Clinical trial NCT03633396
Conditions: Palmoplantar Pustulosis
Keywords: PPP
Sponsor: AnaptysBio, Inc.
Start date: 2019-05-20; Completion date: 2021-04-23
Enrollment: 59 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A study to evaluate the efficacy and safety, and pharmacokinetic (PK) profile of multiple doses of imsidolimab (ANB019) in adults with palmoplantar pustulosis (PPP)

Detailed description:

Arms: arm 1: Participants will receive placebo administered by subcutaneous injection on Day 1 followed by monthly doses of placebo by subcutaneous injection on Days 29, 57, and 85. arm 2: Participants will receive 200 mg imsidolimab by subcutaneous injection on Day 1 followed by monthly doses of 100 mg imsidolimab by subcutaneous injection on Days 29, 57, and 85.
Interventions: intervention 1: Imsidolimab intervention 2: Placebo
Intervention descriptions: intervention 1: Administered by subcutaneous injection once a month intervention 2: Administered by subcutaneous injection once a month

Protocol documents:
Prot_000.pdf: 
DocuSign Envelope ID: 6E36B6E5-F5F9-40E5-91D2-1E939958022C 
29 October 2020 
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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
 
TITLE PAGE 
 
Protocol Title:                           A Phase 2, Randomized, Placebo-controlled, Double-blind, Multiple 
Dose Study to Evaluate the Efficacy and Safety of ANB019 in 
Subjects with Palmoplantar Pustulosis 
 
Protocol Number:                     ANB019-003 
 
Product:                                     ANB019 
 
Study Phase:                              2 
 
Sponsor Name:                          AnaptysBio, Inc. 
Legal Registered Address:       AnaptysBio, Inc. 
10421 Pacific Center Court, Suite 200, 
San Diego, CA 92121, United States 
Regulatory Agency Identifying Number(s): 
 
National Clinical Trial (NCT) Number: 03633396 
 
Investigational New Drug (IND) Number: 136145 
 
European Clinical Trials Database (EudraCT) Number: 
2017-004022-15 
 
Date of Protocol:                       29 October 2020, Amendment 5


DocuSign Envelope ID: 6E36B6E5-F5F9-40E5-91D2-1E939958022C
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CONFIDENTIAL                                                                                                                   Protocol ANB019-003 - Amendment 5
SPONSOR 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.
AnaptysBio Inc.


DocuSign Envelope ID: 6E36B6E5-F5F9-40E5-91D2-1E939958022C 
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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
INVESTIGATOR’S AGREEMENT 
 
 
 
Protocol Title:              A Phase 2, Randomized, Placebo-controlled, Double-blind, Multiple Dose 
Study to Evaluate the Efficacy and Safety of ANB019 in Subjects with 
Palmoplantar Pustulosis 
 
Protocol Number:        ANB019-003 
 
Protocol Version:         Amendment 5; 29 October 2020 
 
This protocol is a confidential communication of the Sponsor. I confirm that I have read this 
protocol; I understand it; and I will work according to this protocol. I will also work consistently 
with the ethical principles that have their origin in the Declaration of Helsinki and that are 
consistent with GCPs and the applicable laws and regulations. Acceptance of this document 
constitutes my agreement that no unpublished information contained herein will be published or 
disclosed without prior written approval from the Sponsor. 
 
 
 
Instructions to the Investigator: Please SIGN and DATE this signature page. PRINT your name, 
title, and the name of the study center in which the study will be conducted. Return the signed 
copy to the Sponsor or designee. 
 
 
 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
 
 
Signature of Investigator:        
 
Date:
 
Printed Name: 
 
Investigator Title:                    
 
 
 
 
Name/Address of Center:        


DocuSign Envelope ID: 6E36B6E5-F5F9-40E5-91D2-1E939958022C 
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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
Protocol Amendment Summary of Changes Table 
 
 
DOCUMENT HISTORY 
Document 
Date 
Amendment 5 
29 October 2020 
Amendment 4 
11 Aug 2020 
Amendment 3 
23 June 2020 
Amendment 2 
19 December 2019 
Amendment 1 
17 October 2019 
Original Protocol 
27 July 2019 
 
Amendment 5 (29 October 2020) 
 
Overall Rationale for the Amendment: 
 
This amendment was prepared to change the primary endpoint to PPASI mean change from Baseline, 
update Statistics, and apply minor edits. 
 
Section # and Name 
Description of Change 
Brief Rationale 
Document Header/Footer 
Amendment number was updated in the 
header. The date was updated in the 
footer. 
For accuracy and consistency with 
AnaptysBio style. 
Title Page; Investigator’s 
Agreement; Section 1.1 
Synopsis 
Updated date of protocol and 
amendment number. 
Administrative for Amendment 5 
Document History 
Addition of Amendment 5 
For accuracy and consistency with 
AnaptysBio style. 
1.1 Synopsis 
Removed text: 
Number of Investigators and  Study 
Centers: Approximately 25 
Investigators and study centers are 
expected to participate in this study. 
Change was made because there 
may be sub-investigators. 
1.1 Synopsis; 3.0 Objectives and 
Endpoints; 9.4.4 Efficacy 
Analysis 
Changed the primary endpoint to mean 
change from Baseline in PPPASI at 
Week 16. Moved proportion of subjects 
achieving PPPASI50 at Week16 from 
primary to secondary objective. 
A continuous measure such as 
change from Baseline may be more 
sensitive to change and is 
appropriate for a proof of concept 
study. A dichotomous measure 
such as PPASI50 may lose the 
granularity of patients who have 
improved but do not meet a 50% 
threshold. 
1.1 Synopsis; 9.1 Statistical 
Hypotheses 
The text “This is an exploratory study 
and no formal hypothesis testing will 
be performed” was replaced with “All 
hypothesis-based statistical testing will 
be considered exploratory in nature for 
this Phase 2 study.” 
Change was made to correct an 
error in description. 
1.1 Synopsis; 9.4.4.1 Analysis of 
Primary Efficacy Endpoint 
Changed description of statistical 
methods for analysis of primary 
efficacy endpoint. 
Change was made due to change 
from a categorical primary 
endpoint of PPPASI50 to a 


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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
 
 
continuous endpoint of change 
from Baseline in PPASI. 
2.2 Background 
Changed first-in-man to first-in-human 
Change was made to be inclusive. 
8.3 Adverse Events 
Word “definitions” was added to 
sentence “The definitions of an AE and 
SAE can be found in Appendix 4.” 
Change was made for clarity. 
Global 
Minor editorial changes for accuracy 
and formatting. 
Administrative 
 
Amendment 4 (11 Aug 2020) 
 
Overall Rationale for the Amendment: 
 
This amendment was prepared to align the study protocol Risk/Benefit Assessment with the Risk/Benefit 
Assessment described in the ANB019 IB V. 6, 30 June 2020 and to apply minor edits. 
 
Section # and Name 
Description of Change 
Brief Rationale 
Document Header/Footer 
Amendment number was updated in the 
header. The date was updated in the 
footer. 
For accuracy and consistency with 
AnaptysBio style. 
Title Page; Investigator’s 
Agreement; Section 1.1 
Synopsis 
Updated date of protocol and 
amendment number. 
Administrative for Amendment 4 
Section 2.2 Background Clinical 
Studies; Section 2.3 Benefit/Risk 
Assessment 
Provide context for clinical studies 
For accuracy and clarification of 
clinical data 
Section 2.3 Benefit/Risk 
Assessment 
Updated Benefit/Risk Assessment to 
include ANB019-005 final TEAE 
results and 26-week toxicology study in 
cynomolgus monkeys 
For accuracy and consistency with 
ANB019 IB V.6 , 30 June 2020 
Document History 
Addition of Amendment 3 and 
Amendment 4 
For accuracy and consistency with 
AnaptysBio style. 
Appendix 1 Abbreviations 
Addition of AST and ALT to 
Abbreviations 
For accuracy and consistency with 
AnaptysBio style. 
 
Amendment 3 (23 June 2020) 
 
Overall Rationale for the Amendment: 
 
This amendment was prepared to make minor clarifications regarding protocol procedures and to apply 
minor edits. 
 
Section # and Name 
Description of Change 
Brief Rationale 
Global 
Minor editorial changes for accuracy and 
formatting. 
Administrative 
Document Header/Footer 
Amendment number was updated in the 
header. The date was updated in the footer. 
For accuracy and consistency with 
AnaptysBio style. 
Title Page; Investigator’s Page; 
Section 1.1 Synopsis 
Updated date of protocol and amendment 
number. 
Administrative for Amendment 3. 


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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1 Synopsis; 
Section 1.2 Schema, Figure 1; 
Section 3 Objectives and 
Endpoints; Section 9.4.4.1 
Analysis of Primary Endpoint 
Removed Week 4 from the primary analysis 
of PPASI50. 
Adjusted the primary response 
endpoint to be assessed only at 
Week 16, though the PPASI50 will 
be collected at each study center 
visit through Week 16. 
Section 1.1. Synopsis, 
Statistical Methods; and 
Section 9.4.4.1 Analysis of 
Primary Efficacy Endpoint 
Revised text describing primary efficacy 
analysis with respect to analysis factors and 
use of 2-sided exact 95% test for the analysis 
of treatment differences. 
To clarify text in Statistical 
Methods sections. 
Section 5.2 Exclusion Criteria 
(#4 and #6) 
Revised the wording of the exclusion criteria 
to permit enrollment of subjects with localized 
oral and genital herpes simplex that is well 
controlled. 
To allow broader flexibility with 
subject screening and recruitment 
and to align with other similar 
studies. 
Section 9.4.4.2 Analysis of 
Secondary Efficacy Endpoints 
Revised description of logistic regression 
model to identify factors used for analysis of 2 
secondary efficacy endpoints (proportion of 
subjects achieving PPPASI50 and PPPASI75 
at all study centers and proportion of patients 
with clear or almost clear assessment score on 
PPPIGA at all study center visits). 
To clarify description of logistic 
regression model used for analysis 
of the 2 endpoints described. 
 
Amendment 2 (19 December 2019) 
 
Overall Rationale for the Amendment: 
 
This amendment was prepared to make minor clarifications regarding protocol procedures and to apply 
minor clarifications. 
 
Section # and Name 
Description of Change 
Brief Rationale 
Global 
Minor editorial changes for accuracy 
and formatting. 
Administrative 
Document Header/Footer 
Amendment number was updated in the 
header. A date was added to the footer. 
For accuracy and consistency with 
AnaptysBio style. 
Title Page; Synopsis 
Changed “Phase II” to “Phase 2.” 
 
 
Updated Date of Protocol. 
To comply with Style Guide, which 
recommends Arabic instead of Roman 
numerals for study phases. 
Administrative for Amendment 2. 
Investigator Signature Page 
Revised to “Investigator’s Agreement.” 
Added protocol title, number, and 
version, as well as additional language 
and instructions for the investigator 
prior to signing. 
To maintain consistency with other 
AnaptysBio protocols. 
Protocol Amendment Summary 
of Changes Table 
New section: moved the summary of 
changes up from Appendix 14 to front 
To comply with format for other 
protocols. 


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CONFIDENTIAL                                                                                                                   Protocol ANB019-003 - Amendment 5
Section # and Name
Description of Change
Brief Rationale
of the document after Investigator
Signature page.
Section 1.3;
Section 5.2 Exclusion Criteria;
Section 8.2.2 Chest X-ray
Revised the duration allowed for
previous chest x-ray from 6 months to
12 months. In Section 8.2.2, removed 
the reference to other timepoints as
noted in the Schedule of Activities.
To allow greater flexibility with subject
screening procedures and ensure
consistency throughout the protocol.
Section 2.1 Rationale
Added 2 sentences to the first and
second paragraph that appear in the
synopsis Rationale section but are
missing in the body.
This edit was applied for consistency in
the description of the rationale for this 
study.
Section 4.5.2 Criteria for
Stopping the Study
Section 6.3 Measures to
Minimize Bias
Appendix 2 Regulatory, Ethical, 
and Study Oversight
Considerations
Removed reference to
and
replaced with “CRO”
will only be referenced for
Lifecycle Safety.
Section 5.1. Inclusion Criteria;
criterion 7
Section 8.2.6 Clinical Safety
Laboratory Assessments
Removed the following sentence: “If
any laboratory results are outside the
upper or lower limits listed above, final
determination of eligibility will be after 
Investigator assessment following
consultation with the Medical Monitor
and Sponsor.
This flexibility is not allowed.
Section 5.2 Exclusion Criteria;
criterion 15 (4th bullet)
Appendix 5 Excluded
Medications
Removed “or twice the duration of the
biological effect of the product prior to 
Baseline.” Added “(whichever is 
longer)” after 3 months or 5 half-lives
to clarify.
Team recommendation to support ex-US
submissions.
Section 8.1.1 Palmoplantar 
Pustulosis Psoriasis Area
Severity Index
Added missing reference to supporting
appendix.
Administrative
Appendix 2 Regulatory, Ethical, 
and Study Oversight
Considerations
Removed the phrase allowing for
subject “or his/her legally authorized 
representative” from the text.
Not allowed; the subject must provide
consent.
Appendix 14
Removed this appendix. Moved the
amendment history information up to 
the front of the protocol. (This change
is not tracked.)
Administrative to align with other 
protocol formats.


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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
Amendment 1 (17 October 2019) 
 
Overall Rationale for the Amendment: 
 
This amendment was prepared to reorganize the immunogenicity endpoints, clarify the name of one of the 
assessment tools, increase the overall number of study centers, and make a few minor adjustments to 
study assessments. 
 
Section # and Name 
Description of Change 
Brief Rationale 
Global 
Minor edits for formatting, spacing, 
spelling. References throughout the 
document were converted from 
numbers to author/year format to align 
with the AnaptysBio Style Guide. 
Any necessary corrections were applied 
for clarity. 
Title Page 
Added NCT number. 
Administrative 
Sponsor Signature Page 
Revised the language on the Sponsor 
signature page to include more detail 
regarding applicable guidelines. 
Administrative 
Investigator Signature Page 
Moved up from Appendix 7 to the front 
of the document 
Administrative; to align with other 
protocols. 
Section 1.1 Synopsis; Section 
3.0 Objectives and Endpoints 
Moved immunogenicity endpoint to 
secondary objectives. 
To clarify this objective and for 
reporting purposes to move this to a 
secondary objective instead of 
exploratory. 
Section 1.1 Synopsis; 
Section 1.3 Schedule of 
Activities; Section 4.1 Study 
Design 
Increased the screening period from 28 
days (4 weeks) to 48 days. 
To allow greater flexibility for 
scheduling and completion of screening 
activities and to align with other 
ANB019 protocols. 
Section 1.1 Synopsis; 
Section 1.3 Schedule of 
Activities; 
Section 3 Objectives and 
Endpoints; Section 4.1 Study 
Design; 
Section 8.1.9 Patient Assessment 
of Palmoplantar Pustulosis 
Disease Activity, 
Section 9.4.4.2 Secondary 
Efficacy Endpoints; 
Appendix 13 
Removed the reference to the Patient 
Global Assessment (PGA) of disease 
activity and replaced with Patient 
Assessment of Palmoplantar Pustulosis 
Disease Activity. 
Clarified the name of the assessment 
scale. 
Section 1.1 Synopsis; Section 
6.1 Study Treatment 
Administered 
Revised the language to describe the 
appearance of placebo. 
To align with other protocols and 
currently approved language for drug 
product description. 
Section 1.1 Synopsis; Section 
9.2 Sample Size Determination 
Increased the number of study centers 
from 10 to 25. 
Administrative 
Section 1.3 Schedule of 
Activities 
Added an additional urine pregnancy 
text collection at the Week 20 study 
visit. 
For added safety and to align with other 
ANB019 protocols. 


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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3 Schedule of 
Activities; Appendix 3 
For FSH collection, removed the 
criteria in the definition of 
postmenopausal that stated women 
must be 45 years of age. 
To align with Appendix 6 on 
Contraceptive Guidance and with other 
protocols. 
Section 1.3 Schedule of 
Activities 
Added a row for telephone contact 
during the study and footnote m to 
clarify the days for the telephone 
contact and the information to be 
collected. 
For safety follow-up and to align with 
other ANB019 studies. 
Section 1.3 Schedule of 
Activities; 
Section 8.2.4 Vital Signs 
For footnote f in the table as well as in 
section text, removed the term 
“axillary” from body temperature 
collection. 
To allow greater flexibility in the 
collection of body temperature and to 
allow body temperature to be taken 
orally. 
Section 1.3 Schedule of 
Activities 
Revised footnote l to expand on the 
timing of the early termination visit for 
subjects who discontinue. 
To provide clarity on follow-up visit 
required. 
Section 2.2 Background 
Added information on the 26-week 
nonclinical toxicity study that was 
conducted. 
For completeness and consistency with 
other protocols. 
Section 2.3 Benefit/Risk 
Assessment 
Added a paragraph to characterize 1 
event of sepsis experienced by a subject 
in an ANB019 study. 
For clarity on safety reporting. 
Section 5.1; Inclusion Criteria, 
criterion 1 
Increased the upper age limit of 
subjects from 70 years to 75 years. 
To increase the available pool of 
potential subjects and improve 
enrollment. 
Section 5.1; Inclusion Criteria, 
criterion 3 
Revised this criterion to remove 
reference to lack of response to prior 
topical or corticosteroid therapy. 
To increase the available pool of 
potential subjects and improve 
enrollment. 
Section 5.1; Inclusion Criteria, 
criterion 7 
Added a caveat that out-of-range 
screening values may be assessed by 
the Investigator and subjects may be 
enrolled at the discretion of the 
Investigator following consultation 
with the Medical Monitor and Sponsor. 
Removed the clause allowing one 
repeat test for abnormal laboratory 
results. 
To allow greater flexibility for 
Investigators to assess eligibility. 
Section 5.1; Inclusion Criteria, 
criterion 10 
Broadened the language on 
contraception to be inclusive of sites 
outside of North America. Added that 
hormonal contraception should be 
started 48 days prior to Day 1. 
Administrative 
Section 5.2; Exclusion Criteria, 
criterion 13 
This was revised to allow squamous 
cell carcinoma as determined by the 
Investigator to be fully treatable. 
To allow greater flexibility in 
enrollment. 


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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 5.2; Exclusion Criteria, 
criterion 17 
Added a phrase that eligibility for 
subjects with a history of drug, alcohol, 
or substance abuse will be determined 
by the Investigator. Removed the 
example of excessive caffeine use. 
To allow greater flexibility for the 
Investigator. 
Section 5.2; Exclusion Criteria, 
criterion 26 
Added a criterion to exclude subjects 
for inability to tolerate SC drug 
administration. 
Administrative 
Section 5.3 Lifestyle 
Considerations 
Added this new section. 
For consistency with other ANB019 
protocols and to clarify the need to avoid 
exposure to sunlight. 
Section 6.1 Treatments 
Administered, Text and Table 1 
Clarified the appearance description of 
ANB019 and placebo. 
Table 1 - Added a row for study 
treatment description to include the 
appearance of the investigational 
product. Clarified the appearance of 
investigational product and placebo in 
running text in this section. Removed 
the rows for packaging and labeling 
and clarified dosing instructions. 
To align with other protocols and for 
clarity in product description. 
Section 6.3 Measures to 
Minimize Bias 
Revised the last paragraph to indicate 
that the Sponsor will be notified for 
safety issues instead of the investigator 
Administrative 
Section 6.7 Treatment After End 
of Study 
Revised the language to indicate that 
pregnancy through EOS or ET visit if 
applicable will be reported and 
followed. 
To correct an error in the reporting 
language for pregnancy. 
Section 7.2 Subject 
Discontinuation/Withdrawal 
from Study 
Added a paragraph to describe the 
study procedures for early withdrawal. 
For clarity with other protocols in the 
language describing early withdrawal. 
Section 8.2.2 Chest X-ray 
Move this up from Section 8.2.6 to 
8.2.2 
To align with other protocols. 
Section 8.2.5 Electrocardiogram 
Added one bullet to clarify that ECG 
information does not need to be entered 
into EDC. 
Administrative to clarify documentation 
procedures. 
Section 8.2.6 Clinical Safety 
Laboratory Assessments 
Added a phrase to the second bullet to 
indicate that when local laboratory 
testing is required for the Investigator 
to make a decision to determine 
eligibility for study entry, the 
laboratory samples must be collected at 
the same time as the central laboratory 
To clarify procedures for the 
Investigator. 


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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
Section # and Name 
Description of Change 
Brief Rationale 
 
sample. Added text to the third bullet 
regarding screening laboratory 
assessments to indicate that the 
Investigator will consult with the 
Medical Monitor and Sponsor to 
determine final eligibility of subjects 
who are outside clinical range for 
screening laboratory assessment. 
Section 8.2.7 Photography 
Added text to explain that the 
collection of photographs will be 
standardized and described in a manual 
of procedures. Included a caveat that 
photographs may be transferred to 
central vendor or third party consultant 
for quality review or additional review. 
For clarity around photograph 
distribution and analysis. 
Section 8.2.8 Telephone Contact 
Added a new section on Telephone 
Contact to clarify what will happen at 
these visits. 
To provide clarity on these visits 
following the addition in Section 1.3 
Schedule of Activities. 
Section 8.3.5 Pregnancy 
Revised the length of time pregnancy 
will be collected to align with text 
elsewhere in the protocol. 
To provide clarity on the timing of 
collection of pregnancy information. 
Section 8.5 Pharmacokinetics 
Removed text describing sample 
volume and Vacutainer collection. 
Clarified that collection time will be 
documented based on a 24-hour clock. 
Text describing separation into aliquots 
was moved. Added Table 2 to outline 
PK and ADA collection procedures and 
timepoints. 
To be less prescriptive and more 
transparent in protocol text and to 
provide clarity of documentation. 
Section 8.7 Biomarkers 
Added a statement that measurement of 
skin biopsy biomarkers may be 
performed by a third party. 
To allow greater flexibility of study 
conduct. 
Section 8.8 Immunogenicity 
Assessments 
Added a statement that study samples 
will be divided into 2 aliquots (1 each 
for primary and a back-up): Removed 
text specifying the length of time that 
study samples will be stored. 
For clarity of expectations. 
Section 9.4.4.1 Analysis of 
Primary Efficacy Endpoints 
Revised the statement on alternate 
statistical methods that are provided in 
the SAP. 
To provide clarity and conciseness in the 
protocol. 
Section 9.4.4.2 Analysis of 
Secondary Efficacy Endpoints 
Added the endpoint for ADA 
assessment, which was missing. 
Clarified that no formal hypothesis 
testing will be performed. 
Administrative 


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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 9.5 Interim Analyses 
Replaced existing text stating no 
interim analysis was planned with text 
to indicate that interim analyses are 
planned and to briefly summarize these 
analyses. 
Revised to reflect change in intent to 
perform interim analyses. 
Section 10 References 
Reordered references into alphabetical 
order. Added 3 additional references. 
To align format and reference 
presentation with the current style guide. 
Appendix 2 Regulatory, Ethical, 
and Study Oversight 
Added additional text to outline 
informed consent process and genetic 
testing as it relates to data privacy. 
To improve transparency on the 
informed consent process. 
Appendix 6 Contraceptive 
Guidance 
Added text to clarify premenarchal 
definition, as well as criteria for 
instances when fertility is unclear. Also 
added bullet to specify that WOCBP 
should refrain from donating oocytes 
for assisted reproduction during study 
conduct. 
To improve the clarity and specificity of 
contraceptive guidelines. 


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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
TABLE OF CONTENTS 
 
TITLE PAGE ...........................................................................................................................1 
 
SPONSOR SIGNATURE PAGE............................................................................................2 
 
INVESTIGATOR’S AGREEMENT......................................................................................3 
 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ................................4 
 
TABLE OF CONTENTS ......................................................................................................13 
 
TABLE OF TABLES.............................................................................................................16 
 
TABLE OF FIGURES...........................................................................................................16 
 
1.0       PROTOCOL SUMMARY ........................................................................................17 
1.1       Synopsis ...........................................................................................................17 
1.2       Schema.............................................................................................................21 
1.3       Schedule of Activities ......................................................................................22 
 
2.0       INTRODUCTION......................................................................................................26 
2.1       Study Rationale................................................................................................26 
2.2       Background ......................................................................................................26 
2.3       Benefit/Risk Assessment .................................................................................29 
 
3.0       OBJECTIVES AND ENDPOINTS ..........................................................................32 
 
4.0       STUDY DESIGN........................................................................................................34 
4.1       Overall Design .................................................................................................34 
4.2       Scientific Rationale for Study Design..............................................................35 
4.3       Justification for Dose .......................................................................................35 
4.4       End of Study Definition ...................................................................................35 
4.5       Study Stopping Criteria....................................................................................36 
4.5.1      Stopping Criteria for Individual Subjects................................................36 
4.5.2      Criteria for Stopping the Study................................................................36 
 
5.0       STUDY POPULATION ............................................................................................37 
5.1       Inclusion Criteria .............................................................................................37 
5.2       Exclusion Criteria ............................................................................................38 
5.3       Lifestyle Considerations ..................................................................................40 
5.4       Screen Failures.................................................................................................40 
 
6.0       STUDY TREATMENT .............................................................................................42 
6.1       Study Treatment Administered ........................................................................42 
6.2       Preparation/Handling/Storage/Accountability.................................................43 
6.3       Measures to Minimize Bias: Randomization and Blinding .............................44 
6.4       Study Treatment Compliance ..........................................................................45 
6.5       Concomitant Therapy.......................................................................................45 
6.5.1      Rescue Medicine .....................................................................................45 
6.6       Dose Modification ...........................................................................................46 
6.7       Treatment After the End of the Study..............................................................46


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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
7.0 
DISCONTINUATION OF STUDY TREATMENT AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ................................................................47 
7.1       Discontinuation of Study Treatment ................................................................47 
7.1.1      Temporary Interruption ...........................................................................47 
7.1.2      Rechallenge .............................................................................................47 
7.2       Subject Discontinuation/Withdrawal from the Study ......................................47 
7.3       Lost to Follow-up.............................................................................................48 
 
8.0       STUDY ASSESSMENTS AND PROCEDURES ....................................................49 
8.1       Efficacy Assessments.......................................................................................49 
8.1.1      Palmoplantar Pustulosis Psoriasis Area Severity Index ..........................49 
8.1.2      Palmoplantar Pustulosis Severity Index ..................................................50 
8.1.3      Palmoplantar Pustulosis (Static) Investigator’s Global 
Assessment ..............................................................................................50 
8.1.4      Psoriasis Area Severity Index..................................................................50 
8.1.5      Total Body Surface Area .........................................................................50 
8.1.6      Pustule Count on Palms and Soles ..........................................................50 
8.1.7      Dermatology Life Quality Index .............................................................51 
8.1.8      Palmoplantar Pustulosis Quality of Life Instrument ...............................51 
8.1.9      Patient Assessment of Palmoplantar Pustulosis Disease Activity...........51 
8.2       Safety Assessments ..........................................................................................51 
8.2.1      Physical Examinations.............................................................................51 
8.2.2      Chest X-ray..............................................................................................52 
8.2.3      Height and Weight...................................................................................52 
8.2.4      Vital Signs ...............................................................................................52 
8.2.5      Electrocardiograms..................................................................................52 
8.2.6      Clinical Safety Laboratory Assessments .................................................53 
8.2.7      Photography.............................................................................................53 
8.2.8      Telephone Contact...................................................................................54 
8.3       Adverse Events ................................................................................................54 
8.3.1      Time Period and Frequency for Collecting AE and SAE 
Information ..............................................................................................54 
8.3.2      Method of Detecting AEs and SAEs .......................................................54 
8.3.3      Follow-up of AEs and SAEs ...................................................................54 
8.3.4      Regulatory Reporting Requirements for SAEs .......................................55 
8.3.5      Pregnancy ................................................................................................55 
8.3.6      Adverse Events of Special Interest..........................................................55 
8.3.7      Disease-related Events and/or Disease-related Outcomes Not 
Qualifying as AEs or SAEs .....................................................................56 
8.4       Treatment of Overdose ....................................................................................56 
8.5       Pharmacokinetics .............................................................................................57 
8.6       Pharmacodynamics ..........................................................................................58 
8.7       Biomarkers.......................................................................................................58 
8.8       Immunogenicity Assessments..........................................................................58 
8.9       Health Economics or Medical Resource Utilization and Health 
Economics........................................................................................................59


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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
9.0       STATISTICAL CONSIDERATIONS .....................................................................60 
9.1       Statistical Hypotheses ......................................................................................60 
9.2       Sample Size Determination..............................................................................60 
9.3       Analyses Sets ...................................................................................................60 
9.4       Statistical Analyses ..........................................................................................60 
9.4.1      Subject Disposition..................................................................................61 
9.4.2      Subject Characteristics and Medical History ..........................................61 
9.4.3      Concomitant Medication .........................................................................62 
9.4.4      Efficacy Analyses ....................................................................................62 
9.4.4.1       Analysis of Primary Efficacy Endpoint .........................................62 
9.4.4.2       Analysis of Secondary Efficacy Endpoints....................................62 
9.4.5      Safety Analyses .......................................................................................64 
9.4.5.1       Adverse Events and Serious Adverse Events ................................65 
9.4.5.2 
Physical Examinations, 12-Lead Electrocardiogram, Vital Signs, 
and Clinical Safety Laboratory Tests (Hematology, Biochemistry, 
and Urinalysis) .......................................................65 
9.4.6      Pharmacokinetic Analyses.......................................................................66 
9.4.6.1       Derivation of Pharmacokinetic Parameters ...................................66 
9.4.6.2       Pharmacokinetic Concentration Data Analysis .............................66 
9.4.6.3       Pharmacokinetic Parameter Data Analysis ....................................67 
9.4.6.4       Population Pharmacokinetics Analysis..........................................67 
9.4.7      Immunogenicity Analyses (Exploratory Endpoint Analysis)..................67 
9.4.8      Biomarker Analyses (Exploratory Endpoint Analysis) ...........................67 
9.4.9      Missing Data............................................................................................67 
9.5       Interim Analyses ..............................................................................................68 
9.6       Data Monitoring Committee ............................................................................68 
 
10.0     REFERENCES...........................................................................................................69 
 
11.0     APPENDICES ............................................................................................................70 
Appendix 1           Abbreviations.................................................................................71 
Appendix 2           Regulatory, Ethical, and Study Oversight Considerations.............74 
Appendix 3           Clinical Laboratory Tests...............................................................81 
Appendix 4           Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ..........................................83 
Appendix 5           Excluded Medications/Therapy .....................................................87 
Appendix 6           Contraceptive Guidance and Collection of Pregnancy 
Information ......................................................................................................88 
Collection of Pregnancy Information.....................................................................91 
Appendix 7           Palmoplantar Pustulosis Psoriasis Area Severity Index.................92 
Appendix 8           Palmoplantar Pustulosis Severity Index.........................................93 
Appendix 9           Palmoplantar Pustulosis (Static) Investigator’s Global 
Assessment.......................................................................................................94 
Appendix 10         Psoriasis Area Severity Index Score ..............................................95 
Appendix 11         Dermatology Life Quality Index....................................................96 
Appendix 12         Palmoplantar Pustulosis Quality of Life Instrument......................98 
Appendix 13         Patient Assessment of Palmoplantar Pustulosis Disease 
Activity    100


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TABLE OF TABLES 
 
Table 1           Study Treatment Details ..................................................................................42 
Table 2           PK/ADA Sample Collection and Timepoints ..................................................58 
Table 3           Analysis Sets ....................................................................................................60 
Table 4           Study Administrative Structure........................................................................76 
Table 5           Protocol-required Safety Laboratory Assessments ..........................................81 
Table 6           List of Excluded Medications ..........................................................................87 
 
 
 
TABLE OF FIGURES 
 
Figure 1          Study Schema...................................................................................................21


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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
1.0   PROTOCOL SUMMARY 
 
1.1     Synopsis 
 
Protocol Title: A Phase II, Randomized, Placebo-controlled, Double-blind, Multiple Dose Study to 
Evaluate the Efficacy and Safety of ANB019 in Subjects with Palmoplantar Pustulosis 
Protocol Number: ANB019-003 
 
Rationale: 
This study is designed to evaluate the efficacy and safety of multiple doses of ANB019 in subjects with 
palmoplantar pustulosis (PPP). Palmoplantar pustulosis is the most common localized form of pustular 
psoriasis confined to the skin of palms and/or soles (Navarini 2017). The interleukin-36 (IL-36) pathway, 
by promoting inflammatory responses, has been shown to play a key role in the disease pathology. 
Recent studies of skin biopsies obtained from patients with clinically confirmed PPP indicated sustained 
activation of IL-36 pathway in PPP compared with normal and chronic plaque psoriasis skin biopsies 
suggesting that IL-36 inflammatory axis may be a main driver of the disease pathology (Johnston 2016). 
The study treatment, ANB019 is a high affinity humanized immunoglobulin G4 monoclonal antibody that 
specifically binds the interleukin-36 receptor (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 in subjects with PPP. The information obtained from this study 
may provide important insights into potential new treatment options for pustular psoriasis including PPP. 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
 
To determine the effect of ANB019 compared with 
placebo in subjects with PPP as measured by the 
Palmoplantar Pustulosis Psoriasis Area Severity 
Index (PPPASI). 
     Mean change from Baseline in PPPASI at Week 
16. 
 
 
To assess the safety and tolerability of ANB019 in 
subjects with PPP. 
     Assessment of adverse events (AEs). 
 
Potentially significant and clinically important 
AEs, adverse events of special interest (AESIs), 
serious adverse events (SAEs), and AEs leading 
to withdrawal. 
     Physical examinations. 
     Vital signs. 
     12-Lead electrocardiogram (ECG). 
 
Clinical safety laboratory tests (hematology, 
biochemistry, and urinalysis). 


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Objectives 
Endpoints 
Secondary 
 
 To determine the effect of ANB019 in subjects 
with PPP as measured by improvement in the 
PPPASI. 
 
Proportion of subjects achieving PPPASI50 at all 
study center visits. 
     Proportion of subjects achieving PPPASI75 at all 
 
 
To determine the effect of ANB019 in subjects with 
PPP as measured by Palmoplantar Pustulosis 
Severity Index (PPSI). 
 
Change from Baseline in PPSI score at all study 
center visits. 
 
 
To determine the proportion of subjects who 
achieved PPP disease clearance after administration 
of ANB019 as measured by the Palmoplantar 
Pustulosis (static) Investigator’s Global Assessment 
(PPPIGA). 
 
Change in PPPIGA score at all study center 
visits. 
 
Proportion of subjects with clear or almost clear 
assessment score on PPPIGA at all study center 
visits. 
     Change in fresh and total pustule count on palms 
 
 
 
To determine the time to response with ANB019 in 
subjects with PPP. 
 
 
To determine the relapse rate with ANB019 in 
subjects with PPP. 
 
 
To evaluate the effect of ANB019 in subjects with 
plaque psoriasis at non-acral sites (if present) as 
measured by the Psoriasis Area Severity Index 
(PASI) and affected body surface area (BSA). 
and soles at all study center visits. 
     Time to response defined as time to achieve 75% 
reduction in fresh pustule count. 
 
Relapse rate defined as return to Baseline in fresh 
pustule count. 
 
Change in PASI score and affected BSA at all 
study center visits, if plaque psoriasis is present at 
non-acral sites. 
 
 
To evaluate the effect of ANB019 in subjects with 
pustular psoriasis at non-acral sites (if present) as 
measured by BSA. 
 
Improvement in pustular psoriasis at non-acral 
site BSA (if present) at all study center visits. 
 
     To evaluate the effect of ANB019 on subject’s 
quality of life. 
 
Change in clinical scores of Palmoplantar 
Pustulosis Quality of Life Instrument (PPPQLI), 
Dermatology Life Quality Index (DLQI), and 
Patient Assessment of Palmoplantar Pustulosis 
Disease Activity at all study center visits. 
Immunogenicity: 
     To test for immunogenicity to ANB019 
     Presence of anti-drug antibodies 
 
Pharmacokinetics (PK): 
PK: 
     To describe the PK of ANB019 in subjects with 
PPP. 
Where possible, the following PK parameters will be 
determined for ANB019 after administration: 
 
 
Serum concentration following ANB019 
administration. 
     Maximum observed concentration (Cmax). 
     Time to maximum observed concentration (Tmax). 
     Area under the concentration-time curve (AUC). 
     Terminal half-life (t1/2). 
     Other parameters as appropriate. 
 
CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
 
 
 
 
 
 
 
study center visits.


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Objectives 
 
Exploratory 
Endpoints 
 
To explore the effect of ANB019 on skin biopsy 
biomarkers. 
 
Skin biopsy biomarkers including but not limited 
to IL-36, IL-17, IL-23, and markers of 
neutrophils and dendritic cells infiltration. 
     To provide photographic documentation of lesions. 
     Photographic documentation of lesions. 
 
Overall Design: 
This is a randomized, multicenter, placebo-controlled, double-blind, multiple dose study designed to 
assess the efficacy as well as safety and tolerability of ANB019 compared with placebo in subjects with 
PPP. This study will also characterize the PK of ANB019 and explore the immune response to ANB019 
in subjects with PPP. 
The study will have a screening period of up to 48 days prior to administration of study treatment on 
Day 1. 
On Day 1, eligible subjects will be randomly allocated in a 1:1 ratio to receive either a 200 mg 
subcutaneous (SC) dose of ANB019 or placebo followed by 3 doses of 100 mg of ANB019 or placebo 
administered subcutaneously on Days 29, 57, and 85. The subjects will leave the study center following 
study treatment administration when all postdose assessments have been completed and with the 
Investigator’s approval. Subjects with any ongoing AEs or SAEs while at 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. If any AE or SAE is reported at this visit, the study center staff will perform a 
telephone contact the next day to ensure that subject’s condition is stable. 
Subjects will return to the study center for study assessments and follow-up study visits on Days 3 and 8; 
weekly from Day 8 up to Day 29; every other week up to Day 85; and then monthly for 12 weeks to 
monitor changes in disease activity, safety, and tolerability. In addition, the subjects will also be contacted 
via telephone by study staff to inquire about the potential AEs and changes in concomitant medications on 
Days 36, 50, 64, and 78. 
Disease activity (response to study treatment) will be evaluated for all subjects using the PPPASI, PPSI, 
PPPIGA, PASI (if plaque psoriasis at non-acral sites is present), total affected BSA (if plaque psoriasis 
and/or pustular psoriasis is present at non-acral sites), PPPQLI, DLQI, and Patient Assessment of 
Palmoplantar Pustulosis Disease Activity (Oji 2015). In addition, relapse rate, time to response, and 
change in fresh and total pustule count on palms and soles will be recorded. 
Blood samples to determine 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). In addition, 
a punch biopsy (biomarker analysis) will be taken during the study. All subjects randomized in the study 
will be asked to participate in the skin biopsy; however, the subject’s participation is optional. 
Safety assessments including AE/SAE monitoring, vital signs, physical examination, ECGs, hematology, 
biochemistry, and urinalysis will be performed during the study period. 
The end of study (EOS) visit will be at Week 24 (Day 169) and all subjects will return to the study center 
for the EOS assessments (see Section 1.3). 
Number of Study Centers: 
Approximately 25 study centers are expected to participate in this study. 
Number of Subjects: 
The sample size is not based on statistical power considerations. 
Approximately 50 subjects will be enrolled at 25 study centers.


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Treatment Groups and Duration: 
The study will have a screening period of up to 48 days, treatment period of 12 weeks, and follow-up 
period of 12 weeks. 
Eligible subjects will be randomly allocated to receive either ANB019 or placebo in a 1:1 ratio. ANB019 
will be provided in a glass vial as a sterile, colorless to yellowish and clear to slightly opalescent solution 
for injection. On Day 1, a dose of 200 mg ANB019 or placebo will be administered SC followed by 
3 doses of 100 mg ANB019 or placebo SC on Days 29, 57, and 85. 
The placebo contains no active drug ingredient and will be provided as a sterile, colorless to slightly 
yellowish and clear to very slightly opalescent solution for injection. 
Statistical Methods: 
This is an exploratory study and the number of subjects to be enrolled is not based on statistical power 
considerations. All hypothesis testing will be considered exploratory in nature. A total of approximately 
50 subjects will be enrolled. All eligible subjects will be randomly allocated in a 1:1 ratio to receive 
multiple doses of ANB019 or placebo. 
Analysis set includes Intent-to-Treat set, Safety analysis set, Per Protocol set, and PK analysis set. 
The default summary statistics for continuous variables include number of contributing observations, 
mean, standard deviation (SD), median, minimum, and maximum. 
For categorical variables, the number and percentage (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. 
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. 
The primary efficacy endpoint is the change from Baseline in PPPASI at Week 16. This will be analyzed 
using a general linear mixed model for repeated measurements (MMRM) to include data collected at 
weeks 4, 8, 12 and 16. The model will include fixed effects for treatment, history of plaque psoriasis 
(Yes/No), categorical visit, the treatment by visit interaction, and Baseline PPPASI score as a covariate. 
Least-squares means (LSM) and associated standards errors for the change from baseline in PPPASI will 
be presented for each treatment group and the least-squares mean difference will be presented with the 
two-sided 95% confidence interval to assess the difference between the active group and placebo. 
Possible effect of any other covariates may also be investigated. Details of such analyses will be 
described in the Statistical Analysis Plan (SAP). Details of specific alternative statistical methods in the 
event model assumptions, if violated will be documented in the SAP. In addition, descriptive statistics 
(sample size, mean, SD, median, minimum, and maximum) will also be presented. 
For safety and tolerability, treatment-emergent adverse events (TEAEs), SAEs, AESIs, vital signs, 
physical examinations, ECGs, and laboratory assessments at specific time points will be evaluated. All 
safety data will be summarized descriptively. Number and percentage of TEAEs will be presented for 
each treatment by Preferred Term and System Organ Class of the current Medical Dictionary for 
Regulatory Authorities. Individual listings of TEAEs, TEAEs leading to death, SAEs, potentially 
significant TEAEs and clinically important TEAEs, AESIs, and TEAEs that led to discontinuation from 
the study or study treatment will be presented by treatment. 
Summaries and listings of data for vital signs, hematology, biochemistry, and urinalysis 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 observed value of the parameter 
of interest prior to the first intake of study treatment. 
The exposure of ANB019 will be evaluated by assessment of drug concentrations in serum. ANB019 
serum concentrations will be listed and summarized for each sampling time point using appropriate


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descriptive statistics. The calculated PK parameters will be summarized using appropriate descriptive 
statistics. Pharmacokinetic data from the study may also be used for population PK and PK/response 
analyses. If done, a separate analysis plan will be prepared, and results will be reported separately from 
the Clinical Study Report. 
 
Data Monitoring Committee: No 
 
1.2     Schema 
 
Figure 1         Study Schema 
 
 
 
 
 
 
 
 
 
 
Week 16 
 
 
 
 
 
 
 
 
 
 
 
 
 
Abbreviations: BSL = baseline; SC = subcutaneous


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1.3     Schedule of Activities 
 
Screening 
period 
 
Treatment Period 
Follow-up Period 
Procedure 
Screening 
(Up to 
48 days 
prior to 
Day 1) 
 
 
 
 
D1 
W 
0 
 
 
 
 
D3 
W 
1 
 
 
 
 
D8 
W 
1 
 
 
 
 
D15 
W2 
(±1 
day) 
 
 
D2 
2 
W3 
(±1 
day) 
D29 
W4 
(±1 
day) 
D36 
W5 
(±2 
days) 
D43 
W6 
(±2 
days) 
D5 
0 
W 
7 
(±2 
days 
) 
D57 
W8 
(±2 
days) 
D64 
W9 
(±2 
days) 
D71 
W1 
0 (±2 
days) 
D78 
W11 
(±2 
days) 
D85 
W12 
(±2 
days) 
D 
113 
W16 
(±2 
days) 
D 
141 
W20 
(±2 
days) 
EOS/ 
D169 
W24/ET 
l 
(±2 days) 
Informed consent 
X 
 
 
 
 
 
Inclusion and 
exclusion criteria 
 
X 
 
X 
 
 
 
 
Medical history 
X 
 
 
 
 
 
Heighta and 
weight 
 
X 
 
 
 
 
 
X 
PPPASI, PPSI, 
PPPIGAb 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PPPQLI, Patient 
Assessment of 
Palmoplantar 
Pustulosis Disease 
Activity, DLQIb 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PASI (plaque 
psoriasis subjects 
only)b 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Total affected 
BSA (for subjects 
with plaque 
psoriasis and/or 
pustular psoriasis 
at non-acral 
sites)b 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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CONFIDENTIAL                                                                                                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
Screening 
period 
 
Treatment Period 
Follow-up Period 
Procedure 
Screening 
(Up to 
48 days 
prior to 
Day 1) 
 
 
 
 
D1 
W 
0 
 
 
 
 
D3 
W 
1 
 
 
 
 
D8 
W 
1 
 
 
 
 
D15 
W2 
(±1 
day) 
 
 
D2 
2 
W3 
(±1 
day) 
D29 
W4 
(±1 
day) 
D36 
W5 
(±2 
days) 
D43 
W6 
(±2 
days) 
D5 
0 
W 
7 
(±2 
days 
) 
D57 
W8 
(±2 
days) 
D64 
W9 
(±2 
days) 
D71 
W1 
0 (±2 
days) 
D78 
W11 
(±2 
days) 
D85 
W12 
(±2 
days) 
D 
113 
W16 
(±2 
days) 
D 
141 
W20 
(±2 
days) 
EOS/ 
D169 
W24/ET 
l 
(±2 days) 
Fresh and total 
pustule count on 
palms and soles 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complete 
physical 
examinationc 
 
X 
 
X 
 
 
 
 
X 
X 
X 
X 
X 
12-Lead ECGd 
X 
X  
 
 
 
X 
X 
X 
Chest X-raye 
X 
 
 
 
 
 
Vital signsf 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology and 
biochemistryg 
 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysisg 
X 
X  
 
 
 
X 
X 
X 
X 
X 
TB screening 
(QuantiFERON®- 
TB Gold test)g 
 
X 
 
 
 
 
 
Virologyg 
X 
 
 
 
 
 
Serum pregnancy 
test (WOCBP 
only)g 
 
X 
 
 
 
 
 
X 
Urine pregnancy 
test 
(WOCBP only)g 
 
 
X 
 
 
 
 
X 
X 
X 
X 
X 


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Screening 
period 
 
Treatment Period 
Follow-up Period 
Procedure 
Screening 
(Up to 
48 days 
prior to 
Day 1) 
 
 
 
 
D1 
W 
0 
 
 
 
 
D3 
W 
1 
 
 
 
 
D8 
W 
1 
 
 
 
 
D15 
W2 
(±1 
day) 
 
 
D2 
2 
W3 
(±1 
day) 
D29 
W4 
(±1 
day) 
D36 
W5 
(±2 
days) 
D43 
W6 
(±2 
days) 
D5 
0 
W 
7 
(±2 
days 
) 
D57 
W8 
(±2 
days) 
D64 
W9 
(±2 
days) 
D71 
W1 
0 (±2 
days) 
D78 
W11 
(±2 
days) 
D85 
W12 
(±2 
days) 
D 
113 
W16 
(±2 
days) 
D 
141 
W20 
(±2 
days) 
EOS/ 
D169 
W24/ET 
l 
(±2 days) 
FSH 
(Postmenopausal 
woman with at 
least 1 year of 
amenorrhea only)g 
 
 
 
X 
 
 
 
 
 
Samples for PKh 
 
Xh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Samples for ADA  
X  
 
 
 
X 
X 
X 
X 
Skin biopsiesi 
 
X  
X  
 
Randomization 
 
X  
 
 
 
Photography 
 
X  
 
 
 
X 
X 
Telephone 
contactm 
 
 
 
 
 
 
X 
X 
X 
X 
ANB019/placebo 
administration 
 
 
,j  
 
 
 
j 
j 
j 
AE/SAE review 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medication review 
 
k 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
CONFIDENTIAL                                                                                                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X                                                 X                                         X                                              X 
 
 
 
 
X 
 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; BSA = body surface area; D = day; DLQI = Dermatology Life Quality Index; 
ECG = electrocardiogram; EOS = end of study; ET = early termination, FSH = follicle stimulating hormone; ICF = informed consent form; IL = interleukin; 
PASI = Psoriasis Area Severity Index; PK = pharmacokinetics; PPPASI = Palmoplantar Pustulosis Psoriasis Area Severity Index; PPSI = Palmoplantar 
Pustulosis Severity Index; PPPIGA = Palmoplantar Pustulosis (static) Investigator’s Global Assessment; PPPQLI = Palmoplantar Pustulosis Quality of Life 
Instrument; SAE = serious adverse event; SC = subcutaneous; TB = tuberculosis; TC = telephone contact; W = week; WOCBP = woman of childbearing 
potential.


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a            Height to be measured at Screening only. 
b 
Refer to Section 8.1 for details and instructions regarding PPPASI, PPSI, PPPIGA, PASI, total affected BSA, and quality of life questionnaires (PPPQLI, 
Patient Assessment of Palmoplantar Pustulosis Disease Activity, DLQI). The quality of life questionnaires should be the first assessments to be 
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 
before any study-related assessments are performed. 
c 
Refer to Section 8.2.1 for details regarding the complete physical examination. A complete physical examination will include assessments of general 
appearance; skin; head/neck; pulmonary, cardiovascular, gastrointestinal, external genitourinary, lymphatic, and musculoskeletal systems; extremities; 
eyes; nose; throat; and neurologic status. 
d 
Refer to Section 8.2.5 for details and instructions regarding the ECG. In addition to the time points specified in the Schedule of Activities, ECGs may be 
performed at any time during the study if in the opinion of the Investigator it is clinically warranted. 
e            Bidirectional posterior-anterior view and lateral view chest X-ray or as indicated by local treatment guidelines or practice will be performed at 
Screening. If a chest X-ray was performed within 12 months of Screening, it can be skipped at Screening. 
f             Vital signs assessment includes body temperature, pulse rate, blood pressure, and respiratory rate. Refer to Section 8.2.4 for details and instructions. 
g            Refer to Appendix 3 for details and instructions regarding clinical laboratory parameters and refer to Appendix 6 for the WOCBP definition. 
h 
On Day 1, samples for PK will be collected at predose, 1 hour and 4 hours post SC administration. In addition, samples for PK will also be collected on 
Days 3, 8, 15, 22, 29, 43, 57, 71, 85, 113, 141, and 169. On Days 29, 57, and 85, the scheduled PK samples will be collected prior to SC administration 
(Refer to Table 2). 
i 
In addition to the time points specified in the Schedule of Activities, skin biopsies (including but not limited to IL-36, IL-17, IL-23, and markers of 
neutrophils and dendritic cells infiltration) may be performed at other visits as appropriate to measure biomarkers. All randomized subjects will be asked 
to participate in the skin biopsy test; however, the subject’s participation is optional. Subjects should provide their consent to participate in the skin 
biopsy. Punch biopsy will be collected on Day 1 (normal and psoriatic skin) and Day 8 (psoriatic skin only). 
j 
On Days 1, 29, 57, and 85, all assessments should be performed prior to study treatment administration except postdose PK samples (on Day 1). The 
specific order for performing the study assessments is as follows (applicable to all visits): First the quality of life questionnaires then the 
efficacy assessments, vital signs, physical examination, ECG, and then the blood sample collection. 
k            At Screening, prior medications should be reviewed and documented. Refer to Section 6.5. 
l 
The ET visit will include all procedures to be done at the ET/EOS visit. In case of early discontinuation, the subject will be encouraged to return to the 
study center for the follow-up period visits (week 16/Day113, and week 20/Day141 visits) followed by early termination/EOS visit (Week 24/Day169 
visit). 
m           At Days 36, 50, 64, and 78, subjects will be contacted by phone  for safety follow-up to assess for AEs and concomitant medications.


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2.0   INTRODUCTION 
 
ANB019 is a high affinity humanized immunoglobulin G4 (IgG4) monoclonal antibody (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 proinflammatory responses. Interleukin-36 signaling is counter-
balanced by the IL-36 receptor antagonist (IL-36Ra) that binds to IL-36R and competes with 
activity of IL-36 cytokines. The IL-36 pathway has been implicated in the pathogenesis of 
inflammatory skin diseases, including palmoplantar pustulosis (PPP). Recent studies of skin 
biopsies obtained from patients with clinically confirmed diagnosis of PPP indicated sustained 
activation of IL-36 pathway in PPP compared with normal and chronic plaque psoriasis skin 
biopsies suggesting a key role of IL-36 inflammatory axis as a main driver of the disease. 
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 activation of the IL-36. 
ANB019 is being developed as a potential first-in-class therapy for pustular psoriasis, including 
PPP and generalized pustular psoriasis, and other inflammatory diseases where the IL-36 
pathway might have a pathogenic role. 
 
2.1     Study Rationale 
 
This study is designed to evaluate the efficacy as well as safety and tolerability of multiple doses 
of ANB019 in subjects with PPP. Palmoplantar pustulosis is the most common localized form of 
pustular psoriasis confined to the skin of palms and/or soles (Navarini 2017). The interleukin-36 
(IL-36) pathway, by promoting inflammatory responses, has been shown to play a key role in the 
disease pathology. 
 
Recent studies of skin biopsies obtained from patients with clinically confirmed PPP indicated 
sustained activation of the IL-36 pathway in PPP compared with normal and chronic plaque 
psoriasis skin biopsies suggesting that the IL-36 inflammatory axis may be a main driver of the 
disease pathology (Johnston 2016). The study treatment, ANB019 is a high affinity humanized 
immunoglobulin G4 monoclonal antibody that specifically binds the interleukin-36 receptor 
(IL-36R) and antagonizes IL-36 signaling. ANB019 is a 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 
in subjects with PPP. The information obtained from this study may provide important insights 
into potential new treatment options for pustular psoriasis including PPP. 
 
2.2     Background 
 
Palmoplantar pustulosis is the most common form of pustular psoriasis characterized by 
development of sterile pustules on palms and/or soles. The disease is strongly associated with 
smoking history and typically manifests between 40 and 50 years of age (Eriksson 1998).


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Although PPP is often listed among pustular forms of psoriasis, recent genetic studies have 
provided evidence that PPP may not be related to psoriasis (Asumalathi 2003). The disease is
persistent and painful, often resulting in significant functional impairment and diminished quality
of life.
Treatment of PPP is challenging with more than two thirds of patients requiring systemic
therapy (Adisen 2010). There is little evidence for the efficacy of any treatment, and commonly
utilized therapies are often hampered by low efficacy and poor tolerability.
Several recent studies have demonstrated the involvement of IL-36 pathway in PPP suggesting 
that IL-36 may be an important contributor to the pathogenesis of PPP. Inhibition of the IL-36
signaling by blocking IL-36R potentially offers an additional and novel treatment approach for 
PPP patients who inadequately benefit from current therapies.
Nonclinical Studies
ANB019 has strong inhibitory activity of human as well as cynomolgus monkey IL-36R. 
Nonclinical data obtained from studies with ANB019 in primary human and cynomolgus
monkey cells and from in vivo nonhuman primate studies demonstrated that:
ANB019 shows reactivity with human and cynomolgus monkey IL-36R (dissociation
constant [KDs] of
, respectively), but not with mouse or
rat IL-36R.
In primary human and cynomolgus monkey cell populations, keratinocytes, peripheral blood
mononuclear cells, and human whole blood, ANB019 inhibits IL-36R mediated release of
IL-8.
The observed serum half-life (t1/2) of ANB019 in cynomolgus monkeys was
hours after a
single intravenous (IV) dose administration, and 
 hours after a single subcutaneous (SC)
dose administration at 10 mg/kg, with bioavailability approximately
% consistent with the 
anticipated pharmacokinetic (PK) characteristics for a human IgG4 scaffold mAb in the 
monkey.
Repeat-dose, Good Laboratory Practice toxicity and toxicokinetic studies of 4,13, and
26 weeks in duration have been conducted with ANB019 administered by weekly SC and IV
injection in 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 (Dubey 2002). ANB019-related
effects during the 26-week toxicity study were limited to a low incidence of nonadverse 
liquid feces for animals administered 60 mg/kg/dose IV. These studies established a no
observed adverse effect level at the 60 mg/kg/dose when administered intravenously or
subcutaneously after 26 weeks of dosing.


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A detailed description of the physical, chemical, and pharmaceutical properties of ANB019 and 
nonclinical studies is provided in the current Investigator’s Brochure (IB). 
 
Clinical Studies 
 
ANB019 was found to be safe and well tolerated in a first-in-human Phase 1 single ascending 
dose (SAD) and multiple ascending dose (MAD) study conducted in healthy subjects. 
 
The SAD part of the study enrolled 48 healthy adults. Six dose levels were administered: 10 mg, 
40 mg, 100 mg, 300 mg, and 750 mg by IV injection and 100 mg by SC injection. In each 
cohort, 6 of the 8 subjects received ANB019 and 2 received placebo. After single dose 
administration, ANB019 was generally well tolerated in male and female healthy adults 18 to 
43 years old. Overall, 40 of 48 subjects (83%) experienced at least 1 treatment-emergent adverse 
event (TEAE). The percentage of subjects who experienced at least 1 TEAE was similar across 
treatment groups: 29 of 36 subjects, 81% in ANB019 group and 11 of 12 subjects, 92% in 
placebo. The most commonly reported TEAEs were upper respiratory tract infection 
(28% ANB019, 50% placebo), headache (28% ANB019, 25% placebo), viral upper respiratory 
tract infection (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), catheter site pain (6% ANB019, 0% placebo), and muscle strain (6% ANB019, 
0% placebo). The majority of TEAEs were mild (73%) and moderate (26%) in severity with 
exception of 1 severe AE of elevated creatine kinase (CK). The AE of elevated CK was reported 
on Day 15 following 100 mg IV administration. The spike in CK levels was caused by strenuous 
exercise and the AE was deemed unrelated to treatment. Creatine kinase levels normalized 
1 week later. 
 
No subject discontinued the study due to an AE. There were no serious adverse events (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. 
 
The 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.


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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 Day 1, 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
μg/mL
following a single maximum dose of 750 mg IV and
μg/mL following a single 100 mg SC
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
hours after SC injection and
between
 hours after IV injection.
ANB019-005 was a Phase 1 ethnobridging, SAD study in healthy Japanese and Caucasian subjects
that evaluated the safety, tolerability, PK, and immunogenicity  of ANB019 in 32 subjects. 
ANB019 was generally well tolerated. All reported TEAEs were mild in severity and there were
no SAEs or SUSARs reported for this study. Transient elevations in liver enzymes were observed
during the study in 9 subjects (8 in the ANB019 treatment group and 1 in the placebo group).
However, only 5 subjects reported TEAEs consistent with elevated liver function test results. The 
elevations were generally mild, not clinically meaningful, and resolved. Two of the 5 subjects with
TEAEs presented with elevated values at Screening that were considered not clinically meaningful
by the investigator. No other clinically meaningful changes or trends were observed in hematology,
clinical chemistry, vital signs, or ECGs.
2.3    Benefit/Risk Assessment
Participants with PPP may or may not receive direct benefit from participating in this study.
Details about expected benefits and risks for participants in this study can be found in the IB and
Informed Consent Form (ICF).
In ANB019-001 after single dose administration up to 750 mg either IV or SC, ANB019 was
generally well tolerated in healthy adults with a similar proportion of subjects reporting TEAEs
in the ANB019 and placebo groups, 81% and 92%, respectively. The most frequently reported
TEAEs in the greatest proportion of subjects receiving ANB019 and placebo groups were upper
respiratory tract infection (28% and 50%, respectively) and headache (28% and 25%,


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respectively). In ANB019-005, single doses of ANB019 up to 750 mg administered by IV 
infusion or SC injection to 32 healthy Japanese and Caucasian adults were generally well 
tolerated. The most common TEAEs were alanine aminotransferase (ALT) increased (3 subjects 
[9.4%]) and aspartate aminotransferase (AST) increased (2 subjects [6.3%]). 
 
There has been 1 SAE of sepsis reported in the ongoing ANB019-002 study in patients with 
generalized pustular psoriasis 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, nonadverse, injection site reactions associated with the SC route of 
administration. 
 
Administration of 60 mg/kg/dose of ANB019 via SC or IV bolus injection to male and female 
sexually mature cynomolgus monkeys once weekly for up to 26 weeks was well tolerated. No 
ANB019-related effects on the duration or number of menstrual cycles in females, or sperm 
density, total sperm count, percent motility, sperm morphology, or testicular measurements in 
males occurred during the dosing or recovery phase. ANB019-related effects were limited to a 
low incidence of nonadverse liquid feces for animals administered 60 mg/kg/dose IV. Thus the 
NOAEL was 60 mg/kg/dose administered by SC or IV injection. 
 
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 considered dose related. The increase in protozoa in the stomach has been observed in 
monkeys treated with immune-modulating drugs (Dubey 2002) 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 can be clinically monitored 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 death was not determined and had an uncertain relationship to ANB019 but 
could be due to treatment-related immune-modulation. However, data published on IL-36R 
deficient humans shows no deleterious effect on general health and normal immune function is 
broadly preserved, indicating that inhibition of the IL-36R, apart from disease modification, does 
not generally compromise host defenses. Similar to other immune-modulating treatment 
paradigms, subjects should be closely monitored for any clinical gastrointestinal manifestations 
including infections and evaluated on an ongoing basis. If a gastrointestinal infection is 
suspected, the subject should be treated as clinically indicated.


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As allergic or anaphylactic reactions may occur in subjects treated with mAbs, subjects should 
be observed during and after investigational product administration. Subjects with true 
allergic/anaphylactic reactions should not receive further doses of the product. 
 
As ANB019 is a 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: 
 
    Mild to moderate fever, chills, headache, nausea, and vomiting. 
 
Moderate to severe 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.


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3.0   OBJECTIVES AND ENDPOINTS 
 
Objectives 
Endpoints 
Primary 
 
To determine the effect of ANB019 compared with 
placebo in subjects with PPP as measured by the 
Palmoplantar Pustulosis Psoriasis Area Severity 
Index (PPPASI). 
     Mean change from Baseline in PPPASI at Week 
16. 
 
 
To assess the safety and tolerability of ANB019 in 
subjects with PPP. 
     Assessment of AEs. 
 
Potentially significant and clinically important 
AEs, adverse event of special interests (AESIs), 
SAEs, and AEs leading to withdrawal. 
     Physical examinations. 
     Vital signs. 
     12-Lead ECG. 
 
Clinical safety laboratory tests (hematology, 
biochemistry, and urinalysis). 
Secondary 
     To determine the effect of ANB019 in subjects with 
PPP as measured by improvement in the PPPASI. 
 
Proportion of subjects achieving PPPASI50 at all 
study center visits. 
     Proportion of subjects achieving PPPASI75 at all 
 
 
     To determine the effect of ANB019 in subjects with 
PPP as measured by Palmoplantar Pustulosis 
Severity Index (PPSI). 
study center visits. 
 
Change from Baseline in PPSI score at all study 
center visits. 
 
 
To determine the proportion of subjects who 
achieved PPP disease clearance after administration 
of ANB019 as measured by the Palmoplantar 
Pustulosis (static) Investigator’s Global Assessment 
(PPPIGA). 
 
Change in PPPIGA score at all study center 
visits. 
 
Proportion of subjects with clear or almost clear 
assessment score on PPPIGA at all study center 
visits. 
     Change in fresh and total pustule count on palms 
 
 
 
To determine the time to response with ANB019 in 
subjects with PPP. 
 
 
To determine the relapse rate with ANB019 in 
subjects with PPP. 
 
 
To evaluate the effect of ANB019 in subjects with 
plaque psoriasis at non-acral sites (if present) as 
measured by the Psoriasis Area Severity Index 
(PASI) and affected body surface area (BSA). 
and soles at all study center visits. 
     Time to response defined as time to achieve 75% 
reduction in fresh pustule count. 
 
Relapse rate defined as return to Baseline in fresh 
pustule count. 
 
Change in PASI score and affected BSA at all 
study center visits, if plaque psoriasis is present at 
non-acral sites. 
 
 
To evaluate the effect of ANB019 in subjects with 
pustular psoriasis at non-acral sites (if present) as 
measured by BSA. 
 
Improvement in pustular psoriasis at non-acral 
site BSA (if present) at all study center visits. 
 
     To evaluate the effect of ANB019 on subject’s 
quality of life. 
 
Change in clinical scores of Palmoplantar 
Pustulosis Quality of Life Instrument (PPPQLI), 
Dermatology Life Quality Index (DLQI), and 


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Objectives 
Endpoints 
 
Patient Assessment of Palmoplantar Pustulosis 
Disease Activity at all study center visits. 
Immunogenicity: 
     To test for immunogenicity to ANB019. 
 
 
PK: 
     To describe the PK of ANB019 in subjects with 
PPP. 
     Presence of anti-drug antibodies 
PK: 
Where possible, the following PK parameters will be 
determined for ANB019 after administration: 
 
Serum concentration following ANB019 
administration. 
     Maximum observed concentration (Cmax). 
     Time to maximum observed concentration (Tmax). 
     Area under the concentration-time curve (AUC). 
     Terminal half-life (t1/2). 
     Other parameters as appropriate. 
Exploratory 
 
To explore the effect of ANB019 on skin biopsy 
biomarkers. 
 
Skin biopsy biomarkers including but not limited 
to IL-36, IL-17, IL-23, and markers of 
neutrophils and dendritic cells infiltration. 
 
     To provide photographic documentation of lesions. 
     Photographic documentation of lesions. 


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4.0   STUDY DESIGN 
 
4.1     Overall Design 
 
This is a randomized, multicenter, placebo-controlled, double-blind, multiple dose study 
designed to assess the efficacy as well as safety and tolerability of ANB019 compared with 
placebo in subjects with PPP. This study will also characterize the PK of ANB019 and explore 
the immune response to ANB019 in subjects with PPP. 
 
The expected duration of the study is approximately 28 weeks. The screening period will be up 
to 48 days prior to administration of study treatment on Day 1. Written informed consent will be 
obtained from each subject prior to initiating any study-related procedures. Subjects will also 
provide consent for skin biopsies if they wish to participate in this test. All screening procedures 
will be conducted in accordance with the Schedule of Activities in Section 1.3. 
 
On Day 1, subjects will present to the study center, and the eligible subjects will be randomly 
allocated in a 1:1 ratio to receive either a 200 mg SC dose of ANB019 or placebo followed by 
3 doses of 100 mg of ANB019 or placebo administered SC on Days 29, 57, and 85. All 
procedures will be carried out in accordance with the Schedule of Activities in Section 1.3. The 
subjects will leave the study center when all postdose assessments have been completed and with 
the Investigator’s approval. Subjects with any ongoing AEs or SAEs while at 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. If any AEs or SAEs reported at this visit, the 
study center staff will perform a telephone contact the next day to ensure that subject’s condition 
is stable. 
 
After completing Day 1 assessments, the subjects will return to the study center for study 
assessments and follow-up visits on Days 3 and 8; weekly from Day 8 up to Day 29; every other 
week up to Day 85; and then monthly for 12 weeks to monitor changes in disease activity, safety, 
and tolerability. In addition, the subjects will be contacted via telephone by study staff to inquire 
about the potential AEs and changes in concomitant medications on Days 36, 50, 64, and 78. 
Disease activity (response to study treatment) will be evaluated for all subjects using the 
PPPASI, PPSI, PPPIGA, PASI (if plaque psoriasis at non-acral sites is present), and total affected 
BSA (if plaque psoriasis and/or pustular psoriasis is present at non-acral sites). In addition, 
relapse rate, time to response, and change in fresh and total number of pustule count on palms 
and soles will be recorded. The subject’s quality of life will be assessed using the PPPQLI, 
DLQI, and Patient Assessment of Palmoplantar Pustulosis Disease Activity (Oji 2015). 
 
Blood samples to determine PK and immunogenicity will be collected before the administration 
of ANB019 and at the other time points specified (refer to Table 2). In addition, a punch biopsy 
(biomarker analysis) will be taken during the study (guidelines for optional punch skin biopsy


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will be located in Lab Manual). All subjects randomized in the study will be asked to participate 
in the skin biopsy; however, the subject’s participation is optional.
Safety assessments including AE/SAE monitoring, vital signs measurements, physical
examinations, ECGs, and laboratory measurements will be performed during the study.
The end of study (EOS) visit will be at Week 24 (Day 169) and all subjects will return to the
study center for the EOS assessments (see Section 1.3).
Concomitant medication use and AEs/SAEs will be recorded and reported throughout the study.
4.2    Scientific Rationale for Study Design
There is little evidence for the efficacy of any treatment of pustular psoriasis and no currently
published guidelines for its management. The use of available treatments is limited by low
efficacy and long-term adverse effects.
In this context, the development of agents with new mechanisms of action is considered
important for future clinical practice. As ANB019 offers the potential for inhibition of IL-36
signaling by blocking IL-36R it may provide a novel strategy for treatment of patients with PPP.
4.3    Justification for Dose
ANB019 will be administered as a single SC dose of 200 mg followed by 3 doses of 100 mg SC
administered on Days 29, 57, and 85.
The doses selected for the study demonstrated favorable safety and tolerability profile in a
Phase 1 study conducted in healthy volunteers. In addition, ANB019 demonstrated linear PK 
with an estimated t1/2 of
 days at all doses tested with persistent pharmacodynamic activity.
The loading dose of 200 mg SC administered on Day 1 was chosen to achieve Cmax soon after
dosing in order to provide optimal potential benefit to PPP patients and to reach steady state 
concentrations rapidly following 100 mg SC dosing. The 12-week treatment period is expected
to provide better clinical outcome, thus potentially benefiting PPP patients and further assessing
long-term safety and efficacy in patients with PPP.
4.4    End of Study Definition
A subject is considered to have completed the study if they have completed the last protocol 
specified visit, including the last visit on Day 169 (see Section 1.3).
The end of the study is defined as the date of the last visit of the last subject in the study.


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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. 
 
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 a regulatory 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 study 
medication. The Sponsor may discontinue the study if it becomes unjustifiable for medical or 
ethical reasons, for poor enrolment, or because of discontinuation of clinical development of 
ANB019 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 the Sponsor or 
contract research organization (CRO). 
 
If the study center has to be closed prematurely, the Sponsor or CRO 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: 
 
    If SAEs occur resulting in the risk-benefit ratio not being reasonable anymore. 
 
 
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. 
 
 
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. 
 
    If the results of parallel studies show evidence for unacceptable risks. 
 
 
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.


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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 the inclusion criteria and none of the exclusion 
criteria. 
 
5.1     Inclusion Criteria 
 
1.   Male and female subjects must be 18 to 75 years of age (inclusive), at the time of signing the 
informed consent. 
2.   Clinically confirmed diagnosis of PPP with disease of sufficient impact and severity 
requiring systemic therapy. 
3.   Disease duration of at least 3 months prior to Screening. 
4.   Present with active pustules on palms or/and soles at Screening and Baseline. 
5.   At least moderate disease severity (score 3 = moderate) based on the PPPIGA (Appendix 9) 
at Screening. 
6.   Subjects with or without a history of plaque psoriasis can be enrolled (number of subjects 
enrolled with plaque psoriasis should not exceed 50%). 
7.   Meet the following laboratory criteria at Screening: 
    Hemoglobin ≥ 90 g/L (≥ 9 g/dL). 
    White blood cell count ≥ 3.0 × 109/L (≥ 3.0 × 103/μL). 
    Platelets ≥ 100 × 109/L (≥ 100 × 103/μL). 
    Serum creatinine <132.6 μmol/L (< 1.5 mg/dL). 
    Alanine aminotransferase and aspartate aminotransferase ≤ 1.5 upper limit of normal 
(ULN). 
    Total bilirubin ≤ 1.5 × (ULN) . Subjects with known Gilbert’s disease who have 
serum bilirubin < 3 × (ULN) may be included. 
8.   Body mass index within the range of 18 to 36 kg/m2, inclusive {body mass index = weight 
(kg)/[height (m)]2} and total body weight > 50 kg (110 lb). 
9.   Subjects must be otherwise in a good health status as judged by the Investigator based on 
medical history, physical examination, ECG, hematology, chemistry, and urinalysis. 
10. 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: 
a)  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. 
b)  Female subjects:


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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 
48 days before Day 1). 
11. 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, erythrodermic, guttate) except plaque psoriasis. 
2.   Have concomitant dermatological (eg, subcorneal pustular dermatosis, impetigo 
herpetiformis, acute generalized exanthematous pustulosis) or medical conditions which may 
interfere with the Investigators’ 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 pressure 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 upper and 
lower respiratory 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. Subjects with a history of localized 
oral or genital herpes simplex that, in the opinion of the Investigator, is well controlled will 
be eligible for study participation. 
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.


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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
6.   History or any evidence of active infection within 4 weeks of Baseline 
(eg, bronchopulmonary, urinary, or gastrointestinal), excluding localized oral or genital 
herpes simplex that, in the opinion of the Investigator, is well-controlled. 
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 such as, but not exclusively, 
helminths, protozoa, Trypanosoma cruzi within 6 months prior to 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, 
systemic lupus erythematosus, polymyalgia rheumatica, giant cell arteritis, Behcet’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 treatment administration. 
13. Malignancy or history of malignancy within 5 years prior to Screening, except for treated 
basal cell or squamous cell in situ carcinoma of the skin or squamous cell carcinomas 
deemed by the Principal Investigator to be fully treatable. 
14. History of any significant drug allergy or reaction (such as anaphylaxis or hepatotoxicity) 
and reactivity to polysorbate 20, a component of ANB019 formulation, or the inactive 
ingredients (excipients). 
15. Have taken the following drugs within the specified period prior to Screening or Baseline 
(Day 1): 
 
Topical medications for (including corticosteroids, 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 preparations within 2 weeks prior to Baseline. 
    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. 
    Phototherapy (ie, ultraviolet light B [UVB]) or photochemotherapy (eg, psoralen and 
ultraviolet A [PUVA]) within 4 weeks prior to Baseline. 
 
Previous treatment with anti-tumor necrosis factor (TNF)/interleukin (IL-12/IL-23) 
and IL-17 or any other mAbs is not allowed within 3 months or 5 half-lives 
(whichever is longer). 
    Antibiotic or antiviral medication within 4 weeks (topical 2 weeks and systemic 
4 weeks) prior to Baseline.


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    Any investigational drug within 4 weeks or 5 half-lives, whichever is longer prior to 
Screening. 
    Live attenuated vaccine within 12 weeks prior to Screening and during the study. 
 
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 (see 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 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 a Screening visit) within 
4 weeks of study treatment administration (within 2 weeks for plasma only). 
20. Blood transfusion within 4 weeks of study treatment administration (Day 1). 
21. Any other physical, mental, or medical conditions, which, in the opinion of the Investigator, 
make study participation inadvisable or could confound study assessments. 
22. Clinically significant abnormality on chest X-ray at Screening or within 12 months prior to 
Screening. 
23. Any clinically significant abnormalities on 12-Lead ECG at Screening. 
24. Evidence of clinically significant abnormality in urinalysis as determined by the Investigator. 
25. Positive blood screen for hepatitis C antibody, hepatitis B surface antigen, or human 
immunodeficiency virus 1 and 2 antibodies. 
26. Inability to tolerate SC drug administration. 
 
 
 
5.3     Lifestyle Considerations 
 
Investigators should counsel subjects on avoidance of excessive exposure to sunlight 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 randomized 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.


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CONFIDENTIAL                                                                                                                    Protocol ANB019-003 - Amendment 5 
 
 
 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once after discussion with the Medical Monitor. Rescreened subjects should not be 
assigned the same subject number as for the initial screening.


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CONFIDENTIAL                                                                                                                   Protocol ANB019-003 - Amendment 5
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 clinical study participant according to the 
study protocol.
6.1    Study Treatment Administered
All eligible subjects in the study will be randomly allocated in a 1:1 ratio to receive 200 mg of
ANB019 or placebo SC on Day 1 followed by 3 doses of 100 mg of ANB019 or placebo
administered SC on Days 29, 57, and 85. Allocation of the subject to a study treatment will be 
performed using a central Interactive Voice/Web Response System (IVRS/IWRS) as defined in 
the User Requirements Specification and the Randomization Requirement Specification by the
IWRS vendor.
ANB019 is a humanized
mAb that belongs in the class of anti-interleukin-
36 receptor mAb.
ANB019 will be provided as a sterile, colorless to yellowish and clear to slightly opalescent
solution for injection.
The placebo contains no active drug ingredient and will be provided as a sterile colorless to
slightly yellowish and clear to very slightly opalescent solution for injection. Detailed
administration instructions will be provided in the Pharmacy Manual.
Study treatment details are provided in Table 1.
Table 1
Study Treatment Details
Study Treatment
Name:
ANB019
Anti-interleukin-36 receptor monoclonal
antibody
Placebo
Study Treatment
Description
ANB019 will be provided as a sterile, 
colorless to yellow and clear to slightly
opalescent solution supplied in a single-use,
2R, Type I glass vial with a fill volume of
mL. Each vial contains
mg/mL.
The placebo contains no active
ingredient and will be provided as a
sterile, colorless to slightly
yellowish, and clear to very slightly
opalescent solution for injection
supplied in a single-use, 2R, Type I
glass vial with a fill volume of
mL.
Dosage Formulation:
The drug product is formulated as
.
The Placebo is formulated:
Unit Dose
Strength(s)/Dosage
Level(s):
A dose of 200 mg SC on Day 1 followed 
by100 mg SC on Days 29, 57, and 85.
An equivalent volume of placebo
will be administered SC on Day 1
and on Days 29, 57, and 85


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Route of 
Administration 
SC injection (4 doses) 
SC injection (4 doses) 
Dosing Instructions: 
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 SC ANB019 will receive 
1 mL × 2 injections for 200 mg dose on 
Day 1 and 1 mL × 1 injection for 100 mg 
dose on Days 29, 57, and 85. 
Subcutaneous 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. 
Detailed administration instructions will be 
provided in the Pharmacy Manual. 
For SC injections, placebo 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 SC placebo (on 
Day 1) will receive a 1 mL × 2 
injections and on Days 29, 57, and 
85, 1 mL × 1 injection. 
Subcutaneous 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. 
Abbreviations: AE = adverse event; NaCl = sodium chloride; SC = subcutaneous 
 
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 randomized in the study may receive study treatment and only authorized 
study center staff may supply or administer study treatment. Further guidance and 
information for the administration of the study treatment are provided in the Pharmacy 
Manual. 
3.   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. 
4.   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 undiluted or 
diluted may be stored at room temperature (8°C to 25°C [46°F to 77°F]) for up to 8 hours. 
Vials are intended for single-use only; therefore, any remaining solution should be discarded. 
5.   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). 
6.   Further guidance and information for the final disposition of unused study treatment are 
provided in the Pharmacy Manual.


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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 medication 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 is a randomized, double-blind, placebo-controlled study with limited access to the 
randomization code. All subjects will be assigned a unique ‘subject identification number’ at the 
time of Screening. On Day 1, after verification that all inclusion and no exclusion criteria have 
been met, the subjects will be randomly allocated in a 1:1 ratio to receive ANB019 or placebo. 
 
Randomization will be stratified based on the patient’s history of plaque psoriasis, to ensure that 
the number of subjects enrolled with plaque psoriasis should not exceed 50%. 
 
As subjects become eligible, they will be assigned sequential randomization numbers which will 
be used to assign the allocated treatment based on a randomization schedule. 
 
The Sponsor, Investigator, and subjects will be blinded to treatment assignment of ANB019 or 
placebo. 
 
Once the subject meets all inclusion and no exclusion criteria and has provided an informed 
consent, the study center will request the treatment assignment using a central IVRS/IWRS. 
 
All randomized subjects will be managed by IVRS/IWRS. 
 
The process for breaking the blind will be handled through the IVRS/IWRS. Unblinding of 
treatment assignment during the study is discouraged and should occur only if it is absolutely 
necessary to know what treatment the subject received. If the Investigator deems identification of 
the study treatment is necessary for the purpose of providing urgent subject care, and knowledge 
of the subject’s treatment assignment (ANB019 or placebo) will alter subsequent care, the 
treatment code for the specific subject will be obtained. Prior to unblinding, the Investigator or 
appropriate designee should attempt to contact the Medical Monitor to discuss the need to 
unblind a subject. In the event the Medical Monitor cannot be reached, the Investigator should 
ensure that the unblinding of the treatment code is performed in a discrete manner and the 
treatment is disclosed only to those persons involved with the direct medical care of the subject. 
The Investigator should contact the Sponsor’s Medical Monitor immediately (within 24 hours to 
include weekends) following emergency unblinding. 
 
The Sponsor and CRO must be notified immediately if a subject and/or Investigator is unblinded 
during the study. Interactive Web Response System can create the blinded and/or unblinded 
notification when the blind is broken, which can be sent via email as per the user role of 
IVRS/IWRS. Pertinent information regarding the circumstances of unblinding of a subject’s 
treatment code must be documented in the subject’s source documents.


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6.4     Study Treatment Compliance 
 
The prescribed dosage, timing, and mode of administration may not be changed. Any departures 
from the intended regimen must be recorded in the electronic case report forms (eCRFs). 
 
For the study treatment administrations, date/time of administration, site of administration, and 
dose administered (entire dose/incomplete dose) will be documented in the 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: 
 
    Reason for use. 
    Dates of administration including start and end dates. 
    Dosage information including dose and frequency. 
 
In addition, all prior medications used to treat PPP 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 (see 
Appendix 5) must be on a stable dose for at least 4 weeks before study treatment administration 
(Day 1). 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 study, except within 24 hours prior to the study visits. 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. 
 
The study team will dispense rescue medication that will be obtained locally and will be 
reimbursed. 
 
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.


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CONFIDENTIAL                                                                                                                   Protocol ANB019-003 - Amendment 5
6.6    Dose Modification
No dose modification is allowed in this study. Study treatment can be interrupted temporarily or
permanently if deemed necessary as per the Investigator’s discretion.
6.7    Treatment After the End of the Study
All subjects will return to the study center for the EOS (Day 169/Week 24) or Early Termination
(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 treatment, SAE, or pregnancy occurring through the EOS and/or ET visit should be 
reported to the
Safety team (see Appendix 4) and followed up until outcome.


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7.0   DISCONTINUATION OF STUDY TREATMENT AND 
SUBJECT DISCONTINUATION/WITHDRAWAL 
 
7.1     Discontinuation of Study Treatment 
 
The subject’s eligibility criteria will be checked prior to administration of the study treatment on 
Day 1. If a clinically significant finding or AE/SAE is identified, the Investigator will determine 
if the subject can receive the study treatment and continue in the study and if any change in 
subject management is needed. 
 
In case of early withdrawal from the study treatment and study, the subject will be required to 
attend the ET visit and other follow-up period visits as soon as possible. 
 
7.1.1          Temporary Interruption 
 
Study treatment can be interrupted temporarily in case of an AE as per the Investigator’s 
discretion. The Medical Monitor should be informed. Restarting of study treatment at the next 
scheduled administration study visits can be done after discussion with the Medical Monitor. 
 
7.1.2          Rechallenge 
 
The study treatment can be reintroduced at the next scheduled administration visit at the 
Investigator’s discretion and after discussion with the Medical Monitor. In case of positive 
rechallenge the study treatment should be withdrawn permanently. 
 
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 the 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 for any events described below, any SAE or significant AE which, in the opinion 
of the Investigator, is related to the study drug, or pregnancy occurring through the EOS should 
be followed until outcome. 
 
The following events are considered sufficient reasons for discontinuing a subject from the study 
treatment and/or the study: 
 
    Any significant AE which in the opinion of the Investigator requires subject withdrawal. 
    Withdrawal of consent. 
    Significant deviation/lack of compliance with protocol. 
    Lost to follow-up.


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Use of any excluded/prohibited medications treatment that in the opinion of the Investigator 
necessitates the subject being withdrawn (Refer to Appendix 5). 
    Termination of the study by the Investigator or Sponsor. 
    Pregnancy (Refer to Appendix 6 and Section 8.3.5). 
    New information suggests taking part in the study may not be in the participant’s best 
interest. 
    Death. 
    Other. 
 
If a 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 (see 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 treatment-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: 
 
 
The study center must attempt to contact the subject, reschedule the missed visit as soon as 
possible, 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. 
    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. 
 
Should the subject continue to be unreachable, he/she will be considered to have withdrawn 
from the study.


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8.0   STUDY ASSESSMENTS AND PROCEDURES 
 
    Study procedures and their timing are summarized in the Schedule of Activities (see 
Section 1.3). 
 
Assessments scheduled on the day of study treatment administration must be performed prior 
to the study treatment administration unless otherwise noted (see Section 1.3). 
    There are visits where the protocol requires more than 1 procedure to be completed at the 
same time point. When indicated, the procedure must follow the specific order of events; 
refer to the Schedule of Activities (see Section 1.3) for instructions. 
    Protocol waivers or exemptions are not allowed. 
 
Immediate safety concerns should be discussed with the Sponsor/designee immediately upon 
occurrence or awareness to determine if the subject should continue or discontinue in the 
study. 
    Adherence to the study design requirements, including those specified in the Schedule of 
Activities, is essential and required for study conduct. 
 
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. 
    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). 
    The maximum amount of blood collected from each subject over the duration of the study, 
including any extra assessments that may be required, will be 184 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 completes the scales and 
questionnaires at all time points for a given subject. 
    Planned time points for all efficacy assessments are provided in the Schedule of Activities 
(see Section 1.3). 
 
8.1.1          Palmoplantar Pustulosis Psoriasis Area Severity Index 
 
The PPPASI score will be used in the study for an overall evaluation of response to treatment (to 
determine the efficacy of ANB019). It uses the key clinical aspects of the disease to enable 
accurate assessment namely: erythema; pustules; desquamation (scaling) and; area of palms and 
soles involved (Bhushan 2001). The PPPASI is presented in Appendix 7.


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8.1.2          Palmoplantar Pustulosis Severity Index 
 
The PPSI score is used for assessing and grading the severity of PPP lesions and their response 
to therapy. The PPSI produces a numeric score that ranges from 0 to 12. In the PPSI, either both 
palms or both soles, whichever has the most severe skin lesion at Screening will be identified as 
the evaluation sites and assessed at all subsequent visits. The evaluation sites will be assessed 
separately for erythema, pustules/vesicle, and desquamation/scaling, and each will be rated on a 
scale of 0 to 4. The PPSI is presented in Appendix 8. 
 
8.1.3          Palmoplantar Pustulosis (Static) Investigator’s Global Assessment 
 
The PPPIGA score will be used in the study to determine the subject’s response to treatment. 
The proportion of subjects who achieved “clear” or “almost clear” will be determined using this 
score. The Investigator will be asked to rate the severity of the subject’s disease. A 5-point rating 
scale will be used as listed below: 
 
0 = clear, 1 = almost clear, 2 = mild, 3 = moderate, 4 = severe. The PPPIGA is presented in 
Appendix 9. 
 
8.1.4          Psoriasis Area Severity Index 
 
The PASI scores will be used to determine the treatment response in subjects with plaque 
psoriasis (Fredriksson 1978). The PASI total score includes plaque characteristics (ie, erythema, 
induration, scaling), percentage of BSA affected and should be calculated by electronic data 
capture (EDC). The PASI is presented in Appendix 10. 
 
8.1.5          Total Body Surface Area 
 
The affected total BSA% of disease will be used to determine the treatment response in subjects 
with plaque psoriasis and/or pustular psoriasis at non-acral sites. This assessment will be 
performed if plaque psoriasis and/or pustular psoriasis at non-acral sites is presented. 
 
8.1.6          Pustule Count on Palms and Soles 
 
Fresh Pustule Count on Palms and Soles 
 
 
To be included in the count, pustules must be macroscopically visible, white/yellow in color 
with no brown color, and present on the glabrous skin of the palms and/or soles. The size of 
the majority of pustules will be noted at each site (<1 mm, 1 to 3 mm, >3 to 10 mm, 
confluent lakes of pus). 
 
Total Pustule Count on Palms and Soles 
 
 
To be included in the count, pustules must be macroscopically visible, white/yellow/brown in 
color, with or without crust, and present on the glabrous skin of the palms and/or soles.


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Time to response and relapse rate will be assessed and recorded. Time to response is defined as 
the time to achieve 75% reduction in fresh pustule count and relapse rate is defined as a return to 
Baseline status in fresh pustule count. 
 
8.1.7          Dermatology Life Quality Index 
 
The DLQI questionnaire will be used to assess treatment response on the subject’s quality of life. 
The aim of this questionnaire is to measure how much the skin condition has affected the 
subject’s life during the previous week. 
 
Subjects will be asked to recall their experiences during the previous week by responding to 
10 questions (Finlay 1994). 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. The DLQI 
questionnaire is presented in Appendix 11. 
 
8.1.8          Palmoplantar Pustulosis Quality of Life Instrument 
 
The PPPQLI is a subject completed 32 item questionnaire capturing symptoms, impact on daily 
activities, and ability to work (Farley 2009). This questionnaire should be completed prior to any 
safety or efficacy assessments. The PPPQLI is presented in Appendix 12. 
 
8.1.9          Patient Assessment of Palmoplantar Pustulosis Disease Activity 
 
The Patient Assessment of Palmoplantar Pustulosis Disease Activity will be an assessment of 
disease activity by subjects. All subjects will be asked to rate how active their disease condition 
on a 0 to100 mm standardized visual analog scale (VAS) (Kane 2005). Symptoms will be 
assessed utilizing the mean VAS score (Schram 2011). It will be completed by the subject on a 
worksheet prior to any efficacy or safety evaluations. The subject will be asked to place a 
vertical stroke on a 100 mm VAS on which the left hand boundary represents very well, and the 
right hand boundary represents very poor. The distance from the mark to the left hand boundary 
will be reported. The Palmoplantar Pustulosis Disease Activity VAS is presented in Appendix 
13. 
 
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).


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A complete physical examination will include assessments of general appearance; skin; 
head/neck; pulmonary, cardiovascular, gastrointestinal, external genitourinary, lymphatic, 
and musculoskeletal system; extremities; eyes; nose; throat; and neurologic status. 
    A detailed examination of the skin should be performed at the time points indicated in the 
Schedule of Activities for the efficacy assessments (eg, PPPASI, PPPIGA, PASI, and BSA, 
pustule count). 
    Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
 
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 12 months prior to 
Screening (see Section 1.3). 
 
8.2.3          Height and Weight 
 
    Height will be measured only at Screening and weight will be measured at Screening and the 
EOS visit. 
 
8.2.4          Vital Signs 
 
 
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). 
    Blood pressure and pulse 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. 
 
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). 
    Vital signs including body temperature, respiratory rate, and pulse rate (after 5 minutes rest) 
should be measured once. Arterial blood pressure should be measured twice (at intervals of 
approximately 5 minutes), using a validated device. The average of the 2 blood pressure 
readings will be entered in the eCRF. 
 
8.2.5          Electrocardiograms 
 
 
A single 12-lead ECG will be obtained at the time points specified in the 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. 
    The ECG will be reviewed by the central ECG laboratory team and the instructions and 
guidelines for collection (eg, equipment), transmission, and archiving of ECG data will be 
provided in the ECG Manual. 
    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.


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The ECG individual data (with the exception of clinical significance) does not need to be 
entered into EDC. 
 
8.2.6          Clinical Safety Laboratory Assessments 
 
    See Appendix 3 for the list of clinical laboratory tests to be performed and the Schedule of 
Activities (see Section 1.3) for the timing and frequency of the tests. 
 
A central laboratory will be used to perform all laboratory tests except urine pregnancy 
dipstick which will be assessed by the study 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 make an immediate decision for any safety concerns based on 
laboratory results. If a local sample is required, it is important that the sample for central 
analysis is obtained at the same time. 
    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 eCRF. 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. 
    All laboratory tests with values considered clinically significantly abnormal during the study 
and including the subject’s last study visit (EOS) 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. 
 
 
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. 
 
8.2.7          Photography 
 
Photography of the lesions will be performed at the time points mentioned in the Schedule of 
Activities (see Section 1.3) for documentation purposes only. A standardized approach to 
collection of photographs will be described in the manual provided to sites. Photographs will be 
transferred to a central vendor for quality review. Any further review of photographs may be 
conducted by a third party consultant.


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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.
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 all AEs
including those 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 AEs as well as 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 AEs or SAEs 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.
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.
8.3.2
Method of Detecting AEs and SAEs
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 AEs will be followed until resolution, stabilization, the event is


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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
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.
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.
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.
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
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.
Details of all pregnancies in female partners of male subjects will be collected while the male
subject is in this study and through EOS (or ET visit if applicable).
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.
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.
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 AESIs in this study.
Serious infection (requiring hospitalization; or with fatal outcome or sepsis; or requiring IV
antibiotics/antimicrobials).
Serious allergic reaction.
Gastrointestinal clinical manifestations including infections.


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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 
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 PPP and can be 
serious/life-threatening: 
 
    Flare of PPP 
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 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 greater than 200 mg within a 24-hour time period on Day 1 
and greater than 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: 
 
    Administration is to be discontinued. 
    The subject is to be monitored clinically. 
    Supportive measures are to be undertaken as clinically indicated. 
 
Electrocardiography and clinical laboratory evaluations (ie, blood glucose, hepatic enzymes, 
creatinine, blood urea nitrogen, CK, and complete blood count) are to be performed and 
followed until all values return to baseline levels and AEs subside. 
 
No information on overdose, maximum tolerated dose, or dose-limiting toxicities for ANB019 
has been established at this time and since there are no known antidotes for ANB019, the 
treatment of overdose is at Investigator’s discretion. 
 
In the event of an overdose, the Investigator should: 
 
1.   Contact the Medical Monitor immediately.


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2.   Closely monitor the subject for any AE/SAE and laboratory abnormalities and follow-up 
until resolution. 
3.   Obtain a serum sample for PK analysis soon after the dose for SC administration and close to 
Tmax (~164 hours) for SC injection. 
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 of Activities (see Section 1.3). 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 within the stability window of the assay will be analyzed. 
 
Subject’s confidentiality will be maintained. Drug concentration information that may unblind 
during the study will not be reported to study centers or blinded personnel until the study has 
been unblinded.


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Table 2           PK/ADA Sample Collection and Timepoints 
 
 
Study Visit 
PK Sample Timepoint 
Plasma 
ADA Sample Timepoint 
Serum 
 
 
Day 1 
Predose 
Predose 
1 hr ( 10 min) postdose 
4 hrs ( 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-antibodies; hr(s) = hour(s); min = minutes; PK = pharmacokinetic. 
 
 
8.6     Pharmacodynamics 
 
Pharmacodynamic parameters are not evaluated in this study. 
 
8.7     Biomarkers 
 
Samples will be collected according to the Schedule of Activities (see Section 1.3) to measure 
skin biopsy biomarkers including but not limited to IL-36, IL-17, IL-23, and markers of 
neutrophils and dendritic cells infiltration. 
 
The actual date and time of the sample collection will be recorded in the subject’s eCRF. The 
details of skin biopsy 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. 
 
8.8     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


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also be collected at the final visit from subjects who discontinued study treatment or were 
withdrawn from the study. These samples will be tested by the Sponsor or Sponsor’s designee. 
Each serum sample will be divided into 2 aliquots (1 each for primary and a back-up). 
 
Anti-drug antibody (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. 
 
8.9     Health Economics or Medical Resource Utilization and Health 
Economics 
 
Health Economics/Medical Resource Utilization and Health Economics parameters are not 
evaluated in this study.


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9.0   STATISTICAL CONSIDERATIONS 
 
9.1     Statistical Hypotheses 
 
All hypothesis-based statistical testing will be considered exploratory in nature for this Phase 2 
study. 
 
9.2     Sample Size Determination 
 
The sample size is not based on statistical power considerations. 
 
Approximately 50 subjects will be enrolled from 25 study centers for study treatment. On Day 1, 
subjects who meet all the entry criteria will receive a 200 mg SC dose of ANB019 or placebo 
followed by 3 doses of 100 mg SC of ANB019 or placebo in a 1:1 ratio. 
 
9.3     Analyses Sets 
 
The analysis sets are defined in Table 3. 
 
Table 3           Analysis Sets 
 
Analysis Set 
Description 
ITT Analysis Set 
The ITT analysis set will include all randomized subjects. In this analysis set, 
treatment will be assigned based upon the treatment arm to which subjects 
were randomized regardless of which treatment they receive. 
Safety Analysis Set 
The safety analysis set will include all randomized subjects who receive 
1 dose of ANB019 or placebo. The safety analysis set will be used for all 
safety analyses. Subjects will be analyzed as treated. 
Per Protocol Set 
The Per Protocol set will include all subjects in the ITT 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 set who have at least 
1 quantifiable postdose PK sample available and who do not have events or 
protocol deviations or events with the potential to affect PK concentrations. 
The PK analysis set will be used for all PK analyses. 
Abbreviations: ITT = intent-to-treat; PK = pharmacokinetics 
 
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, 
listings, and figures will be described in the Statistical Analysis Plan (SAP) and approved by the 
Sponsor before database lock. 
 
The default summary statistics for continuous variables include number of contributing 
observations, mean, standard deviation (SD), median, minimum, and maximum. For PK


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parameters, coefficient of variation (CV) and geometric mean will also be presented, as 
appropriate. 
 
For categorical variables, the number and percentage (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 treatment (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. 
 
Unless otherwise specified, all formal statistical tests will be 2-sided at the 5% significance level. 
Point estimates of treatment differences will be accompanied with 2-sided 95% confidence 
intervals (CIs), where applicable. 
 
In the case of normality assumption violations, appropriate non-parametric methods may 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, randomized, 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/Sponsor 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 
or placebo. Subject characteristics may include, but are not limited to age, gender, height, 
weight, and BMI. 
 
Summaries will include descriptive statistics for continuous variables (sample size [n], mean, 
SD, median, minimum, and maximum) and for categorical variables (n, frequency, and 
percentage). 
 
Medical history will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
latest version and listed for all subjects.


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9.4.3          Concomitant Medication 
 
All medications will be coded using the WHO 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 treatment, or as concomitant medication if it is ongoing at the time 
of the first dose or is started after the first dose of study treatment. Prior, concomitant, and rescue 
medications will be summarized by treatment group and 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 Endpoint 
The primary efficacy endpoint is the mean change from Baseline in PPPASI at Week 16. 
The primary endpoint will be analyzed using a general linear mixed model for repeated 
measurements (MMRM) to include data collected at weeks 4, 8, 12 and 16. The model will 
include fixed effects for treatment, history of plaque psoriasis (Yes/No), categorical visit, the 
treatment by visit interaction, and Baseline PPPASI score as a covariate. Least-squares means 
(LSM) and associated standards errors for the change from baseline in PPPASI will be presented 
for each treatment group and the least-squares mean difference will be presented with the two- 
sided 95% confidence interval to assess the difference between the active group and placebo. 
 
Possible effect of any other covariates may also be investigated. Details of such analyses will be 
described in the SAP. Details of specific alternative statistical methods will be documented in the 
SAP. 
 
In addition, descriptive statistics (n, mean, SD, median, minimum, and maximum) will be 
presented. 
 
9.4.4.2       Analysis of Secondary Efficacy Endpoints 
 
Following are the secondary efficacy endpoints: 
 
    Proportion of subjects achieving PPPASI50 at all study center visits. 
    Proportion of subjects achieving PPASI75 at all study center visits. 
    Change in PPSI score at all study center visits. 
    Change in PPPIGA score at all study center visits. 
 
Proportion of subjects with clear or almost clear assessment score on PPPIGA at all study 
center visits. 
    Change in fresh and total pustule count on palms and soles at all study center visits. 
    Time to response defined as time to achieve 75% reduction in fresh pustule count. 
    Relapse rate defined as return to Baseline status in fresh pustule count.


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Change in PASI score and affected BSA at all study center visits, if plaque psoriasis is 
present at non-acral sites. 
    Improvement in pustular psoriasis at non-acral site BSA (if present) at all study center visits. 
    Change in clinical scores of PPPQLI, DLQI, and Patient Assessment of Palmoplantar 
Pustulosis Disease Activity at all study center visits. 
    Presence of anti-drug antibodies. 
 
Proportion of Subjects Achieving PPPASI50 and PPPASI75 at All Study Center Visits: 
 
Frequency and percentages for each response Yes/No for PPPASI50 and PPPASI75 will be 
presented separately by visit for both treatment arms. 
 
The binary response for each endpoint will be analyzed using logistic regression model using a 
logit link. The model includes factors for treatment, history of plaque psoriasis (Yes/No), and 
Baseline PPPASI score. The results will be presented in terms of odds ratio together with its 
associated 2-sided 95% CIs. 
 
Change in PPSI Score at All Study Center Visits: 
 
Summary statistics will be provided for absolute PPSI scores as well as for change from Baseline 
by visit and treatment group. 
 
Change in PPPIGA Score at All Study Center Visits: 
 
Frequency and percentage will be summarized by each visit for both treatment arms. 
 
A shift table of change in PPPIGA scores from Baseline to EOS visit will be displayed by each 
PPPIGA score for both treatment arms. 
 
Proportion of Subjects with Clear or Almost Clear Assessment Score on PPPIGA at All 
Study Center Visits: 
 
Frequency and percentages for each response Yes/No by visit will be presented for both 
treatment arms. 
 
The binary response at EOS will be analyzed using logistic regression model using a logit link. 
The model includes factors for treatment and history of psoriasis (Yes/No), and Baseline PPPASI 
score as a covariate. 
 
The results will be presented in terms of odds ratio together with its associated 2-sided 95% CIs. 
 
Change in Fresh and Total Pustule Count on Palms and Soles at All Study Center Visits: 
 
Summary statistics for the fresh and total pustule count, as well as change from Baseline, will be 
provided. Frequency and percentages of the size of the majority of pustules will be presented for


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both the treatment arms. Change in fresh and total pustule count data throughout the study will 
also be analyzed. Further details of the analysis will be described in the SAP. 
 
Time to Response defined as time to achieve 75% reduction in fresh pustule count: 
 
Time to response will be analyzed as time-to-event endpoint. The Kaplan-Meier survival curves 
and 25th, 50th (median), and 75th percentiles will be provided along with the 2-sided 95% CIs. 
Subjects without response will be censored at the EOS. 
 
Relapse Rate defined as return to Baseline in fresh pustule count: 
 
Frequency and percentages will be summarized for subjects experiencing relapse. 
 
Change in PASI Score and Affected BSA at All Study Center Visits, if Plaque Psoriasis is 
Present at Non-Acral Sites: 
 
Summary statistics will be provided for absolute PASI scores as well as for percent change from 
Baseline by visit and treatment group. 
 
Summary statistics will be provided for percent change from Baseline in affected BSA by visit 
and treatment group. 
 
Improvement in Pustular Psoriasis at Non-Acral Site BSA (if present) at All Study Center 
Visits: 
 
Summary statistics will be provided for percent change from Baseline in affected BSA by visit 
and treatment group. 
 
Change in Clinical Scores of PPPQLI, DLQI, and Patient Assessment of Palmoplantar 
Pustulosis Disease Activity at All Study Center Visits: 
 
Summary statistics will be provided for absolute scores of PPPQLI, DLQI, and Patient 
Assessment of Palmoplantar Pustulosis Disease Activity, as well as for change from Baseline by 
visit and treatment group. 
 
The PPPQLI, DLQI, and Patient Assessment of Palmoplantar Pustulosis Disease Activity scores 
will be analyzed using a mixed model for repeated measures with treatment as fixed effect, 
history of plaque psoriasis (Yes/No) and Baseline scores as covariates. 
 
By-subject listing will be presented for each questionnaire, by visit. 
 
9.4.5          Safety Analyses 
 
Following are the primary safety and tolerability endpoints: 
 
    Assessment of AEs.


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Potentially significant and clinically important AEs, AESIs, SAEs, and AEs leading to 
withdrawal. 
    Physical examinations. 
    Vital signs. 
    12-Lead ECG. 
    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 
 
TEAE: A TEAE is defined as: 
 
    A new event that occurs during or after first dose of study treatment or, 
 
Any event present at Baseline that worsens in either intensity or frequency after first dose of 
study treatment. 
 
Adverse events will be coded using the MedDRA and only TEAEs will be summarized. Number 
of events and percentage will be tabulated by Preferred Term (PT) and System Organ Class 
(SOC). Multiple occurrences of an AE for a subject will only be counted once per SOC and PT. 
Percentages will be determined relative to all safety subjects exposed to ANB019/placebo. 
 
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, SAEs, TEAEs 
leading to treatment discontinuation, and TEAEs leading to withdrawal of subject will be 
tabulated for each treatment arm. 
 
All AE data will be listed for each subject. 
 
Summaries over SOC and PT of TEAEs, TEAEs leading to death, SAEs, potentially significant 
TEAEs and clinically important TEAEs, AESIs, and TEAEs that led to discontinuation from the 
study or study treatment will be presented by treatment. Summaries will also be presented by 
relatedness to the study treatment and the severity of the TEAE. 
 
9.4.5.2       Physical Examinations, 12-Lead Electrocardiogram, Vital Signs, and Clinical 
Safety Laboratory Tests (Hematology, Biochemistry, and Urinalysis) 
 
Summaries and listings of data for complete physical examination findings, vital signs, and 
safety laboratory tests result (hematology, biochemistry, and urinalysis) 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


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summarized and listed. Hematology and biochemistry 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, and clinical laboratory test results. 
 
Change from Baseline will also be summarized for vital signs, and clinical laboratory tests 
results. 
 
All ECG data results (normal/abnormal) will be summarized using frequency and percentage. 
Clinically significant abnormalities will be presented in by-subject listings. 
 
9.4.6          Pharmacokinetic Analyses 
 
9.4.6.1       Derivation of Pharmacokinetic Parameters 
 
The PK parameters will be derived using noncompartmental methods. 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. 
 
Where possible, the following PK parameters will be determined for ANB019 after the first SC 
administration on Day 1: 
 
    Maximum observed concentration (Cmax). 
 
    Time to maximum observed concentration (Tmax). 
 
 
Area under the curve (AUC) from zero (predose) to last quantifiable concentration 
[AUC(0-last)] and/or AUC determined over the 28-day SC dosing interval [AUC(τ)], if 
appropriate. 
 
Half-life may be estimated, if sufficient data are available, following the last SC administration 
on Day 85 by utilizing ANB019 concentrations collected on Days 113, 141, and 169 (EOS). 
 
Furthermore, the extent of accumulation following monthly 100 mg SC administrations relative 
to the trough obtained after a single 200 mg SC injection dose will be determined or assessed 
graphically. 
 
Additional PK parameters may be determined if deemed appropriate. 
 
9.4.6.2       Pharmacokinetic Concentration Data Analysis 
 
A subject listing of all concentration-time data following SC injections will be presented 
by-subject and scheduled sample collection time. 
 
Concentration data of ANB019 will be summarized by day and nominal time point using the 
number of observations, arithmetic mean, SD, CV, minimum, median, maximum, and geometric 
mean.


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Graphs for mean concentration-time data following SC administration on Day 1 and Day 85 will 
be presented. Individual subject concentration-time plots will also be presented. 
 
Mean trough concentrations-time data will be graphically displayed for samples collected on 
Days 29, 57, 85, and 113 (4-weeks after last dose) to visually assess time to attainment of steady 
state. Time to steady state may also be explored by using inferential statistics, if deemed 
appropriate. 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. 
 
9.4.6.3       Pharmacokinetic Parameter Data Analysis 
 
All PK parameters will be summarized using number of observations, 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. 
 
9.4.6.4       Population Pharmacokinetics Analysis 
 
Pharmacokinetic data from the study may also be used for population PK and PK/response 
analyses. If done, a separate analysis plan will be prepared and results will be reported separately 
from the Clinical Study Report (CSR). 
 
9.4.7          Immunogenicity Analyses (Exploratory Endpoint Analysis) 
 
Observed values for ADA levels/status will be listed by-subject with descriptive statistics based 
on the safety analysis set. The ADA data will be summarized as proportions with 95% CIs from 
a 2-sided exact test for the comparison of treatment arms, using the Clopper-Pearson method. If 
data permits, correlation will be analyzed between ADA levels and safety and efficacy 
endpoints. 
 
Frequency and percentage of ADA response will be presented and listed. 
 
9.4.8          Biomarker Analyses (Exploratory Endpoint Analysis) 
 
Skin biopsy biomarker (including but not limited to IL-36, IL-17, IL-23, and markers of 
neutrophils and dendritic cells infiltration) analysis will be performed by a third party designated 
by the Sponsor. 
 
9.4.9          Missing Data 
 
Missing data handling and possible sensitivity analysis will be described in the SAP.


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9.5     Interim Analyses 
 
An Interim Analysis (IA) might be performed when all active subjects complete their Week 16 
visit for final assessment of all primary and secondary efficacy endpoints (for Week 16) and all 
safety data available (up to Week 24). Final database lock will include exploratory efficacy and 
safety analysis for all subjects for  all visits. 
 
9.6     Data Monitoring Committee 
 
Not applicable.


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10.0 REFERENCES 
 
Adisen E, Gurer MA. Therapeutic options for palmoplantar pustulosis. Clin Exp Dermatol. 
2010;35:219-22. 
 
Asumalathi K, Ameen M, Suomela S, et al. Genetic analysis of PSORS1 distinguishes guttate 
psoriasis and palmoplantar pustulosis. J Invest Dermatol. 2003 Apr;120(4):627-632. 
 
Bhushan M, Burden AD, McElhone K, James R, Vanhoutte FP, Griffiths CE. Oral liarozole in 
the treatment of palmoplantar pustular psoriasis: a randomized, double-blind, placebo-controlled 
study. Br J Dermatol. 2001 Oct;145(4):546-53. 
 
Dubey JP, Markovits JE, Killary KA. Cryptosporidium muris-like infection in stomach of 
cynomolgus monkeys (Macaca Fascicularis). Vet Pathol. 2002;39(3):363-71. 
 
Eriksson MO, Hagforsen E, Lundin IP, Michaelsson G. Palmoplantar pustulosis: a clinical and 
immunohistological study. Br J Dermatol. 1998 Mar;138(3):390-8. 
 
Farley E, Masrour S, McKey J, Menter A. Palmoplantar psoriasis: a phenotypical and clinical 
review with introduction of a new quality-of-life assessment tool. J Am Acad Dermatol. 2009 
Jun;60(6):1024-31. 
 
Farthing MJ. Treatment options for the eradication of intestinal protozoa. Nat Rev Gastroent 
Hepat. 2006; 3:436-445. 
 
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI): A simple practical measure for 
routine clinical use. Clin Exper Dermatol. 1994;19:210-216. 
 
Fredriksson T, Pettersson U. Severe psoriasis-oral therapy with a new retinoid. Dermatologica. 
1978;157(4):238-44. 
 
Johnston A, Xing X, Wolterink L, et al. IL-1 and IL-36 are dominant cytokines in palmar plantar 
pustulosis. J Dermatol Sci. 2016 Oct;84(1):Page e99. 
 
Kane R, Bershadsky B, Rockwood T, Saleh K, Islam N. Visual Analog Scale pain reporting was 
standardized. J Clin Epidemiol. 2005 Jun;58(6):618-623. 
 
Navarini AA, Burden AD, Capon F, et al. European consensus statement on phenotypes of 
pustular psoriasis. J Eur Acad Dermatol Venereol. 2017 Nov;31(11):1792-1799. 
 
Oji V, Luger T. The skin in psoriasis: assessment and challenges. Clin Exp Rheumatol. 2015;33 
(suppl. 93):S14-S19. 
 
Schram M, Roekevisch E, Leeflang M, Bos J, Schmitt J, Spuls P. A randomized trial of 
methotrexate versus azathioprine for severe atopic eczema. J Aller Clin Immunol. August 
2011;28(128):353-359.


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11.0 APPENDICES


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Appendix 1           Abbreviations 
 
Abbreviation                      Definition 
 
ADA                                    Anti-drug antibody 
 
AE                                       Adverse event
 
AESI 
ALT 
AST 
 
Adverse event of special interest 
 
Alanine aminotransferase 
 
Aspartate transaminase
 
ATC                                     Anatomical Therapeutic Chemical 
 
AUC                                    Area under the concentration-time curve 
 
BMI                                     Body mass index 
 
BSA                                     Body Surface Area 
 
CFR                                     Code of Federal Regulations 
 
CI                                         Confidence interval 
 
CK                                       Creatine kinase 
 
Cmax                                                         Maximum observed concentration 
 
CRF                                     Case Report Form CSR                                      
Clinical Study Report CV                                        
Coefficient of variation 
DLQI                                   Dermatology Life Quality Index 
 
DRE                                     Disease-related events 
ECG                                     Electrocardiogram 
EDC                                     Electronic data capture 
eCRF                                   Electronic case report form 
 
EOS                                     End of study 
 
ET                                        Early termination 
 
FSH                                     Follicle stimulating hormone 
 
GCP                                     Good Clinical Practice 
 
HRT                                     Hormonal replacement therapy 
 
IB                                         Investigator’s Brochure 
 
ICF                                       Informed consent form 
 
ICH                                      International Council for Harmonisation 
 
IEC                                      Independent Ethics Committee 
 
IgG4                                     Immunoglobulin G4


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Abbreviation                      Definition 
 
IL                                         Interleukin 
 
IL-36R                                 Interleukin-36 receptor 
 
IL-36Ra                               Interleukin-36 receptor antagonist 
 
IRB                                      Institutional Review Board 
 
ITT                                       Intent-to-treat 
 
IV                                         Intravenous 
 
IVRS                                    Interactive Voice Response System 
IWRS                                   Interactive Web Response System 
mAb                                     Monoclonal antibody 
MAD                                   Multiple ascending dose 
 
MedDRA                             Medical Dictionary for Regulatory Activities 
n                                           Sample size 
NaCl                                    Sodium chloride 
 
PASI                                    Psoriasis Area Severity Index 
 
PK                                        Pharmacokinetic(s) 
 
PPP                                      Palmoplantar pustulosis 
 
PPPASI                                Palmoplantar Pustulosis Psoriasis Area Severity Index 
 
PPSI                                     Palmoplantar Pustulosis Severity Index 
 
PPPIGA                               Palmoplantar Pustulosis (static) Investigator’s Global 
Assessment 
 
PPPQLI                               Palmoplantar Pustulosis Quality of Life Instrument 
 
PUVA                                  Psoralen and ultraviolet A 
PT                                        Preferred Term 
SAD                                     Single ascending dose 
SAE                                     Serious adverse event 
SAP                                     Statistical Analysis Plan 
SC                                        Subcutaneous 
SD                                        Standard deviation 
 
SOC                                     System Organ Class 
 
SOP                                     Standard operating procedure 
t1/2                                                             Terminal half-life 
TB                                        Tuberculosis 
 
TC                                        Telephone contact


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Abbreviation                      Definition 
 
TEAE                                   Treatment-emergent adverse events 
 
Tmax                                                         Time to maximum observed concentration 
 
TNF                                     Tumor necrosis factor 
ULN                                     Upper limit of normal 
UVB                                    Ultraviolet light B 
VAS                                     Visual analog scale 
WOCBP                               Woman of childbearing potential


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Appendix 2           Regulatory, Ethical, and Study Oversight Considerations 
 
Regulatory and Ethical Considerations 
 
    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 International Ethical Guidelines. 
   Applicable International Council for Harmonisation (ICH) GCP Guidelines. 
   Applicable laws and regulations. 
 
 
The protocol, protocol amendments, ICF, IB, 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. 
    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. 
    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 Code of Federal Regulations (21 CFR), ICH guidelines, the IRB/IEC, 
European regulation 536/2014 for clinical studies (if applicable), and all other 
applicable local regulations. 
 
 
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 a 
minimum for the subjects in this study. The terms of the insurance will be kept in the study files. 
 
Informed Consent Process 
 
 
The Investigator or his/her representative will explain the nature of the study to the subject 
and answer all questions regarding the study.


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Subjects must be informed that their participation is voluntary. Subjects will be required to 
sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, Health Insurance Portability and Accountability Act 
requirements, where applicable, and the IRB/IEC or study center. 
    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. 
    Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study. 
    A copy of the ICF(s) must be provided to the subject. 
    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 
 
 
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. 
    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. 
    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. 
    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. 
    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. 
    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


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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.
Administrative Structure
Table 4
Study Administrative Structure
Function
Responsible Organization
Study Operations Management
Medical Monitoring
CRO
Study Master File
CRO
Randomization Code
CRO
Data Management
CRO
Clinical Supply Management
AnaptysBio, Inc./CRO
Quality Assurance Auditing
AnaptysBio, Inc./CRO
Biostatistics
AnaptysBio, Inc./CRO
Medical Writing
AnaptysBio, Inc.
Laboratory Assessments
CRO
Electrocardiogram Collection, Review, and Analysis
CRO
Pharmacokinetic Sample Testing
CRO
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 European Union 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), the CRO 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:


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    Central laboratories for clinical laboratory parameters. 
    Center Initiation visit. 
    Early center visits post-enrollment. 
    Routine center monitoring. 
    Ongoing center communication and training. 
    Data management quality control checks. 
    Continuous data acquisition and cleaning. 
    Internal review of data. 
    Quality control check of the final CSR. 
 
In addition, Sponsor and/or the CRO 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 
 
The Sponsor has engaged the services of a CRO to perform all monitoring functions within this 
clinical study. The CRO’s monitors will work in accordance with the CRO’s SOPs. The monitor 
will establish and maintain regular contact between the Investigator and Sponsor. Monitoring 
will be carried out as determined by the risk assessment process conducted on the study. 
 
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%:


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    Subject identification number. 
    Subject consent obtained. 
    Subject eligibility criteria (inclusion and exclusion criteria). 
    Efficacy variables. 
    Safety variables. 
    Medical record of AE. 
 
Data Management/Coding 
 
Data generated within this clinical study will be handled according to the relevant SOPs of the 
Data Management and Biostatistics departments of the Sponsor and the CRO. 
 
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


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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). 
 
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. 
 
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.


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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 randomized into the study. 
 
The Investigator will allow the Sponsor, CRO, 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 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: 
 
 
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. 
    Inadequate recruitment of subjects by the Investigator. 
    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.


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Appendix 3           Clinical Laboratory Tests 
 
 
The tests detailed in Table 5 will be performed by the central laboratory. The time points are 
specified in the Schedule of Activities (see Section 1.3). 
    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. If a local sample is required, it is important that the sample for central 
analysis is obtained at the same time. Urine pregnancy dipstick will be performed at the study 
center prior to study treatment administration. 
    Protocol-specific requirements for inclusion or exclusion of subjects are detailed in 
Section 5.0 of the protocol. 
 
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 
Parameters 
Assessments 
Hematology 
Hemoglobin 
 
Hematocrit 
 
 
Packed cell volume (PCV) 
Mean cell hemoglobin (MCH) 
Mean cell volume (MCV) 
Mean cell hemoglobin 
concentration (MCHC) 
Red blood cell (RBC) count 
White Blood Cell Count (WBC) with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Platelet count 
Biochemistry 
Alanine aminotransferase (ALT) 
Albumin 
Alkaline phosphatase (ALP) 
Aspartate aminotransferase (AST) 
Bicarbonate 
Bilirubin (Total) 
 
Bilirubin (Direct-only if total is 
elevated) 
 
Calcium 
Chloride 
Uric acid 
Lactate dehydrogenase 
 
Troponin 
Creatinine 
Gamma glutamyl transferase (GGT) 
Glucose 
Potassium 
Phosphate (Inorganic) 
Protein (Total) 
Sodium 
Blood urea nitrogen (urea) 
Creatine kinase (CK) 
Triglycerides 
human C-reactive protein (hsCRP) 
Total cholesterol (fractions) 


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Laboratory 
Parameters 
Assessments 
Serum pregnancy 
Human chorionic gonadotropin (hCG) pregnancy test (as needed for women 
of childbearing potential) 
Follicle 
As needed in women of non-childbearing potential only (Postmenopausal 
woman with at least 1 year of amenorrhea) 
stimulating 
hormone (FSH) 
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 
QuantiFERON-TB Gold® In-Tube, the third-generation test (If the test 
indeterminate it can be retested only once) 
(TB) screening 
NOTES: Please see Schedule of Activities for laboratory tests time points. 
Pharmacokinetics and anti-drug antibody (ADA) samples will be collected as detailed in the 
Schedule of Activities. 
All blood samples must be drawn prior to administration of the study treatment, unless otherwise 
specified. The date and exact time of sample collection must be recorded. 
 
 
Investigators must document their review of each laboratory safety report.


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Appendix 4           Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
 
Definition of AE 
 
AE Definition 
 
 
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. 
 
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 
 
 
Any abnormal laboratory test results (hematology, biochemistry, 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). 
 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
 
New conditions detected or diagnosed after study treatment administration even though it may have 
been present before the start of the study. 
     Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 
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. 
 
“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 fulfill the 
definition of an AE or SAE. 
 
 
 
Events NOT Meeting the AE Definition 
 
 
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. 
 
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. 
 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
 
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.


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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 fulfills 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 
 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
 
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 (Medically Significant Events): 
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. 


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Recording and Follow-up of AE and/or SAE
AE and SAE Recording





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.
The Investigator will then record all relevant AE/SAE information (including event term, start and stop
dates, severity, relationship to study treatment, outcome, if serious or non-serious) in the eCRF. Each
event must be recorded separately.
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 eCRF page.
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.
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:
Mild: An event that is easily tolerated by the subject, causing minimal discomfort and not interfering
with everyday activities.
Moderate: An event that causes sufficient discomfort and interferes with normal everyday activities.
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
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 treatment
administration, and that could be explained by an underlying condition or other drugs or
chemicals or is incontrovertibly not related to the study treatment.
o “Possibly related”: clinical event with a reasonable time relationship to study treatment
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 treatment administration
and that cannot be explained by concurrent condition or other drugs or chemicals.
The Investigator will use clinical judgment to determine the relationship.
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.
The Investigator will also consult the IB in his/her assessment.
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.


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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.
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.
The causality assessment is one of the criteria used when determining regulatory reporting
requirements.
Follow-up of AEs and SAEs
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.
If a subject dies during participation in the study, the Investigator will provide
Safety
with a copy of any postmortem findings.
New or updated information will be recorded in the originally completed eCRF.
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
The primary mechanism for reporting an SAE to
Safety will be the electronic data
collection tool.
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).
The study center will enter the SAE data into the electronic system as soon as it becomes available.
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.
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) and send the paper SAE
form to 
Safety team via facsimile transmission or email.
Contacts for SAE reporting can be found in SAE form.
SAE Reporting to
Safety via Paper Case Report Form (CRF)
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this information to 
the
Safety team.
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.
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.
Contacts for SAE reporting can be found in SAE reporting form.


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Appendix 5           Excluded Medications/Therapy 
 
Excluded medications/therapy are 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 PPP or psoriasis is prohibited. If treatment with any of 
these prohibited medications is essential, then the Investigator must notify the Medical Monitor 
in order to make a decision as to whether the subject will be withdrawn from the study. 
 
All treatments likely to have efficacy in PPP need to be discontinued prior to treatment initiation 
(prior to Baseline [Day 1]) with washout periods as stipulated in the table below: 
 
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 prior to Baseline 
Methotrexate, cyclosporin, acitretin, alitretinoin, fumaric acid 
esters, and corticosteroids or any other immunosuppressant or 
immunomodulation drugs 
4 weeks prior to Baseline 
Anti-TNF/IL-12/IL-23 and IL-17 or any other mAbs 
3 month or 5 half-lives (whichever is 
longer) 
Cyclophosphamide 
6 months prior to Baseline 
Phototherapy (ie, UVB) or photochemotherapy (PUVA) 
4 weeks prior to Baseline 
Other investigational drugs 
30 days or 5 half-lives (whichever is 
longer) prior to Screening 
Live attenuated vaccines 
12 weeks prior to Screening 
Antibiotic or antiviral 
Topical: 2 weeks prior to Baseline 
Systemic: 4 weeks prior to Baseline 
Abbreviations: IL = interleukin; mAb = monoclonal antibody; PUVA = psoralen and ultraviolet A; TNF = tumor 
necrosis factor; UVB = ultraviolet light B. 
 
Note: Topical bland emollients (without pharmacological active ingredients) for pustular psoriasis are allowed 
during the study, except within 24 hours prior to the study visits. 
 
All medications listed above are also restricted during the study period. If treatment with any of 
these prohibited treatments is essential, then the subject must notify the study team.


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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: 
a)  Documented hysterectomy. 
b)  Documented bilateral salpingectomy. 
c)  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: 
a)  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. 
b)  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. 
 
Contraception Guidance 
 
Male subjects 
 
 
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):


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   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. 
 
 
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. 
    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, and 
refrain from donating oocytes for assisted reproduction during this period.


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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 
    Oral. 
    Intravaginal. 
    Transdermal. 
Progestogen only hormonal contraception associated with inhibition of ovulation 
    Oral. 
    Injectable. 
Highly Effective Methods That Are User Independent a 
Implantable progestogen only hormonal contraception associated with inhibition of ovulation 
    Intrauterine device (IUD). 
    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: 
 
 
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). 
 
Women of childbearing potential should refrain from donating oocytes for assisted 
reproduction during this period. 
    Additional pregnancy testing should be performed as mentioned in the as mentioned in the 
Schedule of Activities (see Section 1.3). 
 
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.


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Collection of Pregnancy Information 
 
Male subjects with partners who become pregnant 
 
 
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. 
    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 
 
 
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. 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. 
    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. 
    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. 
    Any female subject who becomes pregnant while participating in the study will be withdrawn 
from the study.


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Appendix 7           Palmoplantar Pustulosis Psoriasis Area Severity Index 
 
 
 
Score 
0 
1 
2 
3 
4 
5 
6 
Erythema (E) 
None 
Slight 
Moderate Severe 
Very 
 
 
 
severe 
 
Pustules (P) 
None 
Slight 
Moderate Severe 
Very 
(total) 
 
 
severe 
 
Desquamation 
None 
Slight 
Moderate Severe 
Very 
(D) (scaling) 
 
 
severe 
Area affected               0            >0<10       10<30       30<50       50<70         70<90      90-100 
(%)1 
 
 
PPPASI = [(E+P+D) Area × 0.2 (right palm)] + [(E+P+D) Area x 0.2 (left palm)] + [(E+P+D) 
Area × 0.3 (right sole)] + [(E+P+D) Area × 0.3 (left sole)] 
 
1 where area assessed is glabrous skin on the palms/soles 
 
 
Adapted from Psoriasis Area Severity Index (PASI) by Bhushan et al for a RCT evaluating 
lizarole in palmoplantar psoriasis. 
 
Bhushan M, et al. Oral liarozole in the treatment of palmoplantar pustular psoriasis: a 
randomized, double-blind, placebo-controlled study. British Journal of Dermatology. 
2001;145(4):546-53.


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Appendix 8           Palmoplantar Pustulosis Severity Index 
 
The PPSI assesses the severity of PPP lesions and their response to therapy with score that 
ranges from 0 to 12. 
 
In the PPSI, the most severely affected location (palms or soles) will be identified as the 
evaluation sites at Screening. 
 
The identified site will be assessed at all subsequent visits. 
 
Evaluation sites will be assessed separately for erythema, pustules/vesicle, and 
desquamation/scale, and each will be rated for the more severely affected location (palms or 
soles) on a scale of 0 to 4. 
 
The severity of the disease is calculated as follows: 
 
The scoring for the signs of the disease (erythema, pustules/vesicle, and desquamation/scale) is: 
 
0 = none, 1 = minimal, 2 = mild, 3 = moderate, and 4 = severe. 
The PPSI formula is: PPSI total score= (E + P + D) 
Where E = erythema, P = pustular/vesicle, and D = desquamation/scale.


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Appendix 9           Palmoplantar Pustulosis (Static) Investigator’s Global 
Assessment 
 
Score 
Wording 
Detailed description 
0 
Clear 
No signs of palmoplantar pustulosis; no scaling or crusts or 
pustules remain 
1 
Almost clear 
Slight scaling and/or erythema and/or slight crusts; very few 
(yellow) and/or old (brown) pustules 
2 
Mild 
Scaling and/or erythema and/or crusts; visible new (yellow) and/or 
old (brown) pustules of limited number and extent 
3 
Moderate 
Prominent scaling and/or erythema and/or crusting; prominent 
new (yellow) and/or old (brown) pustules covering most of the 
area involved 
4 
Severe 
Severe scaling and/or erythema and/or crusting; numerous new 
(yellow) and/or old (brown) pustules with / without major 
confluence, covering the entire area of at least 2 palmoplantar 
sites 


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Appendix 10         Psoriasis Area Severity Index Score 
 
 
 
 
Plaque Characteristic 
 
Lesion Score 
 
Head 
Upper Limbs 
Trunk 
Lower Limbs 
Erythema 
0 = None 
 
Induration/Thickness 
1 = Slight 
 
 
Scaling 
2 = Moderate 
 
3 = Severe 
 
4 = Very severe 
 
Add together each of the 3 scores for each body region to give 4 separate sums (A). 
Lesion Score Sum (A) 
 
Percentage 
 
Area Score 
 
Head 
Upper Limbs 
Trunk 
Lower Limbs 
Area 
 
 
Area Score (B) 
 
Degree of involvement 
as a percentage for 
each body region 
affected (score each 
region with score 
between  0-6) 
0 = 0% 
 
1 = 1% - 9% 
 
2 = 10% - 29% 
 
3 = 30% - 49% 
 
4 = 50% - 69% 
 
5 = 70% - 89% 
 
6 = 90% - 100% 
 
Multiply Lesion Score Sum (A) by Area Score (B), for each body region, to give 4 individual subtotals (C). 
Subtotals (C) 
 
 
Multiply each of the Subtotals (C) by amount of body surface area represented by that region, 
i.e. x 0.1 for head, x 0.2 for upper body, x 0.3 for trunk, and x 0.4 for lower limbs. 
Body Surface Area 
x 0.1 
x 0.2 
x 0.3 
x 0.4 
Totals (D) 
 
Add together each of the scores for each body region to give the final PASI Score. 
 
 
 
 
PASI Score = 
 
Fredriksson T, Pettersson U. Severe psoriasis-oral therapy with a new retinoid. 
1978;157(4):238-44.


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Appendix 11         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? 
 
ٯVery much ٯA lot ٯA little ٯNot at all 
 
2.  Over the last week, how embarrassed or self-conscious have you been because of your skin? 
 
ٯVery much ٯA lot ٯA little ٯ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? 
 
ٯVery much ٯA lot ٯA little ٯNot at all ٯNot relevant 
 
4.  Over the last week, how much has your skin influenced the clothes you wear? 
 
ٯVery much ٯA lot ٯA little ٯNot at all ٯNot relevant 
 
5.  Over the last week, how much has your skin affected any social or leisure activities? 
 
ٯVery much ٯA lot ٯA little ٯNot at all ٯNot relevant 
 
6.  Over the last week, how much has your skin made it difficult to do any sport? 
 
ٯVery much ٯA lot ٯA little ٯNot at all ٯNot relevant 
 
7.  Over the last week, has your skin prevented you from working or studying? 
 
ٯYes ٯNo ٯNot relevant 
 
If "No", over the last week, how much has your skin been a problem at work or 
studying? 
 
ٯA lot ٯA little ٯ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? 
 
ٯVery much ٯA lot ٯA little ٯNot at all ٯNot relevant 
 
9.  Over the last week, how much has your skin caused sexual difficulties? 
 
ٯVery much ٯA lot ٯA little ٯNot at all ٯNot relevant


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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? 
 
ٯVery much ٯA lot ٯA little ٯNot at all ٯNot relevant 
 
 
Finlay AY, Kahn GK. Dermatology Life Quality Index (DLQI): A simple practical measure for 
routine clinical use. Clinical and Experimental Dermatology 1994;19: 210-216.


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Appendix 12         Palmoplantar Pustulosis Quality of Life Instrument 
 
 
 
Palmoplantar quality of life instrument 
 
Hands* 
No 
Mild 
Moderate 
Severe 
Totally 
 
difficulty 
difficulty 
difficulty 
difficulty 
unable 
Open tight/new jar 
 
Heavy household chores 
Carry shopping bag/briefcase 
Use knife to cut food 
Make a bed 
 
Write 
 
Wash/blow-dry hair 
 
Recreational activities 
(eg, golf, tennis, knitting) 
1 
 
1 
 
1 
 
1 
 
1 
 
1 
 
1 
 
1 
2 
2 
2 
2 
2 
2 
2 
2 
3 
3 
3 
3 
3 
3 
3 
3 
4 
4 
4 
4 
4 
4 
4 
4 
5 
5 
5 
5 
5 
5 
5 
5 
During the past month, did your 
hands: 
 
Interfere with normal social 
activities? 
 
Limit work/regular activities? 
Not at all 
 
 
1 
 
 
1 
Slightly 
2 
2 
Moderately 
3 
3 
Quite a 
bit 
4 
4 
Extremely 
5 
5 
During the past month: 
 
Hand pain 
 
Hand burning/itching 
 
Difficulty sleeping because of 
discomfort/pain in hands 
None 
 
1 
 
1 
 
1 
Mild 
2 
2 
2 
Moderate 
3 
3 
3 
Severe 
4 
4 
4 
Extreme 
5 
5 
5 
I feel: 
Strongly 
Disagree 
Neither 
Agree 
Strongly 
 
disagree 
agree nor 
agree 
 
 
disagree 
Embarrassed about my hands/will 
avoid handshakes and/or caressing 
 
Less capable/confident/useful 
because of my hand problem 
1 
 
 
1 
2 
2 
3 
3 
4 
4 
5 
5 


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Feet** 
No 
Mild 
Moderate 
Severe 
Totally 
 
difficulty 
difficulty 
difficulty 
difficulty 
unable 
Walking 
1 
2 
3 
4 
5 
Fast walking/running 
1 
2 
3 
4 
5 
Climbing stairs 
1 
2 
3 
4 
5 
Socks/stockings on/off 
1 
2 
3 
4 
5 
Pain level last month for: 
None 
Mild 
Moderate 
Severe 
Could not 
 
 
do 
Walking 
1 
2 
3 
4 
5 
Fast walking/running 
1 
2 
3 
4 
5 
Climbing stairs 
1 
2 
3 
4 
5 
Standing barefoot 
1 
2 
3 
4 
5 
Standing wearing shoes 
1 
2 
3 
4 
5 
Activity Limitation 
 
How often have you avoided pedicures/other activities that expose your feet, due to embarrassment? 
1: Not at all, 2: Rarely, 3: Sometimes, 4: Frequently, 5: All the time 
 
How much did your feet interfere with normal work, including work outside the home and housework? 
1: Not at all, 2: Rarely, 3: Sometimes, 4: Frequently, 5: All the time 
 
How much did your feet interfere with your life and ability to do what you want? 
1: Not at all, 2: Rarely, 3: Sometimes, 4: Frequently, 5: All the time 
 
How much of the time did you use cane/crutches/walker to get around? 
1: Not at all, 2: Rarely, 3: Sometimes, 4: Frequently, 5: All the time 
 
How much of the time did you stay indoors most of the day due to foot problems? 
1: Not at all, 2: Rarely, 3: Sometimes, 4: Frequently, 5: All the time 
 
* Questions addressing hand functionality, pain, and social impact. 
** Questions oriented at foot functionality, pain, and physical limitations secondary to foot disease. 
 
 
 
Farley E, Masrour S, McKey J, Menter A. Palmoplantar psoriasis: a phenotypical and clinical 
review with introduction of a new quality-of-life assessment tool. J Am Acad Dermatol. 2009 
Jun;60(6):1024-31.


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Appendix 13         Patient Assessment of Palmoplantar Pustulosis Disease 
Activity 
 
 
 
Considering all the ways your psoriasis affects you, on average, how have you been doing in the 
past week? 

SAP_001.pdf: 
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Statistical Analysis Plan
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STATISTICAL ANALYSIS PLAN
ANB019-003
A Phase II, Randomized, Placebo-controlled, Double-blind, Multiple Dose
Study to Evaluate the Efficacy and Safety of ANB019 in Subjects with
Palmoplantar Pustulosis
AUTHORS:
VERSION NUMBER AND DATE: V1.0, 12FEB2021
ClinicalTrials.gov NCT NUMBER: NCT03633396


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Statistical Analysis Plan
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Statistical Analysis Plan
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Statistical Analysis Plan
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TABLE OF CONTENTS
1.
INTRODUCTION ...............................................................................................................................9
2.
STUDY OBJECTIVES .......................................................................................................................9
2.1.
Primary Objective
9
2.2.
Secondary Objectives
9
2.3.
Exploratory Objectives
10
3.
ENDPOINTS......................................................................................................................................10
3.1.
Primary Efficacy Endpoint
10
3.2.
Safety and Tolerability Endpoints
10
3.3.
Secondary Endpoints
11
3.4.
Exploratory Endpoints
11
4.
HYPOTHESIS ...................................................................................................................................12
5.
STUDY DESIGN ...............................................................................................................................12
5.1.
General Description
12
5.2.
Sample size
14
5.3.
Schedule of Activities
14
5.4.
Treatment Assignment
14
5.5.
Changes to Analysis from Protocol
15
6.
PLANNED ANALYSES....................................................................................................................15
6.1.
Data Monitoring Committee (DMC)
15
6.2.
Interim Analysis
15


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6.3.
Final Analysis                                                                                                                                             15
7.
ANALYSIS SETS ..............................................................................................................................15
7.1.
Per Protocol Analysis Set [PPAS]                                                                                                             16
8.
GENERAL CONSIDERATIONS ....................................................................................................17
8.1.
Reference Start Date and Study Day
17
8.2.
Baseline
18
8.3.
Retests, Unscheduled Visits and Early Termination Data
18
8.4.
Windowing Conventions
18
8.5.
Statistical Tests
19
8.6.
Common Calculations
19
8.7.
Software Version
20
9.
STATISTICAL CONSIDERATIONS.............................................................................................20
9.1.
Adjustments for Covariates and Factors to be Included in Analyses
20
9.2.
Multicenter Studies
20
9.3.
Missing Data
21
9.4.
Multiple comparisons
21
9.5.
Examination of Subgroups
21
10.
OUTPUT PRESENTATIONS ......................................................................................................21
11.
DISPOSITION AND WITHDRAWALS .....................................................................................21
11.1.
Protocol Deviations                                                                                                                                    22
12.
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ....................................23


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12.1.
Derivations                                                                                                                                                  23
13.
MEDICAL HISTORY...................................................................................................................23
14.
MEDICATIONS.............................................................................................................................24
15.
STUDY TREATMENT EXPOSURE...........................................................................................24
16.
STUDY MEDICATION COMPLIANCE....................................................................................24
17.
EFFICACY OUTCOMES.............................................................................................................25
17.1.
Primary Efficacy                                                                                                                                        25
17.1.1.
Primary Efficacy Endpoint & Derivation
25
17.1.2.
Missing Data Methods for Primary Efficacy Endpoint
25
17.1.3.
Analysis of Primary Efficacy Endpoint
25
17.1.4.
Sensitivity Analysis of Primary Efficacy Endpoint(s)
26
17.2.
Secondary Efficacy                                                                                                                                    26
17.2.1.
Secondary Efficacy Endpoints, Derivations, and Analysis                                                                     26
17.2.1.1.
Proportion of subjects achieving PPPASI50 and PPPASI75 at all study centers visits.                 26
17.2.1.2.
Change in PPPASI Score at all study center visits                                                                          27
17.2.1.3.
Change in PPSI Score at all study center visits                                                                               27
17.2.1.4.
Change in PPPIGA score at all study center visits                                                                          27
17.2.1.5.
Proportion of subjects with clear or almost clear assessment score on PPPIGA at all study center 
visits          28
17.2.1.6.
Change in fresh and total pustule count on palms and soles at all study center visits                     28
17.2.1.7.
Time to response                                                                                                                            
29
17.2.1.8.
Relapse rate                                                                                                                                      29
17.2.1.9.
Change in PASI score and affected BSA at all study center visits, if plaque psoriasis is present at
non acral sites                                                                                                                                                       29
17.2.1.10.
Improvement in Pustular Psoriasis at non acral site BSA (if present) at all study center visits      30
17.2.1.11.
Change in clinical scores of PPPQLI, DLQI and Patient Assessment of Palmoplantar Pustulosis
Disease Activity at all study center visits.                                                                                                           30
17.2.1.12.
Immunogenicity to ANB019-003 anti-drug antibodies                                                                   30
17.2.1.13.
PK parameters                                                                                                                            
31
17.2.2.
Missing Data Methods for Secondary Efficacy Endpoint(s)                                                                   31
17.3.
Exploratory Efficacy                                                                                                                                  31
17.3.1.
Skin biopsy markers                                                                                                                                 31
17.3.2.
Photographic documentation of lesions                                                                                                   31


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18.
QUALITY OF LIFE (QOL) ANALYSIS ....................................................................................32
18.1.1.
QOL Variables & Derivations                                                                                                                 32
18.1.1.1.
Palmoplantar Pustulosis Quality of Life Instrument (PPPQLI)
32
18.1.1.2.
Dermatology Life Quality Index (DLQI)
32
18.1.1.3.
Patient Assessment of Palmoplantar Pustulosis Disease Activity
33
18.1.2.
Missing Data Methods
34
18.1.3.
Analysis of QOL Variables
34
19.
PHARMACOKINETICS..............................................................................................................34
19.1.
Variables & Derivations                                                                                                                           34
19.1.1.
Serum Concentration Data                                                                                                                       34
19.1.2.
Pharmacokinetic Parameters                                                                                                                    35
19.2.
Missing Data Methods                                                                                                                               37
19.3.
Deviations Related to PK                                                                                                                           37
19.4.
Analysis of PK Parameters                                                                                                                       37
19.5.
Precision of PK Variables                                                                                                                         38
20.
SAFETY OUTCOMES..................................................................................................................39
20.1.
Adverse Events                                                                                                                                           39
20.1.1.
All TEAEs                                                                                                                                                40
20.1.1.1.
Severity
40
20.1.1.2.
Relationship to Study Medication
40
20.1.2.
TEAEs Leading to Discontinuation of Treatment
40
20.1.3.
TEAEs Leading to Withdrawal of Subjects
41
20.1.4.
Serious Adverse Events
41
20.1.5.
Adverse Events Leading to Death
41
20.1.6.
Adverse Events Related to Injection Site Reactions
41
20.1.7.
Adverse Events Of Special Interest
41
20.1.8.
Disease Related Adverse Events
41
20.2.
Laboratory Evaluations                                                                                                                           
42
20.2.1.
Laboratory Reference Ranges                                                                                                                  42
20.3.
ECG Evaluations                                                                                                                                        42
20.4.
Vital Signs                                                                                                                                                   44
20.4.1.
Vital Signs Specific Derivations                                                                                                              44
20.5.
Physical Examination                                                                                                                                44


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21.
DATA NOT SUMMARIZED OR PRESENTED........................................................................44
22.
REFERENCES...............................................................................................................................46
APPENDIX 1.
PROGRAMMING CONVENTIONS FOR OUTPUTS............................................47
APPENDIX 2.
PARTIAL DATE CONVENTIONS ...........................................................................54
APPENDIX 3.
MULTIPLE IMPUTATION STEPS..........................................................................57
APPENDIX 4.
SAS® CODE ..................................................................................................................58
APPENDIX 5.
ABBREVIATIONS ......................................................................................................60


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1. INTRODUCTION
This document describes the rules and conventions to be used in the presentation and analysis of efficacy,
safety and pharmacokinetic (PK) data for Protocol ANB019-003. It describes the data to be summarized 
and analyzed, including specifics of the statistical analyses to be performed. This statistical analysis plan
(SAP) is based on final Protocol Amendment 5 and 5.1, dated 29 October 2020.
Changes to the protocol that impact the design, the data collected, or the statistical methods and that occur 
after the finalization of this SAP may require amendment of the approved SAP. Similarly, changes to the 
planned analysis variables and/or statistical methods described in the approved SAP may also require
amendment of the protocol.
2. STUDY OBJECTIVES
2.1.    PRIMARY OBJECTIVE 
The primary objectives of the study are:
 
To determine the effect of ANB019 compared with placebo in subjects with PPP as
measured by the Palmoplantar Pustulosis Psoriasis Area Severity Index (PPPASI).
             To assess the safety and tolerability of ANB019 in subjects with PPP.
2.2.    SECONDARY OBJECTIVES 
The secondary objectives of the study are:
 
To determine the effect of ANB019 in subjects with PPP as measured by improvement in
the PPPASI.
             To determine the effect of ANB019 in subjects with PPP as measured by Palmoplantar
Pustulosis Severity Index (PPSI).
 
To determine the proportion of subjects who achieved PPP disease clearance after
administration of ANB019 as measured by the Palmoplantar Pustulosis (static) 
Investigator’s Global Assessment (PPPIGA).
             To determine the time to response with ANB019 in subjects with PPP.
             To determine the relapse rate with ANB019 in subjects with PPP.


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To evaluate the effect of ANB019 in subjects with plaque psoriasis at non acral sites (if
present) as measured by the Psoriasis Area Severity Index (PASI) and affected body surface
area (BSA).
             To evaluate the effect of ANB019 in subjects with pustular psoriasis at non acral sites (if
present) as measured by BSA.
             To evaluate the effect of ANB019 on subject’s quality of life.
             To test for immunogenicity to ANB019.
             To describe the PK of ANB019 in subjects with PPP.
2.3.    EXPLORATORY OBJECTIVES 
The exploratory objectives in this study are:
             To explore the effect of ANB019 on skin biopsy biomarkers.
             To provide photographic documentation of lesions.
3. ENDPOINTS
3.1.    PRIMARY EFFICACY ENDPOINT 
             Mean change from Baseline in PPPASI at all study visits.
3.2.    SAFETY AND TOLERABILITY ENDPOINTS 
             Assessment of adverse events (AEs).
             Potentially significant and clinically important AEs, adverse events of special interest
(AESIs), serious AEs (SAEs), and AEs leading to withdrawal.
             Physical examinations.
             Vital signs.
             12-Lead electrocardiogram (ECG).
             Clinical safety laboratory tests (hematology, biochemistry, and urinalysis).


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3.3.    SECONDARY ENDPOINTS 
             Proportion of subjects achieving PPPASI50 at all study center visits.
             Proportion of subjects achieving PPPASI75 at all study center visits.
             Change from Baseline in PPSI score at all study center visits.
             Change in PPPIGA score at all study center visits.
 
Proportion of subjects with clear or almost clear assessment score on PPPIGA at all study
center visits.
             Change in fresh and total pustule count on palms and soles at all study center visits.
             Time to response defined as time to achieve 75% reduction in fresh pustule count.
             Relapse rate defined as return to Baseline in fresh pustule count.
 
Change in PASI score and affected BSA at all study center visits, if plaque psoriasis is
present at non- acral sites.
             Improvement in pustular psoriasis at non- acral site BSA (if present) at all study center
visits.
 
Change in clinical scores of Palmoplantar Pustulosis Quality of Life Instrument (PPPQLI),
Dermatology Life Quality Index (DLQI), and Patient Assessment of Palmoplantar
Pustulosis Disease Activity at all study center visits.
             Presence of anti-drug- antibodies.
             Pharmacokinetic endpoints
                  Serum concentration following ANB019 administration.
                  Maximum observed concentration (Cmax).
                  Time to maximum observed concentration (Tmax).
                  Area under the concentration-time curve (AUC).
                  Terminal half-life (t1/2).
                  Other parameters as appropriate.
3.4.    EXPLORATORY ENDPOINTS 
 
Skin biopsy biomarkers including but not limited to IL-36, IL-17, IL-23, and markers of
neutrophils and dendritic cells infiltration.
             Photographic documentation of lesions.


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4. HYPOTHESIS
No formal hypothesis testing will be performed.
5. STUDY DESIGN
5.1.    GENERAL DESCRIPTION 
This is a randomized, multicenter, placebo-controlled, double-blind, multiple dose study designed to assess
the efficacy as well as safety and tolerability of ANB019 compared with placebo in subjects with PPP. This
study will also characterize the PK of ANB019 and explore the immune response to ANB019 in subjects
with PPP.
Approximately 50 subjects will be enrolled from approximately 35 study centers (approximately 25 for non-
German sites and approximately 10 for German sites) for study treatment. The expected duration of the 
study is approximately 28 weeks for non-German sites and 31 weeks for German sites. The screening period
will be up to 48 days prior to administration of study treatment on Day 1. On Day 1, eligible subjects will be
randomly allocated in a 1:1 ratio to receive either a 200 mg subcutaneous (SC) dose of ANB019 or placebo 
followed by 3 doses of 100 mg of ANB019 or placebo administered SC on Days 29, 57, and 85. The subjects
will leave the study center when all postdose assessments have been completed and with the Investigator’s
approval.
Subjects will return to the study center for study assessments and follow-up visits on Days 3 and 8; weekly
from Day 8 up to Day 29; every other week up to Day 85; and then monthly for 12 weeks to monitor
changes in disease activity, safety, and tolerability. In addition, the subjects will be contacted via telephone 
by study staff to inquire about potential AEs and changes in concomitant medications on Days 36, 50, 64, 
and 78. The end of study (EOS) visit will be on Day 169 for subjects enrolled in non-German sites and Day
218 for subjects enrolled in German sites. All subjects will return to the study center for the EOS
assessments.
Disease activity (response to study treatment) will be evaluated for all subjects using the PPPASI, PPSI,
PPPIGA, PASI (if plaque psoriasis at non-acral sites is present), and total affected BSA (if plaque psoriasis
and/or pustular psoriasis is present at non-acral sites). In addition, relapse rate, time to response, and change
in fresh and total number of pustule count on palms and soles will be recorded. The subject’s quality of life


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will be assessed using the PPPQLI, DLQI, and Patient Assessment of Palmoplantar Pustulosis Disease
Activity.
Blood samples to determine PK and immunogenicity will be collected before the administration of ANB019 
and at the other time points specified in the Schedule of Activities (SOA) in the Protocol. In addition, a 
punch biopsy (biomarker analysis) will be taken during the study (guidelines for optional punch skin biopsy 
will be located in Lab Manual). All subjects randomized in the study will be asked to participate in the skin
biopsy; however, the subject’s participation is optional.
Safety assessments including adverse event (AE)/serious adverse event (SAE) monitoring, vital signs, 
physical examination, ECGs, and laboratory measurements will be performed as specified in SOA.
Study Schema for non-German sites


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Study Schema for German sites
5.2.    SAMPLE SIZE 
The sample size is not based on statistical power considerations. Approximately 50 subjects will be enrolled
from approximately 35 study centers (approximately 25 for non-German sites and approximately
10 for German sites) for study treatment.
5.3.    SCHEDULE OF ACTIVITIES 
Schedule of events can be found in Section 1.3 of the Protocol Ammendment 5 and 5.1.
5.4.    TREATMENT ASSIGNMENT 
This is a randomized, double-blind, placebo-controlled study with limited access to the randomization code. 
All subjects will be assigned a unique ‘subject identification number’ at the time of Screening. On Day 1, 
after verification that all inclusion and no exclusion criteria have been met, the subjects will be randomly
allocated in a 1:1 ratio to receive ANB019 or placebo.
Randomization will be stratified based on the patient’s history of plaque psoriasis, to ensure that the number 
of subjects enrolled with plaque psoriasis should not exceed 50%. As subjects become eligible, they will
be assigned randomization numbers which will be used to assign the allocated treatment based on a 
randomization schedule. The Sponsor, Investigator, and subjects will be blinded to treatment assignment 
of ANB019 or placebo.


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Please refer to the protocol Section 6.3 for more information.
5.5.    CHANGES TO ANALYSIS FROM PROTOCOL 
mITT set is included to analyze primary and some of the key secondary efficacy parameters.
6. PLANNED ANALYSES
6.1.    DATA MONITORING COMMITTEE (DMC) 
There will be no DMC for this study.
6.2.    INTERIM ANALYSIS 
An Interim Analysis (IA) will be performed when all active subjects complete their Week 16 visit. The 
scope of IA will be, to assess the primary and key secondary endpoints as well as key safety, PK and
ADA endpoints.
6.3.    FINAL ANALYSIS 
All final, planned analyses identified in this SAP will be performed by
following AnaptysBio
authorization of this SAP, Sponsor Authorization of the Safety, Per Protocol, Intention-to Treat, modified
Intention-to Treat analysis sets, Database Lock (DBL), and Unblinding of Treatment. Final PK analyses
will be performed by the
research pharmacokineticist. The PK summaries, data listings, and PK 
figures will be the responsibility of the PK biostatistician at
.
7. ANALYSIS SETS
Agreement and authorization of subjects included/excluded from each analysis set, excluding the PK
analysis set will be conducted prior to the final DBL of the study. In order to facilitate this, a Blind Data
Review (BDR) process of non-PK data will be co-ordinated by the 
Statistical Team Lead (STL),
as described in the Blind Data Review Plan prior to the final DBL.


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The analysis sets are defined in Table A.
Table A. Analysis sets
Analysis Set
Description
ITT Analysis Set
The ITT analysis set will include all randomized subjects. In this
analysis set, treatment will be assigned based upon the treatment group
to which subjects were randomized regardless of which treatment they
receive.
mITT Analysis Set
The mITT analysis set will include all subjects in the ITT set with
PPPASI score of at least 12 at Baseline.
Safety Analysis Set
The safety analysis set will include all randomized subjects who 
receive 1 dose of ANB019 or placebo. The safety analysis set will be
used for all safety analyses. Subjects will be analyzed as treated.
Per Protocol Set
The Per Protocol set will include all subjects in the ITT 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 set who have
at least 1 quantifiable postdose PK sample available and who do not
have events or protocol deviations or events with the potential to affect
PK concentrations. The PK analysis set will be used for all PK
analyses.
Abbreviations: ITT = intent-to-treat; mITT = modified intent-to-treat; PK = pharmacokinetics
7.1.    PER PROTOCOL ANALYSIS SET [PPAS] 
The PPAS will include all subjects in the ITT who do not have major protocol deviations (PDs) that
would affect the evaluation of the primary efficacy endpoint. From a statistical analysis perspective, the
reason(s) for exclusion of subjects may be PD or other factors affecting the efficacy outcome or treatment 
of the subject. Protocol deviations identified during the clinical conduct of the study, as authorized in the
final PD log, will also be taken into consideration in the final assignment of subjects to the analysis sets.
All PDs will be reviewed during the Blind Data Review, as described in the Blind Data Review Plan.
The PPAS is further defined by the following criteria:
             Sufficient essential efficacy data


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             Sufficient evidence of the study indication, i.e. palmoplantar pustulosis
 
Eligibility in accordance with the protocol specified inclusion/exclusion criteria, including
the use of only allowed concomitant medications, the use of rescue medications only a
month after dosing and acceptable previous or current medical conditions
             Adherence to the visit schedule
             Overall compliance with the study treatment administration schedule
8. GENERAL CONSIDERATIONS
All data listings, summaries, and analyses will be performed under the guidance and approval of the
Sponsor and in consistency with this SAP. Data for patients excluded from an analysis set will be
included in the data listings, but not in the summaries. Coding of AEs and medical history will be done by
Medical Dictionary for Regulatory Activities (MedDRA) directory Version 22 (or higher) and
medications data by the World Health Organization (WHO)-drug dictionary dated Mar2019 (or higher)
by
The default summary statistics for continuous variables includes number of contributing observations (n),
mean, standard deviation (SD), median, 95% confidence interval (CI) as applicable, minimum, and 
maximum or as described in the respective section. For categorical variables, the number, percentage, and 
exact 95% CI as applicable in each category will be the default summary presentation.
8.1.    REFERENCE START DATE AND STUDY DAY 
Study Day will be calculated from the reference start date, and will be used to show start/stop day of 
assessments and events. Reference start date, or reference date, is defined as the day of the first dose of 
study treatment (i.e. Day 1).
             If the date of the event is on or after the reference date then:
Study Day = (date of event – reference date) + 1.
             If the date of the event is prior to the reference date then: 
Study Day = (date of event – reference date).
In the situation where the event date is partial or missing, Study Day and any corresponding durations
will appear partial or missing in the listings.


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8.2.    BASELINE 
Unless otherwise specified, “Baseline” is defined as the last observed value of the parameter of interest
prior to the Reference Start Date and time (including unscheduled visits). In the case where the last
observed measurement and the reference start date coincide, that measurement other than Adverse Events
(AEs) and concomitant medications (CMs) will be considered pre-treatment, but AEs and medications
commencing on the reference start date will be considered post-treatment (therefore treatment-emergent).
All assessments scheduled on the day of treatment administration, except postdose PK samples, should be 
performed before study treatment administration, unless otherwise noted.
8.3.    RETESTS, UNSCHEDULED VISITS AND EARLY TERMINATION DATA 
In general, for by-visit summaries, data recorded at the nominal visit will be presented. Unscheduled
measurements will not be included in by-visit summaries, but will contribute to the Baseline or best/worst
case value where required (e.g. shift table). In the case of a retest (same visit number assigned), the last
available assessment will be used for by-visit summaries. Subjects terminating treatment or study early
are required to attend the EOS visit at Day 169 for non-German subjects or at Day 218 for German
subjects.  Early termination data will be recorded at the nearest scheduled visit based on actual days from 
the reference date in by-visit summaries.
Listings will include scheduled, unscheduled, and early discontinuation data, with unscheduled visits
sorted chronologically.
8.4.    WINDOWING CONVENTIONS 
Target study days are presented below:
Study day
Visit
Target
Lower limit
Upper limit
Screening
n/a
-48
n/a
Day 1 (Baseline)
1
n/a
n/a
Day 3
3
n/a
n/a
Day 8
8
n/a
n/a
Day 15
15
14
16


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Study day
Visit
Target
Lower limit
Upper limit
Day 22
22
21
23
Day 29
29
28
30
Day 36 (telephone call)
36
34
38
Day 43
43
41
45
Day 50 (telephone call)
50
48
52
Day 57
57
55
59
Day 64 (telephone call)
64
62
66
Day 71
71
69
73
Day 78 (telephone call)
78
76
80
Day 85
85
83
87
Day 113: (follow-up)
113
111
115
Day 141 (follow-up)
141
139
143
Day 169 (follow-up)
169
167
171
Day 197 (follow-up) for
German sites only
197
195
199
Day 218 (follow-up) for
German sites only
218
216
220
8.5.    STATISTICAL TESTS 
There will be no hypothesis testing conducted in the study. Point estimates of treatment differences will
be accompanied with two-sided 95% confidence intervals (CIs), where applicable. In the case of
normality assumption violations, appropriate non-parametric methods, will be used for analysis. 
Statistical analyses of PK data are detailed under Section 19.
8.6.    COMMON CALCULATIONS 
For quantitative measurements, change from baseline will be calculated as:
             Change from Baseline = Test Value at Visit X – Baseline Value
Percentage change from baseline will be calculated as:


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             Percent change from Baseline = [(Test Value at Visit X – Baseline Value) / Baseline Value]
x 100
8.7.    SOFTWARE VERSION 
Non-compartmental PK parameter calculations will be performed using Phoenix® WinNonlin® 8.3 or 
higher (Certara, Princeton, New Jersey). All other derivations, statistical analyses, summaries, and listings
will be generated using SAS® version 9.4 (SAS® Institute, Inc., Cary, North Carolina). Graphics will be
prepared using the same versions of SAS®.
9. Statistical Considerations
9.1.    ADJUSTMENTS FOR COVARIATES AND FACTORS TO BE INCLUDED IN ANALYSES 
The following covariates and factors are used in the analyses. For details of their inclusion in the models,
see the specific analysis section.
Covariates:
             Baseline PPPASI score
             Baseline Palmoplantar Pustulosis Quality of Life Instrument (PPPQLI)
             Baseline Dermatological Life Quality Index (DLQI) and
             Baseline Patient Assessment of Palmoplantar Pustulosis Disease Activity
Factors:
             Treatment (ANB019/Placebo)
             History of plaque psoriasis (Yes/No)
9.2.    MULTICENTER STUDIES 
This study will be conducted by multiple investigators at multiple centers internationally. Randomization 
to treatment groups is stratified by history of plaque psoriasis. Data from all sites will be pooled for
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9.3.    MISSING DATA 
Missing safety data will not be imputed. Partial dates for safety data will be imputed as outlined in
Appendix 2. Missing efficacy data will be handled as described in section 17.1.2 of this analysis plan.
Missing PK data will be handled as described in Section 19.2.
9.4.    MULTIPLE COMPARISONS 
No formal hypothesis testing will be performed for this study, therefore no adjustment for multiple
comparisons will be done. Planned statististical tests will be presented with their nominal p-value.
9.5.    EXAMINATION OF SUBGROUPS 
Descriptive analysis of the primary efficacy endpoint (PPPASI) will be performed for each category of 
history of plaque psoriasis (Yes/No) and will be performed based on ITT and mITT population.
10.
OUTPUT PRESENTATIONS
Appendix 1 contains conventions for the presentation of data in outputs. The templates provided with this
SAP describe the presentations for this study and therefore the format and content of the summary tables,
figures, and listings to be provided by
Biostatistics. Minor modifications may be made to the
tables, figures and listings to accommodate the data.
11.
DISPOSITION AND WITHDRAWALS
All subjects who provide informed consent will be accounted for in this study.
Subject disposition will be listed and summarized, to include:
        Total subjects screened
 
Number of screen failures (subjects who consent to participate in the clinical study but are not 
subsequently entered in the study), and by reason for screen failure
        Total number of subjects in the ITT
        Total number of subject in the mITT
        Total number of subjects in the SAF
        Total number of subjects in the PPAS


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        Total number of subjects in the PK Analysis Set
 
Total number of subjects who discontinue from study treatment, and by reason for
discontinuation from study treatment
        Total number of subjects who discontinue from the study, and by reason for discontinuation from
study treatment.
11.1.  PROTOCOL DEVIATIONS 
All protocol deviations observed during study conduct will be captured in the Clinical Trial Management 
System (CTMS). The Investigator and Sponsor will review the protocol deviation records from the CTMS
and provide confirmation on the categorization of deviations.
Categorization definitions per the Protocol Deviation Plan are:
Important protocol deviations (IPD): Subset of protocol deviations that might significantly affect the 
completeness, accuracy, and/or reliability of the study data or that might significantly affect a subject’s
rights, safety, or wellbeing.
Non-important protocol deviations (N-IPD): Other deviation from the approved study protocol that have
minimal impact on subject’s rights, safety, or well-being, or integrity of data.
PDs will be grouped into standardized terms , e.g. “Informed Consent”, “Eligibility”, “Investigational 
Product” or equivalent terms in the PD log as per the Protocol Deviation Management Plan (PDMP) and
will be used for reporting purpose in Statistical tables and listings.
PDs may include Covid-19 related deviations, if any, including but not limited to inability to travel to
study site, travel restrictions interfering with administration of investigational product, illness interfering 
with administration of investigational product, and others. Covid-19 related PDs may be identified from 
the protocol deviation description if they are not classified seperately in the CTMS.
Protocol Deviations identified during the clinical conduct of the study, as authorized in the final PD log,
will be summarized and presented in a listing that includes the type of deviation and whether it is
Important or Non-Important based on PDMP.


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12.
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS
Demographic data and other baseline characteristics will be listed and summarized by treatment group,
overall and by history of psoriasis for the SAF analysis set. No statistical testing will be carried out for
demographic or other baseline characteristics. The following demographic and other baseline
characteristics will be reported for this study: age at IC (years), gender, race, ethnicity, weight (kg), height 
(cm), Body Mass Index (BMI) (kg/m2), baseline PPPASI score, baseline PPSI score, baseline PPPIGA
score, baseline PPPASI score of atleast 12, baseline total and fresh pustule count. Smoking history and 
current smoking status will also be summarized and listed. History of psoriasis will be included in the
listing.
12.1.  DERIVATIONS 
BMI (kg/ m2) = weight (kg)/ [height (m)]2.
For current smokers:
If full Smoking start date  and end date is available, then:
Smoking period duration (years) until informed consent = (Date of informed consent – Smoking start date
+ 1) / 365.25
If only month and year of Smoking start date and/or end date is available, then:
Smoking period duration (years) until informed consent = (Year/Month of informed consent –
Year/Month of Smoking start date+1) / 12
If only year of Smoking start date and/or end date is available, then:
Smoking period duration (years) until informed consent = (Year of informed consent – Year of Smoking
start date+1)
Baseline characteristics will include Baseline values of efficacy and safety variables.
13.
MEDICAL HISTORY
Medical History will be coded using the the Medical Dictionary for Regulatory Activities (MedDRA)
latest version. Medical History information will be listed for all subjects.


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14.
MEDICATIONS
Medications will be presented for the SAF and coded using the latest version of the World Health
Organization (WHO) Drug Dictionary and Anatomical Therapeutic Chemical (ATC) system. Prior,
concomitant and rescue medications will be listed and summarized by treatment group, ATC level 2
categories and preferred name.
Prior and Concomitant medications will be identified as follows:
           ‘Prior’ medications are medications which started and stopped prior to the first dose of study
medication.
 
‘Concomitant’ medications are medications which started prior to, on or after the first dose of 
study medication, but before the last dose of study medication, AND ended on or after the date
of first dose of study medication or were ongoing at the end of the study.
See Appendix 2 for handling of partial dates for medications. In the case where it is not possible to define 
a medication as prior or concomitant, the medication will be classified as the worst case i.e. concomitant.
15.
STUDY TREATMENT EXPOSURE
The prescribed dosage may not be changed. Study treatment can be interrupted temporarily or 
permanently per the Investigator’s discretion. Exposure to study treatment will be listed and summarized
for the SAF, and will be based on the number of dose administrations received by subjects.
Duration of treatment exposure (days) = (Date of last study medication administration – Date of first
study medication administration) +1
Information on IP overdose will be presented in a listing.
16.
STUDY MEDICATIONCOMPLIANCE
Compliance to study medication is defined as the administration of the study medications conforming to
100% of the dose specified in the protocol. Noncompliance is defined as taking less than 80% or more than
120% of IP during any evaluation period (during treatment period).
Compliance to study medication will be presented for safety population.
Overall Compliance to study medication will be summarized with respect to treatment groups. The formula
used for calculation of Overall Compliance will be as follows :
Overall Compliance (%)= (Total number of doses received / total number of planed doses) * 100.


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List of treatment noncompliance will be provided for safety population.
17.
EFFICACY OUTCOMES
17.1.  PRIMARY EFFICACY 
17.1.1.          PRIMARY EFFICACY ENDPOINT & DERIVATION 
The primary efficacy endpoint is the change from Baseline in PPPASI at all study visits.
The PPPASI score is determined by assessing the glaborous skin of palms and soles, and adding scores
for the characteristics of PPP viz. erythema (E), pustules (P) and desquamation (D). This total (E+P+D)
is adjusted for the percentage area of palm and soles affected to obtain the total PPPASI score.
Total PPPASI Score = [(E+P+D) x Area x 0.2] (right palm) + [(E+P+D) x Area x 0.2] (left palm) +
[(E+P+D) x Area x 0.3] (right sole) + [(E+P+D) x Area x 0.3] (left sole).
E, P and D scores: 0 = None, 1 = Slight, 2 = Moderate, 3 = Severe, 4 = Very severe.
Area affected (%): 0 = 0, 1 = >0 to <10, 2 = 10 to <30, 3 = 30 to <50, 4 = 50 to <70, 5 = 70 to <90, 6 =
90-100.
A lower PPPASI score indicates an improvement in a subject’s condition.
17.1.2.          MISSING DATA METHODS FOR PRIMARY EFFICACY ENDPOINT 
Analysis of the primary endpoint will apply a general linear mixed model for repeated measures (MMRM)
that uses all available data and assumes missing data due to dropouts to be missing at random. The Kenward
Roger method will be used to calculate the denominator degrees of freedom and adjust standard errors for
the test of fixed effects.
17.1.3.          ANALYSIS OF PRIMARY EFFICACY ENDPOINT 
This is an exploratory study and no hypothesis testing will be performed. The primary efficacy analysis


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will be performed on the ITT and mITT at all study visits.
The change from Baseline in PPPASI at Week 4, 8, 12 and 16 will be analysed using a general linear 
MMRM. The model will include fixed effects for treatment, history of plaque psoriasis (Yes/No), visit,
treatment by visit interaction, and baseline PPPASI score as covariate. Least-squares means (LSM) and
associated standard errors for the change from baseline in PPPASI will be presented for each treatment 
group and the least-squares mean difference will be presented with the two-sided 95% confidence interval 
to assess the difference between the active and placebo group. In addition, descriptive statistics (n, mean, 
SD, median, minimum, and maximum) will be presented for PPPASI score and its change from baseline
at all applicable visits.
SAS code to be used for this analysis can be found in Appendix 4.
17.1.4.          SENSITIVITY ANALYSIS OF PRIMARY EFFICACY ENDPOINT(S) 
For the primary efficacy analysis, an MMRM model will be fit. The robustness of that approach will be
explored by duplicating the primary analysis using the PP set.
17.2.  SECONDARY EFFICACY 
The secondary efficacy analyses will be performed on the analyzable ITT. PPPASI will also be analyzed 
using mITT.
17.2.1.          SECONDARY EFFICACY ENDPOINTS, DERIVATIONS, AND ANALYSIS 
17.2.1.1.          Proportion of subjects achieving PPPASI50 and PPPASI75 at all study centers 
visits. 
PPPASI50 is achieved when a subject experiences at least 50% reduction in PPPASI score from baseline.
If a subject’s percentage change from baseline in PPPASI score is less than or equal to -50, the subject 
will be counted as a responder and included in the count of subjects achieving PPPASI50. PPPASI75 is
achieved when a subject achieves at least 75% reduction in PPPASI score from baseline PPPASI score. If
a subject's percentage change in PPPASI score is less than or equal to -75, the subject will have achieved 
PPPASI75. This outcome will be measured for applicable every visit.
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PPPASI score will be handled by multiple imputation while deriving the PPPASI50 and PPPASI75
responses and will be used to analyze the efficacy data using logistic regression. The details of the 
imputation is provided in section 17.2.2.
Frequency and percentages of response for PPPASI50 and PPPASI75 will be presented by visit and
treatment group.
The bar plots for proportion of subjects achieving PPPASI50 and PPPASI75 will be presented by visit
and treatment group.
The binary response for each endpoint will be analyzed using a logistic regression model using a logit
link. The model includes treatment as fixed effect, and history of plaque psoriasis (Yes/No) and Baseline
PPPASI score as covariate. The results will be presented in terms of odds ratio together with its
associated 2-sided 95% CIs for each visit.
17.2.1.2.          Change in PPPASI Score at all study center visits 
Summary statistics will be provided for absolute PPPASI scores and change and percentage change from
Baseline by visit and treatment group.
The Mean ± Standard Deviation (SD) plot for change from baseline PPPASI will be presented by visit
and treatment using ITT.
17.2.1.3.          Change in PPSI Score at all study center visits 
The PPSI score assesses the severity of PPP lesions and response to therapy, with scores ranging from 0
to 12. Erythema (E), Pustules (P) and Desquamation (D) will be assessed separately at the evaluation site
(palms or soles) and scored as follows:
PPSI Score = E + P + D
where 0 = none, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe
Change and percent change from Baseline in PPSI score will be determined for every visit. Change and
percent change from Baseline is defined in Section 8.6.
Summary statistics will be provided for absolute PPSI scores as well as for change and percent change
from Baseline by visit and treatment group.
17.2.1.4.           Change in PPPIGA score at all study center visits 
PPPIGA score ranges from from 0 (clear) to 4 (severe) and is assessed by the investigator at each visit. A
detailed description of the PPPIGA score can be found in Appendix 9 of the protocol.


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Frequency and percentage of each category will be summarized by visit and treatment group.
A shift table of change in PPPIGA scores from Baseline to Week 16 visit will be displayed by each
PPPIGA category for both treatment groups.
17.2.1.5.          Proportion of subjects with clear or almost clear assessment score on PPPIGA 
at all study center visits 
The proportion of subjects with clear or almost clear assessment score on PPPIGA will be calculated for
each visit as follows:
Proportion of subjects with clear or almost clear assessment score =
Number of subjects scoring 0 or 1 on the PPPIGA scale
Total number of subjects in treatment group
Subjects with missing data will be considered as not achieving 0 or 1 on the PPPIGA scale.
Frequency and percentages will be presented by visit and treatment group.
The binary response at Week 16 will be analyzed with a logistic regression model using a logit link. The 
model includes treatment as fixed effect, and history of psoriasis (Yes/No) and Baseline PPPIGA score as
covariate. The results will be presented as odds ratio and 2-sided 95% CI.
The bar plot for proportion of subjects with clear or almost clear PPPIGA assessment will be presented by 
visit and treatment group.
17.2.1.6.          Change in fresh and total pustule count on palms and soles at all study center 
visits 
Change and percent change from Baseline in number of fresh and total pustule count on palms and soles
will be determined for every applicable visit. Change and percent change from Baseline is defined in
Section 8.6. Number and percentage of pustules will be reported by location, visit, and treatment for the
following size categories: ‘<1 mm’, ‘1-3 mm’, ‘>3 to 10 mm’, and ‘confluent lakes of pus’.
Summary statistics for the fresh and total pustule count, as well as change from Baseline, will be provided 
by visit and treatment group. Frequency and percentages of the size of the majority of pustules will be
presented for both the treatment groups for each visit.
The Mean ± Standard Deviation (SD) plots for change from baseline fresh and total pustule count for 
palms and soles will be presented by visit and treatment.


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x 100
17.2.1.7.          Time to response 
Time to response is defined as the time in days to achieve 75% reduction in fresh pustule count from 
Baseline pustule count. If 75% reduction is not achieved, time to response will be censored at the time the
subject discontinued the study, or 169 days (218 days for subjects in German sites) if the subject
completed the study.
Time to response will be analyzed as a time-to-event endpoint. Response is defined as the achievement of
75% reduction in fresh pustule count from baseline pustule count. Subjects withdrawing from the study,
lost to follow up or subjects without response at EOS will be censored. The Kaplan-Meier survival curves
and 25th, 50th (median), and 75th percentiles will be provided by treatment group along with the 2-sided
95% CIs. Estimated survival distribution function along with the number of subjects at risk will be
presented for each time point.
17.2.1.8.          Relapse rate 
Relapse rate is defined as a return to Baseline status in fresh pustule count, and is calculated as follows:
ൌ



Frequency and percentages will be summarized by visit and treatment group for subjects experiencing
relapse.
17.2.1.9.          Change in PASI score and affected BSA at all study center visits, if plaque 
psoriasis is present at non acral sites 
Change and percentage change from Baseline in PASI score and affected BSA will be determined for all
study visits for subjects with plaque psoriasis at non-acral sites. Change and percentage change from 
Baseline is defined in Section 8.6.
Summary statistics will be provided for absolute PASI scores of subjects with plaque psoriasis present at 
non-acral sites, as well as for percent change from Baseline in PASI score, by visit and treatment group 
(where reduction is improvement).


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Summary statistics will also be provided for absolute affected BSA and percent reduction from Baseline
in affected BSA by visit and treatment group.
The Mean ± Standard Deviation (SD) plot for change from baseline total PASI score will be presented by 
visit and treatment.
17.2.1.10.        Improvement in Pustular Psoriasis at non acral site BSA (if present) at all study 
center visits 
Improvement in Pustular Psoriasis at a non-acral site is defined as a reduction in the affected BSA.
Percentage change from Baseline in affected BSA will be calculated by visit and treatment group for 
subjects with plaque psoriasis at non-acral sites. Percentage change from Baseline is defined in Section
8.6.
Summary statistics will be provided for percent change from Baseline in affected BSA at non acral site by
visit and treatment group in subjects with pustular psoriasis (reduction is improvement).
17.2.1.11.        Change in clinical scores of PPPQLI, DLQI and Patient Assessment of 
Palmoplantar Pustulosis Disease Activity at all study center visits. 
Quality of Life (QoL) will be assessed using the Palmoplantar Pustulosis Quality of Life Instrument 
(PPPQLI), Dermatology Life Quality Index (DLQI) and Patient Assessment of Palmoplantar Pustulosis
Disease Activity at all study center visits. See further details in Section 18.
Summary statistics, change and percent change from Baseline will be provided for absolute scores of 
PPPQLI, DLQI and Patient Assessment of Palmoplantar Pustulosis Disease Activity, by visit and
treatment group. Additionally, DLQI will be summarized with counts and percentages for further
different interpretable ranges: “0-1”, ”2-5”, ”6-10”, ”11-20”, ”21-30”.
By-subject listing will be presented for each questionnaire, by visit.
See Section 18 for a description of Quality of Life (QOL) Analyses.
17.2.1.12.        Immunogenicity to ANB019-003 anti-drug antibodies 
The Safety Analysis set will be used for immungenicity analysis.


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A subject will be considered to be positive for ANB019-induced immunogenicity if the subject has one
confirmed positive (in the confirmatory assay) immunogenicity response after dosing.
The frequency and percentage of positive immunogenicity response will be summarized by cohort and visit.
Titer values will be summarized by cohort using appropriate descriptive statistics.
Observed values for ADA levels/status will be listed by-subject with descriptive statistics based on the
safety analysis set. The ADA data will be summarized by visit as proportions with 95% CIs from a 2-sided 
exact test for the comparison of treatment groups, using the Clopper-Pearson method. If data permits,
correlation will be analyzed between ADA levels and safety and efficacy endpoints.
17.2.1.13.        PK parameters 
Computation of PK parameters is described in Section 19.1
17.2.2.          MISSING DATA METHODS FOR SECONDARY EFFICACY ENDPOINT(S) 
Missing responses for categorical secondary response variables (PPPASI75 and PPPASI50) will be
imputed using multiple imputation for the analysis of logistic regression. The method will first use non-
responder imputation for missing values of PPPASI scores and then the imputed values along with the
other available values will be used to derive the categorical responses variables PPPASI50 and PPPASI75
for applicable visits. Detailed multiple imputation steps are provided in the Appendix 3.
17.3.  EXPLORATORY EFFICACY 
17.3.1.          SKIN BIOPSY MARKERS 
Skin biopsy biomarker (including but not limited to IL-36, IL-17, IL-23, and markers of neutrophils and
dendritic cells infiltration) analysis will be performed by a third party designated by the Sponsor. A listing
of biomarker blood sample collection date and times will be provided. Biomarker data and change in
serum cytokine concentrations from Baseline will be summarized.
17.3.2.          PHOTOGRAPHIC DOCUMENTATION OF LESIONS 
No analyses or summaries will be provided for photographic documentations of lesions.


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18.
QUALITY OF LIFE (QOL) ANALYSIS
All QOL analyses will be performed on the ITT.
18.1.1.          QOL VARIABLES & DERIVATIONS 
18.1.1.1.          Palmoplantar Pustulosis Quality of Life Instrument (PPPQLI) 
The PPPQLI evaluates the impact of PPP on a subject’s daily activities and ability to work by means of a
29 item questionnaire. Subjects rate their ability to perform daily activities with a response of No
Difficulty, Mild Difficulty, Moderate Difficulty, Severe Difficulty or Totally Unable. The severity of PPP
as experienced by the subject is assessed by means of a None, Mild, Moderate, Severe or Extreme
response. The social impact of the disease, as well as the limitation of activity is also assessed.
Each of the responses is scored between 1 to 5, with a score of 5 representing the most severe level of 
limitation or pain. The total score for each subject will range from 29 to a maximum of 145, with a higher 
value indicating greater disease impact and poorer quality of life.
18.1.1.2.          Dermatology Life Quality Index (DLQI) 
The DLQI questionnaire will be used to assess treatment response on the subject’s quality of life. The
DLQI aims to measure how much a subject’s skin problem affected their life in the preceding week.
Subjects respond to 10 questions concerning daily activities with either Very much, A lot, A little, Not at
all, Not relevant. Each question is scored as follows: (Finlay AY, 1994)
Response
Score
Very much
3
A lot
2
A little
1
Not at all / Not relevant
0
Question unanswered
0
Question 7: Yes (i.e. “prevented work or studying”)
3


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Response
Score
Question 7: No, but skin has been a problem at work or 
studying a lot
2
Question 7: No, but skin has been a problem at work or 
studying a little
1
Question 7: No, and skin has not been a problem at 
work or studying
0
Question 7: Not relevant
0
The score for each question is summed, resulting in a total DLQI score with a maximum of 30 and a 
minimum of 0. The higher the score, the more quality of life is impaired. The total DLQI score can be
interpreted as follows:
0 -1
no effect at all on patient’s life
2-5
small effect on patient’s life
6-10
moderate effect on patient’s life
11-20
very large effect on patient’s life
21-30
extremely large effect on patient’s life
Additional scoring notes:
 
If one question is left unanswered this is scored 0 and the scores are summed and expressed
out of a maximum of 30. If 2 or more questions are left unanswered the questionnaire is not 
scored.
18.1.1.3.           Patient Assessment of Palmoplantar Pustulosis Disease Activity 
The Patient Assessment of Palmoplantar Pustulosis Disease Activity will be an assessment of disease 
activity by subjects. All subjects will be asked to rate how active their disease condition on a 0 to100 mm
standardized visual analog scale (VAS). Symptoms will be assessed utilizing the mean VAS score.


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18.1.2.          MISSING DATA METHODS 
Refer Section 18.1.1.2 under “Additional scoring notes” for missing data handling for the DLQI. For the
other QOL variables, there will be no imputation of missing data.
18.1.3.          ANALYSIS OF QOL VARIABLES 
Summary statistics will be provided for absolute PPPQLI, DLQI and Patient Assessment of Palmoplantar
Pustulosis Disease Activity scores as well as for change from Baseline (see Section 8.6) by visit and
treatment.
19.
PHARMACOKINETICS
Derivation of serum PK parameters following ANB019 treatment will be the responsibility of the clinical 
pharmacokineticist at
. The PK summaries, summary figures, and data listings as well as the
statistical analysis of the PK variables will be the responsibility of the study biostatistician at
.
Some minor modifications may be necessary to the planned design of tables, figures, and listings to
accommodate data collected during the actual study conduct.
19.1.  VARIABLES & DERIVATIONS 
19.1.1.           SERUM CONCENTRATION DATA 
The actual dates/time of PK sample collections and PK concentration of ANB019 will be listed.
Concentration data of ANB019 will be summarized (n≥3) by day and nominal time point using N (sample
size), n (available data), arithmetic mean, SD, coefficient of variation (CV), minimum, median, maximum,
geometric mean, and geometric CV% using the PK analysis set. Concentrations that are below the limit of
quantitation (BLQ) will be treated as zero for the computation of descriptive statistics. BLQ values set to
zero for summary statistics, will be excluded from calculation of geometric mean.
Individual by-subject concentration-time data will be plotted by actual sampling times on linear and semi-
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Graphs for ANB019 mean (±SD) concentration-time data following SC administration on Day 1 and Day
85 will be presented in linear and semi-logarithmic scale. Individual and mean trough concentrations for
samples collected on Days 29, 57, 85 and 113 (4 weeks after last dose of 100 mg SC) will be graphically
presented to visually assess time to attainment of steady state.
For ANB019 and where data are available, a statistical evaluation of the steady state will also be made using
the trough (predose) plasma concentrations collected on Days 29, 57, 85, and 113 (4 weeks after last dose
of 100 mg SC). All valid concentrations on the natural-log scale will be analyzed using mixed-effect analysis
of variance (ANOVA) model with treatment day as a fixed repeated effect. From this model, orthogonal
contrasts with 90% CI will be formed between the adjusted mean concentration at each study day and the
mean concentrations for all the following study days using Helmert contrasts. Precisely, Day 29 will be
compared to Days 57 through 113, Day 57 will be compared to Days 85 through 113 and so on. Prior to
estimating the fixed effects and the contrasts, an appropriate treatment-specific covariance structure will be
selected using corrected Akaike’s information criterion (AICC).
Other presentations of data may be added at the discretion of the PK scientist, as appropriate. By-subject 
plots will be presented in linear and semi-logarithmic scale.
19.1.2.           PHARMACOKINETIC PARAMETERS 
Pharmacokinetic parameters will be calculated from the concentration-time data using noncompartmental
techniques (Phoenix™WinNonlin®, 8.3 or higher or later; Certara L.P., Princeton, New Jersey, USA). The
actual (rather than nominal) sampling times will be used in the PK parameter calculations. If the collection 
time of a sample is not recorded, then the nominal time will be used to determine PK parameters.
The PK analysis set will be used for PK parameter analysis. The following PK parameters will be reported
if data permits:
Cmax
Maximum observed concentration, obtained directly from the observed concentration
versus time data.
tmax
Time of maximum observed concentration, obtained directly from the observed
concentration versus time data.
AUC(0-last)
Area under the concentration-time curve (AUC) from time zero (predose) to time of last
quantifiable concentration, calculated by linear up/log down trapezoidal summation.
AUC(0-672)
Area under the curve determined over the 28 day SC dosing interval following 1st SC dose
[Note: this parameter will not be calculated if Day 29 predose data is missing. AUC(0-last)


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will be equal to AUC(0-672) if Day 29 data is available]
AUCoverall
Area under the curve across the 3 SC doses (Day 1 to Day 169) [Note: this parameter will
not be calculated if Day 169 data is missing]
λz
terminal elimination phase rate constant
Cl/F
Apparent Clearance following SC dose
Vd/F
Apparent Volume of distribution following SC dose
t1/2
Terminal half-life associated with λz
Note: The data from Day 1 to predose Day 29 will be used to calculate the above parameters except
where noted.
Additionally:
AUCs will be derived using the linear up/log down trapezoidal rule. Half life may also be estimated if
appropriate and if sufficient data are available, following the last SC administration on Day 85 by utilizing 
ANB019 concentrations collected on Days 113, 141 and 169 (EOS). Only data points that describe the
terminal elimination log-linear decline will be used in the regression equation for calculation of terminal
elimination phase rate constant; Cmax and any data point in the distribution phase are not included in the
calculation. A general rule of adjusted R2 > 0.80 will be considered as acceptable for calculation of the
terminal elimination phase rate constant. If the adjusted R2  falls below 0.80 and  then the terminal
elimination phase rate constant (λz ), Cmax, Tmax AUC(0-last), AUC(0-672), AUCoverall Vd/F, CL/F and t1/2 will be 
reported as not determined (ND) from and that subject.
The extent of accumulation following monthly 100 mg SC administrations relative to the trough obtained
after a single 200 mg SC injection dose will be calculated:
             RCmin,D57: Predose Day 57/Predose Day 29
             RCmin,D85: Predose Day 85/Predose Day 29
Subjects with partial data will be evaluated on a case-by-case basis to determine if sufficient data are
available for reliable estimation of PK parameters.
For PK parameter calculations following Day 1 SC dose, the following conventions will be followed:
 
Concentrations that are BLQ or missing at predose or the beginning of the curve will be set to
zero.
        Any other BLQ concentrations will be assigned a value of zero if they precede quantifiable
samples in the initial portion of the profile.


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A BLQ value that occurs between quantifiable data points, especially prior to Cmax, will be
evaluated to determine if an assigned concentration of zero makes sense, or if exclusion of the
data is warranted.
        Following Cmax, BLQ values embedded between two quantifiable data points will be treated as
missing when calculating PK parameters.
 
If a BLQ value occurs at the end of the collection interval (after the last quantifiable
concentration), it will be set to zero.
        If consecutive BLQ concentrations are followed by quantifiable concentrations in the terminal
portion of the concentration curve, these quantified values will be excluded from the PK analysis
by setting them to missing, unless otherwise warranted by the concentration-time profile.
19.2.  MISSING DATA METHODS 
Missing PK data will not be imputed.
19.3.  DEVIATIONS RELATED TO PK 
Changes to the procedures or events which may impact the quality of the PK data, will be considered
significant protocol deviations with respect to PK and will be described within the clinical study report body
text.
These changes or events include any circumstances that could alter the evaluation of the PK. Examples 
include, but may not be limited to, sample processing errors that lead to inaccurate bioanalytical results,
and/or inaccurate or missed dosing on or before the day of PK sampling.
In the case of a significant protocol deviation or event, PK data collected during the affected time period
will be excluded from the study summaries.
Other changes to the procedures or events which do not impact the quality of the PK data will not be
considered significant with respect to PK. Protocol deviations affecting PK will be determined post DBL
and unblinding.
19.4.  ANALYSIS OF PK PARAMETERS 
All PK parameters will be summarized for the PK analysis set using descriptive statistics, including N, n,


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arithmetic mean, SD, CV%, median, minimum, maximum, geometric mean and geometric CV%, with the
exception of tmax, which will be reported with n, minimum, median and maximum, only. Summary
statistics will be determined (n≥3) from available data with no imputation of missing values.
A subject listing of individual PK parameters for ANB019 will be provided.
In addition to the graphical assessment of ANB019 and where data are available, a statistical evaluation of
the steady state will also be made using the trough (predose) plasma concentrations collected on Days 29,
57, 85, and 113 (4 weeks after last dose of 100 mg SC; See Section 19.1.1).
19.5.  PRECISION OF PK VARIABLES 
All PK concentrations will be reported and analyzed with the same precision as the source data provided
by the bioanalytical laboratory regardless of how many significant figures or decimals the data carry.
Derived PK parameters will be rounded for reporting purposes in by-subject listings.
The unrounded derived PK data will be considered the source data for the calculation of descriptive
statistics.
For most derived PK parameters, three significant digits will be used as the standard rounding procedure
for listings, with the following exceptions:
 
Parameters directly derived from source data (e.g., Cmax) will be reported and analyzed with the
same precision as the source data.
        Parameters derived from actual elapsed sample collection times (e.g., tmax) will be reported to 2
decimal places with units of hours.
For the reporting of descriptive statistics for concentration and PK parameter variables:
 
The mean, SD, and geometric mean will be presented to one digit more precision than the source
data.
        The minimum, median, and maximum will be presented to the same precision as the source data.
        CV% and geometric CV% will always be reported to one decimal place.


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20.
SAFETY OUTCOMES
All outputs for safety outcomes (AEs, SAEs, vital signs, ECGs, ADA, neutralizing antibodies, and 
clinical laboratory assessments at each specific time points) will be listed and summarized descriptively
using the SAF. There will be no statistical comparisons between the treatment groups for safety data,
unless otherwise specified within the relevant section.
Individual listings of SAEs and AEs will be summarized using the current MedDRA. Summaries and
listings of data for vital signs, haematology, clinical chemistry and urinalysis laboratory tests, and ECGs
will be presented. Appropriate descriptive statistics will be summarized for the observed value at each 
scheduled assessment and for the corresponding change from Baseline.
20.1.  ADVERSE EVENTS 
Adverse Events (AEs) will be coded using the most recent version of Medical Dictionary for Regulatory
Activities (MedDRA) central coding dictionary.
Treatment emergent adverse events (TEAEs) are defined as:
        A new event that occurs during or after first dose of study treatment or,
 
Any event present at Baseline that worsens in either intensity or frequency after first dose of study 
treatment.
Only TEAEs will be summarized and number of subjects and percentage will be tabulated by Preferred 
Term (PT) and System Organ Class (SOC). Multiple occurrences of an AE for a subject will only be
counted once per SOC/PT. Percentages will be determined relative to all safety subjects exposed to
ANB019 or placebo.
Adverse events with missing start dates will be considered treatment-emergent. AEs with missing stop
dates or with stop dates after the end of the study date will be considered to have been ongoing at the end 
of the study.
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, SAEs, TEAEs leading to treatment 
discontinuation, and TEAEs leading to withdrawal of subject will be tabulated for each treatment group. 
See Appendix 2 for handling of partial dates for AEs. In the case where it is not possible to define an AE
as treatment emergent or not, the AE will be classified by the worst case; i.e. treatment emergent.
An overall summary (frequencies and percentages) of number of subjects within each of the sub-
categories described below will be presented by treatment, SOC and PT, as specified in the templates.


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Summaries over SOC and PT of TEAEs, TEAEs leading to death, SAEs, potentially significant TEAEs
and clinically important TEAEs, AESIs, and TEAEs that led to discontinuation from the study or study 
treatment will be presented by treatment. Summaries will also be presented by relatedness to the study 
treatment and the severity of the TEAE.
Listings will include TEAEs and Non-TEAEs, with TEAEs flagged. All AE data will be listed for each 
subject.
20.1.1.          ALL TEAES 
Incidence of TEAEs will be summarized by SOC and PT and also broken down further by maximum
severity and relationship to study treatment.
20.1.1.1.          Severity 
Severity is classed as mild, moderate or severe (increasing severity). TEAEs starting after the first dose of
study treatment with a missing severity will be reported as the worst case (severe). If a subject reports a
TEAE more than once within that SOC/ PT, the AE with the worst case severity will be used in the
corresponding severity summaries.
20.1.1.2.          Relationship to Study Medication 
Relationship, as indicated by the Investigator, is classed as unrelated, possibly related or related
(increasing severity of relationship). A ”related” TEAE is defined as a TEAE with a relationship to study
treatment as “possibly related” or “related” to study treatment. TEAEs with a missing relationship to
study treatment will be reported as “related”. If a subject reports the same AE more than once within that 
SOC/ PT, the AE with the worst case relationship to study treatment will be used in the corresponding
relationship summaries.
20.1.2.          TEAES LEADING TO DISCONTINUATION OF TREATMENT 
TEAEs leading to permanent discontinuation of study treatment will be identified by the “Drug
permanently discontinued” option in the “Action taken with the study treatment” question on the AE 
eCRF page. A summary by SOC and PT will be prepared, as well as a subject listing.


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20.1.3.          TEAES LEADING TO WITHDRAWAL OF SUBJECTS 
TEAEs leading to the withdrawal of subjects from the study will be identified by using the response to the 
question “Did the AE cause the subject to discontinue from the study?” on the AE eCRF page. A
summary by SOC and PT will be prepared, as well as a subject listing.
20.1.4.          SERIOUS ADVERSE EVENTS 
Serious adverse events (SAEs) are those events recorded as ”Serious” on the AE page of the eCRF. A
summary of serious TEAEs by SOC and PT will be prepared, as well as a subject listing.
20.1.5.          ADVERSE EVENTS LEADING TO DEATH 
TEAEs leading to Death are those events which are recorded as ”Fatal” in the “Final Outcome” question 
on the Adverse Events page of the eCRF. A summary of TEAEs leading to death by SOC and PT will be
prepared.
20.1.6.          ADVERSE EVENTS RELATED TO INJECTION SITE REACTIONS 
Injection site reactions will be identified by the AE eCRF, using the question “Is this an injection site
reaction?” A summary by SOC and PT will be prepared, as well as a subject listing.
20.1.7.          ADVERSE EVENTS OF SPECIAL INTEREST 
Adverse events of special interest (AESI) will be identified by the AE eCRF, using the question “Is this
Adverse Event of Special Interest (AESI)?”. A summary of TEAEs of special interest by SOC and PT
will be prepared, as well as a subject listing.
20.1.8.          DISEASE RELATED ADVERSE EVENTS 
Disease related TEAEs will be identified by the AE eCRF, using the question “Is this a disease related
event?”, and will be listed and summarized.


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20.2.  LABORATORY EVALUATIONS 
Results from the central laboratory will be included in the reporting of this study for Hematology,
Biochemistry and Urinalysis. A list of laboratory assessments to be included in the outputs is included in
Appendix 3 of the protocol.
Local laboratory tests will be allowed in the event that the central laboratory results will not be available
immediately, and decisions regarding safety concerns need to be made. A central laboratory analysis will
also be performed at the same time as the local laboratory test. Only the central laboratory test results
will be summarized and reported.
Presentations will use Système International (SI) units.
Quantitative laboratory measurements reported as “< X”, i.e. below the lower limit of quantification
(BLQ), or “> X”, i.e. above the upper limit of quantification (ULQ), will be converted to X for the 
purpose of quantitative summaries, but will be presented as recorded, i.e. as “< X” or “> X” in the
listings.
The following summaries and listings will be provided for laboratory data:
             Actual and change from baseline by visit (for quantitative measurements)
             Frequency and percentages by visit (for categorical measurements)
 
A listing of all laboratory results, including follicle stimulating hormone (FSH) and 
pregnancy tests results, TB evaluations and serology and virology results.
             Abnormal hematology and biochemistry values, according to normal range criteria, will be
flagged in the listing.
20.2.1.          LABORATORY REFERENCE RANGES 
Quantitative laboratory measurements will be compared with the relevant laboratory reference ranges in
SI units and categorized as:
             Low: Below the lower limit of the laboratory reference range.
             Normal: Within the laboratory reference range (upper and lower limit included).
             High: Above the upper limit of the laboratory reference range.
             Summaries and shift tables from baseline to EOS will be reported.
20.3.  ECG EVALUATIONS 
Results from the central electrocardiogram (ECG) Reading Centre will be included in the reporting of this


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study.
The following ECG parameters will be reported for this study:
PR Interval (msec)
             QRS Interval (msec)
             QT Interval (msec)
             QTcF Interval (msec) [derived]
             HR (bpm)
             Overall assessment of ECG (Investigator’s judgment) as:
             Normal

Abnormal, Not Clinically Significant (ANCS)

Abnormal, Clinically Significant (ACS) 
The following summaries will be provided for ECG data:
             Actual and change from baseline by visit (for quantitative measurements)
             Shift from baseline by visit and treatment group (for qualitative measurements)
             Listing of clinically significant abnormalities
Electrocardiogram data will be listed using the actual and change from baseline values for the above
parameters and will be summarized using descriptive statistics (n, mean, SD, median, and range) by
treatment groups and all available visits.
The overall assessment of ECG data results (normal/abnormal) will be summarized using frequency and
percentages.
             Absolute values for QT and QTcF interval will be classified as:
             ≥450 msec
             ≥480 msec
             ≥500 msec
Since there are different ranges for QTcF between the males and females, we will summarize the QTcF
by gender as defined below:
Absolute values of the QT interval as: Males: 431- 450 msec; Female: 451- 470 msec.
             Abnormal values of the QT interval as: Males: > 450 msec Females: > 470 msec
             Change from Baseline for QT and QTcF interval will be classified as:
             >30 msec increase from Baseline
             >60 msec increase from Baseline
A listing of ECG parameters and of the overall assessment will be provided.


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20.4.  VITAL SIGNS 
The following Vital Signs measurements will be reported for this study:
             Supine Systolic Blood Pressure (mmHg)
             Supine Diastolic Blood Pressure (mmHg)
             Supine Pulse Rate (bpm)
             Respiratory Rate (breaths/min)
             Body Temperature (ͼC)
             Weight (kg)
             BMI (kg/m2)
The following outputs will be provided for vital signs data:
             Summary of actual and change from baseline by visit
             A listing of vital signs observations will also be provided for each subject by visit.
20.4.1.          VITAL SIGNS SPECIFIC DERIVATIONS 
Body temperature will be presented in ͼC. All values in ͼF will be converted as follows:
°C = (°F – 32) / 1.8
20.5.  PHYSICAL EXAMINATION 
The following assessments will be taken at every physical examination: general appearance, skin,
head/neck, pulmonary, cardiovascular, gastrointestinal, external genitourinary, lymphatic, and 
musculoskeletal system, extremities, eyes, nose, throat and neurologic status.
Results will be captured and summarized by the following categories:
             Normal
             Abnormal, not clinically significant (NCS)
             Abnormal, clinically significant (CS)
Only abnormal findings will be presented in the listing.
21.
DATA NOT SUMMARIZED OR PRESENTED
The other variables and/or domains not summarized or presented are:


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             Chest X-ray results
These domains and/or variables will not be summarized or presented, but will be available in the clinical
study database, SDTM and/or ADaM datasets.


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22.
REFERENCES
Protocol: MYA11999-ANB019-003_Original Protocol_FINAL_27 Jul 2018-0001.pdf
Protocol: ANB019-003_AMD5_Final_29Oct2020_clean.pdf
Protocol: ANB019-003_AMD5.1_Final_29Oct2020_clean.pdf
eCRF: AnaptysBio Inc_ANB019-003_ASB_V03_21FEB2019.pdf
Finlay AY, Khan GK (1994). Cardiff University, Department of Dermatology. Quality of Life Questionnaires –
DLQI Instructions for use and scoring. Retrieved November 8, 2018, from
http://sites.cardiff.ac.uk/dermatology/quality-of-life/dermatology-quality-of-life-index-dlqi/dlqi-instructions-for-use-
and-scoring/


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