for the 
well-being of the patient, in the opinion of the PI. 
14.1.3. 
Body Height and Weight 
Body height (cm) and body weight (kg) will be measured at screening Visit 3a. Body weight will 
be measured throughout the study as part of the physical examination. 
14.1.4. 
Physical Examination 
All full physical examinations will include, at a minimum, assessment of the following: general, 
head, ears, eyes, nose and throat, dentition, thyroid (endocrine), heart, chest, lungs, abdomen, 
skin, extremities, back/neck, musculoskeletal, and lymph nodes. 
Brief physical examinations will include general appearance, heart, lungs, abdomen, extremities, 
and weight. 
The investigator (or designee) at the study site will examine each subject as outlined in the 
Schedule of Events in Section 4. 

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Additional symptom-driven physical examinations may be performed at any time, as deemed 
necessary by the investigator. 
14.1.5. 
Vital Signs 
Single measurements of body temperature, respiratory rate, blood pressure, and heart rate will be 
measured prior to and 30 minutes after dosing as outlined in the Schedule of Events in Section 4. 
This will include daily measurements during Days 2 to 7 by the health care professional 
conducting the self-administration qualification (ie, at-home nurse). 
Vital signs may be taken at any other times, if deemed necessary. Blood pressure and heart rate 
measurements will be performed with subjects in a seated position after resting for 5 minutes, 
except when they are supine or semireclined because of study procedures and/or AEs (eg, 
nausea, dizziness) or if deemed necessary by the PI. 
Vital signs will be measured before venipuncture and ECG assessment, vital signs collected post 
dose will be timed from the completion of the study drug administration. 
Additional monitoring of vital signs will occur on Day 1 (Visit 4) and Week 48 (Visit 15) at 2 
and 4 hours after dosing, with a ±15-minute window of occurrence. 
14.1.6. 
Electrocardiogram Monitoring 
Triplicate 12-lead ECGs will be measured at the time points outlined in the Schedule of Events 
in Section 4. There is a ±5-minute window for the start of the triplicate ECGs. Once each 
triplicate ECG begins, subsequent ECGs should be at least one minute and no more than 
2 minutes apart. ECGs will be taken following resting in the supine position for 10 minutes in a 
quiet environment and prior to any blood sampling procedures, unless specified at time points 
after timed blood sampling procedures. 
All ECGs will be recorded at the sites using the equipment provided by the vendor performing 
the centralized ECG analysis. 
The ECGs will be classified as normal, having a not clinically significant abnormality, or having 
a clinically significant abnormality. In addition, ECG parameters of ventricular rate, PR interval, 
QRS duration, and QT interval (corrected using Fridericia’s method, and uncorrected) will be 
reviewed for eligibility and ongoing safety. 
Please see the Study Operations Manual for further details on ECG collection, and reporting. 
14.1.7. 
24 Hour Urine Collection 
Subjects will be provided with a container for 24-hour urine collection that can begin at the site 
or at home. The baseline 24-hour urine collection (during screening at Visit 3a, within the visit 
window) should be obtained within 2 weeks of the first dose of pegcetacoplan, and final 24-hour 
urine collection during the treatment period should be obtained within 2 weeks prior to Visit 15. 
Twenty-four-hour urinary output will be collected in order to determine eligibility for entry into 
the study by a uPCR on a 24-hour urine collection. Twenty-four-hour urine collection is defined 
as a total urine collection for the 24-hour period following the (discarded) first urinary output for 
the day. Urine container will need to be stored at 2-8 °C (ie, in refrigerator). Courier 

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arrangements will be made by the site to pick up the collection container for the patients and 
return to it the site. Urinary PCR and ACR on the 24-hour collection will be determined. 
14.1.8. 
Consecutive Spot uPCR 
Subjects will receive separate spot urine collection containers at the scheduled clinic visits 
indicated in the schedule of events. Biweekly, subjects will complete urine collection from their 
first urinary output upon awakening for the day, for 3 consecutive days (see schedule of events 
for visit window details). On weeks leading up to the scheduled clinic visit subjects will return 
triplicate uPCR as indicated. On weeks where no clinic visit is scheduled, courier service will be 
arranged to pick up samples from the patient’s home for delivery to the clinic. It is important to 
have these collections be from the first urinary output upon awakening on each of those days. 
After collection, the urine samples must be stored at a refrigerated temperature (2-8 °C) until 
they are returned to the site. Both uPCR and uACR values should be calculated on all spot urine 
samples.  
14.1.9. 
Clinical Laboratory Tests 
All tests listed below will be performed as outlined in the Schedule of Events in Section 4. In 
addition, laboratory safety tests may be performed at various unscheduled time points, if deemed 
necessary by the PI or recommended by the SMC. The clinical laboratory tests include (but are 
not limited to) the following: 
14.1.9.1. Hematology 
• Hb 
• Hematocrit 
• RBC count 
• Platelet count  
• WBC count with differential 
14.1.9.2. Coagulation* 
• Activated partial thromboplastin time (aPTT) 
• Fibrinogen 
• INR 
*The use of silica reagents in coagulation panels should be avoided in subjects treated with 
pegcetacoplan. 

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14.1.9.3. Serum Chemistry 
• Blood urea nitrogen (BUN) 
• Creatinine 
• Estimated Glomerular Filtration 
Rate (using CKD-EPI formula)  
• Bilirubin (total and conjugated) 
• Albumin 
• Alkaline phosphatase (ALP) 
• Lactate dehydrogenase (LDH) 
• Gamma-glutamyl transferase 
(GGT) 
• Calcium 
• Phosphorus 
• Aspartate aminotransferase 
(AST) 
• Alanine Aminotransferase 
(ALT) 
• Uric acid 
• Glucose  
• Sodium 
• Potassium 
• Chloride 
• Creatinine Kinase (CK) 
• Bicarbonate 
14.1.9.4. Urinalysis 
• pH 
• Specific gravity 
• Protein 
• Glucose 
• Ketones 
• Albumin-to-creatinine ratio 
(ACR) 
• Protein-to-creatinine ratio (PCR) 
• Bilirubin 
• Blood 
• Nitrite 
• Urobilinogen 
• Leukocyte esterase 
• Urine Sediment 
Microscopic examination for protein, blood, nitrite, and/or leukocyte esterase will be performed 
on all urinalyses. 
14.1.9.5. Serum Pregnancy Test and Screening Assays 
Serum pregnancy test (beta human chorionic gonadotropin; β-HCG) will be performed for 
females only. Follicle-stimulating hormone will be performed for postmenopausal females at 
screening Visit 3a only. Blood tests for HIV, HCV, and HBV will be performed at Screening 
Visit 3a only. 
14.1.9.6. Vaccination Antibody Titer 
Serum samples will be collected at Visit 3b and Visit 7 (prior to administration of vaccinations) 
for analysis of antibody titers to Neisseria meningitidis (types A, C, W, Y, and B), Pneumococcal 
conjugate vaccine or Pneumococcal polysaccharide vaccine 23 (PCV13 or PPSV23, 

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respectively) and the Haemophilus influenza Type B (Hib) vaccination. The serum samples will 
only be analyzed in the event that a patient has a positive infection for Streptococcus 
pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. 
14.1.10. 
Injection/Infusion Site and Pump Safety Assessment 
On the days of clinical visits pump use safety will be assessed within 30 minutes after study drug 
administration. This technique evaluation will be performed by a physician or other licensed 
health care provider (eg, study nurse) as delegated by the investigator. The subject will be asked 
about any issue related to pump use. 
Subjects will be instructed to notify the PI or other study personnel in the event that an injection 
site reaction occurs after self-administration of pegcetacoplan. All CS findings from injection 
site assessment or related to pump use will be recorded as AEs. 
14.2. 
Pharmacokinetic Assessments 
14.2.1. 
Blood Sampling and Processing 
Blood samples for PK assessment of pegcetacoplan will be collected via direct venipuncture at 
the time points delineated in the Schedule of Events in Section 4. 
PK samples will be taken predose at all other visits. 
Instructions for collection, handling, processing, storage, and shipping of samples will be 
provided in a separate Laboratory Reference Manual prior to study initiation. 
14.2.2. 
Analytical Method 
Serum sample analysis will be performed using GLP-compliant validated procedures and 
methods. The methods used and the results obtained will be included in the final report as an 
appendix. 
14.3. 
Pharmacodynamic Assessments 
Blood samples will be collected via direct venipuncture at the time points delineated in the 
Schedule of Events in Section 4. for PD assessment of complement activation through the 
alternative (ie, AH50) pathways. Blood samples will also be collected to measure CH50, C3, 
C3a, C4, C5a, and sC5b9 levels. Other relevant PD markers may also be assessed. 
Instructions for collection, handling, processing, storage, and shipping of samples will be 
provided in a separate Laboratory Reference Manual prior to study initiation. 
14.4. 
Antidrug Antibody Assessment  
Antidrug antibodies (ADAs) include both anti–pegcetacoplan peptide and anti-PEG antibodies. 
The proposed ADA sampling schedule was established to capture the ADA signal at baseline, 
along with any potential early onset and the dynamic profile (transient or persistent) of antibody 
formation. 
Patients who discontinue dosing will need to have ADA samples collected 6 and 12 weeks 
following their last treatment.  

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Patients who test positive for ADAs at any time will be followed up with ADA samples being 
collected every 6 months until the antibody levels are considered to be negative. Antibody levels 
will be considered to be negative when they revert to baseline or any titer that is less than a 4-
fold increase from the baseline titer. Samples that test positive will be characterized by an assay 
that will determine antibody titer and measure neutralizing capacity. 
14.5. 
Blood Volume for Study Assessments 
Table 3: 
Blood Volume During Part A, the Core Study Phase 
Sample Type 
Number of Visits 
Approximate 
Volume per Visit 
(mL) 
Approximate 
Volume Over 
Course of Study 
(mL) 
Screening laboratory safety tests (including hematology, 
serum chemistry, coagulation serology), FSH (for 
postmenopausal female patients only) 
1 
25 
25 
On-study serum chemistry 
20 
11 
220 
On-study hematology 
20 
4 
80 
On-study coagulation 
20 
3 
60 
PK 
19 
4 
76 
PD (C3, C3a, C4, C5a, and sC5b9) 
16 
10 
160 
Disease-Specific Biomarkers 
17 
2 
34 
Immunogenicity (Antidrug antibodies) 
16 
5 
80 
Vaccination titer sample 
2 
7 
14 
Total Approximate Blood Volume for Study: 
749 
Abbreviations: FSH = follicle-stimulating hormone; sC5b9 = soluble C5b9 complex. 
Note: represents the standard collection volume planned over the duration of the study, actual volume may vary. 
 
For subjects who enter the Part B Long-Term Extension Phase, the volumes noted above will 
continue to be collected as noted in the Study Flow Chart for the Part B Long-Term Extension 
Phase (Table A1). 
14.6. 
Pregnancy Tests 
For WOCBP, a serum pregnancy test will be performed at screening (Visit 3a) and during 
treatment (Visits 4 and 15). Subjects with a positive test will be excluded or discontinued from 
the study. A urine pregnancy test will also be performed at each site visit during the treatment 
period (predose). For subjects entering the follow-up period, urine pregnancy tests will be 
performed at each follow-up visit through 12 weeks after the last dose of pegcetacoplan 
(Visit 19). Male subjects will be counseled to avoid donating sperm during the time between the 
first screening and the final Exit Visit. 

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14.7. 
COVID-19 Assessments 
If a subject has been tested for COVID-19, the results, if available, will be documented in the 
subject’s source document. 

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15. 
ADVERSE EVENTS 
15.1. 
Definitions 
15.1.1. 
Adverse Events 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not it is considered drug related. An AE can, therefore, be any unfavorable and unintended 
sign, including a clinically significant abnormal laboratory finding, symptom, or disease 
temporally associated with the use of an investigational product, whether or not it is considered 
related to the investigational product. 
AEs can be spontaneously reported by the subject and/or in response to an open question from 
the study personnel or revealed by observation, and will be recorded during the study at the 
investigational site. All identified AEs must be recorded and described in the subject’s source 
document.  
Fluctuating or nonsignificant changes in laboratory values do not necessarily qualify for AE 
reporting. If changes in laboratory values are assessed as clinically significant and/or lead to 
discontinuation of administration of investigational product, they should be reported as an AE. If 
these laboratory values are linked to a diagnosis, only the diagnosis should be reported as an AE.  
15.1.2. 
Serious Adverse Events 
An SAE is any AE or suspected adverse reaction that, in the view of the investigator, results in 
death, is life threatening, requires inpatient hospitalization or prolongation of existing 
hospitalization, results in a persistent or significant incapacity or substantial disruption of the 
ability to conduct normal life functions, or is a congenital anomaly or birth defect. 
Important medical events that may not result in death, be life threatening*, or require 
hospitalization may be considered serious when, according to appropriate medical judgment, 
they may jeopardize the subject or may require medical or surgical intervention to prevent one of 
the outcomes listed in the above definition.  
Examples of important medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
*Life threatening is defined as an AE or suspected adverse reaction that, in the view of either the 
investigator or sponsor, placed the subject at immediate risk of death as it occurred. It does not 
include an AE or suspected adverse reaction that, had it occurred in a more severe form, might 
have caused death. 
15.1.3. 
Unexpected Adverse Events 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the reference 
safety information section of the IB that is in effect at the time of event onset. 

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Rec or di n g a n d Re p orti n g A d verse E ve nt s 
A Es a n d S A Es will be c ollecte d fr o m t he si g ni n g of t he i nf or me d c o ns e nt f or m (I C F) u ntil t he 
exit/earl y ter mi nati o n  visit.  
Al l S A Es will be f oll o we d u ntil satisfact or y res ol uti o n, u ntil baseli ne le vel is reac h e d, or u ntil 
t he S A E is c o nsi dere d b y t he i n vesti gat or t o be c hr o nic or t he s u bject is sta ble, as a p pr o pri ate.  
All S A Es  t hat are s us pect e d of bei n g r elate d t o st u d y treat me nt m ust be re p orte d i m me diatel y t o 
t he s p o ns or if t he i n vesti gat or bec o mes a ware of t he m, re gar dless of t he ti me si nce t he 
c o m pleti o n of t he cli nical trial.  
A n y e ve nts t hat occ ur pri or t o t he start of d osi n g will be cate g orize d as pretreat me nt e ve nt s; 
e ve nts occ urri n g aft er t he start of d osi n g will be rec or de d as treat me nt-e mer ge nt A Es  (T E A Es ) 
(t he start date of d osi n g a n d, t heref or e, cate g orizati o n of t he e ve nt will be d e pe n de nt o n 
ra n d o mizati o n assi g n me nt).  
F or eac h A E, t h e i n vesti gat or will e val u ate a n d re p ort t he o nset date (a n d ti me, if a p plica ble), 
res ol uti o n date (a n d ti me, if a p plica ble), i nte nsit y, ca usalit y, acti o n ta ke n, s eri o us ness criteria 
met (if a p plica ble), a n d w het her or n ot t he s u bject disc o nti n ue d t he st u d y as a res ult of t he e v e nt. 
If p ossi ble, t he o utc o me of a n y A E r es ulti n g i n per ma ne nt disc o nti n uati o n or t hat was prese nt at 
t he e n d of t he st u d y s h o ul d be re p orte d. S u bjects e x perie nci n g A Es t hat ca use i nterr u pti o n or 
disc o nti n uati o n of i n vesti gati o nal pr o d uct a n d t h os e e x peri e nci n g A Es t hat are prese nt at t he last 
visit or earl y ter mi nati o n visit s h o ul d recei ve f oll o w - u p as a p pr o priate.  
All S A Es m ust be re p orte d t o t he s p o ns or/ A pellis Safet y b y c o m pleti n g t he S A E f or m wit hi n 
2 4 h o urs of t he i n vesti gat or or t heir r e pres e ntati ve bec o mi n g a ware of t h e e ve nt, w het her or n ot 
t he e ve nt is dee me d treat me nt relate d. C o m plete d S A E f or ms s h o ul d be e m aile d t o 
  
A Es  will be c o de d i n acc or da nce wit h t he Me dical Dicti o nar y f or Re g ul at or y Acti vities 
( Me d D R A). If k n o w n, t h e dia g n osis of t he u n derl yi n g ill ness or dis or der s h o ul d be rec or de d, 
rat her t ha n its i n di vi d ual s y m pt o ms. 
1 5. 2. 1.  
Rel ati o ns hi p t o St u d y Dr u g  
T he i n vesti gat or will re vi e w eac h e v e nt a n d assess its relati o ns hi p t o st u d y dr u g treat me nt ( n ot 
relate d, u nli kel y r elate d, p ossi bl y relate d, or defi nitel y relate d). T h e date a n d ti me of o nset, ti me 
relati o ns hi p t o dr u g d osi n g, d urati o n, se verit y, acti o n ta ke n, a n d o utc o me (rec o vere d/res ol ve d, 
rec o vere d/r es ol ve d wit h se q uelae, rec o v eri n g/res ol vi n g, n ot rec o vere d/ n ot res ol ve d, fatal, or 
u n k n o w n) of eac h e v e nt will be n ote d. 
Ta ble  4 s h o ul d be c o nsi d ere d w h e n e val u ati n g t he relati o ns hi p of A Es/ S A Es t o st u d y treat me nt.  
P P D

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Table 4: 
Definitions of Adverse Event Relatedness 
Classification 
Definition 
Definitely related 
Strong evidence of a causal relationship; the influence of other factors is unlikely. 
Possibly related 
Some evidence of a causal relationship, but other factors may have caused or contributed 
to the event (eg, another illness or concomitant treatment). 
Unlikely related 
A causal relationship is not a reasonable possibility, but it cannot be completely ruled out 
with the available evidence. 
Not related 
No evidence of a causal relationship. 
 
15.2.2. 
Severity of Events 
The investigator will review each event and assess its severity. Note that severity is a measure of 
intensity, whereas seriousness is defined by the criteria in Section 15.1.2. An AE can be of 
severe intensity but not be considered serious.  
Table 5 presents the severity definitions that should be considered when evaluating the severity 
of AEs and SAEs. 
Table 5: 
Severity of Events 
Severity 
Definition 
Mild 
Event results in mild or transient discomfort, not requiring intervention or treatment; does not 
limit or interfere with daily activities (eg, insomnia, mild headache). 
Moderate 
Event is sufficiently discomforting so as to limit or interfere with daily activities; may require 
interventional treatment (eg, febrile illness requiring oral medication). 
Severe 
Event results in significant symptoms that prevents normal daily activities; may require 
hospitalization or invasive intervention (eg, anemia resulting in blood transfusion). 
 
15.2.3. 
Reporting Adverse Events to Health Authorities, Institutional Review Boards, 
and Ethics Committees 
The sponsor has the responsibility to inform concerned health authorities, IRBs, IECs, and 
investigators about suspected unexpected serious adverse reactions in line with GCP guidance 
and applicable regulatory requirements. 
If required, specific SAEs should be reported to the concerned IRB or IEC in compliance with 
local requirements. 
15.3. 
Pregnancy  
Although pregnancy is not considered an AE, all pregnancies and suspected pregnancies 
(including a positive pregnancy test regardless of age or disease state) occurring with a female 
subject or the female partner of a male subject must be followed to conclusion to determine their 
outcome and are considered immediately reportable events.  

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A n y pre g na n c y, s us pect e d pre g na nc y, or p ositi ve pre g na nc y t est m ust be re p orte d t o A pellis 
Safet y b y c o m pleti n g t he pre g na nc y re p ort f or m wit hi n 2 4 h o urs of t he i n vesti gat or bec o mi n g 
a war e of t he e ve nt. T he c o m plete d p re g na n c y re p o rt for m m ust be e mail e d t o 
 
T he i n vesti gat or m ust f oll o w u p t he s u bject u ntil c o m pleti o n of t he pre g na n c y a n d m ust re p ort 
t he o utc o me of t he pr e g n a nc y (e g, d eli ver y, ter mi nati o n, etc) a n d n e o natal stat us u p t o 1 2 m o nt hs 
p ost deli ver y . A n a b n or m al o utc o me is defi ne d as t he birt h of a c hil d wit h p ersiste nt or 
si g nifica nt i nca pacit y or s u bsta ntial disr u pti o n of t he a bilit y t o c o n d uct n or mal life f u ncti o ns 
(f or merl y r ef err e d t o as disa bilities), c o n ge nital a n o mal y, or birt h defects. I n t he e ve nt of a n 
a b n or mal o utc o me, a n S A E m ust be re p orte d usi n g t he S A E re p ort f or m , as descri be d i n 
Secti o n  1 5. 2 .  
1 5. 4.  
A b use, Mis use, O ver d ose, a n d Me dic ati o n Err or  
Occ urre nces of e v e nts of o ver d ose, dr u g mis use, dr u g a b use, a n d m e dicati o n err or m ust be 
re p orte d t o t he S p o ns or.  
A b use of a m e dici n al pr o d uct : Persiste nt or s p ora dic, i nte nti o nal, e xcessi ve use of me dici n al 
pr o d ucts t hat is acc o m pa nie d b y har mf ul p h ysical or ps yc h ol o gical effects.  
Mis use:  I nte nti o nal a n d i na p pr o priate us e of a m e dici nal pr o d uct n ot i n acc or da nce wit h t he 
prescri be d or a ut h orize d d ose, r o ute of a d mi nistrati o n, a n d/ or i nte n de d i n dicati o n(s) or n ot wit hi n 
t he le gal stat us of its s u p pl y.  
O ver d ose:  A n y d ose a d mi nistere d t o or ta ke n b y a s u bject (acci de ntall y or i nte nti o nall y) t hat 
e xcee ds t he hi g hest dail y d ose or is at a hi g her fre q ue nc y t ha n is descri be d i n t he pr ot oc ol.  
Me dic ati o n Err or:  A n err or ma de i n prescri bi n g, dis pe nsi n g, a d mi nistrati o n, a n d/ or use of t he 
st u d y dr u g. Me dicati o n err ors are r e p orta ble t o t he S p o ns or as f oll o ws:  
•  T he dis pe nsi n g, a d mi nistrati o n, a n d/ or use of u n assi g ne d st u d y dr u g 
•  T he a d mi nistrati o n a n d/ or use of a n e x pire d st u d y dr u g 
All A Es or S A Es ass ociate d wit h dr u g a b use, mis use, o ver d ose, or me dicati o n err or m ust be 
re p orte d as a p pr o priate. T he i n vesti gat or will deci de w het her a d ose is t o be c o nsi dere d a n 
o ver d ose i n c o ns ultati o n wit h t he s p o ns or. I n t h e e ve nt of a n o ver d ose, t he act ual d ose 
a d mi nistere d m ust be rec or de d i n t he s u bject’s s o urce d oc u m e nt. 
P P D

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16. 
STATISTICS  
16.1. 
Sample Size Justification 
Given the exploratory nature of the study no formal statistical hypothesis testing will be 
performed and so the sample sizes of both parts of the study are not based upon statistical power 
of the study. 
Approximately 48 patients (6-12 per indication) will be enrolled into this study (patients with 
either IgAN, primary MN, LN, or C3G, enrolled 1:1:1:1). As these complement-mediated 
glomerulopathies are rare diseases it may be difficult to recruit subjects from 1 or more of the 
disease types; hence the range of 6-12 subjects per type. The intention is to recruit safety, PK, 
PD, and efficacy data to support the progress of pegcetacoplan into further clinical studies. 
With 6 subjects treated with pegcetacoplan in each disease type there is a 95% chance of an AE 
being reported if its true incidence is over 40%. Similarly, there is a 47%, 74% and 88% chance 
if the true incidence is 10%, 20%, or 30% respectively. With 12 subjects treated in each disease 
type the chance increases to >93% for true incidences over 20% and 72% if the true incidence is 
10%. 
16.2. 
Statistical Analysis Methodology  
A formal Statistical Analysis Plan (SAP) will be developed and finalized prior to locking the 
database. The full details of data presentations and analyses will be provided in the SAP. 
Additional statistical analyses other than those described in this section may be performed if 
deemed appropriate and included in the SAP. Any deviations from the final SAP or from what is 
outlined in the protocol will be discussed in the final study report.  
All endpoints will be summarized by the diagnosed complement-mediated glomerulopathy 
(IgAN, LN, primary MN, or C3 glomerulopathy) and visit. Continuous data will be summarized 
using descriptive statistics (eg, mean and standard deviation) and categorical data will be 
summarized using frequency tables (counts and percentages). 
16.2.1. 
Analysis Populations 
16.2.1.1. Screened Population 
The screened analysis set will include all patients who signed the ICF, are screened for 
participation. This set will be used only for the purpose of describing patient disposition.  
16.2.1.2. Safety Population/ Intent-to-Treat (ITT) Population 
The safety analysis set will include all patients who receive a dose of pegcetacoplan. 
16.2.1.3. Per Protocol Population 
The PP set will include all subjects in the ITT set who have not violated any inclusion or 
exclusion criteria and/or deviated from the protocol, in a way that could influence their efficacy 
assessment.  

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16.2.1.4. Pharmacokinetic (PK) Population 
The PK population will include all subjects in the ITT population who receive pegcetacoplan and 
have at least 1 evaluable post-dose PK measurement. 
16.2.1.5. Pharmacodynamic Population 
The PD population will include all subjects in the ITT population who have at least 1 evaluable 
post-dose PD measurement. 
16.2.1.6. Data Review for Analysis Populations  
After all the data have been verified/coded/entered into the database, a review will be performed. 
The purpose of this review will be to define the analysis populations. The review will also check 
the quality of the data, identifying outliers, and make decisions on how to deal with any data 
issues (eg, missing values, withdrawals, protocol deviations). After the preanalysis review, 
resolution of all issues, and documentation of all decisions, the database will be locked. 
16.2.2. 
Efficacy Analyses 
No formal inferential statistics will be applied to data collected in the study 
16.2.2.1. Primary Endpoint 
Changes from baseline in proteinuria, percentage changes from baseline in proteinuria, and 
percentage change in mean proteinuria is the primary efficacy endpoint. They will be calculated 
by using mean of the 3 spot uPCR samples collected for baseline (Day 1) and the subsequent 
treatment visits. In addition, these calculations will be repeated using the 24-hour urine 
proteinuria sample which is collected at baseline (Day 1) and Week 48. If additional unscheduled 
24-hour urine samples are collected then these will be included as well. 
16.2.2.2. Secondary Endpoints 
Changes from baseline and percentage changes in baseline eGFR and disease-specific 
biomarkers are the secondary efficacy endpoints. Changes from baseline and percentage changes 
from baseline in biomarkers for serum C3, C3a, C4, C5a, and sC5b9, and AH50 levels will be 
summarized. They will be calculated for each postdose assessment, while the baseline will be 
taken as the predose assessment on Day 1. Additional disease parameters and/or biomarkers may 
also be analyzed.  
16.2.2.3. Exploratory Endpoints 
Changes from baseline and percentage changes from baseline in biomarkers for LN 
(autoantibodies to double-stranded DNA, C3, and C1q), primary MN (PLA2R autoantibodies), 
and C3G (C3NeF; Part A only) levels will be summarized. They will be calculated for each 
postdose assessment, while the baseline will be taken as the predose assessment on Day 1. 
Additional disease parameters and/or biomarkers may also be analyzed. 
16.2.3. 
Safety Analyses  
All safety endpoints will be evaluated using the safety population. 

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16.2.3.1. Adverse Events 
TEAEs are defined as those AEs that develop or worsen after the first dose of study medication 
and up to 8 weeks beyond the last dose of study medication. The current version of MedDRA at 
the time of analysis will be used to classify all AEs.  
TEAEs will be summarized by System Organ Class and Preferred Term, in accordance with the 
MedDRA coding dictionary. The number of subjects reporting each AE Preferred Term will be 
tabulated for all TEAEs and separately for those considered as possibly related to study treatment 
by the investigator. Number of subjects reporting SAEs will also be tabulated. AE summaries 
will be presented for each period of the study separately within each complement-mediated 
glomerulopathy group. 
16.2.3.2. Clinical Laboratory Tests 
Changes from baseline in laboratory will be summarized using descriptive statistics by treatment, 
visit, and nominal time post dose. Baseline will be taken as the last measurement prior to the first 
dose of pegcetacoplan.  
Out of range values will be flagged in the data listings. 
16.2.3.3. Vital Signs and ECGs 
Changes from baseline in vital signs and ECG parameters will be summarized using descriptive 
statistics by treatment, visit, and nominal time post dose. Baseline will be taken as the last 
measurement prior to the first dose of pegcetacoplan.  
Values of potential clinical significance (eg, increase in QTcF ≥30 ms from baseline) will be 
flagged in listings and summarized by treatment. 
ECG parameters will be analyzed using concentration effect models. 
16.2.4. 
Pharmacokinetic Analyses  
The PK concentrations will be evaluated using the PK population. 
Concentrations will be summarized using descriptive statistics over time by complement-
mediated glomerulopathy.  
Individual subject concentration-time data will be plotted against actual sampling time. Median 
profiles of the concentration-time data, using nominal sampling times, will also be presented. 
Both linear-linear and linear-log plots will be presented.  
16.2.5. 
Pharmacodynamic Analyses  
The PD endpoints will be evaluated using the PD population. 
Absolute values, changes from baseline, and % changes from baseline will be summarized using 
descriptive statistics over time by complement-mediated glomerulopathy.  
Individual subject time profiles will be plotted against actual sampling time. Median profiles 
over time, using nominal sampling time, will also be presented.  

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16.2.6. 
Other Data Analyses 
Demographic data, baseline characteristics, physical examination, concomitant medication, 
medical history data, and study medication exposure will be summarized by complement-
mediated glomerulopathy. 
World Health Organization and MedDRA coding dictionaries will be used for the concomitant 
medications and medical histories, respectively. 
16.3. 
Interim Analyses 
No formal interim analyses are planned for the primary endpoint. 

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17. 
REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
17.1. 
Direct Access to Source Data/Documents 
The PI must maintain, at all times, the primary records (ie, source documents) of each subject’s 
data for data verification. Examples of source documents are medical records, laboratory reports, 
study drug records, and eCRFs that are used as the source. 
The PI will permit study-related monitoring, audits, and inspections by the sponsor and/or its’ 
designee, IRB/IEC, and the regulatory agencies at any time during the study. The PI will ensure 
that the auditor is allowed direct access to the source data, medical records, eCRFs, and the site’s 
regulatory file for the study and any other pertinent information.  
17.2. 
Quality Control and Quality Assurance 
This study is to be performed in full compliance with the protocol, GCP, and applicable 
regulatory requirements. The PI and sponsor and/or its designee are responsible for ensuring that 
the study staff receive appropriate training on the protocol, study procedures, and any other 
relevant information.  
Quality assurance and quality control systems are implemented and maintained using written 
investigative site, sponsor, and/or designee standard operating procedures to ensure that the study 
is conducted and data are generated, documented (recorded), and reported in compliance with the 
protocol, GCP, and the applicable regulatory requirement(s) national and local laws, rules, 
regulations. 
Quality control checks will be applied at each stage of data handling (eg, edit checks) to ensure 
that all data are reliable and have been processed correctly.  
17.2.1. 
Monitoring 
On-site monitoring will be performed by the sponsor’s designee for the duration of the study. 
The monitor will ensure that the study is conducted, recorded, and reported in accordance with 
the protocol, standard operating procedures, GCP, and the applicable regulatory requirements. 
Monitoring activities will include (but are not limited to): 
• Provide information and support to the investigator(s) 
• Confirm that facilities remain acceptable 
• Confirm that all subject data relating to the study is being recorded on printed or 
electronic CRFs unless transmitted to the sponsor/designee electronically 
(eg, laboratory data). The investigator is responsible for verifying that data entries are 
accurate and correct by physically or electronically signing the CRF  
• Ensure that the investigator maintains accurate documentation (source data) that 
supports the information entered in the CRF 
• Confirm that the investigational team is adhering to the protocol and verify the 
accuracy and completeness of the eCRF entries against source documents 

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• Confirm that investigational product accountability checks are being performed and 
documented 
• Record and report any protocol deviations not previously sent to the Sponsor 
• Confirm that all AEs and SAEs have been properly documented on CRFs and 
confirm that any SAEs have been forwarded to Apellis and those SAEs that met 
criteria for reporting have been forwarded to the IRB 
• Confirm that suspected unexpected serious adverse reactions are being acknowledged 
and submitted to the IRB as necessary 
The PI will provide direct access to source data/documents for study-related monitoring, as 
described in Section 17.1. It is important that the PI and the staff are available at these visits. The 
monitor will record the date of each visit together with a summary of the status and progress of 
the study. Proposed actions will be documented in writing to the PI. 
17.3. 
Ethics 
17.3.1. 
Ethical Conduct of the Study 
This research will be carried out in accordance with the protocol, applicable regulations, the 
ethical principles set forth in the Declaration of Helsinki, and the ICH Harmonized Tripartite 
Guidance for Good Clinical Practice, E6, R2 (ICH GCP). 
17.3.2. 
Institutional Review Board or Independent Ethics Committee Review 
The study protocol, any amendments to the protocol, ICF, the IB, and other study specific 
information will be reviewed and approved by the IRB or IEC. The study will not be initiated 
until the IRB/IEC has approved the protocol or a modification thereof. All records pertaining to 
IRB/IEC submission and approval should be kept in the site’s regulatory files and sponsor’s trial 
master file. 
The IRB/IEC must be constituted and operate in accordance with the principles and requirements 
described in ICH Guidance E6 and national and local regulations as deemed appropriate. 
17.3.3. 
Subject Information and Consent 
The PI is responsible for obtaining an informed consent. A written informed consent, in 
compliance with ICH Guidance E6, must be obtained from each subject prior to screening and 
enrollment or performing any study-related procedures. 
The purpose of the study, the procedures to be carried out and the potential hazards will be 
described to the subjects in nontechnical terms. The subject will be given sufficient time to 
consider the study’s implications before deciding to participate in the study. The subject and/or 
legal guardian will be required to sign and date an ICF and will be assured that they may 
withdraw from the study at any time without jeopardizing their medical care. The PI shall retain 
the original, signed informed consent for study participation in the subject’s medical record and 
shall provide the subject and/or legal guardian with a copy of the signed consent. 
Patients who live outside the United States or are not proximal to their nearest active site, who 
may wish to participate in this study for a period of time within the United States will be pre-

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consented by the PI and the local physician. The ICF (in local language) will be emailed to the 
subject’s local physician. The ICF will be provided in advance to the patients to ensure adequate 
time is provided to ask questions and discuss any concerns. This procedure is completed to 
ensure patients understand the study, procedures, risks, and benefits, etc., before traveling to 
their activated site for a screening visit. The patient will be consented by the PI over the 
phone/video with the local physician present on the call/video to aid in the discussion. Additional 
trained translators will be provided if needed to ensure subjects fully understand the protocol and 
can ask questions. The ICF will be signed by the patient, local physician, and PI once the patient 
arrives to the site for the screening visit. The executed ICF will be stored locally at the PI’s 
office. The PI may wish to re-consent the patient again once arriving to the United States. 
If there are any changes/amendments to the approved protocol, which may directly affect the 
subject’s decision to continue participation in the study, the ICF shall be amended to incorporate 
the changes to the protocol and the subject must re-sign the IRB/IEC approved amended ICF. 
17.3.4. 
Confidentiality  
Confidentiality of subject’s information must be maintained in accordance with national and 
local privacy laws. 
17.3.5. 
ClinicalTrials.gov  
This study has been listed with ClinicalTrials.gov, as required. 
17.3.6. 
Termination of Study 
The sponsor reserves the right to suspend or discontinue this study for administrative and/or 
safety reasons at any time. The PI reserves the right to discontinue dosing subjects at any time 
for safety reasons. 
17.4. 
Data Handling and Record Keeping 
Subject information will be captured and managed by study sites on eCRFs by a web-based EDC 
tool developed and supported by the Contract Research Organization (CRO) assisting with the 
conduct of the study and configured by sponsor. It is recommended that data be entered into the 
EDC system within 5 business days of collection, including batched records and records with 
source documents. 
Data management will be performed by the CRO according to their standard operating 
procedures. The Data Management Plan will be approved by the sponsor. 
The PI must maintain all documentation related to this study. All essential documents (as defined 
in the ICH Guideline E6) and the data generated in connection with this study, together with the 
original copy of the final report, will be retained for at least 5 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or at least 5 years have elapsed since the formal discontinuation of 
clinical development of the investigational product. These documents should be retained for a 
longer period if required by the applicable regulatory requirements or by an agreement with the 
sponsor.  

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It is the responsibility of the sponsor to inform the PI/Institution as to when these documents no 
longer need to be retained. 
17.5. 
Protocol Amendments 
Any amendments to the study protocol deemed necessary as the study progresses will be 
discussed between sponsor and the PI. The PI will not implement any changes to the protocol 
without an agreement by the sponsor and prior review and documented approval from the 
IRB/IEC of an amendment, except where necessary to eliminate immediate hazards to study 
subject or when the changes involve only logistical or administrative aspects of the study (eg, 
change in staff, telephone numbers). 
Changes resulting in amendments will be made jointly between the sponsor and the PI and must 
be confirmed in writing. Amendment(s) will be approved and signed off in the same way as the 
original protocol.  
17.6. 
Report Format 
According to the ICH Harmonized Tripartite Guideline (Organization of the Common Technical 
Document for the Registration of Pharmaceuticals for Human Use M4 and the ICH M2 Expert 
Working Group), the final report will be written according to the ICH E3 Guideline (Structure 
and Content of Clinical Study Reports). 
17.7. 
Finance and Insurance 
Finance and insurance will be addressed in a Clinical Trial Agreement between the PI/Institution 
and the sponsor. 
17.8. 
Publication Policy 
The data generated for this study are considered confidential information and are the property of 
the sponsor. All study information provided to the PI and site personnel by the sponsor shall not 
be published or disclosed to a third party without the prior written consent of the sponsor.  
Apellis will endeavor to publish the results of all qualifying, applicable, and covered studies 
according to external guidelines in a timely manner regardless of whether the outcomes are 
perceived as positive, neutral, or negative. Additionally, Apellis adheres to external guidelines 
(eg, Good Publication Practices 2) when forming a publication steering committee, which is 
done for large, multicenter Phase 2-4 and certain other studies as determined by Apellis. The 
purpose of the publication steering committee is to act as a noncommercial body that advises or 
decides on dissemination of scientific study data in accordance with the scope of this policy. 
All publications relating to Apellis products or projects must undergo appropriate technical and 
intellectual property review, with Apellis agreement to publish prior to release of information. 
The review is aimed at protecting the sponsor’s proprietary information existing either at the 
commencement of the study or generated during the study. To the extent permitted by the 
publisher and copyright law, the principal investigator will own (or share with other authors) the 
copyright on his/her publications. To the extent that the principal investigator has such sole, 
joint, or shared rights, the principal investigator grants the sponsor a perpetual, irrevocable, 
royalty-free license to make and distribute copies of such publications. 

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The term “publication” refers to any public disclosure including original research articles, review 
articles, oral presentations, abstracts, and posters at medical congresses, journal supplements, 
letters to the editor, invited lectures, opinion pieces, book chapters, electronic postings on 
medical/scientific websites, or other disclosure of the study results, in printed, electronic, oral, or 
other form. 
Subject to the terms of the paragraph below, the investigator shall have the right to publish the 
study results, and any background information provided by the sponsor that is necessary to 
include in any publication of study results, or necessary for other scholars to verify such study 
results. Notwithstanding the foregoing, no publication that incorporates the sponsor’s 
confidential information shall be submitted for publication without the sponsor’s prior written 
agreement to publish and shall be given to the sponsor for review at least 60 days prior to 
submission for publication. If requested in writing by Apellis, the institution and principal 
investigator shall withhold submission of such publication for up to an additional 60 days to 
allow for filing of a patent application. 
If the study is part of a multicenter study, the first publication of the study results shall be made 
by the sponsor in conjunction with the sponsor’s presentation of a joint, multicenter publication 
of the compiled and analyzed study results. If such a multicenter publication is not submitted to a 
journal for publication by the sponsor within an 18-month period after conclusion, abandonment, 
or termination of the study at all sites, or after the sponsor confirms there shall be no multicenter 
study publication of the study results, an investigator may individually publish the study results 
from the specific site in accordance with this section. The investigator must, however, 
acknowledge in the publication the limitations of the single-site data being presented. 
Unless otherwise required by the journal in which the publication appears, or the forum in which 
it is made, authorship will comply with the International Committee of Medical Journal Editors 
current standards. Participation as an investigator does not confer any rights to authorship of 
publications. 

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uACR = urine albumin-to-creatinine ratio; uPCR = urine protein-to-creatinine ratio; WBC = white blood cell(s); 
WOCBP = women of childbearing potential. 
 
a 
Subjects who discontinue treatment early should complete one ETF 6 weeks after discontinuation of treatment and one ETE 
Visit 6 weeks after the ETF.  
b 
If subjects have not transitioned to twice-weekly dosing before entry into Part B, then transition visits T1, T2, and T3 need 
to be scheduled. Patients who had transitioned to twice-weekly dosing prior to entry into Part B may omit the Part B dose 
transition visits.  
c 
Following Extension Visit 18 (Week 84) subjects should continue to schedule visits at 12-week intervals (±7 days) until 
pegcetacoplan is commercially available for the disease under treatment. 
d 
A full physical examination should be performed at 24-week intervals (ie, at Week 48 and then every other visit starting at 
Week 72). Additional symptom-driven physical examinations may be performed at unscheduled time points if deemed 
necessary by the PI. 
e 
Triplicate 12-lead ECGs are to be performed before dosing and before blood sampling procedures. 
f 
Subjects will self-administer SC pegcetacoplan, after receiving appropriate training by a research nurse or other personnel. 
During site visits subjects will self-administer pegcetacoplan at the site if it occurs on a dosing day.  
g 
Between site visits, subjects will be instructed to report any injection site reaction to the study coordinator. 
h 
On clinic dosing days vital signs will be measured within 2 hours before dosing, venipuncture, and ECG assessments. On 
clinic dosing days, vital signs will be measured within 30 minutes after dosing. 
i 
24-hour urine collected for ACR and PCR, defined as collection for a 24-hour period in a urine pooling container following 
the first urinary output on that day (first urinary output is discarded). Courier arrangements will be made by site personnel to 
pick up urine containers from patient’s home. Urine ACR and PCR will be calculated on 24-hour urine collections for 
accuracy in estimating 24-hour proteinuria. Starting with the collection at Week 72, 24-hour urine collections will be every 
other visit (ie, every 24 weeks). 
j 
Urinary PCR samples (first urinary output for the day) should be collected on 3 consecutive days, biweekly, for both 
uACR/uPCR analysis with a ±3-day window. On weeks of scheduled clinic visits, samples will be brought with patient 
during the site visit. No biweekly uPCR collection will occur between extension visits, but 1 uPCR collection will occur 
halfway between each extension visit at the 6-week time point and will be picked up by courier.  
k 
Urinalysis—routine dipstick for protein, glucose, hemoglobin, blood, ketones, ACR, pH, bilirubin, urobilinogen, leukocyte 
esterase, specific gravity. 
l 
All blood samples will be taken predose. 
m 
All PK collections will be taken predose for treatment visits and following ECGs at all other visits. Predose PK collections 
to occur within 1 hour before dose. For subject visits falling outside of dosing schedule, PK samples can be taken following 
ECGs as mentioned for all other visits.  
n 
ADA samples should be collected at approximately 24-week intervals (ie, at Week 48 and then every other visit starting at 
Week 72). For subjects with positive ADA in last dose samples, additional samples of 6 and 12 months from last dose will 
be collected for further assessments. 
o 
Hematology consists of Hemoglobin, Hematocrit, RBC count, Platelet count, WBC count with differential (basophils, 
eosinophils, monocytes, lymphocytes, neutrophils), aPTT, INR. The use of silica reagents in coagulation panels should be 
avoided in subjects treated with pegcetacoplan.  
p 
Chemistry consists of BUN, Creatinine (b), Bilirubin (total and conjugated), Uric acid, Albumin, ALP, LDH, Creatine 
kinase, AST, ALT, GGT, Glucose, Sodium, Potassium, Chloride, Bicarbonate.  
q 
CKD-EPI creatinine equation (see https://www.niddk.nih.gov/); the CKD-EPI creatinine-cystatin C equation (if 
confirmation required). 
r 
Urine pregnancy test should be completed for WOCBP prior to dosing. 
 
A1.1.2. 
Part B Long-Term Extension Phase: Study Design and Procedures 
Following Visit 15 (Week 48), subjects who elect to continue in Part B, the Long-Term 
Extension Phase, will return to the site at 12-week intervals until pegcetacoplan is commercially 
available for the disease under treatment. 
Specific procedures for each visit are listed in the Study Flow Chart for the Long-Term 
Extension Phase in Table A1. 
The vaccination history for each subject should be reviewed prior to entry into the Long-Term 
Extension Phase, and any additional vaccinations or boosters against N. meningitidis, 
S. pneumoniae, or H. influenzae as recommended in the Advisory Committee on Immunization 

Pe gcetac o pla n ( A P L‑ 2)  
A P L 2 -2 0 1 Pr ot oc ol A me n d me nt 7 
0 7 J ul y 2 0 2 2  
A pellis P har mace uticals, I nc  
Pa ge 8 1   
 
C o nfi de ntial  
Practices ( A CI P) g ui d eli nes f or patie nts wit h i m m u n oc o m pr o misi n g c o n diti o ns ( a vaila ble at 
htt ps:// w w w.c dc. g o v/ vacci nes/sc he d ules/ hc p/i mz/ a d ult-c o n diti o ns. ht ml) s h o ul d be pr o vi de d. If 
a d diti o nal vacci nati o ns or b o osters ar e re q uire d, v acci nati o n titer sa m ples s h o ul d be c ollecte d 
bef ore a d mi nistrati o n of t he vacci nati o n a n d at t he ne xt sc he d ule d visit. 
At Visit 1 5 ( Wee k 4 8), s u bjects w h o are i n vite d t o partici pate i n Part  B, t he L o n g-Ter m 
E xte nsi o n P hase w h o ha ve n ot alrea d y tra nsiti o ne d t o 1 0 8 0 m g t wice -wee kl y  pe gcetac o pla n  
treat me nt d uri n g Part A, will be gi n a pe gcet ac o pla n  d ose re gi me n of p e gcet ac o pla n  1 0 8 0 m g 
t wice wee kl y ( wit h p ote ntial t o escalate t o pe g cetac o pla n  1 0 8 0 m g e ver y 3 da ys). S u bjects 
s h o ul d f oll o w t he D ose Tra nsiti o n visits as o utli ne d i n Ta ble A 1 .  
If a s u bject will i nitiate t he pe gcetac o pla n  1 0 8 0 m g t wice  wee kl y  d ose re gi me n at Visit 1 5, he or 
s he s h o ul d be i nstr ucte d t o s ki p t heir dail y Part A C ore St u d y P hase D ose t he da y pri or t o Visit 
1 5 (ie, t he s u bject s h o ul d n ot self- a d mi nister pe gcetac o pla n  o n D a y 3 3 5).  
S u bjects w h o disc o nti n ue treat me nt earl y s h o ul d c o m plete a n Earl y T er mi nati o n F oll o w-u p Visit 
6 wee ks after disc o nti n uati o n of treat me nt, a n d a n Earl y Ter mi nati o n E xit Visit 6  wee ks later  as 
o utli ne d i n  Ta ble A 1 . 
St u d y Assess me nts ali g n wit h t h ose c o n d ucte d i n t he C ore St u d y P hase a n d are des cri be d i n 
Secti o n  1 4. 1 . 
A 1. 1. 3.  
P art B L o n g- Ter m E xte nsi o n P h ase: D ose R ati o n ale 
T he rati o nale f or t he Part A pe gcet ac o pla n  d ose re gi me n is pr o vi de d i n Secti o n  8. 2 . 
A 1. 1. 3. 1.  T ar get Le vel of P e gcet a c o pl a n  Ser u m C o nce ntr ati o n  
T he t o xic ol o gical data acc u m ulate d fr o m t he a ni mal st u dies were us e d t o g ui de d ose selecti o n 
d uri n g t he P hase 1 si n gle asce n di n g d ose a n d m ulti ple asce n di n g d ose st u di es i n healt h y 
v ol u nteers ( St u d y 
). I n 
partic ular, t he hi g h est d oses wer e select e d, base d o n e x p os ure pre dicte d b y a P K m o del a n d 
c o m pare d wit h t he e x p os ures o bser v e d at t he N O A E L  i n c y n o m ol g us m o n ke ys.  
T he pla n ne d t wice-w ee kl y d ose of pe gcetac o pl a n  is 1, 0 8 0 m g S C t wice wee kl y, e q ui vale nt t o 
3 0 8 m g/ da y. D ose selecti o n is base d o n past cli nical e x perie n ce wit h S C pe gcetac o pl a n , c o u ple d 
wit h n o ncli nical t o xic ol o gical st u dies. Dail y d oses u p t o 3 6 0 m g/ da y ha ve b ee n teste d i n past a n d 
o n g oi n g cli nical trials , i ncl u di n g t his o n g oi n g trial, a n d ha ve b ee n f o u n d t o be well t olerate d, 
wit h e x p os ures t hat ar e w ell bel o w t he pe gcetac o pl a n  le vels ass ociat e d wit h t he N O A E L i n 
m o n ke ys.  
Usi n g a tar get -me di ate d dr u g dis p ositi o n p har mac o ki netic/ p har mac o d y n a mic ( P K/ P D) m o del 
(Ma ger a n d J us k o, 2 0 0 1 ), t he relati o ns hi p bet wee n d osi n g re gi me n a n d pe gcetac o pl a n  ser u m 
c o nce ntr ati o n is well - u n derst o o d a n d well- pre dicte d b y t he m o del. Fi g ure A 1 is t he pre dicte d P K 
pr ofile f or t he d os e of 1 0 8 0 m g t wice wee kl y ( gree n li ne), c o m pare d t o t he N O A E L P K data 
o bser ve d i n t he pi v otal 9- m o nt h c hr o nic t o xic ol o gical st u d y i n m o n ke ys ( St u d y 1 3 C A T X- 0 0 4 
[ blac k li ne]). F or c o m paris o n wit h pre vi o us h u ma n e x p os ure, als o i ncl u de d is t he s u m mar y P K 
data fr o m t he o n g oi n g P N H st u d y, St u d y A P L - C P 0 5 1 4 ( 2 7 0 m g/ da y c o h ort [ bl ue li ne]), a n d 
healt h y v ol u nteer st u d y, St u d y  
, at 3 6 0 m g/ da y ( br o w n li ne) a n d 1 3 0 0 m g bi wee kl y 
(li g ht bl ue li ne). B ot h st u dies de m o nstrate d pe g cet ac o pla n  t o be safe a n d w ell t olerate d. T he 
fi g ure ill ustrates t hat t he P K e x p os ure at t he d os e of  1 0 8 0 m g t wice wee kl y s h o ul d deri ve a P K 
C CI
C CI

Pe gcetac o pla n ( A P L‑ 2)  
A P L 2 -2 0 1 Pr ot oc ol A me n d me nt 7 
0 7 J ul y 2 0 2 2  
A pellis P har mace uticals, I nc  
Pa ge 8 2   
 
C o nfi de ntial  
e x p os ure sli g htl y bel o w t hat of 3 6 0 m g dail y a n d s h o ul d be safel y bel o w t h at o bser ve d at t he 
N O A E L.  
A 1. 1. 3. 2.  D osi n g A dj ust m e nt O pti o n  
Tra nsiti o n fr o m 3 6 0 m g dail y t o 1 0 8 0 m g t wice wee kl y ma y res ult i n a s mall decreas e i n 
e x p os ure. T heref ore, if a n i ncreas e i n pr otei n uria is o bser ve d u p o n tra nsiti o n t o t wice- wee kl y 
d osi n g, t he n a n i ncrease i n d ose t o 1 0 8 0 m g e ver y 3 da ys ma y be c o nsi dere d, u p o n a gree m e nt 
wit h t he s p o ns or. T his a me n de d d osi n g re gi me n will res ult i n a hi g her P K e x p os ure t ha n t hat 
ac hie ve d wit h t wice - w ee kl y d osi n g. H o we ver, as ill ustrate d i n Fi g ure A 1 , t his i ncrease i n P K 
e x p os ure ( C ma x ) will still be l o wer t ha n t hat o bs er v e d i n St u d y  
 ( 1 3 0 0 m g t wice 
wee kl y ) a n d will still be safel y bel o w t hat o bser ve d at t he N O A E L.  
A n y a dj ust me nt i n d ose will be disc usse d a n d c o nfir me d i n writi n g b y t he s p o ns or. I n t he e v e nt 
of a d ose a dj ust me nt, pr otei n uria le vels will be m o nit ore d bi wee kl y  ( wit h u nsc he d ule d 
assess me nts, if necessar y) f or at least 4 wee ks t o assess t he i m pact of t he d ose a dj ust me nt. I n t h e 
e ve nt t hat t he d ose is a dj uste d, t he n a ne w d osi n g sc he d ule will be esta blis he d f or t hat patie nt. 
Fi g ure  A 1 : 
O bser ve d a n d Pre dicte d P K P r ofiles f or Pe g cet ac o pl a n 
 
A b bre viati o ns: c y n o  = c y n o m ol g us m o n ke y ; H V = healt h y v ol u nteer; N O A E L  = n o -o bser ve d -a dverse -effect -le vel; P K = p har mac o ki netic; 
P N H  = par o x ys mal n oct ur nal he m o gl o bi n uria  
N ote: P re dicte d P K p r ofiles f or p e gcetac o pla n ( gree n li ne) at t he pla n ne d d ose of 1, 0 8 0 m g t wice wee kl y, c o m pare d t o t he s u m mar y P K data at 
t he N O A E L ( 1 3 C A T X-0 0 4 [ blac k li ne]), o n g oi n g P N H st u d y A P L -C P 0 5 1 4 2 7 0 m g/ da y c o h ort ( bl ue li ne), a n d healt h y v ol u nteer st u d y 
 f or b ot h t he 3 6 0 m g/ da y ( br o w n li ne) a n d 1, 3 0 0 m g t wice wee kl y c o h orts (li g ht bl ue line).  
 
 
 
 
  
 
 
 
 
  
 
  
 
 
 
 
   
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
C CI
C CI

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Confidential 
A1.1.4. 
Part B Long-Term Extension Phase: Study Treatments 
This section contains study treatment information for the Part B Long-Term Extension Phase.  
A1.1.4.1. Part B Identity of Investigational Product 
The test product is pegcetacoplan, which will be provided as a sterile solution of pegcetacoplan 
(54 mg/mL) in acetate-buffered sorbitol, supplied in stoppered glass vials. Additional 
information regarding the investigational product is provided in the pegcetacoplan IB. 
A1.1.4.2. Part B Pegcetacoplan Dosing 
Starting at Week 48, subjects will receive SC infusions pegcetacoplan at a dosage of 1080 mg 
twice weekly. During the course of the study, subjects may be switched to an alternate dosing 
regimen of pegcetacoplan at 1080 mg every 3 days, if warranted, based on clinical response and 
agreement from the sponsor (see Section A1.1.3.2). 
Dosing diaries will be utilized for pegcetacoplan and are to be completed for each dose 
administered at the study site or outside regular clinic visits. Subjects should not deviate from 
their pegcetacoplan dosing schedule: Day 1 and Day 4 of each treatment week (eg, 
Monday/Thursday/Monday) or every 3 days (eg, Monday/Thursday/Sunday).  
A1.1.4.3. Part B Pegcetacoplan Administration 
Pegcetacoplan will be administered as a 20-mL SC infusion. The preferred site of infusion will 
be the abdomen; however, if a subject does not tolerate administration to the abdomen, 
alternative sites may be considered. 
Note: Self-administration may also be conducted by a member of the subject’s household or 
family member, etc. It is not intended to be restricted to the individual subject. Please refer to the 
Study Operations Manual for further details regarding the self-administration qualification. 
A1.1.5. 
Part B Long-Term Extension Phase: Labeling, Packaging, Storage, and 
Handling 
A1.1.5.1. Part B Labeling 
Labels containing study information and pack identification are applied to the investigational 
product(s) container. 
All investigational product is labeled with a minimum of the following: protocol number, dosage 
form (including product name and quantity in pack), route of administration, directions for use, 
storage conditions, batch number, and/or packaging reference; the statements, “For clinical trial 
use only,” and/or “CAUTION: New Drug – Limited by Federal (or US) Law to Investigational 
Use,” and name/address of sponsor. 
Space is allocated on the label so that the site representative can record a unique subject 
identifier and date dispensed by the site to the subject. 
Additional labels may, on a case-by-case basis, be applied to the investigational product in order 
to satisfy national, local, or institutional requirements, but it must not: 
• Contradict the clinical study label 

Pegcetacoplan (APL‑2) 
APL2-201 Protocol Amendment 7 
07 July 2022 
Apellis Pharmaceuticals, Inc 
Page 84 
 
Confidential 
•
Obscure the clinical study label
•
Identify the study subject by name
Additional labels may not be added without the sponsor’s prior full agreement. 
A1.1.5.2. Part B Packaging 
Investigational product is supplied in 20-mL glass vials. 
Changes to sponsor-supplied packaging prior to dosing may not occur without full agreement, in 
advance, by the sponsor. 
A1.1.5.3. Part B Infusion Supplies 
The sponsor will supply syringes, vial adapters, infusion sets, and ambulatory syringe infusion 
pumps, as required. Refer to the Study Operations Manual for further details. 
A1.1.5.4. Part B Storage 
The investigational product should be stored refrigerated at 2-8 °C. 
The investigator has overall responsibility for ensuring that investigational product is stored in a 
secure, limited-access location. Limited responsibility may be delegated to the pharmacy or 
member of the study team, but this delegation must be documented. 
A pharmacist or appropriately qualified designated person will be responsible for storing the 
investigational product at the site appropriately and dispensing the vials of investigational 
product to the subject. The pharmacist/nominated team member will enter the unique subject 
identifier on the investigational product bottle/carton labels, as they are distributed. 
Temperature monitoring is required at the investigator site (or documented storage location) to 
ensure that the investigational product is maintained within an established temperature range. 
The investigator is responsible for ensuring that the temperature is monitored at the site 
throughout the duration of the study and that records are maintained. 
The investigational product should be transported from the clinic to the subject’s residence as 
described in the pharmacy manual, using the preconditioned phase change material plates and 
cooler bags. Temperature monitoring will not be required during transport or at the subject’s 
residence, but a log will be kept for every infusion to ensure that all investigational product was 
kept refrigerated.  
With sponsor prior approval, investigational product and/or ancillary supplies may be shipped 
from the study site to a subject’s designated location. Such shipments will only be implemented 
at sites where this activity is approved by the IRB/EC and health authority (if required). Subject 
consent will be required prior to any subject information being provided to a courier. The 
responsibility to return both empty vials and any unused investigational product shall remain 
unchanged, as described in Section 12.5.