A Single Arm Multiple Dose Study to Assess the Efficacy and Safety of ANB019 in Subjects With Generalized Pustular Psoriasis
Phase: PHASE2
Conditions: Generalized Pustular Psoriasis
Sponsor: Vanda Pharmaceuticals

TITLE PAGE
Protocol Title: 
A Single Arm Multiple Dose Study to Assess the Efficacy and Safety
of ANB019 in Subjects with Generalized Pustular Psoriasis
Protocol Number: 
ANB019-002
Product: 
ANB019
Study Phase: 
2a
Sponsor Name: 
AnaptysBio Inc.
Legal Registered Address: 
10421 Pacific Center Court, Suite 200,
San Diego, CA 92121, United States
Regulatory Agency Identifying Number(s):
Investigational New Drug (IND) number: 136145
National Clinical Trial (NCT) number: NCT03619902
European Clinical Trials Database (EudraCT) Number: 
2017-004021-33
Date of Protocol: 
29 Oct 2019, Amendment 5
Protocol Amendment Number
Date
5
29 October 2019
4
30 August 2019
3
20 March 2019
2
27 July 2018
1
15 January 2018
Original Protocol
12 December 2017
CONFIDENTIALITY STATEMENT
The information contained in this document is the property of AnaptysBio, Inc. and is confidential. This 
information may not be disclosed, reproduced, or distributed to anyone other than personnel directly 
involved in the conduct of the study and in response to a relevant Institutional Review Board and review 
by a Regulatory Authority as required by the applicable laws and regulations, without the written 
authorization of AnaptysBio, Inc. These restrictions will continue to apply after the study has closed.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
3
INVESTIGATOR SIGNATURE PAGE:
I confirm that I have read and approved this protocol in its entirety and will comply with the 
obligations as detailed in all applicable regulations and guidelines (eg, ICH GCP guidelines) and 
the protocol.
Name 
 
Date
Title 

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
4
TABLE OF CONTENTS
INVESTIGATOR SIGNATURE PAGE: ..............................................................................3 
TABLE OF CONTENTS ........................................................................................................4 
TABLE OF TABLES...............................................................................................................7 
1.0 
PROTOCOL SUMMARY ..........................................................................................8 
1.1 
Synopsis.............................................................................................................8 
1.2 
Study Schema .................................................................................................12 
1.3 
Schedule of Activities.....................................................................................13 
2.0 
INTRODUCTION......................................................................................................16 
2.1 
Study Rationale..............................................................................................16 
2.2 
Background ....................................................................................................17 
2.2.1 
Nonclinical Studies............................................................................17 
2.2.2 
Clinical Studies..................................................................................18 
2.3 
Benefit/Risk Assessment................................................................................19 
3.0 
OBJECTIVES AND ENDPOINTS ..........................................................................22 
4.0 
STUDY DESIGN........................................................................................................24 
4.1 
Overall Design................................................................................................24 
4.2 
Scientific Rationale for Study Design...........................................................25 
4.3 
Justification for Dose.....................................................................................25 
4.4 
End of Study Definition.................................................................................25 
4.5 
Study Stopping Criteria ................................................................................25 
4.5.1 
Stopping Criteria for Individual Subjects..........................................25 
4.5.2 
Criteria for Stopping the Study..........................................................26 
5.0 
STUDY POPULATION ............................................................................................27 
5.1 
Inclusion Criteria...........................................................................................27 
5.2 
Exclusion Criteria..........................................................................................28 
5.3 
Lifestyle Considerations................................................................................30 
5.4 
Screen Failures...............................................................................................30 
6.0 
STUDY TREATMENT .............................................................................................32 
6.1 
Study Treatment Administered....................................................................32 
6.2 
Preparation/Handling/Storage/Accountability ...........................................33 
6.3 
Measures to Minimize Bias: Randomization and Blinding........................34 
6.4 
Study Treatment Compliance.......................................................................34 
6.5 
Concomitant Therapy....................................................................................34 

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
5
6.5.1 
Rescue Medicine ...............................................................................35 
6.6 
Dose Modification ..........................................................................................35 
6.7 
Treatment After the End of the Study.........................................................35 
7.0 
DISCONTINUATION OF STUDY TREATMENT AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ................................................................36 
7.1 
Discontinuation of Study Treatment............................................................36 
7.1.1 
Temporary Interruption .....................................................................36 
7.1.2 
Re-challenge......................................................................................36 
7.2 
Subject Discontinuation/Withdrawal from the Study................................36 
7.3 
Lost to Follow-up ...........................................................................................37 
8.0 
STUDY ASSESSMENTS AND PROCEDURES....................................................38 
8.1 
Efficacy Assessments .....................................................................................38 
8.1.1 
Clinical Global Impression................................................................38 
8.1.2 
Modified Japanese Dermatology Association (JDA) Severity 
Index..................................................................................................38 
8.1.3 
Psoriasis Area Severity Index (Only in Subjects With PP)...............39 
8.1.4 
Generalized Pustular Psoriasis Physician’s Global 
Assessment Scale...............................................................................39 
8.1.5 
Dermatology Life Quality Index .......................................................39 
8.2 
Safety Assessments.........................................................................................39 
8.2.1 
Physical Examinations.......................................................................39 
8.2.2 
Chest X-ray........................................................................................40 
8.2.3 
Height and Weight.............................................................................40 
8.2.4 
Vital Signs .........................................................................................40 
8.2.5 
Electrocardiograms............................................................................40 
8.2.6 
Photography.......................................................................................40 
8.2.7 
Clinical Safety Laboratory Assessments ...........................................41 
8.2.8 
Telephone Contact.............................................................................41 
8.3 
Adverse Events...............................................................................................41 
8.3.1 
Time Period and Frequency for Collecting AE and SAE 
Information........................................................................................42 
8.3.2 
Method of Detecting AEs and SAEs.................................................42 
8.3.3 
Follow-up of AEs and SAEs .............................................................42 
8.3.4 
Regulatory Reporting Requirements for SAEs .................................42 
8.3.5 
Pregnancy ..........................................................................................43 
8.3.6 
Adverse Events of Special Interest....................................................43 
8.3.7 
Infusion-related Adverse Events .......................................................43 
8.3.8 
Disease-related Events and/or Disease-related Outcomes Not 
Qualifying as AEs or SAEs ...............................................................44 
8.4 
Treatment of Overdose..................................................................................44 
8.5 
Pharmacokinetics...........................................................................................45 
8.6 
Pharmacodynamics........................................................................................46 
8.7 
Genetics...........................................................................................................46 
8.8 
Biomarkers .....................................................................................................46 

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
6
8.9 
Immunogenicity Assessments .......................................................................47 
8.10 
Health Economics or Medical Resource Utilization and Health 
Economics .......................................................................................................47 
9.0 
STATISTICAL CONSIDERATIONS .....................................................................48 
9.1 
Statistical Hypotheses....................................................................................48 
9.2 
Sample Size Determination ...........................................................................48 
9.3 
Populations for Analyses...............................................................................48 
9.4 
Statistical Analyses.........................................................................................48 
9.4.1 
Subject Disposition............................................................................49 
9.4.2 
Subject Characteristics and Medical History ....................................49 
9.4.3 
Concomitant Medication ...................................................................50 
9.4.4 
Efficacy Analyses..............................................................................50 
9.4.5 
Safety Analyses .................................................................................51 
9.4.6 
Immunogenicity Analyses.................................................................52 
9.4.7 
Pharmacokinetic/Pharmacodynamic Analyses..................................53 
9.4.8 
Exploratory Biomarker Analyses ......................................................53 
9.4.9 
Missing Data......................................................................................54 
9.5 
Interim and Final Analyses...........................................................................54 
10.0 
REFERENCES...........................................................................................................55 
11.0 
APPENDICES............................................................................................................57 
Appendix 1 
Abbreviations...................................................................................58 
Appendix 2 
Regulatory, Ethical, and Study Oversight Considerations..........60 
Appendix 3 
Clinical Laboratory Tests ...............................................................67 
Appendix 4 
Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting.....................................69 
Appendix 5 
Excluded Medications/Therapy .....................................................73 
Appendix 6 
Contraceptive Guidance and Collection of Pregnancy 
Information.....................................................................................................74 
Appendix 7 
Genetics ............................................................................................78 
Appendix 8 
Clinical Global Impression .............................................................79 
Appendix 9 
Modified Japanese Dermatological Association (JDA) 
Severity Index.................................................................................................80 
Appendix 10 
Psoriasis Area Severity Index Score (PASI) .................................81 
Appendix 11 
Generalized Pustular Psoriasis Physician Global 
Assessment Scale ............................................................................................82 
Appendix 12 
Dermatology Life Quality Index ....................................................83 
Appendix 13 
Summary of Changes ......................................................................85 

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
7
TABLE OF TABLES
Table 1 
Study Treatment Details ..................................................................................33 
Table 2 
PK/ADA Sample Collection and Timepoints..................................................46 
Table 3 
Analysis Sets....................................................................................................48 
Table 4 
Study Administrative Structure........................................................................62 
Table 5 
Protocol-required Safety Laboratory Assessments..........................................67 
Table 6 
List of Excluded Medications..........................................................................73 

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
8
1.0
PROTOCOL SUMMARY
1.1
Synopsis
Protocol Title: A Single Arm Multiple Dose Study to Assess the Efficacy and Safety of ANB019 in 
Subjects with Generalized Pustular Psoriasis
Rationale:
This study is designed to evaluate the efficacy and safety of multiple doses of ANB019 in subjects with 
generalized pustular psoriasis (GPP). Generalized pustular psoriasis is a severe, debilitating, and 
life-threatening systemic inflammatory disease (Marrakchi 2011, Benjegerdes 2016). The interleukin-36
(IL-36) pathway, by promoting inflammatory responses, has been shown to play a key role in 
pathogenesis of GPP.
In individuals with a normal IL-36/interleukin-36 receptor (IL-36R) axis, the action of the IL-36
cytokines is counter-balanced by IL-36Ra, an IL-36 receptor antagonist. This natural antagonist reduces 
excessive IL-36 response by blocking the binding of IL-36 agonist ligands to the IL-36R.
Several studies have identified IL-36RN mutations, the gene coding for IL-36Ra, in a subset of GPP 
patients (Marrakchi 2011; Onoufriadis 2011; Sugiura 2012; Capon 2013, Navarini 2017). These mutations 
disrupt the inhibitory function of IL-36Ra, leading to uncontrolled IL-36R activation. Other genetic 
defects have also been associated with GPP, including mutations in the AP1S3 and CARD14 genes (Mahil 
2016; Jordan 2012; Farooq 2013). Regardless of the presence of known mutations, activation of IL-36
pathway has been associated with sustained inflammatory response in GPP suggesting a key role of IL-36
in inflammatory skin diseases.
Currently, there is no approved and registered marketed therapy for GPP. Present treatment options are 
limited to existing plaque psoriasis and systemic immunomodulatory therapies, which have limited 
efficacy in GPP (Benjegerdes 2016). The investigational product, ANB019, is a monoclonal antibody
(mAb) that specifically binds to IL-36R and antagonizes IL-36 signaling. Therefore, inhibition of IL-36
signaling by blocking IL-36R may provide a novel strategy to control the pathological inflammatory 
cascade driven by the IL-36 pathway in patients with GPP. The information obtained from this study may 
provide important insights into potential new treatment options for GPP.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
11
Subjects who are nonresponders will be early terminated 4 weeks after the 750 mg IV dose 
administration. Refer to Section 4.1 for the definition of a nonresponder.
Subject’s disease activity (response to study treatment) will be evaluated using the CGI, JDA, GPPPGA
scale, total BSA, DLQI, and PASI (if plaque psoriasis is present) (Oji 2015; Navarini 2017).
Serum samples for PK and immunogenicity will be collected prior to administration of ANB019 and at 
the other time points specified in the Schedule of Activities (see Section 1.3). In addition, blood samples 
for genetic analysis and a punch biopsy will also be taken during the study. All subjects enrolled in the 
study will be asked to participate in the skin biopsy and/or genetic analysis; however, subject participation 
is optional.
Safety assessments including AE/SAE monitoring, vital signs, physical examination, ECGs, laboratory 
measurements, and urine assessments will be performed during the study period.
The End of Study (EOS) Visit will be on Day 169 and all subjects will return to the study center for the 
EOS procedures (see Section 1.3).
Number of Investigators and Study Centers:
Approximately 8-10 Investigators and 8-10 study centers are expected to participate in this study.
Number of Subjects:
The sample size is not based on statistical power considerations.
Approximately 10 subjects will be enrolled at 8-10 study centers.
Treatment Groups and Duration:
The study will have a screening period of up to 42 days (6 weeks), treatment period of 12 weeks, and
follow-up period of 12 weeks.
Eligible subjects will receive 750 mg IV (1-hour duration) of ANB019 in an open-label manner in 
polyvinyl chloride or polyolefin bags following dilution to a total volume of 100 mL with 0.9% sodium 
chloride followed by 3 doses of 100 mg SC administered on Days 29, 57, and 85.
Statistical Methods:
The default summary statistics for continuous variables includes number of contributing observations (n), 
mean, standard deviation (SD), median, minimum, and maximum.
For categorical variables, the number and percentage (the percentage of subjects in each category relative 
to the total number of subjects in the relevant analysis population or relative to the total number of 
subjects in the relevant analysis population, with assessments available [where appropriate]) in each 
category will be the default summary presentation.
For primary and secondary continuous endpoints, change from Baseline will be evaluated where possible. 
Actual and change in data from baseline will be summarized descriptively for each treatment.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
12
Frequency and percentages for each response Yes/No will be presented separately by visit. A shift table 
of change from Baseline to EOS will be displayed for each score.
For safety and tolerability, AEs, SAEs, vital signs, physical examinations, and laboratory assessments at 
specific time points will be evaluated. All safety data will be summarized descriptively. Number and 
percentage of AEs will be presented for each treatment by preferred term and system organ class of the 
current Medical Dictionary for Regulatory Authorities (MedDRA) dictionary. Individual listings of all 
SAEs and AEs leading to discontinuation from the study drug will be summarized using the current 
MedDRA dictionary. Similar analyses will be performed for potential significance and clinical 
importance of AEs.
Summaries and listings of data for vital signs, hematology, biochemistry, and urinalysis laboratory tests 
will be presented. Appropriate descriptive statistics will be summarized for the observed value at each 
scheduled assessment and for the corresponding change from Baseline. Baseline will be the last 
assessment before ANB019 dosing.
The PK of ANB019 will be evaluated by assessment of drug concentrations in serum. These drug 
concentrations will be listed and summarized for each sampling time point using appropriate 
descriptive statistics. The PK parameters will be summarized using appropriate descriptive 
statistics. Attainment of steady state will be graphically evaluated over the sampling period for 
the IV/SC treatment regimen.
An interim analysis will be performed when approximately 50% of subjects have completed their 
Week 4 visit or when at least 2 subjects have reached 16 weeks postdosing. The interim analysis 
will assess primary efficacy and all safety data.
1.2
Study Schema
Abbreviations: BSL = baseline; IV = intravenous, SC = subcutaneous.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
13
1.3
Schedule of Activities
Screening
Period
Treatment Period
Follow-up Period
Procedure
(up
to -42 day
s prior to 
D1/W-0)
D1
W0
D3
W1
D8
W1
D15
(±1)
W2
D22
(±1)
W3
D29
(±2)
W4
D36
(±2)
W5a
D43
(±2)
W6
D50
(±2)
W7a
D57
(±2)
W8
D64
(±2)
W9a
D71
(±2)
W10
D78
(±2)
W11a
D85
(±2)
W12
D113
(±2)
W16
D141
(±2)
W20
D169
(±2)
W24/EOS/
ETb
Informed consent
X
Inclusion/exclusion 
criteria
X
X
Medical history and prior 
medications
X
Heightc and weight
X
X
CGIj
X
X
X
X
X
X
X
X
X
X
X
X
Modified JDA, DLQId,n
X
X
X
X
X
X
X
X
X
X
X
X
X
X
GPPPGAd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PASI if plaque psoriasis is 
presentd,n
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Serum cytokinesl
X
X
X
X
X
X
X
X
Complete physical 
examinatione,l
X
X
X
X
X
X
X
12-lead electrocardiogramf
X
X
X
X
X
Vital signsg
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Safety laboratory testingh,l
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Quantiferon®-TB Gold 
Testh,l
X
Virologyh,l
X
Chest x-rayn
X
Urinalysish,l
X
X
X
X
X
X
X

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
14
Screening
Period
Treatment Period
Follow-up Period
Procedure
(up to -
42 days 
prior to 
D1/W-0)
D1
W0
D 3
W1
D8
W1
D15
(±1)
W2
D22
(±1)
W3
D29
(±2)
W4
D36
(±2)
W5a
D43
(±2)
W6
D50
(±2)
W7a
D57
(±2)
W8
D64
(±2)
W9a
D71
(±2)
W10
D78
(±2)
W11a
D85
(±2)
W12
D113
(±2)
W16
D141
(±2)
W20
D169
(±2)
W24/EOS
/ETb
Serum pregnancy testh
X
X
Urine pregnancy test
(WOCBP only)h
X
X
X
X
X
X
FSH (postmenopausal 
woman aged over 45 
years with at least 1 year 
of amenorrhea only)h
X
Samples for PKj,l
X
X
X
X
X
X
X
X
X
X
X
X
X
Skin biopsiesk
X
X
Photography
X
X
X
Whole blood for DNA 
samplingm
Xj,k
Whole blood for mRNA 
samplingm
Xj,k
Xk
Blood collection for 
ADAn
X
X
X
X
X
Telephone contact only
X
X
X
X
ANB019 administrationo
X
X
X
X
AEs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medication
Xo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Abbreviations: ADA = anti-drug antibody; AE = adverse event; BSA = body surface area; CGI = Clinical Global Impression; D = day; DLQI = Dermatology 
Life Quality Index; ECG = electrocardiogram; EOS = end of study; ET = early termination, FSH = follicle stimulating hormone; ICF = Informed consent form; 
PASI = Psoriasis Area Severity Index; JDA = Japanese Dermatology Association; PK = pharmacokinetics; QoL = Quality of Life; SAE = serious adverse event; 
TB = tuberculosis; W = week; WOCBP = Woman of childbearing potential.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
15
a.
At Days 36, 50, 64, and 78, subjects will be contacted by phone for safety follow-up to assess for AEs and concomitant medications.
b.
In case of early discontinuation, the subject will be encouraged to return to the study center for the ET/EOS visit (Week 24/Day 169).
c.
Height to be measured at Screening only.
d.
Refer to Section 8.1 for details and instructions regarding CGI, JDA, PASI, total BSA as measured by modified JDA, GPPPGA, and QoL questionnaire 
(DLQI). The QoL questionnaire should be the first assessment completed by the subject before all other assessments at the study center except at the 
screening visit. At the screening visit, the ICF should be signed prior to QoL questionnaire and other study related assessments.
e.
Refer to Section 8.2.1 for details regarding complete physical examination. A complete physical examination will include assessments of general 
appearance; skin; head/neck; pulmonary, cardiovascular, gastrointestinal, external genitourinary, lymphatic, and musculoskeletal system; extremities; 
eyes (inspection and vision control); nose; throat; and neurologic status.
f.
Refer to Section 8.2.5 for details and instructions regarding ECG. In addition to the time points specified in SoA, ECGs may be performed at any time 
during the study if in the opinion of the Investigator it is clinically warranted.
g.
Vital signs assessment includes body temperature, pulse rate, blood pressure, and respiratory rate. Refer to Section 8.2.4 for details and instructions.
h.
Refer to Appendix 3 for details and instructions regarding clinical laboratory parameters and refer to Appendix 6 for the WOCBP definition.
i.
Bidirectional posterioanterior view and lateral view chest x-ray or as indicated by local treatment guidelines or practice will be performed at Screening, 
A chest x-ray is not required if performed within 6 months of Screening.
j.
Refer to Section 8.5 and Table 2 for complete information on sample collection and time points.
k.
Skin biopsies may be performed at other visits as appropriate. All subjects enrolled will be asked to participate in the skin biopsy test and/or genetic 
analysis; however, the subject’s participation is optional. Subjects should provide their consent to participate in skin biopsy and genetic analysis. Punch 
biopsy will be collected on Day 1 (Normal and Psoriatic skin) and Week 16 (psoriatic skin only).
l.
Samples must be collected before study drug administration on Day 1.
m.
Optional whole blood collection for DNA and mRNA requires separate pharmacogenetic informed consent form (ICF).
n.
On Days 1, 29, 57, and 85, all assessments should be performed prior to study treatment administration except for the postdose PK samples on Day 1
(Table 2). The specific order for performing the study procedures is as follows (applicable to all visits): First QoL questionnaires then the efficacy 
assessments, vital signs, physical examination, ECG, and blood sample collection.
o.
Subjects will remain in the study center for approximately 5 hours for the postdose assessments after IV administration and the 3 hours postdose
assessments after the first and second SC injections and will be discharged as per the Investigator’s judgment.
.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
16
2.0
INTRODUCTION
ANB019 is a high affinity humanized IgG4 mAb that specifically binds the interleukin-36
receptor (IL-36R) and antagonizes interleukin-36 (IL-36) signaling. The IL-36 cytokines 
(IL-36α, IL-36β, and IL-36γ) engage with IL-36R to initiate signaling events leading to 
pro-inflammatory responses. IL-36 signaling is counter balanced by IL-36Ra, an IL-36 receptor
antagonist that binds to IL-36R and competes with activity of IL-36 cytokines. Mutations in the
gene encoding the IL-36Ra (IL-36RN) result in uncontrolled activation of the IL-36 pathway 
leading to the development of generalized pustular psoriasis (GPP), a severe and life-threatening 
disease (Marrakchi 2011, Benjegerdes 2016). As such, inhibition of IL-36 signaling, by targeting 
IL-36R with a specific mAb, may represent a novel strategy to control the pathological 
inflammatory cascade driven by the IL-36 pathway activation. ANB019 is being developed as a 
potential first-in-class therapy for GPP, palmoplantar pustular psoriasis (PPP), and other 
inflammatory diseases where the IL-36 pathway might play a pathogenic role.
2.1
Study Rationale
This study is designed to evaluate the efficacy and safety of multiple doses of ANB019 in 
subjects with GPP. Generalized pustular psoriasis is a severe, debilitating, and life-threatening 
systemic inflammatory disease (Marrakchi 2011, Benjegerdes 2016). Skin lesions manifest with 
widespread sterile pustules on erythematous skin over large BSAs. Skin rash is accompanied by 
high fever, general malaise, leukocytosis, elevated C-reactive protein (CRP), and frequently 
includes functional extracutaneous organ involvement that might lead to mortality (Marrakchi 
2011). The IL-36 is associated with acute and chronic inflammation and has been shown to play 
a key role in pathogenesis of GPP. Several studies have identified GPP-associated IL-36RN in a 
subset of GPP patients (Marrakchi 2011; Onoufriadis 2011; Sugiura 2012; Capon 2013, Navarini 
2017). These mutations disrupt the inhibitory function of IL-36Ra, leading to uncontrolled 
IL-36R activation. Other genetic defects have also been associated with GPP, including 
mutations in the AP1S3 and CARD14 genes (Mahil 2016; Jordan 2012; Farooq 2013). Regardless 
of mutations, activation of the IL-36 pathway has been associated with a sustained inflammatory 
response in pustular psoriasis suggesting a key role of IL-36 in inflammatory skin diseases. 
Currently there is no approved therapy for GPP. Treatment options are limited to existing plaque 
psoriasis (PP) and systemic immunomodulatory therapies, which have limited and inconsistent 
efficacy (Benjegerdes 2016). ANB019 is an mAb that specifically binds the IL-36R and 
antagonizes IL-36 signaling. Therefore, inhibition of IL-36 signaling by blocking IL-36R may 
provide a novel strategy to control the pathological inflammatory cascade driven by IL-36
pathway in patients with pustular psoriasis. The information obtained from this study is
considered important for future clinical practice as it may provide important insights into
potential new treatment options for GPP.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
17
2.2
Background
Generalized pustular psoriasis is a severe inflammatory skin disease characterized by the 
presence of widespread pustules covering almost the entire body along with systemic 
inflammatory manifestations, such as fever, leukocytosis, and elevated CRP.
Generalized pustular psoriasis is a rare disease in the US, and although the exact prevalence has 
not been fully estimated, it is considered to affect only a few thousand individuals. The 
prevalence of GPP has been studied in Japan and France and reported as approximately 7.46 and 
1.76 cases per million of the population, respectively (Ohkawara 1996; Augey 2006). Although 
GPP has been associated with psoriasis, it is considered as a distinct disease entity based on 
different pathological pathways. Several studies have identified GPP-associated IL-36RN
mutations in a subset of GPP patients (Marrakchi 2011; Onoufriadis 2011; Sugiura 2012; 
Capon 2013, Navarini 2017). These mutations disrupt the inhibitory function of IL-36Ra, leading 
to uncontrolled IL-36R activation. While a significant proportion of GPP cases are associated 
with deficiency of IL-36Ra, also known as DITRA, approximately 51% to 84% of patients
reported no mutation of the IL-36RN. Other genetic defects have also been associated with GPP, 
including mutations in the AP1S3 and CARD14 genes (Mahil 2016; Jordan 2012; Ohkawara 
1996). Regardless of the presence of known mutations, activation of IL-36 pathway has been 
associated with sustained inflammatory response in GPP suggesting a key role of IL-36 in 
inflammatory skin diseases.
There is no effective and approved treatment for GPP. Recurrent flares are common, even years 
after diagnosis (Benjegerdes 2016, Oji 2015, Navarini 2017). Patients often require continued 
systemic immunomodulatory therapy causing significant and severe AEs. Therefore, inhibition 
of IL-36 by targeting the IL-36R with ANB019 will control excessive activation of the IL-36
pathway and potentially offer a novel and effective treatment for patients with GPP.
2.2.1
Nonclinical Studies
ANB019 has strong inhibitory activity of human as well as the cynomolgus monkey IL-36R. 
Nonclinical data obtained from studies with ANB019 in primary human and cynomolgus 
monkey cells and from in vivo non-human primate studies demonstrated that:
x
ANB019 shows reactivity with human and cynomolgus monkey IL-36R (dissociation 
constant
), but not with mouse or 
rat IL-36R.
x
In primary human and cynomolgus monkey cell populations, keratinocytes, peripheral blood 
mononuclear cells and human whole blood, ANB019 inhibits IL-36R-mediated release of
interleukin-8 (IL-8).
x
The observed serum half-life of ANB019 in cynomolgus monkeys was 304 hours after single 
IV dose administration, and 310 hours after single SC dose administration at 10 mg/kg, with

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
18
bioavailability approximately 76% consistent with the anticipated PK characteristics for a 
human IgG4 scaffold mAb in the monkey.
x
Repeat-dose, Good Laboratory Practice toxicity and toxicokinetic studies of 4 and 13 weeks 
in duration have been conducted with ANB019 administered by weekly SC and IV injection 
to cynomolgus monkeys. There were only minor treatment-related injection site findings in 
the 4-week repeat-dose study. Treatment-related effects in the 13-week toxicity study 
included increased observations of nonformed feces and prolapsed rectum, and protozoa in 
the stomachs of monkeys, the latter being consistent with the mechanism of action of an 
immune-modulator in cynomolgus monkeys (Augey 2006). These studies established a no
observed adverse effect level for males at 60 mg/kg/dose administered IV and for females at 
60 mg/kg/dose administered SC after 13 weeks of dosing.
2.2.2
Clinical Studies
ANB019-001, a first in human Phase I study in healthy subjects and subjects with psoriasis has 
been conducted (ANB019-001 2018).
The Single Ascending Dose (SAD) part of the study enrolled 48 healthy adults and has been 
completed. Six dose levels were administered to 8 subjects in each cohort: 10 mg, 40 mg, 
100 mg, 300 mg, and 750 mg by IV injection and 100 mg by SC injection. After single dose 
administration, ANB019 was generally well tolerated in male and female healthy adults 
18-43 years old. Overall, 40 subjects (83%) experienced at least one treatment-emergent adverse 
event (TEAE). The percentage of subjects who experienced at least 1 TEAE was similar across 
treatment groups: 29 subjects, 81% in ANB019 group and 11 subjects, 92% in placebo. The most 
commonly reported AEs were upper respiratory tract infection (URTI) (28% ANB019, 
50% placebo), headache (28% ANB019, 25% placebo), viral URTI (11% ANB019, 
8% placebo), oropharyngeal pain (8% ANB019, 0% placebo), nausea (8% ANB019, 
0% placebo), tension headache (6% ANB019, 8% placebo), gastroenteritis (6% ANB019, 
0% placebo), herpes simplex (6% ANB019, 0% placebo), acne (6% ANB019, 0% placebo), and 
catheter site pain (6% ANB019, 0% placebo). All other SAEs occurred as single events. The 
majority of TEAEs were mild (73%) and moderate (26%) in severity with exception of 1 severe 
AE of elevated creatine kinase deemed unrelated to study treatment. No subject discontinued the 
study due to AE. There were no SAEs reported in the SAD portion of the study. No clinically 
relevant abnormalities were noted in vital signs, physical examinations, electrocardiograms 
(ECGs), or laboratory parameters.
One subject with PP was enrolled and completed the study as per protocol. This subject received 
a single dose of 750 mg by IV injection. The PP cohort was removed from the study and no 
further subjects were enrolled. No TEAEs were reported for the subject with PP in the SAD part 
of the study.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
19
The Multiple Ascending Dose (MAD) part of the study enrolled 24 healthy adults. Three dose 
levels were administered to 8 subjects in each cohort: 40 mg, 100 mg, and 300 mg by IV infusion 
once a week for 4 weeks. In each cohort, 6 of 8 subjects received ANB019 and 2 subjects 
received placebo. In the MAD part of the study, 19 of 24 subjects (79%) experienced at least 
1 TEAE. Overall, ANB019 was generally well tolerated in healthy adults (20 to 37 years old). 
The TEAEs were reported by 16 of 18 subjects (89%) in the ANB019 treatment group and in 
3 of 6 subjects (50%) in the placebo group following IV infusion once a week for 4 weeks. The 
most common TEAEs were headache (39% ANB019, 17% placebo) and upper respiratory tract 
infection (17% ANB019, 17% placebo). The majority of AEs were mild (83%) and moderate 
(17%) in severity with no severe events reported.
There was no AE leading to study treatment withdrawal reported. One subject developed AE of 
neutropenia 7 days after the last dose of ANB019 100 mg IV with absolute neutrophil count of 
0.7 × 109/L (previously 2.3 × 109/L on Day1, 2.1 × 109/L on Day 7, 2.0 × 109/L on Day 14, and 
2.0 × 109/L on Day 21). The subject was completely well and asymptomatic with no recent 
illness reported. All other laboratory parameters were normal. The absolute neutrophil count
returned to within the normal range 4 days later (3.1 × 109/L) and the subject completed the 
study. The AE was assessed by the Investigator as moderate and related to study treatment.
There were no SAEs reported in the MAD part of the study. No meaningful trends were 
observed in vital signs, physical examinations, ECGs, or laboratory parameters.
The PK data generated after either a single or multiple IV dose administration indicated linear 
PK with area under the concentration-time curve (AUC) increasing in a generally dose 
proportionate manner. The mean maximum observed concentration (Cmax) was 
 
following a single maximum dose of 
 following a single 
administration. The Cmax increased with weekly IV dosing indicating accumulation during the 
4-week dosing period. However, there was little change in serum concentration on Day 29
compared with predose Day 22, indicating that steady state had been achieved after 4 weekly 
doses. The terminal half-life of ANB019 was approximately 597 hours after SC injection and 
between 
 after IV injection.
2.3
Benefit/Risk Assessment
Subjects with GPP may or may not receive direct benefit from participating in this study. Details 
about specific benefits and risks for participants in this clinical trial can be found in the 
Investigator’s Brochure (IB) and ICF.
The safety profile of ANB019 in humans is limited.
ANB019 was well tolerated in healthy male and female adults, and in 1 subject with PP, in first 
in human Phase I study (Australian Study ANB019-001) when administered as single or multiple 
doses, up to 100 mg by SC and 750 mg by IV injection. Overall summaries of TEAEs by 
severity and relationship showed no marked differences between treatments (ANB019 versus

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
20
placebo) and no apparent dose-related trends in subjects following ANB019 administration.
Commonly occurring TEAEs of headache and upper respiratory tract infection occurred in both 
the SAD and MAD parts of the study. There were no death or serious adverse events (SAEs) and 
no subjects withdrawn due to TEAEs.
There has been 1 SAE of sepsis reported in the ongoing ANB019-002 study that was considered
possibly related to the study drug. The subject had a medical history of sepsis and experienced 
the SAE after the 750 mg IV dose administration. Antibiotic treatment rapidly resolved the 
sepsis episode with complete patient recovery.
No major toxicities were observed in the 4-week, repeat-dose toxicity study. The main finding 
consisted of minor, non-adverse, injection site reactions associated with the SC route of 
administration.
Treatment-related effects observed in the 13-week, repeat-dose toxicity study included protozoa 
in the stomach, an increase in nonformed feces and prolapsed rectum observations, the latter was 
not dose-related. The increase in protozoa in the stomach has been observed in monkeys treated 
with immune-modulating drugs (Augey 2006) and is consistent with the putative mechanism of 
action of ANB019. The increased incidence of protozoa, nonformed feces and prolapsed rectum 
were not considered adverse as they responded to veterinarian intervention. Gastrointestinal 
infections are clinically monitorable and, in the case of most protozoa, are readily treatable even 
in the context of immunocompromised individuals (Farthing 2006). One female monkey 
receiving 60 mg/kg ANB019 IV was found moribund on Study Day 34. The cause of the 
moribund nature was not determined and had an uncertain relationship to ANB019 but could be 
due to treatment-related immune-modulation. However, data published on IL-36 R deficient 
humans shows no deleterious effect on general health and normal immune function broadly
preserved, indicating that inhibition of IL-36 R, apart from disease modification, does not 
compromise host defenses. Similar to other immune-modulating treatment paradigms, subjects
should be closely monitored for any gastrointestinal clinical manifestations including infections 
and evaluated on ongoing basis. If a gastrointestinal infection is suspected, the subject should be 
treated as clinically indicated.
As allergic or anaphylactic reactions may occur in subjects treated with mAbs, subjects should 
be observed during and after study drug administration. Subjects with true allergic/anaphylactic 
reactions should not receive further doses of the product.
As ANB019 is an mAb, based on clinical studies with other mAbs, study participants may 
experience symptoms of an apparent allergic reaction to the drug, also known as ‘cytokine 
release syndrome.’ The symptoms of this vary dramatically but can include:
x
Mild to moderate fever, chills, headache, nausea, and vomiting.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
21
x
Moderate to severe signs and symptoms such as edema, hypotension, and pulmonary 
infiltrates (eg, blood and mucus in the lung).
Such reactions should be managed as clinically indicated and according to standard clinical 
practice.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
24
4.0
STUDY DESIGN
4.1
Overall Design
This is an open-label, single arm, multiple dose study to assess the clinical efficacy, as well as 
the safety, tolerability, and PK of multiple doses of ANB019 in subjects with GPP.
The screening period will be up to 42 days (6 weeks) prior to administration of study drug on
Day 1. Written informed consent will be obtained from each subject prior to initiating any study 
related procedures. All screening procedures will be conducted in accordance with the Schedule 
of Activities (see Section 1.3).
On Day 1, subjects who meet the entry criteria will receive a 750 mg IV dose of ANB019 in an 
open-label manner followed by 3 doses of 100 mg SC administered on Days 29, 57, and 85.
Subjects will leave the study center after completion of the 5 hours postdose assessments 
following IV administration and the 3 hours postdose assessments after the first and second SC 
injections and with the Investigator’s approval. Subjects with any ongoing AEs or SAEs at the 
time of scheduled discharge from the study center should remain at the study center until the 
Investigator has determined that these events have resolved or are deemed as not clinically 
significant.
After completing Day 1 assessments, the subjects will return to the study center for follow-up
visits on Days 3, 8, weekly from Day 8 to Day 29, and every other week up to Day 85, and 
monthly for 12 weeks to monitor changes in disease activity, safety, and tolerability. In addition, 
subjects will be contacted via phone by study staff to assess for safety (eg, AEs and changes in 
concomitant medications) on Days 36, 50, 64, and 78.
Subjects who are nonresponders will be early terminated 4 weeks after the 750 mg IV dose 
administration. A nonresponder is defined as:
x
“No change” on CGI: 0 points change in JDA total score and not meeting “other criteria” for 
minimally improved.
x
“Worsened” based on CGI: ≥1-point increase in JDA total score.
Disease activity (response to study treatment) will be evaluated using the CGI scale according to 
the modified JDA severity index, change in total BSA as measured by modified JDA index
affected by GPP, systemic manifestations and laboratory findings as per modified JDA severity 
index, GPPPGA scale, and PASI score (if PP is present). In addition, change in serum cytokines 
(including but not limited to IL-8) will be recorded. Quality of life (QoL) will be assessed using 
the DLQI.
Serum samples for PK and immunogenicity will be collected before the administration of 
ANB019 and at the other time points specified in the Schedule of Activities (see Section 1.3).
Refer to Table 2 for additional information on sample collection and time points. All subjects

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
25
enrolled in the study will be asked to participate in the skin biopsy and/or genetic analysis; 
however, participation is optional and subjects will be asked to give specific consent for these 
assessments.
Safety assessments including AE/SAE monitoring, vital signs measurements, physical 
examination, ECGs, laboratory measurements, and urine assessments will be performed during
the study.
The EOS visit will be on Day 169 and all subjects will return to the study center for the EOS 
procedures (see Section 1.3).
4.2
Scientific Rationale for Study Design
Currently there are no approved treatment modalities for use in subjects with GPP, and there is 
little evidence-based information to guide the management of this severe, life-threatening type of 
psoriasis.
In this context, the development of agents with new mechanisms of action is considered 
important for future clinical practice. This open-label single arm multiple dose study may 
provide evidence-based information about the clinical effect of this novel treatment.
4.3
Justification for Dose
ANB019 will be administered as a single IV dose of 750 mg followed by 3 doses of 100 mg SC 
administered on Days 29, 57, and 85.
The doses selected for this study have demonstrated favorable safety profile and prolonged 
pharmacodynamic activity in a Phase I study (ANB019-001). A loading dose of 750 mg IV will 
be administered on Day 1 to enable steady state concentration to be reached faster at initiation of 
the ANB019 l00 mg SC dose. The 12-week treatment duration is expected to provide adequate 
time to assess the safety and efficacy of ANB019 in subjects with GPP.
4.4
End of Study Definition
A subject is considered to have completed the study if they have completed all protocol specified 
visits including the last visit on Day 169 (see Section 1.3).
The EOS is defined as the date of the last visit of the last subject in the study.
4.5
Study Stopping Criteria
4.5.1
Stopping Criteria for Individual Subjects
Dosing for any individual subject will be stopped if the subject experiences a SAE or a clinically 
significant possibly drug related AE, which in the opinion of the study physician, Investigator, or 
Sponsor’s medical representative, warrants discontinuation of the study for that subject’s 
wellbeing. Details on subject withdrawal are presented in Section 7.0.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
26
4.5.2
Criteria for Stopping the Study
Termination of a study may occur upon decision of the Sponsor, upon decision of the 
Investigator, by request of an authority, because of withdrawal of a positive vote by the 
responsible Independent Ethics Committee (IEC)/Institutional Review Board (IRB); or if new 
safety or efficacy information leads to an unfavorable risk-benefit judgment for any trial 
medication. The Sponsor may discontinue the trial if it becomes unjustifiable for medical or 
ethical reasons, for poor enrollment, or because of discontinuation of clinical development of 
ANB0019 for safety reasons. Furthermore, the Investigator and/or Sponsor have the right to 
close a study center, at any time, after consultation between the involved parties.
The IEC/IRB, the competent authority and the local authority must be informed within 15 days 
of a decision being made. The Investigator is obliged to inform the local authority whereas 
information of the IEC/IRB and competent authority is to be performed by
.
If the study center has to be closed prematurely, 
will provide all essential documents 
necessary for the Sponsor’s Trial Master File as defined in the Note for Guidance on Good
Clinical Practice (GCP) (CPMP/ICH/135/95).
The study will be terminated prematurely in the following cases:
x
If SAEs occur resulting in the risk-benefit ratio not being reasonable anymore.
x
If the pattern of AEs observed in the study interferes significantly with the risk-benefit 
evaluation provided to the Investigator prior to the start of the study.
x
If the number of discontinued subjects is so high or the number of included subjects is so 
low that proper completion of the study could not realistically be expected.
x
If the results of parallel studies show evidence for unacceptable risks.
x
If severe protocol violations and misconduct occur which unacceptably affect the safety 
or rights of the subjects, or render questionable the validity of the study results.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
27
5.0
STUDY POPULATION
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted.
It is imperative that subjects fully meet all of the inclusion criteria and none of the exclusion 
criteria.
5.1
Inclusion Criteria
Subjects are eligible to be included in the study only if all of the following criteria apply:
1. Male and female subjects must be 18 to 75 years of age inclusive, at the time of 
signing the informed consent.
2. Have clinically confirmed diagnosis of active GPP.
3. Have a Japanese Dermatology Association severity index total score of >6 and must
be present with active pustules and erythema accounting for at least 10% of BSA or
have a GPPPGA score of at least moderate severity.
4.
Must be candidates for systemic therapy or phototherapy as assessed by the 
Investigator.
5. Meet the following laboratory screening criteria:
a)
Hemoglobin ≥90 g/L (≥9 g/dL)
b)
White blood cell count ≥3.0 × 109/L (≥3.0 × 103/μL)
c)
Platelets ≥100 × 109/L (≥100 × 103/μL)
d)
Serum creatinine <132.6 μmol/L (<1.5 mg/dL)
e)
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels 
≤1.5× upper limit of normal (ULN)
f)
Total bilirubin ≤1.5 × ULN. Subjects with known Gilbert’s disease who have a
serum bilirubin <3 × ULN may be enrolled
6. Body mass index (BMI) of 18 to 36 kg/m2, inclusive, {BMI = weight (kg)/ [height 
(m)]2}, and total body weight >50 kg (110 lb).
7. Subjects must be otherwise in a good health as judged by the Investigator based on 
medical history, physical examination, ECG, hematology, and chemistry laboratory 
parameters, and urinalysis.
8. Contraceptive use by men or women should be consistent with local regulations 
regarding the methods of contraception for those participating in clinical studies.
Contraception and pregnancy:
x
A male subject must agree to use contraception as detailed in Appendix 6
of this protocol during the treatment period and for at least 220 days (which 
includes the duration of relevant exposure plus the duration of sperm cycle) after 
the study treatment and refrain from donating sperm during this period.
x
Female subjects:

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
28
A female subject is eligible to participate if she has a negative serum pregnancy 
test (beta-human chorionic gonadotropin) at Screening and a negative urine 
pregnancy test at baseline (see Appendix 6), is not breastfeeding, and at least 1 of
the following conditions apply:
i) Not a woman of childbearing potential (WOCBP) as defined in Appendix 6.
OR
ii) A WOCBP who agrees to follow the contraceptive guidance in Appendix 6 during 
the treatment period and for at least 6 months after receiving the study treatment and 
refrain from donating oocytes for assisted reproduction during this period. The female 
subject’s selected form of contraception must be effective by the time the female 
subject enters into the study (eg, hormonal contraception should be initiated at least 
28 days before Day 1).
9. Capable of giving signed informed consent as described in Appendix 2, which 
includes compliance with the requirements and restrictions listed in the ICF and in this 
protocol.
5.2
Exclusion Criteria
Subjects are excluded from participating in the study if any of the following apply:
1. Have other forms of psoriasis (eg, guttate) except PP.
2. Have concomitant dermatological (eg, subcorneal pustular dermatosis, impetigo 
herpetiformis, acute generalized exanthematous pustulosis) or medical conditions 
which may interfere with the Investigator’s ability to evaluate the subject’s response to 
therapy.
3. Have a history of clinically significant (as determined by the Investigator) cardiac, 
pulmonary, neurologic, gastrointestinal, endocrine, hematological, renal, hepatic, 
cerebral or psychiatric disease, or other major uncontrolled disease (a poorly 
controlled medical condition, such as but not limited to, poorly controlled diabetes, 
unstable ischemic heart disease, uncontrolled hypertension (systolic ≥160 mmHg
and/or diastolic ≥95 mmHg based on the average of 2 blood tension measurements),
and moderate to severe heart failure [New York Heart Association Class III/IV]).
4. History of chronic or recurrent infectious disease, including but not limited to chest 
infection (eg, sinusitis, bronchitis, and bronchiectasis), urinary tract infection (eg, 
recurrent pyelonephritis), and skin infection (eg, abscesses, infected skin wounds, or
ulcers) within 24 months prior to Screening.
5. History of a serious infection (eg, hepatitis, pneumonia) that led to hospitalization or 
treatment with IV antibiotics or antiviral treatment for an infection within 3 months 
prior to Screening or any recent infection requiring systemic antibiotic or systemic 
antiviral treatment within 4 weeks of baseline.
6. History or any evidence of active infection within 4 weeks of baseline (eg,
bronchopulmonary, urinary, or gastrointestinal).

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
29
7. Presence of any factors that would predispose the subject to develop infection, eg,
rectal fissures, poor dentition.
8. History of an opportunistic infection (eg, Pneumocystis carinii, aspergillosis, or
mycobacteria other than tuberculosis [TB]), parasitic infections, including, but not 
limited to,, helminths, protozoa, Trypanosoma cruzi within 6 months of screening.
9. History of a herpes zoster infection within 2 months prior to screening.
10. Known or suspected autoimmune disorder, including but not limited to rheumatoid 
arthritis, fibromyalgia, systemic lupus erythematosus, polymyalgia rheumatica, giant 
cell arteritis, Bechet’s disease, dermatomyositis, multiple sclerosis, moderate to severe 
asthma, or other severe forms of atopy, any autoimmune vasculitis, autoimmune 
hepatitis, or any other active autoimmune disease for which a subject requires medical 
follow-up or medical treatment.
11. Any history of known or suspected congenital or acquired immunodeficiency state or 
condition that would compromise the subject’s immune status (eg, history of 
splenectomy).
12. Any major surgery within 4 weeks of study drug administration.
13. Malignancy or history of malignancy within 5 years, except for treated basal cell or 
squamous cell in situ carcinomas of the skin or squamous cell carcinomas deemed by 
the Principle Investigator to be fully treated.
14. History of any significant drug allergy or reaction (such as anaphylaxis or 
hepatotoxicity) and reactivity to 
, a component of ANB019 formulation, 
or the inactive ingredients (excipients).
a) Have taken the following drugs within the specified period prior to Screening or
Baseline:Topical medication (including corticosteroid, retinoids or vitamin A or D
analog preparations, tacrolimus, calcineurin inhibitor, topical H1 and H2 
antihistamines, tar preparations, topical antimicrobials, other medicated topical 
agents) or herbal preparation within 2 weeks prior to baseline.
b) Systemic therapy including but not limited to cyclosporine, methotrexate, 
acitretin, alitretinoin, fumaric acid esters, corticosteroids or any other 
immunosuppressant or immunomodulation drugs within 4 weeks prior to baseline. A
tapering washout of systemic therapies (eg, cyclosporine, methotrexate, and retinoids) 
can be used and the study drug can be introduced before the end of the washout 
period.
c) Phototherapy ie, ultraviolet light B and photochemotherapy (eg, psoralen and 
ultraviolet A [PUVA]) within 4 weeks prior to baseline.
d) Previous treatment with anti-tumor necrosis factor/interleukin (IL-12/IL-23) and 
IL-17 or any other mAbs is not allowed within 3 months or 5 half-lives or twice the 
duration of the biological effect of the product prior to baseline.
e)
Live attenuated vaccine within 12 weeks of screening and during the study.
f)
Any investigational drug within 4 weeks or 5 half-lives, whichever is longer, of
screening.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
30
g) Antibiotic or antiviral medication within 4 weeks of baseline.
15. Topical bland emollients (without pharmacological active ingredients) for pustular 
psoriasis are allowed during the study, except within 24 hours prior to the study visits. 
Rescue medication will be directed by the Investigator as needed. (Refer Section
6.5.1).
16. History of active TB or latent TB infection as indicated by a positive 
QuantiFERON®-TB Gold test at Screening or within 6 months prior to Day 1 (If the 
test is indeterminate, it can be repeated only once), chest x-ray, and/or clinical 
examination or has had active TB disease at any time in the past.
17. History of drug, alcohol, or other substance abuse, or other factors (eg, excessive 
caffeine use) limiting the ability to cooperate and to comply with the study protocol, as 
determined by the Investigator.
18. Pregnant or lactating females, or females who intend to become pregnant during the 
study period.
19. Donation of blood to a blood bank or in a clinical study (except at the Screening Visit)
within 4 weeks of study drug administration (within 2 weeks for plasma only).
20. Blood transfusion within 4 weeks of study drug administration.
21. Inability to tolerate IV drug administration.
22. Any other physical, mental, or medical conditions, which, in the opinion of the 
Investigator, make study participation inadvisable or could confound study 
assessments.
23. Clinically significant abnormality on chest x-ray at Screening or within 6 months prior 
to Screening.
24. Clinically significant abnormalities on 12-lead ECG at Screening.
25. Evidence of clinically significant abnormality in urinalysis as determined by the 
Investigator.
26. Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or HIV-1 or 
HIV-2 antibodies.
5.3
Lifestyle Considerations
Exposure to sunlight should be avoided during the study.
5.4
Screen Failures
Screen failures are defined as subjects who consent to participate in the clinical study but are not 
subsequently enrolled in the study. A minimal set of screen failure information is required to 
ensure transparent reporting of screen failure subjects to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory authorities. 
Minimal information includes demography, screen failure details, eligibility criteria, and any 
SAE.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
31
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once after discussion with Medical Monitor. Rescreened subjects should not be 
assigned the same subject number as for the initial screening.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
32
6.0
STUDY TREATMENT
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or
medical device(s) intended to be administered to a subject according to the study protocol.
6.1
Study Treatment Administered
Eligible subjects will receive 750 mg of ANB019 IV in an open-label manner followed by 
3 doses of 100 mg SC administered on Days 29, 57, and 85.
Due to the potential for infusion reactions with protein drugs, ANB019 should be administered in 
an environment under close supervision of a physician and where full resuscitation facilities are 
immediately available. Allergic/anaphylactic reactions and infusion-related reactions typically 
begin during, or within several hours of dose administration. The onset of symptoms may be 
rapid, and some reactions may be life-threatening. The study treatment should be immediately 
stopped and permanently withdrawn in case of severe allergic/anaphylactic reactions. For 
treatment of allergic reactions, current local standard of care guidelines should be followed.
Study treatment details are provided in Table 1.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
33
Table 1
Study Treatment Details
Study Treatment Name:
ANB019
(anti-interleukin-36 receptor [IL-36R] monoclonal antibody)
Dosage Formulation:
The drug product is formulated as 
Study Treatment Description
ANB019 drug product is a sterile, clear to slightly opalescent and 
colorless to yellow solution supplied in a single-use, 2R, Type I 
glass vial with a 
Unit Dose Strength(s)/Dosage Level(s):
A dose of 750 mg/
intravenously (IV) followed by 3 doses 
of 100 mg/mL subcutaneously (SC) administered on Days 29, 57, 
and 85.
Route of Administration
IV infusion (1 dose) and SC injections (3 doses).
Dosing Instructions:
ANB019 will be administered to subjects by IV infusion in 
polyvinyl chloride or polyolefin bags following dilution to a total 
volume of 
 with sterile normal saline (0.9% NaCl).
Infusions will be administered over 
. The infusion may be 
slowed or interrupted for subjects experiencing infusion-related 
AEs.
For SC injections, ANB019 should be prepared by drawing up the 
required dosing volume into suitable sized syringe and attaching a 
dosing needle. No further dilution is required. Subjects receiving 
ANB019 will receive 
(100 mg) SC injection. The injections 
should be rotated with each dose and should not be given into 
moles, scars, tattoos or areas where the skin is tender, bruised, red, 
hard, or not intact. Abdominal administration is the preferred site 
for SC doses.
6.2
Preparation/Handling/Storage/Accountability
1. The Investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study treatment received and any discrepancies 
are reported and resolved before use of the study treatment.
2. Only subjects enrolled in the study may receive study treatment and only authorized 
study center staff may supply or administer study treatment. All study treatments must 
be stored in a secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions with access limited 
to the Investigator and authorized study center staff.
3. ANB019 vials must be refrigerated at 2°C to 8°C (36°F to 46°F) until the day of use. 
ANB019 should not be used beyond the re-test or expiration date provided by the 
manufacturer. Vial contents should not be frozen or shaken. ANB019 vials may be 
stored at room temperature (8°C to 25°C [46°F to 77°F]) in a diluted or undiluted state 
for up to a maximum of
. Once ANB019 has been diluted with sterile 0.9% 
NaCl, the solution may be stored at room temperature (8°C to 25°C [46°F to 77°F]) for 

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
34
up to
. Vials are intended for single-use only; therefore, any remaining solution 
should be discarded.
4. The Investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study treatment accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records).
5. Further guidance and information for the final disposition of unused study treatment 
are provided in the Pharmacy Manual.
The Investigator, a member of the study center staff, or a hospital pharmacist must maintain an 
adequate record of the receipt and distribution of all study drug using the Drug Accountability 
Form. These forms must be available for inspection at any time.
6.3
Measures to Minimize Bias: Randomization and Blinding
This section is not applicable as this is an open-label study.
6.4
Study Treatment Compliance
The prescribed dosage, timing, and mode of administration may not be changed except in cases 
of infusion-related AEs, the study drug administration may be slowed or interrupted. Any 
departures from the intended regimen must be recorded in the electronic case report forms 
(eCRFs). Infusion start date/time and infusion end date/time will be documented in the subject’s
eCRF. Any infusion interruptions (stop date/time and restart date/time), changes in infusion rate,
and/or incomplete dose administration will also be documented in the subject’s eCRF.
6.5
Concomitant Therapy
Any medication or vaccine (including over-the-counter or prescription medicines, vitamins,
and/or herbal supplements) that the subject is receiving at the time of enrollment and receives 
during the study must be recorded on the eCRF along with:
x
Reason for use.
x
Dates of administration including start and end dates.
x
Dosage information including dose and frequency.
In addition, all prior medications used to treat GPP disease conditions and any other medications 
taken within 6 months prior to enrollment must be recorded in the eCRF. The concomitant 
treatments for other indications that are not listed in the prohibited medication section must be on 
a stable dose for at least 4 weeks before study treatment administration. Dose adjustments of 
these treatments should be avoided during the study.
The Medical Monitor should be contacted if there are any questions regarding concomitant or 
prior therapy.
Treatment with bland emollients (without pharmacological active ingredients) will be permitted 
throughout the trial, except within 24 hours prior to the study visits.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
35
A list of excluded medications/therapy is provided in Appendix 5.
6.5.1
Rescue Medicine
Rescue medication will be directed by the Investigator as needed. Rescue medication in the form 
of topical corticosteroids (eg, betamethasone valerate ointment and cream, mometasone furoate 
ointment and cream) can be used during the study for a period of up to 1 week on a daily basis 
on affected areas to provide symptomatic relief. The introduction of any rescue medication must 
be communicated and discussed with the Medical Monitor. Rescue medication will be provided 
by the site and reimbursed by the Sponsor.
The use of rescue medications should be delayed, if possible, for at least 1 month following the 
administration of study treatment. Rescue medication may be used at the Investigator’s 
discretion only if medically indicated for the wellbeing of the subject. The date and time of
rescue medication administration as well as the name and dosage regimen of the rescue 
medication must be recorded.
The addition of any systemic psoriasis medication that is likely to impact psoriasis signs and 
symptoms (eg, cyclosporine, methotrexate, and retinoid) will require the subject to be withdrawn 
from the study.
6.6
Dose Modification
No dose modification is allowed in this study. Study treatment can be interrupted temporarily 
only once or permanently if deemed necessary as per the Investigator’s discretion. Refer to 
Section 7.1.
6.7
Treatment After the End of the Study
All subjects will return to the study center for the EOS (Day 169) or ET visit for final safety and 
EOS assessments. After this visit, subjects should be treated according to the Investigator’s 
clinical judgment. Care after EOS/ET will not be provided by AnaptysBio Inc. Any significant 
AE which in the opinion of the Investigator is related to the study drug, SAE, or pregnancy 
occurring through the EOS visit and should be reported to the
 Safety team (see 
Appendix 4) and followed-up until outcome.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
36
7.0
DISCONTINUATION OF STUDY TREATMENT AND
SUBJECT DISCONTINUATION/WITHDRAWAL
7.1
Discontinuation of Study Treatment
Discontinuation from study treatment will require subjects to discontinue from the study. Study 
treatment may be interrupted only once during the study for an AE at the Investigator’s 
discretion.
7.1.1
Temporary Interruption
Only one dose of study treatment may be interrupted temporarily in the case of an AE per the 
Investigator’s discretion. The Medical Monitor and the Sponsor should be informed of all details 
pertaining to the decision. Study drug may be resumed at the next scheduled dosing visit after 
discussion with the Medical Monitor. In the case of a recurring or new AE after study treatment 
has resumed, the subject will be early terminated. If a clinically significant finding is identified 
(including, but not limited to changes from baseline) after enrollment, the Investigator or 
qualified designee will determine if any change in subject management is needed. Any new 
clinically relevant finding will be reported as an AE.
7.1.2
Re-challenge
Not applicable for this study.
7.2
Subject Discontinuation/Withdrawal from the Study
A subject may withdraw from the study at any time at his/her own request, or may be withdrawn 
at any time at the discretion of the Investigator for safety, behavioral, compliance, or
administrative reasons.
In case of early withdrawal from the study drug and study, the subject will be required to attend 
the ET visit (see the Schedule of Activities in Section 1.3).Subjects must be withdrawn from the 
study under the following circumstances, any significant AE which in the opinion of the 
Investigator is related to the study drug or SAE, or pregnancy occurring through the EOS visit 
and should be followed-up until outcome:
x
Prior to study treatment administration, the Investigator decides that the subject should be 
withdrawn or is at risk. If this decision is made because of an AE or a clinically significant 
laboratory value, the study drug should not be administered and appropriate measures are to 
be taken. AnaptysBio Inc. and/or
is to be notified immediately.
x
Significant deviation/lack of compliance with protocol other than the use of 
excluded/prohibited medications.
x
Use of any excluded/prohibited medications that in the opinion of the Investigator
necessitates the subject being withdrawn (Appendix 5).
x
Termination of the study by the Investigator or Sponsor.
x
Pregnancy (Appendix 6 and Section 8.3.5 Pregnancy).

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
37
x
New information suggests taking part in the study may not be in the participant’s best 
interest.
If the subject withdraws consent for disclosure of future information, the Sponsor may retain and 
continue to use any data collected before such a withdrawal of consent.
If a subject withdraws from the study, he/she may request destruction of any samples taken and 
not tested, and the Investigator must document this in the study center study records.
See Schedule of Activities (Section 1.3) for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed.
Subjects withdrawing from the study prematurely for reasons other than a study drug related AE 
may be replaced at the discretion of the Investigator and Sponsor to ensure the required number 
of evaluable subjects.
7.3
Lost to Follow-up
A subject will be considered lost to follow-up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study center.
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit:
x
The study center must attempt to contact the subject and reschedule the missed visit as soon 
as possible and counsel the subject on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the subject wishes to and/or should continue in the 
study.
x
Before a subject is deemed lost to follow-up, the Investigator or designee must make every 
effort to regain contact with the subject (where possible, 3 telephone calls and, if necessary, a
certified letter to the subject’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the subject’s medical record.
x
Should the subject continue to be unreachable, he/she will be considered to have withdrawn 
from the study.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
38
8.0
STUDY ASSESSMENTS AND PROCEDURES
x
Study procedures and their timing are summarized in Section 1.3.
x
Protocol waivers or exemptions are not allowed.
x
Immediate safety concerns should be discussed with the Medical Monitor and the Sponsor or
designee immediately upon occurrence or awareness to determine if the subject should 
continue or discontinue in the study.
x
Adherence to the study design requirements, including those specified in the Schedule of 
Activities (see Section 1.3), is essential and required for study conduct.
x
All screening evaluations must be completed and reviewed to confirm that potential subjects
meet all eligibility criteria. The Investigator will maintain a screening log to record details of 
all subjects screened and to confirm eligibility or record reasons for screening failure, as 
applicable.
x
Procedures conducted as part of the subject’s routine clinical management (eg, blood count) 
and obtained before signing of the ICF may be utilized for screening or baseline purposes 
provided the procedures met the protocol specified criteria and were performed within the
time frame defined in the Schedule of Activities (see Section 1.3).
x
The maximum amount of blood collected from each subject over the duration of the study, 
including any extra assessments that may be required, will not exceed 204 mL. Repeat or 
unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.
8.1
Efficacy Assessments
It is recommended that the same Investigator/Sub-Investigator complete the scales and 
questionnaires at all time points for a given subject.
8.1.1
Clinical Global Impression
The CGI scale will be used to assess the clinical response to study treatment. The change will be 
categorized as “Very much improved,” “Much improved,” “Minimally improved,” “No change,”
and “Worsened” according to the modified JDA severity index total score (see Appendix 8).
8.1.2
Modified Japanese Dermatology Association (JDA) Severity Index
The modified JDA severity index score will be used for the assessment of the skin lesions, 
assessment of systemic manifestations and laboratory findings, and change in affected BSA of
erythema, pustules, and edema (see Appendix 9).
The total severity score is categorized as Mild (total score: 1 to 6), Moderate (total score: 7 to 
10), or Severe (total score: 11 to 17).

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
39
8.1.3
Psoriasis Area Severity Index (Only in Subjects With PP)
Psoriasis Area Severity Index scores will be used to determine the treatment response in subjects 
with PP. The PASI total score includes plaque characteristics (ie, erythema, induration, scaling), 
percentage of BSA affected and should be calculated by electronic data capture (EDC) (see
Appendix 10).
8.1.4
Generalized Pustular Psoriasis Physician’s Global Assessment Scale
The GPPPGA is a physician-based assessment of the severity of GPP (specifically pustules, 
erythema, and scaling or crusting of pustular psoriasis lesions). Each component is scored on a 5-
point scale, ranging from 0 (least severe) to 4 (most severe) to assess the severity of GPP
(Bachelez 2019; Marrakchi 2019). The average is calculated for scoring.
Subjects will be assessed using the GPPPGA at each study visit (excluding those visits that are 
phone calls). Refer to Appendix 11 for additional information.
8.1.5
Dermatology Life Quality Index
The DLQI Questionnaire will be used to assess treatment response on the subject’s QoL. The 
aim of this questionnaire is to measure how much the skin condition has affected subject’s life 
during the previous week.
Subjects will be asked to recall their experiences during the previous week by responding to 
10 questions. The DLQI will be completed by the subject on a worksheet prior to any safety or 
efficacy evaluations. The questionnaire is self-explanatory and handed to the subject who is 
asked to fill it in without the need for a detailed explanation (see Appendix 12).
8.2
Safety Assessments
Planned time points for all safety assessments are provided in the Schedule of Activities (see
Section 1.3).
8.2.1
Physical Examinations
Complete physical examinations will be performed at the time points indicated in the Schedule 
of Activities (see Section 1.3).
x
A complete physical examination will include assessments of general appearance; skin; 
head/neck; pulmonary, cardiovascular, gastrointestinal, external genitourinary, lymphatic, 
and musculoskeletal system; extremities; eyes (inspection and vision control); nose; throat; 
and neurologic status.
x
A detailed examination of the skin should be performed at the time points indicated in the 
Schedule of Activities for the efficacy assessments (eg, CGI, modified JDA severity index, 
PASI [if PP is present]).
Investigators should pay special attention to clinical signs related to previous serious illnesses.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
40
8.2.2
Chest X-ray
Bidirectional posterior-anterior and lateral view chest x-ray or as indicated by local treatment 
guidelines or practice will be performed at Screening if not performed within 6 months prior to 
screening and other time points specified in the Schedule of Activities (see Section 1.3).
8.2.3
Height and Weight
Height will be measured only at the Screening Visit. Weight will be measured at the Screening 
and EOS Visits.
8.2.4
Vital Signs
x
Body temperature, pulse rate, blood pressure, and respiratory rate will be assessed at the time 
points specified in Schedule of Activities (see Section 1.3).
x
Blood pressure and pulse measurements will be assessed in the supine position with a 
completely automated device. Manual techniques will be used only if an automated device is 
not available.
x
Blood pressure and pulse measurements should be preceded by approximately 5 minutes of 
rest for the subject in a quiet setting without distractions (eg, television, cell phones).
x
Vital signs including body temperature, respiratory rate, and pulse rate (after 5 minutes of
rest) should be measured once. Arterial blood pressure should be measured twice (at intervals 
of approximately 5 minutes), using a validated device. Average of both the readings will be 
entered in eCRF.
8.2.5
Electrocardiograms
x
A single 12-lead ECG will be obtained at the time points specified in Schedule of Activities 
(see Section 1.3) using a validated ECG machine that automatically calculates the pulse rate 
and measures PR, QRS, QT, and QTcF intervals.
x
The ECG will be reviewed by the central laboratory team for quality and interpretation. 
Instructions and guidelines for collection (e.g, equipment), transmission, and archiving of 
ECG data will be provided in the ECG Manual.
x
The ECG will be reviewed by the Investigator or an authorized representative who is 
experienced in the evaluation of ECGs and assessed for clinical significance which will be 
documented in the EDC.
x
The ECG individual data (with the exception of clinical significance) does not need to be 
entered into EDC.
8.2.6
Photography
Photography of the lesions will be performed at the time points mentioned in Schedule of 
Activities (see Section 1.3) for documentation purpose only. A standardized approach to
collection of photographs will be described in the manual provided to sites. Photographs will be 

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
41
transferred to a central vendor for quality review. Any further review of photographs may be 
conducted by a third party consultant.
8.2.7
Clinical Safety Laboratory Assessments
x
See Appendix 3 for the list of clinical laboratory tests to be performed and to the Schedule of 
Activities (see Section 1.3) for the timing and frequency of the tests.
x
A central laboratory will be used to perform all laboratory tests except urine pregnancy 
dipstick which will be assessed by the center staff. However, local laboratory tests will be 
allowed in the event that the central laboratory results will not be available immediately and 
the Investigator needs to take an immediate decision for any safety concerns based on 
laboratory results.
x
The Investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the case report 
form. The laboratory reports must be filed with the source documents. Clinically significant 
abnormal laboratory findings are those that are not associated with the underlying disease, 
unless judged by the Investigator to be more severe than expected for the subject’s condition.
x
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study including the subject’s last EOS visit should be repeated until 
the values return to normal or baseline or are no longer considered clinically significant 
or judged medically stabilized by the Investigator or Medical Monitor.

If such values do not return to normal/baseline within a period of time judged 
reasonable by the Investigator, the etiology should be identified and the Sponsor
notified.

All protocol-required laboratory assessments, as defined in Appendix 3, must be 
conducted in accordance with the Laboratory Manual and the Schedule of Activities 
(see Section 1.3).

If laboratory values from non-protocol specified laboratory assessments performed at 
the institution’s local laboratory require a change in subject management or are 
considered clinically significant by the Investigator (eg, SAE or AE or dose 
modification), then the results must be recorded in the eCRF.
8.2.8
Telephone Contact
At Days 36, 50, 64 and 78, subjects will be contacted by phone to assess for safety. Study staff 
will review for any new AEs or changes in concomitant medications. Any new/changed AEs and 
concomitant medications will be recorded on the eCRF.
8.3
Adverse Events
The definitions of an AE and SAE can be found in Appendix 4.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
42
Adverse events will be reported by the subject (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized representative).
The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs,
including that are serious, considered related to the study treatment or study procedures, or that 
caused the subject to discontinue the study (see Section 7.0).
8.3.1
Time Period and Frequency for Collecting AE and SAE Information
All SAEs will be collected from the signing of the ICF until the EOS visit at the time points 
specified in the Schedule of Activities (see Section 1.3).
All SAEs will be recorded and reported to the Sponsor or designee within 24 hours, as indicated 
in Appendix 4. The Investigator will submit any updated SAE data to the 
Safety within 24 hours of it being available.
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a subject has been discharged from the study, and he/she considers the event to be reasonably 
related to the study treatment or study participation, the Investigator must promptly notify the
 Safety.
8.3.2
Method of Detecting AEs and SAEs
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 4.
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrences.
8.3.3
Follow-up of AEs and SAEs
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs, and non-serious AEs of special interest (as defined in 
Section 8.3.6), will be followed until resolution, stabilization, the event is otherwise explained, 
or the subject is lost to follow-up (as defined in Section 7.3). Further information on follow-up
procedures is given in Appendix 4.
8.3.4
Regulatory Reporting Requirements for SAEs
x
Prompt notification by the Investigator to the 
 Safety of an SAE is essential 
so that legal obligations and ethical responsibilities towards the safety of subjects and the 
safety of a study treatment under clinical investigation are met.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
43
x
The 
 Safety has a legal responsibility to notify both the local regulatory 
authority and other regulatory agencies about the safety of a study treatment under clinical 
investigation. The 
 Safety will comply with country specific regulatory 
requirements relating to safety reporting to the regulatory authority, IRB/IEC, and 
Investigators.
x
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and 
 Safety policy and 
forwarded to Investigators as necessary.
x
An Investigator who receives an Investigator safety report describing an SAE or other 
specific safety information (eg, summary or listing of SAEs) from the 
Safety will review and then file it along with the IB and will notify the IRB/IEC, if
appropriate according to local requirements.
8.3.5
Pregnancy
x
Details of all pregnancies in female subjects will be collected after the start of study 
treatment and until at least 28 days after the last dose.
x
Details of all pregnancies in female partners of male subjects will be collected while the male 
subject is in this study and until at least 28 days after the last dose.
x
If a pregnancy is reported, the Investigator should inform the 
 Safety within 
24 hours of learning of the pregnancy and should follow the procedures outlined in
Appendix 6.
x
If a pregnancy occurs, it will be followed-up to determine the outcome, but no longer than 
6 to 8 weeks after the estimated delivery date.
x
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, and ectopic pregnancy) are considered SAEs.
8.3.6
Adverse Events of Special Interest
The following events are considered AESI in this study.
x
Serious infection (requiring hospitalization; or with fatal outcome or sepsis; or requiring IV 
antibiotics/antimicrobials).
x
Serious allergic reaction.
x
Gastrointestinal clinical manifestations including infections.
All AESI, including follow-up, should be reported in an expedited manner. (Please follow 
procedures for AE/SAE recording and reporting outlined in Appendix 4).
8.3.7
Infusion-related Adverse Events
The ANB019 infusion may be slowed or interrupted for subjects experiencing infusion-related 
AEs. Following the infusion, all subjects will be observed for fever, chills, rigors, hypotension, 
nausea, or other infusion-related AEs. The subjects will leave the study center after completing 

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
44
the 5 hours postdose assessments after IV administration and the 3 hours postdose assessments 
after the first and second SC injections and with the Investigator’s approval.
8.3.8
Disease-related Events and/or Disease-related Outcomes Not Qualifying as 
AEs or SAEs
The following disease-related events (DREs) are common in subjects with GPP and can be 
serious/life-threatening:
x
Flare of GPP.
Because these events are typically associated with the disease under study, they will not be 
reported according to the standard process for expedited reporting of SAEs even though the 
event may meet the definition of a SAE. These events will be recorded on the corresponding 
eCRF page in the subject’s eCRF.
NOTE: If either of the following conditions applies, then the event must be recorded and 
reported as an SAE (instead of a DRE):
The event is, in the Investigator’s opinion, of greater intensity, frequency, or duration than 
expected for the individual subject.
OR
The Investigator considers that there is a reasonable possibility that the event was related to 
study treatment.
8.4
Treatment of Overdose
For this study, any dose of ANB019 >750 mg/
within a 24-hour time period on Day 1
and >100 mg on Days 29, 57, and 85 will be considered an overdose.
In the improbable event of a suspected overdose, the following procedures should be executed:
x
Administration is to be discontinued.
x
The subject is to be monitored clinically.
x
Supportive measures are to be undertaken as clinically indicated.
x
Electrocardiography and clinical laboratory evaluations (ie, blood glucose, hepatic enzymes, 
creatinine, blood urea nitrogen, creatine kinase, and complete blood count) are to be 
performed and followed until all values return to baseline levels and AEs subside.
Sponsor does not recommend specific treatment for an overdose.
In the event of an overdose, the Investigator should:
1. Contact the Medical Monitor immediately.
2. Closely monitor the subject for any AE/SAE and laboratory abnormalities and follow-
up until resolution.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
45
3. Obtain a serum sample for PK analysis within 24 hours from the date of the last dose 
of study treatment if requested by the Medical Monitor (determined on a case-by-case 
basis).
4. Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF.
Decisions regarding dose interruptions or modifications will be made by the Investigator in
consultation with the Medical Monitor based on the clinical evaluation of the subject.
8.5
Pharmacokinetics
Whole blood will be obtained for the determination of ANB019 in human serum. Samples will 
be collected according to the schedule presented in Section 1.3. Approximately 65 mL total of
whole blood will be obtained from each subject for PK assessments during the study. Each serum 
sample will be divided into 2 aliquots (1 each for primary and a back-up). Samples collected for 
analyses of ANB019 serum concentration may also be used to correlate exposure to safety or 
efficacy aspects related to concerns arising during or after the study.
The actual date and time (24-hour clock) of the blood sample collection will be recorded in the 
subject’s eCRF. The details of blood sample collection, sample tube labeling, sample 
preparation, storage, and shipping procedures will be described in a separate Laboratory Manual.
The measurement of the concentrations of ANB019 will be performed using a validated assay 
method. The analytical methods used to measure concentrations of ANB019 will be described in 
a separate bioanalytical report. Only samples which are within the stability window of the 
bioanalytical assay will be analyzed.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
46
Table 2
PK/ADA Sample Collection and Timepoints
Study Visit
PK Sample Timepoint
Plasma
ADA Sample Timepoint
Serum
Day 1a
Predose
Predose
1 hr (r 10 min) postdose
4 hrs (r 10 min) post-dose
Day 3
Anytime
Day 8
Anytime
Day 15
Anytime 
Day 22
Anytime
Day 29
Predose
Predose
Day 43
Anytime
Day 57
Predose
Predose
Day 71
Anytime
Day 85
Predose
Predose
Day 113
Anytime
Day 141
Anytime
Day 169
Anytime
Anytime
ADA = anti-drug antibodies; hr(s) = hour(s); min = minutes; PK = pharmacokinetic.
a Infusion of study treatment will take approximately 1 hour. Therefore, the 1-hour PK sample collection on Day 1 
must start immediately at the end of the infusion. The 4-hour collection must occur exactly 3 hours after the 1-hour 
collection is completed.
8.6
Pharmacodynamics
Pharmacodynamic parameters will not be evaluated in this study.
8.7
Genetics
Pharmacogenomic testing is optional and voluntary. For those patients who signed the original 
pharmacogenomics ICF, a whole blood sample will be collected at the study visit as specified in 
the study flow chart and this sample will be stored for future analysis. Specific procedures for 
storage and shipping of pharmacogenomic samples will be provided in a lab manual.
DNA testing will be performed only at Day 1. Ribonucleic acid (RNA) testing will be performed 
on Day 1 and Week 16. The DNA and RNA samples may be used to determine a possible 
relationship between genes and response to treatment with ANB019 and possible side effects to 
ANB019. Genes that may be studied will be identified later as these are for exploratory purposes. 
These prepared samples will be transferred to the pre-identified lab that will, on behalf of 
AnaptysBio, extract DNA and RNA from the samples (See Appendix 7 for information 
regarding genetic research). Details on processes for collection and shipment and destruction of
these samples can be found in a separate Laboratory Manual.
8.8
Biomarkers
Samples will be collected according to the schedule presented in Section 1.3 to measure skin 
biopsy biomarkers. Measurements may include but are not limited to immunohistochemistry and
Reverse Transcription Polymerase Chain Reaction to assess psoriasis associated markers of 

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
47
inflammation (eg, IL-17, IL-23, IL-8, dendritic cells, epidermal thickness, and leukocytes 
infiltration).
The actual date and time of the sample collection will be recorded in the subject’s eCRF. The 
details of blood sample collection, sample tube labeling, sample preparation, storage, and 
shipping procedures will be described in a separate Laboratory Manual.
The measurement of skin biopsy biomarkers may be performed by an additional third party (eg, a 
university Investigator) designated by the Sponsor.
Samples may be stored for a maximum of 5 years (or according to local regulations) following 
the last subject’s last visit for the study at a facility selected by the Sponsor to enable further 
analysis of biomarker responses to study treatment.
A 5 mL blood sample will be collected in a serum separator tube to measure change in serum 
cytokine (including but not limited to IL-8) concentration at each time point mentioned in the 
Schedule of Activities (see Section 1.3). A qualified fit for purpose assay will performed by or 
under the supervision of the Sponsor.
8.9
Immunogenicity Assessments
Antibodies to ANB019 will be evaluated in serum samples collected from all subjects according 
to the Schedule of Activities (see Section 1.3 ) and Table 2. Additionally, serum samples should 
also be collected at the EOS visit from subjects who discontinued study treatment or were 
withdrawn from the study. Each serum sample will be divided into 2 aliquots (1 each for primary 
and a back-up).
The ADA analysis will be conducted using a screening assay against ANB019 to identify 
potential positive ADA samples. Samples testing positive for ADA in the screening assay will be 
further evaluated in a confirmatory assay against ANB019 to confirm the positive status of 
samples scored potentially positive by the screening assay. In confirmed positive samples, a third 
assay will be performed to determine the titer of confirmed positive samples. Confirmed positive 
ADA samples may be further evaluated for neutralizing activity.
The detection and characterization of antibodies to ANB019 will be performed using a validated 
assay method by or under the supervision of the Sponsor. All samples collected for detection of 
antibodies to study treatment will also be evaluated for ANB019 serum concentration to enable 
interpretation of the antibody data. Only samples within the stability window of the assay will be 
analyzed.
8.10
Health Economics or Medical Resource Utilization and Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters will not be
evaluated in this study.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
48
9.0
STATISTICAL CONSIDERATIONS
9.1
Statistical Hypotheses
This is an exploratory study and no formal hypothesis testing will be performed.
9.2
Sample Size Determination
The sample size is not based on statistical power considerations.
Approximately 10 subjects will be enrolled at 8 study centers for study treatment. On Day 1,
subjects who meet all of the entry criteria will receive a 750 mg IV dose of ANB019 in an 
open-label manner followed by 3 doses of 100 mg SC administered on Days 29, 57, and 85.
9.3
Populations for Analyses
For purposes of analysis, the analysis sets in Table 3 are defined.
Table 3
Analysis Sets
Full Analysis Set (FAS)
The FAS analysis set will include all subjects, 
regardless of whether or not the treatment was 
received. Subjects will be analyzed according 
to treatment received.
Safety Analysis Set
The Safety Analysis Set will include all 
enrolled subjects who receive at least 1 dose 
of ANB019. The Safety Analysis Set will be 
used for all safety analyses. Subjects will be 
analyzed according to treatment received.
Per Protocol Analysis Set (PPS)
The Per Protocol analysis set will include all 
subjects in the FAS analysis set who do not 
have major protocol violations that would 
affect the evaluation of the primary efficacy 
endpoint.
PK Analysis Set
The PK analysis set will include all subjects 
in the Safety Analysis Set who have at least 1 
quantifiable PK sample available and who do 
not have events or deviations with the 
potential to affect PK concentrations. The PK 
analysis set will be used for all PK analyses.
9.4
Statistical Analyses
The statistical analysis will be performed using statistical analysis system (SAS®) Version 9.4 or 
higher if available. All details regarding the statistical analysis and the preparation of tables, 

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
49
listings and figures will be described in the statistical analysis plan (SAP). The SAP will be 
developed and finalized before database lock and will describe the subject analysis sets to be 
included in the analyses, and procedures for accounting for missing, unused, and spurious data. 
This section is a summary of the planned statistical analyses of the primary and secondary 
endpoints.
The default summary statistics for continuous variables includes number of contributing 
observations (n), mean, standard deviation (SD), median, minimum, and maximum. (See 
Section 9.4.7 for PK).
For categorical variables, the number and percentage (the percentage of subjects in each category 
relative to the total number of subjects in the relevant analysis set or relative to the total number 
of subjects in the relevant analysis set, with assessments available [where appropriate]) in each 
category will be the default summary presentation.
Unless otherwise specified, “baseline” is defined as the last observed value of the parameter of 
interest prior to the first intake of study drug (this includes unscheduled visits). For numerical 
variables, change from Baseline will be calculated as the difference between the value of interest
and the corresponding baseline value.
Point estimates will be accompanied with 2-sided 95% confidence interval (CIs), where 
applicable.
In the case of normality assumption violations, appropriate non-parametric methods will be used 
for analysis.
All data will be presented in by subject listings.
9.4.1
Subject Disposition
A tabular presentation of the subject disposition will be provided. It will include the number of 
subjects screened, enrolled, treated, completed as well as the number of dropouts, with reasons
for discontinuation, and major protocol deviations or violations.
A listing will be presented to describe dates of screening, assigned treatment, screen failed with 
reason, completion or early withdrawal, and the reason for early discontinuation, if applicable, 
for each subject. A list of protocol deviations/violations will be identified and discussed with the 
Investigator/AnaptysBio Inc. in dry-run to categorize as major or minor and the same will be 
reported.
9.4.2
Subject Characteristics and Medical History
Subject characteristics obtained at Screening will be summarized for all subjects taking 
ANB019. Subject characteristics may include, but are not limited to age, gender, height, weight, 
and BMI.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
50
Summaries will include descriptive statistics for continuous variables (sample size [n], mean, 
SD, median, minimum, and maximum) and for categorical variables (sample size, frequency, and 
percent).
Medical history will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
dictionary latest version and listed for all subjects.
9.4.3
Concomitant Medication
All medications will be coded using the World Health Organization Drug Dictionary and 
Anatomical Therapeutic Chemical (ATC) system. Each medication will be classified as prior 
medication if it is stopped prior to the first dose of study drug, or as concomitant medication if it 
is ongoing at the time of the first dose or is started after the first dose of study drug. Prior, 
concomitant and rescue medications will be summarized by ATC level 2 categories and 
preferred name.
A listing of prior, concomitant, and rescue medications will be presented.
9.4.4
Efficacy Analyses
9.4.4.1
Analysis of Primary Efficacy Endpoints
The primary efficacy endpoint is the proportion of subjects achieving clinical response at 
Weeks 4 and 16. Clinical response is defined as “Very much improved”, “Much improved”, and 
“Minimally improved” on CGI scale according to modified JDA severity index total score. The 
number and percentage of subjects achieving clinical response will be summarized in tabular 
form at Weeks 4 and 16. Each subjects CGI score will be plotted at all study visits.
9.4.4.2
Analysis of Secondary Efficacy Endpoints
Following are the secondary efficacy endpoints:
x
Change in modified JDA severity index total skin lesions score (sum of erythema, erythema 
with pustules, edema) at all study visits.
Descriptive statistics will be presented at all study visits. Each subject’s modified JDA severity 
index total skin lesion score will be plotted at all study visits.
x
Change in affected BSA of erythema with pustules, erythema, and edema as measured by 
modified JDA severity index score at all study visits:
Descriptive statistics will be generated at all study visits. An overlay plot of each subject’s value 
over all study visits will be generated for each component score.
x
Change in total and individual scores in systemic manifestations and laboratory findings as 
measured by modified JDA severity index at all study visits.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
51
Descriptive statistics will be generated at each measurement time for each numeric systemic 
manifestation and laboratory finding. An overlay plot of each subject’s value over all study visits 
will be generated for each measurement time.
x
GPPPGA change from Baseline scores for all study visits.
x
GPPPGA score at all study visits.
The GPPPGA will be summarized at each postbaseline visit for change from Baseline scores and 
for the proportion of subjects achieving a GPPPGA score of 0 or 1. A separate overlay plot will 
display each subject’s GPPPGA score for all study visits.
x
Change in PASI score to evaluate a subject’s overall PP disease state if present for all study 
visits:
Summary statistics will be provided for absolute PASI scores as well as for percent change from 
Baseline for all study visits.
x
Change in DLQI total score at all study visits:
Summary statistics will be provided for average DLQI scores, as well as for percent change from 
Baseline for all study visits.
9.4.5
Safety Analyses
x
Assessment of AEs/SAEs (potentially significant and clinically important AEs, SAEs, and 
AEs leading to withdrawal)
x
Physical examinations
x
12-lead ECG
x
Vital signs
x
Clinical safety laboratory tests (hematology, biochemistry, and urinalysis).
All safety analyses will be performed on the Safety Analysis Set.
9.4.5.1
Adverse Events and Serious Adverse Events
Treatment-emergent adverse event: A TEAE is defined as:
x
A new event that occurs during or after first dose of study treatment or,
x
Any event present at baseline that worsens in either intensity or frequency after first dose of 
study treatment.
Only TEAEs will be summarized.
Adverse events will be coded using the MedDRA. Number of events and percentage will be 
tabulated by preferred term and system organ class. An event that occurred one or more times on 
treatment period for a subject will contribute 1 observation to the numerator and denominator 

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
52
comprising all safety subjects exposed to ANB019. If the intensity or seriousness of the AE 
changes, the overall intensity or seriousness will be the maximum intensity or seriousness of the 
multiple occurrences. The TEAEs, AESIs, SAEs, TEAEs leading to treatment discontinuation,
and TEAEs leading to withdrawal of subject will be tabulated for each treatment period.
Adverse events, AESIs, and SAEs will be listed for each subject.
Summaries over SOC, PT and listings of TEAEs, TEAEs leading to death, SAEs, potentially 
significant TEAEs, clinically important TEAEs, and TEAEs that led to discontinuation from the 
study or of the study drug will be presented. Summaries will also be presented by relatedness to 
the study drug and the severity of the TEAE.
9.4.5.2
Physical Examinations, 12-Lead ECG, Vital Signs and Clinical Safety Laboratory 
Tests (Hematology, Biochemistry, and Urinalysis)
Summaries and listings of data for both limited and complete physical examination findings, 
vital signs, hematology, biochemistry, and urinalysis laboratory tests will be presented. 
Appropriate descriptive statistics will be summarized for the observed value at each scheduled 
assessment and for the corresponding change from Baseline.
For hematology and biochemistry tests, listings of subject data will also flag up any abnormal or 
out-of-range values. Clinically significant changes in the laboratory test parameters will be 
summarized and listed. Hematology and clinical laboratory data will be reported in System 
International units.
Descriptive statistics will be used to present the safety outcomes including, physical examination 
results, weight, BMI, 12-lead ECG, vital signs measurements, and clinical laboratory test results.
Change from Baseline will also be summarized for vital signs measurements, clinical laboratory 
test results.
All ECG data results (normal/abnormal) will be summarized using frequency and percentages. 
Clinically significant abnormalities will be presented in by subject listings.
9.4.6
Immunogenicity Analyses
Observed values for ADA status/titers will be listed by subject and summarized with descriptive
statistics based on the Safety Analysis Set. If data permits, any correlation between ADA status
and safety and efficacy endpoints will be evaluated.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
53
9.4.7
Pharmacokinetic/Pharmacodynamic Analyses
9.4.7.1
Derivation of Pharmacokinetic Parameters
The PK parameters will be derived using non-compartmental methods using the PK analysis set.
The actual sampling times will be used in the PK parameter calculations. Further details of PK 
analysis, data handling, analysis procedures, and data reporting will be detailed in the SAP.
The following PK parameters will be determined for ANB019:
x
Maximum observed concentration (Cmax).
x
Time to maximum observed concentration (Tmax).
x
Area under the curve (AUC).
Additional PK parameters may be determined if deemed appropriate.
9.4.7.2
Pharmacokinetic Concentration Data Analysis
A subject listing of all concentration-time data following study drug administration will be 
presented by subject and scheduled sample collection time.
Concentration data of ANB019 will be summarized by route/day and nominal time point using
the number of observations (n), arithmetic mean, SD, coefficient of variation (CV), minimum, 
median, maximum, and geometric mean.
Graphs for mean concentration-time data following IV administration will be presented. 
Individual subject plots will also be presented. Other presentations of data may be added at the 
discretion of the PK scientist, as appropriate, and will be described in detail in the SAP.
9.4.7.3
Pharmacokinetic Parameter Data Analysis
All PK parameters will be summarized using n, arithmetic mean, SD, CV, minimum, median, 
maximum, geometric mean, and geometric CV, with the exception of Tmax, which will be 
reported with n, minimum, median, and maximum only.
Graphs of parameters may be added at the discretion of the PK scientist, as appropriate, and will 
be described in detail in the SAP.
9.4.8
Exploratory Biomarker Analyses
Observed and change from Baseline for circulating biomarkers will be listed and summarized 
descriptively by nominal time point and treatment using the Safety Analysis Set. Baseline will be 
the last assessment before study treatment administration.
The relationship between ANB019 concentrations and biomarker endpoints will be explored 
graphically.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
54
Skin biomarker analysis may be performed by additional third party (eg, a university 
Investigator) designated by the Sponsor.
9.4.9
Missing Data
Missing data handling and possible sensitivity analysis will be described in the SAP.
9.5
Interim and Final Analyses
An interim analysis will be performed when approximately 50% of subjects have completed their 
Week 4 visit or when at least 2 subjects have reached 16 weeks postdosing. The interim analysis 
will assess primary efficacy and all safety data. Data from interim analyses might be used as a
guideline for possible protocol modifications and planning of future clinical studies.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
55
10.0 REFERENCES
ANB019-001, AnaptysBio, San Diego, CA. A Double-Blind, Randomized, Placebo-Controlled, 
Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Study to Evaluate the 
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of ANB019 in Healthy Subjects 
and Psoriasis Patients. Clinical Study Report; 22 June 2018.
Augey F, Renaudier P, and Nicolas J-F. Generalized pustular psoriasis (Zumbusch): a French 
epidemiological survey. Eur J Dermatol. 2006;16(6):669-73.
Bachelez H, Choon SE, Marrakchi S, et al. Inhibition of the IL-36 Pathway for the Treatment of 
Generalized Pustular Psoriasis. N Engl J Med 2019; 380:(10).
Benjegerders K, Hyde K, Kivelevitch D, Mansouri B. Pustular psoriasis: pathophysiology and 
current treatment perspectives. Psoriasis (Auckl). 2016 Sep 12;6:131-144.
Capon F. IL36RN mutations in generalized pustular psoriasis: just the tip of the iceberg? J Invest 
Dermatol. 2013;133(11):2503-4.
Dubey JP, Markovits JE, and Killary KA. Cryptosporidim muris-like infection in stomach of 
cynomolgus monkeys (Macaca Fascicularis). Vet Pathol 2002;39(3):363-71.
Fagerland, M. W., Hosmer, D. W., and Bofin, A. M. (2008). “Multinomial Goodness-of-Fit 
Tests for Logistic Regression Models.” Statistics in Medicine 27:4238–4253.
Farthing MJ. Treatment options for the eradication of intestinal protozoa. Nat. Rev. Gastroent. 
Hepat. 2006;3:436-45.
Farooq M, Nakai H, Fujimoto A, Fujikawa H, Matsuyama A, Kariya N, et al. Mutation analysis 
of the IL36RN gene in 14 Japanese subjects with generalized pustular psoriasis. Hum. Mutat. 
2013;34:176-83.
Finlay AY, Kahn GK. Dermatology Life Quality Index (DLQI): A simple practical measure for 
routine clinical use. Clinical and Experimental Dermatology. 1994;19:210-6.
Fredriksson T, Pettersson U. Severe psoriasis-oral therapy with a new retinoid. 1978;157(4):238-
44.
Imafuku S, Honma M, Okubo Y, Komine M, Ohtsuki M, Morita A, et al. Efficacy and safety of 
secukinumab in patients with generalized pustular psoriasis: A 52 week analysis from phase 3 
open-label multicenter Japanese study. The Journal of Dermatology. 2016;43:1011-17.
Jordan C, Cao L, Roberson E, Pierson K, Yang CF, Joyce CE, et al. PSORS2 Is Due to 
Mutations in CARD14. The American J of Human Genetics. 2012;90:784-95.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
56
Marrakchi S, Guigue P, Renshaw BR., Puel A, Pei XY., Fraitag S, et al. Interleukin-36-receptor 
antagonist deficiency and generalized pustular psoriasis. N. Engl. J. Med. 2011;365:620-8.
Marrakchi S, Burden A, Tsai T, et al. Inhibition of the Interleukin-36 Pathway for the Treatment 
of Generalized Pustular Psoriasis [To the Editor]. N. Engl. J. Med. 2019; 380:10
Mahil S, Twelves S, Farkas K, Setta-Kaffetzi N, Burden AD, Gach JE, et al. AP1S3 Mutations 
Cause Skin Autoinflammation by Disrupting Keratinocyte Autophagy and Up-Regulating IL-36
Production. J of Invest Dermatol. 2016;136:2251-59.
Navarini A, Burden A, Capon F, Mrowietz U, Puig L, Koks S. European consensus statement on 
phenotypes of pustular psoriasis. J Eur Acad Dermatol Venereol. 2017 Nov;31(11):1792-1799.
Ohkawara A, Yasuda H, Kobayashi H, Inaba Y, Ogawa H, Hashimoto I, et al. Generalized 
pustular psoriasis in Japan: Two distinct groups formed by differences in symptoms and genetic 
background. Acta Derm Venereol (Stockh).1996;76:68-71.
Oji V, Luger T. The skin in psoriasis: assessment and challenges. Clin Exp Rheumatol. 2015;33 
(suppl. 93):S14-S19.
Onoufriadis A, Simpson M. A, Pink A. E, Di Meglio P, Smith C. H, Pullabhatla V, et al.
Mutations in IL36RN/IL1F5 are associated with the severe episodic inflammatory skin disease 
known as generalized pustular psoriasis. Am. J. Hum. Genet. 2011;89:432-7.
Sugiura K, Takeichi T, Kono M, Ogawa Y, Shimoyama Y, Muro Y, et al. A novel 
IL36RN/IL1F5 homozygous nonsense mutation, p.Arg10X, in a Japanese patient with adult 
onset generalized pustular psoriasis. Br. J. Dermatol. 2012;167:699-701.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
57
11.0 APPENDICES

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
58
Appendix 1
Abbreviations
Abbreviation
Definition
ADA
Anti-drug antibodies
AE
Adverse event
AESI
Adverse event of special interest
ALT
Alanine aminotransferase
AST
Aspartate aminotransferase
ATC
Anatomical Therapeutic Chemical
AUC
Area under the concentration-time curve
BMI
Body mass index
BSA
Body surface area
CGI
Clinical Global Impression
CI
Confidence interval
Cmax
Maximum observed concentration
CRF
Case report form
CRP
C-reactive protein
CSR
Clinical Study report
CV
Coefficient of variation
DLQI
Dermatology Life Quality Index
DNA
Deoxyribonucleic acid
DRE
Disease-related events
ECG
Electrocardiogram
eCRF
Electronic case report form
EOS
End of study
ET
Early termination
FAS
Full Analysis Set
FSH
GLP
Follicle stimulating hormone
Good Laboratory Practices.
GPP
Generalized pustular psoriasis
GPPPGA
Generalized Pustular Psoriasis Physician’s Global Assessment
IB
Investigator’s Brochure
ICF
Informed consent form
ICH
International Council for Harmonisation

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
59
Abbreviation
Definition
IEC
Independent Ethics Committee
IL-36
Interleukin-36
IL-36R
Interleukin-36 receptor
IRB
Institutional Review Board
IV
Intravenous
JDA
Japanese Dermatology Association
mAb
Monoclonal antibody
MAD
Multiple Ascending Dose
MedDRA
Medical Dictionary for Regulatory Activities
mRNA
Messenger ribonucleic acid
NaCl
Sodium chloride
PASI
Psoriasis Area Severity Index
PK
Pharmacokinetic
PP
Plaque psoriasis
PPP
Palmoplantar pustular psoriasis
PT
Preferred term
PUVA
Psoralen and Ultraviolet A
QoL
Quality of life
RNA
Ribonucleic acid
SAD
Single Ascending Dose
SAE
Serious adverse event
SAP
Statistical analysis plan
SC
Subcutaneous
SD
Standard deviation
SOC
System Organ Class
SOP
Standard operating procedures
TB
Tuberculosis
TEAE
Treatment-emergent adverse event
Tmax
Time to maximum observed concentration
ULN
Upper limit of normal
URTI
Upper respiratory tract infection
WBC
White blood cell
WOCBP
Women of childbearing potential

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
60
Appendix 2
Regulatory, Ethical, and Study Oversight Considerations
Regulatory and Ethical Considerations
x
This study will be conducted in accordance with the protocol and with the following:

Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines.

Applicable International Council for Harmonisation (ICH) GCP Guidelines.

Applicable laws and regulations.
x
The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant 
documents (eg, advertisements) must be submitted to an IRB/IEC by the Investigator and 
reviewed and approved by the IRB/IEC before the study is initiated.
x
Any amendments to the protocol will require IRB/IEC and regulatory authority approval, 
when applicable, before implementation of changes made to the study design, except for 
changes necessary to eliminate an immediate hazard to subjects.
x
The Investigator will be responsible for the following:

Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC.

Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures.

Providing oversight of the conduct of the study at the study center and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations.
x
After reading the protocol, each Investigator will sign the protocol signature page and send a 
copy of the signed page to the Sponsor or representative. The study will not start at any study 
center at which the Investigator has not signed the protocol.
Insurance
Sponsor will provide insurance in accordance with local guidelines and requirements as 
minimum for the subjects in this study. The terms of the insurance will be kept in the study files.
Informed Consent Process
x
The Investigator or his/her representative will explain the nature of the study to the subject or 
his/her legally authorized representative and answer all questions regarding the study.
x
Subjects must be informed that their participation is voluntary. Subjects or their legally 
authorized representative will be required to sign a statement of informed consent that meets 
the requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance 

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
61
Portability and Accountability Act requirements, where applicable, and the IRB/IEC or study 
center.
x
The medical record must include a statement that written informed consent was obtained 
before the subject was entered in the study and the date the written consent was obtained. 
The authorized person obtaining the informed consent must also sign the ICF.
x
Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study.
x
A copy of the ICF(s) must be provided to the subject or the subject’s legally authorized 
representative.
x
Subjects who are rescreened are required to sign a new ICF.
The ICF will contain a separate section that addresses the use of remaining mandatory samples 
for optional exploratory research. The Investigator or authorized designee will explain to each 
subject the objectives of the exploratory research. Subjects will be told that they are free to 
refuse to participate and may withdraw their consent at any time and for any reason during the 
storage period. A separate signature will be required to document a subject’s agreement to allow 
any remaining specimens to be used for exploratory research. Subjects who decline to participate 
in this optional research will not provide this separate signature.
Data Protection
x
Subjects will be assigned a unique identifier by the Sponsor. Any subject records or datasets 
that are transferred to the Sponsor will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred.
x
The subject must be informed that his/her personal study related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject.
x
The subject must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities.
x
The ICF will incorporate (or, in some cases, be accompanied by a separate document 
incorporating) wording that complies with relevant data protection and privacy legislation.
x
The Sponsor or its representative will not provide individual genotype results to subjects, any 
insurance company, any employer, their family members, general physician, or any other 
third party, unless required to do so by law.
x
Extra precautions are taken to preserve confidentiality and prevent genetic data being linked 
to the identity of the subject. In exceptional circumstances, however, certain individuals 
might see both the genetic data and the personal identifiers of a subject. For example, in the 
case of a medical emergency, the Sponsor or representative physician or an Investigator
might know a subject’s identity and also have access to his or her genetic data. Also 
regulatory authorities may require access to the relevant files.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
62
Administrative Structure
Table 4
Study Administrative Structure
Function
Responsible Organization
Study Operations Management
Medical Monitoring
Study Master File
Data Management
Clinical Supply Management
Quality Assurance Auditing
Biostatistics
Medical Writing
Laboratory Assessments
Electrocardiogram Collection, Review, and Analysis
Pharmacokinetic Sample Testing
Medical Monitor
Further details can be found in the Medical Monitoring Plan. In case of any urgent medical issue 
contact: 
Dissemination of Clinical Study Data
The results of the study should be reported within 1 year from the end of the clinical study. 
Irrespective of the outcome, the Sponsor will submit to the EU database a summary of the results 
of the clinical study within 1 year from the end of the clinical study. It shall be accompanied by a 
summary written in a manner that is understandable to laypersons.
Quality Control and Quality Assurance
According to the Guidelines of GCP (CPMP/ICH/135/95), 
is responsible for 
implementing and maintaining quality assurance and quality control systems with written 
standard operating procedures (SOPs). Quality control will be applied to each stage of data 
handling.
The following steps will be taken to ensure the accuracy, consistency, completeness, and 
reliability of the data:
x
Central laboratories for clinical laboratory parameters.
x
Center Initiation visit.
x
Early center visits post-enrollment.
x
Routine center monitoring.
x
Ongoing center communication and training.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
63
x
Data management quality control checks.
x
Continuous data acquisition and cleaning.
x
Internal review of data.
x
Quality control check of the final clinical study report (CSR).
In addition, Sponsor and/or 
 may conduct periodic 
audits of the study processes, including, but not limited to study center, central laboratories, 
vendors, clinical database, and final CSR. When audits are conducted, access must be authorized 
for all study related documents including medical history and concomitant medication 
documentation to authorized Sponsor’s representatives and regulatory authorities.
Monitoring
Sponsor has engaged the services of a contract research organization,
 to perform all 
monitoring functions within this clinical study.
’ monitors will work in accordance with 
SOPs. The monitor will establish and maintain regular contact between the Investigator
and Sponsor.
The monitor will evaluate the competence of the study center, informing Sponsor about any 
problems relating to facilities, technical equipment, or medical staff. During the study, the
monitor will check that written informed consent has been obtained from all subjects correctly 
and that data are recorded correctly and completely. The monitor is also entitled to compare 
entries in eCRFs with corresponding source data and to inform the Investigator of any errors or 
omissions. The monitor will also assess and control adherence to the protocol and ICH/GCP 
guidelines at the study center. The monitor will arrange for the supply of study treatment, ensure 
proper study treatment dispensing/accountability, and appropriate storage conditions are 
maintained.
Monitoring visits will be conducted according to all applicable regulatory requirements and 
standards. Regular monitoring visits will be made to each center while subjects are enrolled in 
the study.
During monitoring visits, all entries in the eCRFs will be compared with the original source 
documents (source data verification). For the following and all other items, this check will be 
100%:
x
Subject identification number.
x
Subject consent obtained.
x
Subject eligibility criteria (inclusion and exclusion criteria).
x
Efficacy variables.
x
Safety variables.
x
Medical record of AE.
Data Management/Coding

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
64
Data generated within this clinical study will be handled according to the relevant SOPs of the 
Data Management and Biostatistics departments of 
.
Electronic data capture will be used for this study, meaning that all eCRF data will be entered in 
electronic forms at the study center. Data collection will be completed by authorized study center 
staff designated by the Investigator. Appropriate training and security measures will be 
completed with the Investigator and all authorized study center staff prior to the study being 
initiated and any data being entered into the system for any study subjects.
All data must be entered in English. The eCRFs should always reflect the latest observations on 
the subjects participating in the study. Therefore, the eCRFs are to be completed as soon as 
possible during or after the subject’s visit. To avoid inter-observer variability, every effort should 
be made to ensure that the same individual who made the initial baseline determinations 
completes all efficacy and safety evaluations. The Investigator must verify that all data entries in 
the eCRFs are accurate and correct. If some assessments are not done, or if certain information is 
not available or not applicable or unknown, the Investigator should indicate this in the eCRF. 
The Investigator will be required to electronically sign off on the clinical data.
The monitor will review the eCRFs and evaluate them for completeness and consistency. The 
eCRF will be compared with the source documents to ensure that there are no discrepancies 
between critical data. All entries, corrections and alterations are to be made by the responsible 
Investigator or his/her designee. The monitor cannot enter data in the eCRFs. Once clinical data 
of the eCRF have been submitted to the central server, corrections to the data fields will be audit 
trailed, meaning that the reason for change, the name of the person who performed the change, 
together with time and date will be logged. Roles and rights of the center staff responsible for 
entering the clinical data into the eCRF will be determined in advance. If additional corrections 
are needed, the responsible monitor or Data Manager will raise a query in the EDC application.
The appropriate study center staff will answer queries sent to the Investigator. This will be audit 
trailed by the EDC application meaning that the name of investigational staff, time and date 
stamp are captured.
The eCRF is essentially considered a data entry form and should not constitute the original (or 
source) medical records unless otherwise specified. Source documents are all documents used by 
the Investigator or hospital that relate to the subject’s medical history, that verify the existence of
the subject, the inclusion and exclusion criteria and all records covering the subject’s 
participation in the study. They include but are not limited to laboratory notes, ECG results, 
memoranda, pharmacy dispensing records, subject files, etc. Source data should be attributable, 
legible, contemporaneous, original, accurate, and complete. Changes to source data should be 
traceable, should not obscure the original entry, and should be explained if necessary (eg, via an 
audit trail).

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
65
The Investigator is responsible for maintaining source documents. These will be made available 
for inspection by the study monitor at each monitoring visit. The Investigator must submit a 
completed eCRF for each subject who receives study treatment, regardless of duration. All
supportive documentation submitted with the eCRF, such as laboratory or hospital records, 
should be clearly identified with the study and subject number. Any personal information, 
including subject name, should be removed or rendered illegible to preserve individual 
confidentiality.
Electronic case report form records will be automatically appended with the identification of the 
creator, by means of their unique User ID. Specified records will be electronically signed by the 
Investigator to document his/her review of the data and acknowledgement that the data are 
accurate. This will be facilitated by means of the Investigator’s unique User ID and password; 
date and time stamps will be added automatically at time of electronic signature. If an entry on 
an eCRF requires change, the correction should be made in accordance with the relevant 
software procedures. All changes will be fully recorded in a protected audit trail, and a reason for 
the change will be required.
Data Handling and Record Keeping
The Investigator must maintain essential study documents (protocol and protocol amendments, 
completed eCRFs, signed ICFs, relevant correspondence, and all other supporting 
documentation). The study center should plan on retaining such documents for approximately 
15 years after study completion. The study center should retain such documents until at least 
2 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 2 years after the 
formal discontinuation of clinical development of the study treatment (ANB019). These 
documents should be retained for a longer period if required by the applicable regulatory 
requirements or the hospital, institution, or private practice in which the study is being 
conducted. Subject identification codes (subject names and corresponding study numbers) will 
be retained for this same period of time. These documents may be transferred to another 
responsible party, acceptable to Sponsor, who agrees to abide by the retention policies. Written 
notification of transfer must be submitted to Sponsor. The Investigator must contact Sponsor
prior to disposing of any study records.
Direct Access to Source Documents
The Investigator will prepare and maintain adequate and accurate source documents to record all 
observations and other pertinent data for each subject enrolled into the study.
The Investigator will allow Sponsor,
, and authorized regulatory authorities to have direct
access to all documents pertaining to the study, including individual subject medical records, as 
appropriate. Such information must be kept confidential and must have locked facilities that 

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
66
allow for this. Subject identification number will be recorded on all documents related to the 
study.
Study and Study Center Closure
The Sponsor designee reserves the right to close the study center or terminate the study at any
time for any reason at the sole discretion of the Sponsor. Study centers will be closed upon study 
completion. A study center is considered closed when all required documents and study supplies 
have been collected and a study center closure visit has been performed.
The Investigator may initiate study center closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study center by the Sponsor or Investigator may include but 
are not limited to:
x
Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor’s procedures, or GCP guidelines.
x
Inadequate recruitment of subjects by the Investigator.
x
Discontinuation of further study treatment development.
Publication Policy
The data generated by this study are confidential information of the Sponsor. The Sponsor will 
make the results of the study publicly available. The publication policy with respect to the 
Investigator and study center will be set forth in the Clinical Trial Agreement.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
67
Appendix 3
Clinical Laboratory Tests
x
The tests detailed in Table 5 will be performed by the central laboratory. The time points are 
specified in Schedule of Activities (see Section 1.3).
x
Local laboratory tests will be allowed in the event that the central laboratory results will not 
be available immediately and the Investigator need to take an immediate decision for any 
safety concerns. If a local sample is required, it is important that the sample for central 
analysis is obtained at the same time.
x
Urine pregnancy dipstick will be performed at the study center prior to study treatment 
administration.
x
Protocol-specific requirements for inclusion or exclusion of subjects are detailed in 
Section 5.0 of the protocol.
x
Additional tests may be performed at any time during the study as determined necessary by 
the Investigator or required by local regulations.
Table 5
Protocol-required Safety Laboratory Assessments
Laboratory 
Assessments
Parameters
Hematology
Hemoglobin
Red Blood Cell Count
Hematocrit
White Blood Cell Count (WBC) with 
Differential:
Neutrophils
Mean cell hemoglobin (MCH)
Lymphocytes
Mean cell volume (MCV)
Monocytes
Mean cell hemoglobin 
concentration (MCHC)
Eosinophils
Platelet count 
Basophils
Clinical 
Chemistry
Alanine Aminotransferase (ALT)
Creatinine
Albumin
Gamma glutamyl transferase (GGT)
Alkaline phosphatase (ALP)
Glucose
Aspartate Aminotransferase (AST)
Potassium
Bicarbonate
Phosphate (Inorganic)
Bilirubin (Total)
Protein (Total)
Bilirubin (Direct-only if total is 
elevated)
Sodium
Calcium
Blood urea nitrogen (urea)
Chloride
Creatine Kinase (CK)
Uric acid
Triglycerides
Lactate dehydrogenase
human C-reactive protein (hCRP)

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
68
Laboratory 
Assessments
Parameters
Troponin
Total Cholesterol 
Serum pregnancy
Human chorionic gonadotropin (hCG) pregnancy test (as needed for women 
of childbearing potential)
FSH
As needed in women of non-childbearing potential only (Postmenopausal 
woman aged over 45 years with at least 1 year of amenorrhea)
Urinalysis
Bilirubin 
pH
Blood
Protein
Glucose
Specific gravity
Ketones
Urobilinogen
Leukocytes
Microbiology (At discretion of 
Investigator based on urinalysis 
results)
Nitrites
Microscopy (At discretion of 
Investigator based on urinalysis 
results)
Viral serology
Hepatitis B surface antigen
Hepatitis C Antibody
Human immunodeficiency virus
Antibodies
Tuberculosis 
(TB) screening
Quantiferon® - TB Gold In-tube, the third-generation test (If the test 
indeterminate it can be retested only once)
NOTES: Please see Schedule of Activities (Section 1.3) for laboratory tests time points.
PK and ADA samples will be collected as detailed in the Schedule of Activities All blood samples 
must be drawn prior to administration of the study drug on Day 1. The date and exact time of 
sample collection must be recorded
Investigators must document their review of each laboratory safety report.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
69
Appendix 4
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
Definition of AE
AE Definition
x
An AE is any untoward medical occurrence in a subject or subject, temporally associated with the use 
of study treatment, whether or not considered related to the study treatment.
x
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of 
study treatment.
Events Meeting the AE Definition 
x
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety 
assessments (eg, ECG, radiological scans, vital signs measurements), including those that worsen from 
baseline, considered clinically significant in the medical and scientific judgment of the Investigator (ie,
not related to progression of underlying disease).
x
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition.
x
New conditions detected or diagnosed after study treatment administration even though it may have 
been present before the start of the study.
x
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
x
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study treatment or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an intentional 
overdose taken with possible suicidal/self-harming intent. Such overdoses should be reported 
regardless of sequelae.
x
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be reported as an AE 
or SAE. Such instances will be captured in the efficacy assessments. However, the signs, symptoms, 
and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE if they fulfil the 
definition of an AE or SAE. 
Events NOT Meeting the AE Definition 
x
Any clinically significant abnormal laboratory findings or other abnormal safety assessments which are 
associated with the underlying disease, unless judged by the Investigator to be more severe than 
expected for the subject’s condition.
x
The disease/disorder being studied or expected progression, signs, or symptoms of the disease/disorder 
being studied, unless more severe than expected for the subject’s condition.
x
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE.
x
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital).
x
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at the 
start of the study that do not worsen.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
70
Definition of SAE
An SAE is defined as any untoward medical occurrence that, at any dose:
a)
Results in death
b)
Is life-threatening
The term ‘life-threatening’ in the definition of “serious” refers to an event in which the subject was at risk 
of death at the time of the event. It does not refer to an event, which hypothetically might have caused 
death, if it were more severe.
c)
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the subject has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfils any other serious criteria, the 
event is serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE should 
be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is not 
considered an AE.
d)
Results in persistent disability/incapacity
x
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions.
x
This definition is not intended to include experiences of relatively minor medical significance such as 
uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (eg, sprained 
ankle) which may interfere with or prevent everyday life functions but do not constitute a substantial 
disruption.
e)
Is a congenital anomaly/birth defect
f)
Other situations:
x
Medical or scientific judgment should be exercised in deciding whether SAE reporting is appropriate 
in other situations such as important medical events that may not be immediately life-threatening or 
result in death or hospitalization but may jeopardize the subject or may require medical or surgical
intervention to prevent 1 of the other outcomes listed in the above definition. These events should 
usually be considered serious.
Examples of such events include invasive or malignant cancers, intensive treatment in an emergency 
room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that do not result in 
hospitalization, or development of drug dependency or drug abuse.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
71
Recording and Follow-up of AE and/or SAE
AE and SAE Recording
x
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation (eg, 
hospital progress notes, laboratory reports, and diagnostics reports) related to the event.
x
The Investigator will then record all relevant AE/SAE information in the CRF. Each event must be 
recorded separately.
x
It is not acceptable for the Investigator to send photocopies of the subject’s medical records to 
 Safety in lieu of completion of the /AE/SAE CRF page.
x
There may be instances when copies of medical records for certain cases are requested by 
 Safety. In this case, all subject identifiers, with the exception of the subject number, will be 
redacted on the copies of the medical records before submission to 
 Safety.
x
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) will 
be documented as the AE/SAE.
Assessment of Intensity
The Investigator will make an assessment of intensity for each AE and SAE reported during the study and 
assign it to 1 of the following categories:
x
Mild: An event that is easily tolerated by the subject, causing minimal discomfort and not interfering 
with everyday activities.
x
Moderate: An event that causes sufficient discomfort and interferes with normal everyday activities.
x
Severe: An event that prevents normal everyday activities. An AE that is assessed as severe should not 
be confused with a SAE. Severe is a category utilized for rating the intensity of an event; and both AEs 
and SAEs can be assessed as severe.
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as described in the 
definition of an SAE, NOT when it is rated as severe.
Assessment of Causality
x
The Investigator is obligated to assess the relationship between study treatment and each occurrence of 
each AE/SAE. The AE must be characterized as unrelated, possibly related, and related.
o
“Unrelated” clinical event with an incompatible time relationship to study drug
administration, and that could be explained by an underlying condition or other drugs or 
chemicals or is incontrovertibly not related to the IP
o
“Possibly related” Clinical event with a reasonable time relationship to study drug
administration, and that is unlikely to be attributed to concurrent condition or other drugs or 
chemicals
o
“Related” Clinical event with plausible time relationship to study drug administration and that 
cannot be explained by concurrent condition or other drugs or chemicals
x
The Investigator will use clinical judgment to determine the relationship.
x
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, as well 
as the temporal relationship of the event to study treatment administration will be considered and 
investigated.
x
The Investigator will also consult the IB and/or Product Information, for marketed products, in his/her 
assessment.
x
For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed the 
AE/SAE and has provided an assessment of causality.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
72
x
There may be situations in which an SAE has occurred and the Investigator has minimal information to 
include in the initial report to 
 Safety. However, it is very important that the 
Investigator always make an assessment of causality for every event before the initial transmission of 
the SAE data to 
 Safety.
x
The Investigator may change his/her opinion of causality in light of follow-up information and send a 
SAE follow-up report with the updated causality assessment.
x
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.
Follow-up of AEs and SAEs
x
The Investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by 
 Safety to elucidate the 
nature and/or causality of the AE or SAE as fully as possible. This may include additional laboratory 
tests or investigations, histopathological examinations, or consultation with other health care 
professionals.
x
If a subject dies during participation in the study, the Investigator will provide 
 Safety
with a copy of any postmortem findings.
x
New or updated information will be recorded in the originally completed CRF.
x
The Investigator will submit any updated SAE data to the 
 Safety within 24 hours of 
receipt of the information.
Reporting of SAEs
SAE Reporting to 
 Safety via an Electronic Data Collection Tool
x
The primary mechanism for reporting an SAE to 
 Safety team will be the electronic 
data collection tool.
x
If the electronic system is unavailable for more than 24 hours, then the study center will use the paper 
SAE data collection tool (see next section).
x
The study center will enter the SAE data into the electronic system as soon as it becomes available.
x
After the study is completed at a given study center, the electronic data collection tool will be taken 
off-line to prevent the entry of new data or changes to existing data.
x
If a study center receives a report of a new SAE from a subject or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken off-line, then the study 
center can report this information on a paper SAE form (see next section) or (see next section) and 
send the paper SAE form to 
Safety team via facsimile transmission.
x
Contacts for SAE reporting can be found in SAE form.
SAE Reporting to 
 Safety via Paper CRF
x
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this information to 
the 
 Safety team.
x
In rare circumstances and in the absence of facsimile equipment, notification by telephone is 
acceptable with a copy of the SAE data collection tool sent by overnight mail or courier service.
x
Initial notification via telephone does not replace the need for the Investigator to complete and sign the 
SAE CRF pages within the designated reporting time frames.
x
Contacts for SAE reporting can be found in SAE reporting form.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
73
Appendix 5
Excluded Medications/Therapy
Excluded medications/therapy is listed below. The use of an excluded medication/therapy is a 
protocol violation and must be recorded in the eCRF.
Any therapy likely to have efficacy in GPP or psoriasis is prohibited. If treatment with any of 
these prohibited treatments is essential then the subject must notify the study team and they will 
be withdrawn from the trial.
All treatments likely to have efficacy in GPP need to be discontinued prior to treatment initiation 
(prior to Day 1) with washout periods as stipulated in Table 6.
A tapering washout of systemic therapies (eg, cyclosporine, methotrexate, and retinoids) can be 
used and the study drug can be introduced before the end of the washout period. Systemic 
conventional medications (eg, cyclosporine, methotrexate, and retinoids) must be stopped at the 
day the study drug has been administered.
Table 6
List of Excluded Medications
Treatment
Washout period
Topical medication (including corticosteroid, retinoids or vitamin 
A or D analog preparations, tacrolimus, calcineurin inhibitor, 
topical H1 and H2 antihistamines, tar preparations, keratolytics, 
topical antimicrobials, other medicated topical agents) or herbal 
preparation
2 weeks 
Methotrexate, cyclosporin, acitretin, alitretinoin, Fumaric acid 
esters, and corticosteroids or any other immunosuppressant or 
immunomodulating drugs
4 weeks 
Anti-tumor necrosis factor/interleukin (IL-12/IL-23) and IL-17 or 
any other mAbs
3 months or 5 half -lives
Cyclophosphamide
6 months
Phototherapy or PUVA 
4 weeks 
Antibiotics and antivirals
Topical: 2 weeks
Systemic: 4 weeks
Other investigational drugs 
30 days or 5 half-lives (whichever 
is longer) 
Live attenuated vaccines 
3 months
Abbreviations: mAbs = monoclonal antibodies; PUVA = psoralen and ultraviolet A.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
74
Appendix 6
Contraceptive Guidance and Collection of Pregnancy 
Information
Definitions:
Woman of childbearing potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below).
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot be 
confirmed before first dose of study intervention, additional evaluation should be considered.
Women in the following categories are not considered WOCBP
1. Premenarchal
2. Premenopausal female with 1 of the following:
x
Documented hysterectomy.
x
Documented bilateral salpingectomy.
x
Documented bilateral oophorectomy.
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), Investigator discretion should be 
applied to determining study entry.
Note: Documentation can come from the study center personnel’s: review of the subject’s 
medical records, medical examination, or medical history interview.
3. Postmenopausal female:
x
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient.
x
Females on HRT and whose menopausal status is in doubt will be required to use 1 of the 
non-estrogen hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation 
of postmenopausal status before study enrollment.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
75
Contraception Guidance
Male subjects
x
Male subjects with female partners of childbearing potential are eligible to participate if they
agree to ONE of the following (during the protocol-defined time frame in Section 5.1):

Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle 
(abstinent on a long-term and persistent basis) and agree to remain abstinent.

Agree to use a male condom plus partner use of a contraceptive method with a failure 
rate of <1% per year when having penile-vaginal intercourse with a WOCBP who is 
not currently pregnant.
x
In addition, male subjects must refrain from donating sperm for the duration of the study and 
for 220 days (which includes the duration of relevant exposure plus the duration of sperm 
cycle) after the last dose of study treatment.
x
Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom during each episode of penile penetration 
for the duration of the study and for 220 days (which includes the duration of relevant 
exposure plus the duration of sperm cycle) after the last dose of study treatment.
Female subjects
Female subjects of childbearing potential are eligible to participate if they agree to use highly 
effective methods of contraception consistently and correctly as described in the table below.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
76
Highly Effective Contraceptive Methods
Highly Effective Contraceptive Methods That Are User Dependent a
Failure rate of <1% per year when used consistently and correctly. 
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
x
Oral.
x
Intravaginal.
x
Transdermal.
Progestogen only hormonal contraception associated with inhibition of ovulation
x
Oral.
x
Injectable.
Highly Effective Methods That Are User Independent a
Implantable progestogen only hormonal contraception associated with inhibition of ovulation
x
Intrauterine device (IUD).
x
Intrauterine hormone-releasing system (IUS).
Bilateral tubal occlusion.
Vasectomized Partner
A vasectomized partner is a highly effective birth control method provided that the partner is the sole male sexual 
partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method 
of contraception should be used. 
Sexual Abstinence
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the subject.
NOTES:
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent with 
local regulations regarding the use of contraceptive methods for subjects participating in clinical studies. 
Pregnancy Testing:
x
Women of childbearing potential should only be included after a confirmed menstrual period 
and a negative highly sensitive serum pregnancy test at Screening and urine pregnancy test 
on Day 1 (prior to study treatment administration).
x
Women of childbearing potential should refrain from donating oocytes for assisted 
reproduction during this period.
x
Additional pregnancy testing should be performed as mentioned in the Schedule of Activities 
(see Section 1.3).
x
Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected. Positive urine pregnancy test result should be confirmed 
with serum test.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
77
Collection of Pregnancy Information
Male subjects with partners who become pregnant
x
The Investigator will attempt to collect pregnancy information on any male subject’s female 
partner who becomes pregnant while the male subject is in this study. This applies only to 
male subjects who receive study treatment.
x
After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate pregnancy 
form and submit it to the Sponsor within 24 hours of learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the Sponsor. Generally, the follow-
up will be no longer than 6 to 8 weeks following the estimated delivery date. Any 
termination of the pregnancy will be reported regardless of fetal status (presence or absence 
of anomalies) or indication for the procedure.
Female subjects who become pregnant
x
The Investigator will collect pregnancy information on any female subject who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the Sponsor within 24 hours of learning of a subject’s pregnancy.
x
The subject will be followed to determine the outcome of the pregnancy. The Investigator
will collect follow-up information on the subject and the neonate and the information will be 
forwarded to the Sponsor. Generally, follow-up will not be required for longer than 6 to 8 
weeks after the delivery date. Any termination of pregnancy will be reported, regardless of 
fetal status (presence or absence of anomalies) or indication for the procedure.
x
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous 
abortion is always considered to be an SAE and will be reported as such.
x
Any post-study pregnancy related SAE considered reasonably related to the study treatment 
by the Investigator will be reported to the Sponsor as described in Section 8.3.5. While the 
Investigator is not obligated to actively seek this information in former subjects, he or she 
may learn of an SAE through spontaneous reporting.
x
Any female subject who becomes pregnant while participating in the study will be withdrawn 
from the study.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
78
Appendix 7
Genetics
Use/Analysis of DNA/mRNA
x
Genetic variation may impact a subject’s response to study treatment, susceptibility to, and 
severity and progression of disease. Variable response to study treatment may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and excretion; 
mechanism of action of the drug; disease etiology; and/or molecular subtype of the disease 
being treated. Therefore, where local regulations and IRB/IEC allow, a blood sample will be 
collected for DNA analysis from consenting subjects.
x
DNA/mRNA samples will be used to study disease pathogenesis and to determine potential 
genetic biomarkers of response to treatment. Genetic research may consist of the analysis of 
1 or more candidate genes or the analysis of genetic markers throughout the genome or 
analysis of the entire genome.
x
DNA samples will be analyzed for genetic analysis.
x
The samples may be analyzed as part of a multi-study assessment of genetic factors involved 
in the response to study treatment or study treatments of this class to understand study 
disease or related conditions.
x
Samples will be sent to the designated laboratory where they will be stored according to ICH
GCP and GLP requirements with adequate measures to protect confidentiality. Genetic 
analysis using DNA/mRNA samples may be performed by additional third party (eg, a 
university Investigator) designated by the Sponsor. The results of genetic analyses may be 
reported in the CSR or in a separate study summary.
x
The samples may be retained while research on study treatment or study treatments of this 
class or indication continues as described in the ICF.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
79
Appendix 8
Clinical Global Impression
Category
Change in modified 
JDA severity index total 
score for GPP
and/or
Category description
Very much improved
Reduction by 3 or >points 
or
Clear or almost clear of signs of GPP
Much improved
Reduction by 1 or 2 
points
or
At least one of the following:
x
Area of erythema with pustules (%) 
reduced by <30%
or
x
Clinically meaningful improvement 
in at least 2 other components of
the modified JDA severity index 
for GPP (area of erythema, area of 
edema, fever, WBC, CRP, Alb)
Minimally improved
0 points (no change)
and
At least one of the following:
x
Area of erythema with pustules (%) 
reduced by <20%
or
x
Clinically meaningful improvement 
in at least 1 other components of 
the modified JDA severity index 
for GPP (area of erythema, area of 
edema, fever, white blood cell 
[WBC], C-reactive protein [CRP],
Alb)
No change
0 points (no change)
and
Not meeting the other criteria of “minimally 
improved”
Worsened
> + 1 point
-
Not applicable

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
80
Appendix 9
Modified Japanese Dermatological Association (JDA) 
Severity Index
Score
0
1
2
3
Assessment of skin lesions
Area of erythema with pustules
0%
> 0%, < 10%
≥ 10%, < 50%
≥ 50%
Area of erythema (total)
0%
> 0%, < 25%
≥ 25%, < 75%
≥ 75%
Area of edema
0%
> 0%, < 10%
≥ 10%, < 50%
≥ 50%
Assessment of systemic manifestations and laboratory findings
Fever
<37oC
(<98.6 F)
≥ 37oC, < 38.5oC
≥98.6 F, <101.3 F
≥ 38.5oC
(≥101.3 F)
_
WBC count
<10,000/μL
(<10 × 109/L)
≥10,000/μL, <15,000 μL
(≥10 × 109/L, <15 × 109/L)
≥15,000/μL
(≥15 × 109/L)
_
CRP
< 0.3 mg/dL
(<3 mg/L)
≥ 0.3 mg/dL, < 7 mg/dL
(≥3 mg/L, < 70 mg/dL)
≥7 mg/dL
(≥ 70 mg/dL)
_
Serum albumin
≥ 3.8 mg/dL
(≥ 38 g/L)
< 3.8 g/dL, ≥3 mg/dL
(< 38 g/L, ≥ 30 g/L)
< 3 mg/dL
(< 30 g/L)
_
Severity index (total score): 1-6=mild; 7-10=moderate; 11-17=severe
The table is adapted from Imafuku S, Honma M, Okubo Y, Komine M, Ohtsuki M, Morita A, et 
al. Efficacy and safety of secukinumab in patients with generalized pustular psoriasis: A 52 week 
analysis from phase 3 open-label multicenter Japanese study. The Journal of Dermatology. 
2016;43:1011-1017.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
82
Appendix 11
Generalized Pustular Psoriasis Physician Global 
Assessment Scale
The GPPPGA scale will be used to assess the impact and severity of GPP. The Investigator will 
rate the impact and severity of disease at each study visit (excluding those that are phone calls) 
using the following scale.
Score 
Wording  
Detailed description
0
Clear 
Normal skin or post - inflammatory hyperpigmentation, no visible 
pustules, no scaling or crusting
1
Almost clear 
Faint, diffuse pink or slight red erythema, low density occasional 
small discrete pustules (noncoalescent), superficial focal scaling 
or crusting restricted to periphery of lesions
2
Mild 
Light red erythema, moderate density grouped discrete small 
pustules (noncoalescent), predominantly fine scaling or crusting
3
Moderate 
Bright red erythema, high density pustules with some coalescence, 
moderate scaling or crusting covering most or all lesions
4
Severe 
Deep fiery red erythema, very high density pustules with pustular
lakes, severe scaling or crusting covering most or all lesions
 
The table is adapted from Bachelez H, Choon SE, Marrakchi S, et al. Inhibition of the IL-36
Pathway for the Treatment of Generalized Pustular Psoriasis. N Engl J Med 2019; 380:(10).

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
83
Appendix 12
Dermatology Life Quality Index
The aim of this questionnaire is to measure how much your skin problem has affected your 
life OVER THE LAST WEEK. Please tick ; one box for each question.
1. Over the last week, how itchy, sore, painful or stinging has your skin been?
❏Very much ❏A lot ❏A little ❏Not at all
2. Over the last week, how embarrassed or self-conscious have you been because of your skin?
❏Very much ❏A lot ❏A little ❏Not at all
3. Over the last week, how much has your skin interfered with you going shopping or looking 
after your home or garden?
❏Very much ❏A lot ❏A little ❏Not at all ❏Not relevant
4. Over the last week, how much has your skin influenced the clothes you wear?
❏Very much ❏A lot ❏A little ❏Not at all ❏Not relevant
5. Over the last week, how much has your skin affected any social or leisure activities?
❏Very much ❏A lot ❏A little ❏Not at all ❏Not relevant
6. Over the last week, how much has your skin made it difficult to do any sport?
❏Very much ❏A lot ❏A little ❏Not at all ❏Not relevant
7. Over the last week, has your skin prevented you from working or studying?
❏Yes ❏No ❏not relevant
If "No", over the last week, how much has your skin been a problem at work or
studying?
❏A lot ❏A little ❏Not at all
8. Over the last week, how much has your skin created problems with your partner or any of 
your close friends or relatives?
❏Very much ❏A lot ❏A little ❏Not at all ❏Not relevant
9. Over the last week, how much has your skin caused sexual difficulties?
❏Very much ❏A lot ❏A little ❏Not at all ❏Not relevant

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
84
10.Over the last week, how much of a problem has the treatment for your skin been, for 
example by making your home messy, or by taking up time?
❏Very much ❏A lot ❏A little ❏Not at all ❏Not relevant
AY Finlay, GK Kahn. Dermatology Life Quality Index (DLQI): A simple practical measure for 
routine clinical use. Clinical and Experimental Dermatology 1994; 19: 210-216.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
85
Appendix 13
Summary of Changes
Protocol ANB019-002: Amendment 1, 15 January 2018
Replaces: Original Protocol, 12 December 2017
Section 1.1 Synopsis, Section 4.1 Overall Design and Table 1 Schedule of Activities (footnote)
x
Description of Change: Added text to indicate that a minimum 3 hour observation period is 
required after the first and second subcutaneous injections and deleted from the following 
text ‘no such limit for study center observation after SC administration’.
x
Purpose of Change: Medicines and Healthcare Products Regulatory Agency (MHRA)
request.
Section 5.1 Inclusion Criteria and Appendix 6 Contraceptive Guidance and Collection of Pregnancy 
Information:
x
Description of Change: Text revised to specify that in addition to prohibition on sperm 
donation for the specified duration, ova donation for assisted reproduction is also prohibited. 
The duration for males was revised to 220 days (from 6 months).
x
Purpose of Change: MHRA request.
Protocol ANB019-002: Amendment 2, 27 July 2018
Replaces: Amendment 1, 15 January 2018
Section 1.1 Synopsis and Section 4.1 Overall Design:
x
Description of Change: Text revised to remove a minimum of 7 days screening period 
requirement and updated ‘up to 28 days’.
x
Purpose of Change: To simplify enrollment of newly diagnosed subjects.
x
Description of change: Updated the number of Investigators and number of study centers 
from 3 to 5.
x
Purpose of change: To reflect the updated number of Investigators and study centers 
(administrative change).
Section 2.2 Background (Clinical studies).
x
Description of Change: Added the percentage for mild and moderate TEAEs and details 
about 1 severe AE.
x
Purpose of Change: To reflect the updated Phase I Study results (ANB019-001, SAD part).
Section 2.2 Background and Section 2.3 Benefit/Risk Assessment:
x
Description of Change: Text revised to include SAD (PP) safety and MAD (healthy 
volunteers) safety and PK data from the Phase I study (ANB019-001) in healthy volunteers 
and PP subjects.
x
Purpose of Change: To reflect New safety and PK data from the Phase I study (ANB019-
001).

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
86
Section 5.1 Inclusion Criteria:
x
Description of Change: Added SI and conventional units for hemoglobin, white blood cell 
count, platelets, and serum creatinine.
x
Purpose of Change: To reflect both SI and conventional units for hemoglobin, white blood 
cell count, platelets, and serum creatinine.
Section 5.2 Exclusion Criteria:
x
Description of Change: Text revised to clarify the requirement to stop all systemic
conventional therapies (eg. cyclosporine, methotrexate, and retinoid) the day the study drug 
is administered.
x
Purpose of Change: To clarify the use of systemic therapies in case of tapering washout at 
study start.
x
Description of Change: Revised to remove definition of regular alcohol consumption and 
excessive smoking
x
Purpose of Change: Text removed as definition is not applicable in United Kingdom.
Section 5.3 1 Meals and Dietary Restrictions:
x
Description of Change: Removed Meals and Dietary Restrictions.
x
Purpose of Change: Section removed as study centers are not going to provide meal and
subjects are allowed to bring meal for themselves.
Section 6.2 Preparation /Handling/Storage/Accountability
x
Description of Change: Text regarding ANB019 storage reworded slightly and deleted the 
repetitive text
x
Purpose of Change: Sentence combined to avoid repetition.
Section 6.5.1 Rescue Medicine:
x
Description of Change: Section revised to include guidance for using rescue medication in 
the form of topical corticosteroids (eg. betamethasone valerate ointment and cream, 
mometasone furoate ointment and cream) and guidance for adding any systemic psoriasis 
medication that is likely to impact psoriasis signs and symptoms (eg. cyclosporine, 
methotrexate, retinoid).
x
Purpose of Change: To provide clarity on rescue medication usage.
x
Description of Change: Added text to indicate ‘introduction of any rescue medication must 
be communicated and discussed with the Sponsor’.
x
Purpose of Change: To ensure that use of rescue medication must be communicated and 
discussed with the Sponsor.
Section 8.0 Study Assessments and Procedures.
Section 8.1.4 Total Body Surface Area (Study Assessments and Procedures).
x
Description of Change: Revised to remove the section 8.1.4 describing assessment of body 
surface area affected by GPP.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
87
x
Purpose of Change: Text removed as BSA involvement is measured as part of modified JDA 
scale.
Section 8.2.5 Chest X-ray and Table 1 Schedule of Assessment (footnote).
x
Description of Change: Bidirectional posterior-anterior and lateral view chest X-ray or as 
indicated by local treatment guidelines or practice is updated to include that it will be 
performed at Screening if not performed within 6 months prior to screening and other 
time points specified in the Schedule of Activities.
x
Purpose of Change: To provide clarity on the time point of X-ray.
x
Description of Change: Added text to indicate that ‘In case of early discontinuation, the 
subject will be encouraged to return to the study center for the follow-up period visits 
(Week 16/Day 113 and Week 20/Day 141) and ET/EOS visit (Week 24/Day 169). The 
follow-up period visits are not actual calendar weeks and have to occur 4/8/12 Weeks post-
discontinuation.’
x
Purpose of Change: To provide clarity in case of early discontinuation and follow-up period 
(ET/EOS visit).
Section 8.3.7 Infusion-related adverse events:
x
Description of Change: Added text to indicate that a minimum 3 hour observation period is 
required after the first and second SC injections and deleted the following text: “no such limit 
for study center observation after SC administration”. In addition, text regarding IV 
administration modified to improve clarity.
x
Purpose of Change: To provide details regarding duration of assessment period after SC 
administration and text reworded for clarity.
Section 8.8 Biomarkers:
x
Description of Change: Storage duration of biomarkers sample were updated to 5 years from 
1 year.
x
Purpose of Change: To reflect the country specific storage requirement.
Section 8.9 Immunogenicity assessment:
x
Description of Change: Immunogenicity Sample storage time period updated from 1 to 5 
years.
x
Purpose of Change: To reflect the country specific storage requirement.
x
Description of Change: Added text to indicate that “only samples within the stability window 
of the assay will be analyzed”.
x
Purpose of Change: Updated to clarify that only the samples within the stability window of 
assay will be analyzed.
Appendix 2 Regulatory, Ethical, and Study Oversight Considerations (Administrative Structure),
Medical Monitor.
x
Description of Change: 
 emergency contact number updated.
x
Purpose of Change: Administrative change.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
88
Appendix 8 Signature of Investigator.
x
Description of Change: Protocol version updated to ‘Amendment 2’.
x
Purpose of Change: Administrative change.
Additional changes in Table 1 Schedule of Activities:
x
Description of Change: Screening period updated to include “up to 28 days.
x
Purpose of Change: To simplify the enrollment of newly diagnosed subjects.
x
Description of Change: Removed “total BSA”.
x
Purpose of Change: Text removed as BSA involvement is measured as part of modified JDA 
scale.
In addition, minor spelling, grammar, abbreviations, and formatting corrections have been made
Protocol ANB019-002: Amendment 3, 20 March 2019
Replaces: Amendment 2, 27 July 2018
Title Page:
x
Description of the change: Title page updated to reflect ‘Amendment 3.’
x
Purpose of the change: Administrative change.
Sponsor Signature Page:
x
Description of the change: Updated wording added to indicate Sponsor’s responsibilities in 
signing the signature page; revised Sponsor signatory information
x
Purpose of the change: To better align with the format in other clinical program protocols.
Investigator Signature Page:
x
Description of the change: Moved the Investigator Signature Page from Appendix 2 to just 
after the Table of Contents and updated wording to indicate Investigator’s responsibilities in 
signing the signature page.
x
Purpose of the change: As requested by the clinical development team to align with other 
similar protocols.
Synopsis and Global
x
Description of the change: Formatted references from superscript to author/year format to 
align with regulatory publication guidelines.
x
Purpose of the change: To align with revised Anaptys Style Guide.
x
Description of change: Updated the number of Investigators and number of study centers 
from 5 to 8-10.
x
Purpose of change: To reflect the updated number of Investigators and study centers 
(administrative change).

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
89
Synopsis and Section 3:
x
Description of the change: Additional wording added to the secondary endpoints for PK 
analysis; moved immunogenicity objective (to assess ADA) from exploratory to secondary 
endpoint; retitled tertiary/exploratory endpoints section to exploratory endpoints.
x
Purpose of the change: To capture an additional endpoint and to better clarify the PK and 
pharmacogenomic testing; to place greater emphasis on immunogenicity testing.
x
Description of the change: Added an additional secondary endpoint to assess the proportion 
of subjects achieving a score of 0 or 1 on the Generalized Pustular Psoriasis Physician’s 
Global Assessment scale.
x
Purpose of the change: To further characterize efficacy assessments for GPP.
Synopsis, Section 1.3 Schedule of Activities, and Section 4 Study Design
x
Description of the change: Revised the screening period from “up to 28 days” to “up to 
42 days (Week -0).”
x
Purpose of the change: To allow for more flexibility during the screening period.
1.3 Schedule of Activities
x
Description of the change: Added a row for whole blood collection for mRNA; added a 
footnote to clarify those study visits that were phone contact only; rearranged order of 
footnotes
x
Purpose of the change: To align with the additional PK endpoint added in the synopsis and 
Section 3; to improve clarity on phone visits versus site visits.
2.2 Background
x
Description of the change: Added a reference in the text to a previously published CSR.
x
Purpose of the change: To cite data that had been described in this section.
4 Study Design, 8.2.4 Pharmacokinetics
x
Description of the change: Added Table to detail the sample collection and time points for 
PK and ADA testing
x
Purpose of the change: To easily identify collection times and visit requirements for PK and 
ADA testing.
5.1 Inclusion Criteria
x
Description of the change:
o
Revised criterion #1 to increase the upper age limit from 65 to 75.
o
Revised criterion #3 regarding disease criteria for study entry during the screening
period;
o
Revised criterion #6 to omit repeat confirmation for ALT or AST that was above the 
ULN

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
90
x
Purpose of the change:
o
To clarify requirements for subjects entering the study with regards to JDA score and 
percentage of affected BSA;
o
To streamline and clarify procedures.
5.2 Exclusion criteria
x
Description of the change:
o
Criterion #1: Removed 2 examples of other forms of psoriasis that were excluded 
from participation
o
Criterion #17: Added a phrase that history of drug and alcohol abuse and any 
potential impact on the ability to participate would be “determined by the 
Investigator.”
x
Purpose of the change: To allow greater flexibility for eligibility.
6.5.1 Rescue Medication
x
Description of the change: Minor wording edits to this section regarding use of rescue 
medication and withdrawal of subjects.
x
Purpose of the change: To improve text clarity and streamline details.
6.6 Dose Modification
x
Description of the change: Added wording to clarify that study treatment may be interrupted 
only once before being permanently discontinued.
x
Purpose of the change: To clarify dose modification versus when subjects should be 
withdrawn.
7.1 Discontinuation of Study Treatment
x
Description of the change: Revised the wording of this section to clarify discontinuation from 
treatment versus study and to better characterize subjects who are considered early 
termination.
x
Purpose of the change: To align with common protocol template language.
7.1.1 Temporary Interruption
x
Description of the change: Revised the heading title. Added some additional text about 
recurring or new AEs related study treatment interruption.
x
Purpose of the change: To clarify guidelines for interruption of study treatment and to 
specify that interruption would be allowed only once per subject.
7.1.2 Re-challenge
x
Description of the change: Added a statement that this was not applicable.
x
Purpose of the change: Details about restarting treatment that has been interrupted is 
covered in the previous section and this section is not needed; however, a placeholder 
sentence was added to cover this section.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
91
8.1.4 Generalized Pustular Psoriasis Physician’s Global Assessment Scale
x
Description of the change: New section added to describe the GPPPGA scale.
x
Purpose of the change: This assessment scale was added as a secondary endpoint to assess 
the impact of GPP at each study visit. Appendix 12 was also added to include the scale.
8.2.4 Electrocardiograms
x
Description of the change: Clarified that ECGs will be reviewed by the central laboratory 
“for quality and interpretation” and that ECG data would not be entered into EDC with the 
exception of clinical significance.
x
Purpose of the change: To reduce confusion over procedures and clarify the central lab’s role 
in ECG processing.
8.2.6 Photography
x
Description of the change: Language was revised to describe a standardized approach for 
collection of photographs and the process for transfer and quality review.
x
Purpose of the change: To provide further guidance and clarity.
8.2.8 Telephone Contact
x
Description of the change: Added this section to clarify the visits that are phone contact only 
versus site visits.
x
Purpose of the change: To clarify visit purpose and procedures for phone contact.
8.5 Pharmacokinetics
x
Description of the change: Added Table 2 to outline the collection schedule for 
pharmacokinetic assessments during the study.
x
Purpose of the change: To clarify PK collection time points.
8.7 Genetics
x
Description of the change: Revised language to characterize additional DNA/RNA testing
and optional pharmacogenomic testing
x
Purpose of the change: To align with revisions made to exploratory endpoints for PK and 
pharmacogenomics
9.3 Populations for Analyses
x
Description of the change: Updated Table 3 to describe analysis populations.
x
Purpose of the change: To better align with the statistical analysis plan for this study.
9.4.4 Efficacy Analyses
x
Description of the change: Added additional text to support the added efficacy endpoint for 
the GPPPGA at Weeks 1 through 16.
x
Purpose of the change: To describe the analysis associated with this endpoint.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
92
9.4.6 Immunogenicity Analyses
x
Description of the change: added description of how statistical data will be presented
x
Purpose of the change: Text added to better characterize the presentation of statistical data for 
ADA status and efficacy and safety endpoints
9.4.8 Biomarker Analyses
x
Description of the change: Removed the following sentences – Results will be presented in
terms of 95% CIs. In addition, the n, mean, SD, median, minimum and maximum will also be 
prevented.
x
Purpose of the change: To clarify language in this section, as well as presentation of data.
10
References
x
Description of the change:
o
Added the following reference: A Double-Blind, Randomized, Placebo-Controlled, 
Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) Study to 
Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of 
ANB019 in Healthy Subjects and Psoriasis Patients. Protocol No.: ANB019-001.
Clinical Study Report. 22 June 2018
o
Added the following reference: Bachelez H, Choon SE, Marrakchi S, et al. 
Inhibition of the IL-36 Pathway for the Treatment of Generalized Pustular 
Psoriasis. N Engl J Med 2019; 380:(10).
o
Added the following reference: Marrakchi S, Burden A, Tsai T, et al. Inhibition of 
the Interleukin-36 Pathway for the Treatment of Generalized Pustular Psoriasis 
[To the Editor]. N. Engl. J. Med. 2019; 380:10.
x
Purpose of the change:
o
To provide a citation for clinical trial data and information provided in Section 2.
o
To provide a citation for the GPPPGA scale in the objectives and endpoints, as well 
as Appendix 11.
o
To provide a citation for the description of the GPPPGA scale in Section 8.1.4.
Appendix 8 Signature of Investigator
x
Description of the change: Removed this appendix and renumbered remaining appendices.
x
Purpose of the change: Moved the Investigator’s signature up to immediately follow the 
Sponsor’s signature at the beginning of the document to better align with AnaptysBio 
preferences for protocol organization.
Appendix 11 Generalized Pustular Psoriasis Physician’s Global Assessment
x
Description of the change: New appendix was added.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
93
x
Purpose of the change: To support the added secondary endpoint of the GPPPGA assessment 
at each study visit.
In addition, minor spelling, grammar, abbreviations, editing, and formatting corrections have 
been made throughout, as needed.
Protocol ANB019-002: Amendment 4, 30 August 2019
Replaces: Amendment 3, 20 March 2019
Overall Rationale for the Amendment: 
This amendment was prepared to incorporate significant changes to the statistical methods section to 
characterize how the study endpoints would be analyzed, as well as to modify the eligibility criteria and 
correct other inconsistencies within the text.
Global Changes
x
Description of the change: Minor edits applied for spelling and grammar, formatting, consistency, 
and spacing as needed.
x
Purpose of the change: To clean-up for consistency, style, and formatting
Section 1.1 Protocol Synopsis, Section 3 Study Objectives
x
Description of the change: Revised the secondary objectives to remove change from Baseline in 
GPPPGA score at all study visits and to assess change in Dermatology Life Quality Index (DLQI) 
total score instead of improvement in DLQI total score at all visits. Exploratory endpoint was 
revised for skin biopsies to assess IL-8 dendritic cells, not IL-6 dendritic cells. Removed 
references to logistic regression model using logit link.
x
Purpose of the change: Statistical methods were revised to better characterize the proposed 
endpoints and goals of the study. The IL-8 change was necessary to correct inconsistencies in the 
protocol.
Section 1.1. Synopsis
x
Description of the change: In the statistical methods section, a paragraph regarding the primary 
endpoint analysis was deleted.
x
Purpose of the change: The discussion in the protocol is designed to be more brief and concise, 
with full details provided in the SAP.
Section 1.3 Schedule of Activities
x
Description of the change: Footnote p was removed. Additional footnotes were moved and 
adjusted as needed on the schedule.
x
Purpose of the change: To provide clarity and consistency in the table.
Section 2.3 Benefit/Risk Assessment
x
Description of the change: Added one paragraph about an SAE of sepsis that has been reported 
during the study for 1 subject.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
94
x
Purpose of the change: To better characterize known safety issues to date. This event was 
considered possibly related; the subject had a medical history of sepsis.
Section 5.1 Inclusion Criteria
x
Description of the change:
o
Criterion 5 was removed which specified the enrollment of subjects with or without a 
history of PP and PsA.
o
Criterion 5 (formerly 6): a statement was added that any laboratory values that are out-of-
range at Screening will be left to the Investigator’s discretion as to whether or not a 
subject is eligible.
x
Purpose of the change: To clarify permitted disease characteristics of the study population. 
Subjects must have active diagnosis of generalized pustular psoriasis (GPP) and to allow greater 
flexibility for Investigator assessment after consultation with 
 Medical Monitor and the 
Sponsor for determination of eligibility for out or range laboratory assessments
Section 5.2 Exclusion Criteria
x
Description of the change: Criterion 13 was modified to include squamous cell carcinoma 
deemed fully treatable by the Investigator as permissible.
x
Purpose of the change: To clarify permitted disease characteristics of the study population. 
Subjects must have active diagnosis of generalized pustular psoriasis (GPP) and to allow greater 
flexibility for Investigator assessment
Section 6.1 Study Treatments Administered, Table 1
x
Description of the change: Revised the table to clarify the language around dose administration 
and to state that infusions may be slowed for subjects experiencing infusion-related reactions. 
Removed rows for packaging and manufacturing.
x
Purpose of the change: To clarify the study treatment language and make the table more concise.
Section 6.7 Treatment After End of Study
x
Description of the change: Revised the statement on collection of AEs to include any occurring 
through End of Study (rather than 30 days after End of Study
x
Purpose of the change: To clarify collection and timing of adverse events.
Section 8.2.7 Clinical Safety Laboratory Assessments
x
Description of the change: Added a bullet to indicate that screening laboratory assessments that 
were out-of-range would be reviewed by the Investigator to determine eligibility.
x
Purpose of the change: To allow greater flexibility for Investigator assessment and determination 
of eligibility for out or range laboratory assessments.
Section 8.5 Pharmacokinetics
x
Description of the change:
o
Added a paragraph to the text to indicate how samples will be collected and divided for 
primary and back-up analysis.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
95
o
Removed collection specification for 5 mL Vaccutainer X tube.
o
Clarified that sample collection time will be documented using a 24-hour clock. Included 
a statement on procedures is a subject refuses PK blood sample collection.
o
Revised Table 2 to add a footnote to the Day 1 PK collection timepoint to clarify that the 
PK collection must begin immediately at the end of the infusion.
x
Purpose of the change: For clarity on sample collection and documentation.
Section 8.8 Biomarkers
x
Description of the change: Revised the sentence on measurement of skin biopsy markers to 
clarify that analyses may be performed by a third party. Revised the language on blood sample 
collection to clarify the assay to be used. IL-6 was deleted from the list of biomarkers.
x
Purpose of the change: To allow greater flexibility on sample analysis.
Section 8.9 Immunogenicity Assessments
x
Description of the change: Added a statement to clarify how aliquot samples will be divided. 
Removed a statement that clarified the length of time for sample storage.
x
Purpose of the change: To provide clarity on sample collection procedures.
Section 9.3 Population for Analyses, Table 3
x
Description of the change: Removed the ITT Analysis Set and replaced with Full Analysis Set 
(FAS) in the table. Removed any references to randomization. The PPS will now be based on the 
FAS instead of the ITT set.Additional text was added to clarify use of the PK analysis set.
x
Purpose of the change: This is an open-label study. All enrolled subjects will be analyzed 
according to treatment received.
Section 9.4.4.1 Primary Efficacy Endpoint Analyses
x
Description of the change: Added a clarification on the analysis of clinical response and Clinical 
Global Impression (CGI) score. Deleted detailed text on statistical analysis as it will be moved to 
the SAP.
x
Purpose of the change: For clarity on statistical analysis presentation.
Section 9.4.4.2 Secondary Efficacy Endpoint Analyses
x
Description of the change:
o
Clarified that secondary endpoints will be analyzed at all study visits through Week 16 
for modified JDA severity index score, descriptive statistics, GPPPGA score, and PASI 
score. Deleted detailed text on statistical analysis as it will be moved to the SAP.
o
Included a statement that summary statistics will be provided for average DLQI scores 
instead of absolute scores, in addition to the percent change from Baseline through Week 
16 instead of by study visit.
x
Purpose of the change: For greater clarity on secondary endpoint analysis.
Section 9.4.7.1 Derivation of PK Parameters

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
96
x
Description of the change: Clarified that PK parameters will be analyzed using the PK analysis 
set.
x
Purpose of the change: For clarity of analysis description.
Section 9.4.7.2 Pharmacokinetic Concentrations
x
Description of the change: Removed the trough concentrations from plots.
x
Purpose of the change: For clarity of PK analysis.
Section 9.4.8 Exploratory Biomarker Analyses
x
Description of the change: Added additional text to clarify the analysis of exploratory biomarkers 
and how their relationship to ANB019 concentrations will be characterized.
x
Purpose of the change: For greater clarity on exploratory analyses objectives and goals.
Section 9.5 Interim and Final Analyses
x
Description of the change: Added a paragraph to clarify the timing of interim analysis for this 
study.
x
Purpose of the change: Administrative change to clarify interim and final analyses for this study.
Appendix 1 Abbreviations
x
Description of the change: Abbreviations added or removed to align with usage following edits 
for amendment 4.
x
Purpose of the change: Administrative
Appendix 2 Regulatory, Ethical, and Study Oversight
x
Description of the change: Revised Table 4 to clarify study roles between 
 and Anaptys
x
Purpose of the change: For clarity on study administrative structure.
Appendix 7 Genetics
x
Description of the change: Clarified when mRNA will be analyzed. Deleted text regarding the 
duration of retention of samples.
x
Purpose of the change: to align with analysis of DNA samples. The duration of sample retention 
is specified in the ICF.

CONFIDENTIAL
Protocol ANB019-002 – Amendment 5
29 October 2019
97
Protocol ANB019-002: Amendment 5, 29 October 2019
Replaces: Amendment 4, 30 August 2019
Overall Rationale for the Amendment: 
This amendment was prepared to comply with a request from the Medicines and Healthcare Products 
Regulatory Agency to remove the flexibility for Investigators to discuss eligibility for those patients who 
do not meet screening laboratory eligibility criteria.
Global Changes
x
Description of the change: Minor edits applied for formatting and consistency.
x
Purpose of the change: Administrative
Section 5.1 (Inclusion Criterion #5) and Section 8.2.7 Clinical Safety Laboratory Assessments
x
Description of the change: The sentence permitting the Investigator to assess eligibility in 
consultation with the Medical Monitor and the Sponsor, for those subject who fail to meet 
laboratory screening criteria, has been removed.
x
Purpose of the change: To remove this flexibility for subject enrollment and to comply with the 
Medicines and Healthcare Products Regulatory Agency request.