A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ANB019 in the Treatment of Acneiform Rash in Subjects With Neoplasm Receiving EGFRi or MEKi Therapy
Phase: PHASE2
Conditions: Acneiform Eruptions
Sponsor: Vanda Pharmaceuticals

Confidential and proprietary. Permission should be obtained before any reproduction. 
1 
A Phase 2a, Randomized, Double-Blind, Placebo-
Controlled Study to Evaluate the Efficacy and Safety of 
ANB019 in the Treatment of Acneiform Rash in Subjects 
with Neoplasm Receiving EGFRi or MEKi Therapy
Protocol Number: ANB019-207 
Investigational New Drug (IND) Number: 136145
European Clinical Trials Database (EudraCT) Number: 2020-003494-22
Sponsor Name: AnaptysBio, Inc.
Sponsor Address: 10770 Wateridge Circle, Suite 210 
San Diego, CA 92121, United States
Sponsor Medical Expert and Signatory:
Amendment 2 
05 August 2021 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
Amendment 2
Protocol ANB019-207 
05 August 2021 
 
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
3 
INVESTIGATOR’S AGREEMENT 
PROTOCOL TITLE:  
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the 
Efficacy and Safety of ANB019 in the Treatment of Acneiform Rash in Subjects with 
Neoplasm Receiving EGFRi or MEKi Therapy 
PROTOCOL NO: 
ANB019-207 
VERSION:  
Amendment 2 
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 GCP 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unpublished information contained herein will be published or disclosed without prior written approval 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 (05 August 2021) 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:  
______________________________ 
 
______________________________ 
 
______________________________ 
 
______________________________ 
 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
Amendment 2
Protocol ANB019-207 
05 August 2021 
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
4 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE  
DOCUMENT HISTORY
Document
Date
Amendment 2
05 August 2021 
Amendment 1
11 February 2021 
Original Protocol (Version 1.0) 
28 September 2020
Amendment 2  
Date: 05 August 2021 
Overall rationale for amendment: 
This amendment was prepared to address the following issues: 
 
Permit small editorial changes for clarity and correctness 
 
Update the name of the Sponsor medical expert and signatory, and address of the Sponsor 
 
Allow inclusion of subjects with benign neoplasm (not cancer) 
 
Revised eligibility criteria for body weight to  40kg 
 
Updated tuberculosis screening as inclusion criteria 
 
Clarified definition of childbearing potential in contraceptive use exclusion criteria 
 
Allow screening of subjects prior to rash onset 
 
Reduce the number of study visits by removing Week 1 and Week 6 visits 
 
Modify the list of study endpoints by removing percent change from Baseline from some endpoints 
and revised exploratory endpoints based on planned data collection 
 
Clarify the recommended order of assessments to be followed during the study visits  
 
Add an evaluation of the Fitzpatrick Skin Type Classification 
 
Reduce the number of electrocardiograms (ECGs) to be performed during the study 
 
Reduce the number of tape strip samples to be collected and clarify the location for sample 
collection 
 
Reduce the number of blood samples to be collected for pharmacokinetic (PK) evaluations  
 
Removal of noncompartmental analysis (NCA) due to limited PK sampling 
 
Update washout periods for prohibited treatments 
 
Add clarification related to vaccines allowed during the study 
 
Clarify if a subject were to discontinue early from the study, an early termination visit will be 
required 
 
Remove the possibility of subjects’ replacement  
 
Clarify assessment of facial lesions 
 
Remove facsimile as an option to report serious adverse events (SAEs) 
 
Update the text to indicate local laboratory tests will be allowed at Screening for TB and viral 
serology testing 
 
Section # and Name 
Description of Change 
Brief Rationale 
Global  
Small editorial changes and 
corrections. 
To add clarity and 
implement corrections to 
text.

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
Amendment 2
Protocol ANB019-207 
05 August 2021 
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
5 
Section # and Name 
Description of Change 
Brief Rationale 
Global
Change language from final 
screening to Screening Part 2. 
Change made to ensure 
clarity throughout 
document. 
Global
Change language from cancer to 
neoplasm. 
Change made to include 
subjects with neoplasm (not 
cancer). 
Document Header; Title Page; 
Investigator’s Agreement; Protocol 
Amendment Summary of Changes 
Table
Updated amendment number 
and date.  
Administrative changes for 
Amendment 2. 
Title Page; Sponsor Signature Page 
Updated the name of the 
Sponsor medical expert and 
signatory, and address of the 
Sponsor.  
To implement modification 
in study administrative 
structure. 
Abbreviations; Section 1.3 Schedule 
of Activities; Section 1.1 Synopsis; 
Section 7.2 Subject 
Discontinuation/Withdrawal from 
the Study
Clarified that upon early 
discontinuation of study 
treatment, subjects must attend 
an early termination visit. 
Change was made to clarify 
discontinuation/withdrawal 
from study. 
Section 1.1 Synopsis; Section 1.3 
Schedule of Activities; Section 4.1 
Overall Design; Section 8.3.3 
Pharmacokinetics, Table 15 
Pharmacokinetic Sample Collection 
and Time Points 
Removed visits at Week 1 (Day 8) 
and Week 6 (Day 43). Table 1 
footnote edited to remove Day 1. 
To reduce number of study 
visits required of subjects 
and align visit schedule with 
oncology visits.  
Section 1.1 Synopsis; Section 3.3
Exploratory Objectives and 
Endpoints; Section 9.4.7 Analysis of 
the Exploratory Efficacy Endpoints 
Removed percent change from 
Baseline in endpoints assessing 
change in acneiform rash 
modified MESTT grading scale at 
individual locations (face, scalp, 
chest, and back); acneiform rash 
CTCAE grading scale; IGA; and 
facial IGA.
These assessments use 4- to 
6-point scales and percent 
change is not needed. 
Section 1.1 Synopsis; Section 3.3 
Exploratory Objectives and 
Endpoints; Section 9.4.7 Analysis of 
the Exploratory Efficacy Endpoints 
Added endpoints based on 
change in facial papules and 
pustules as well as proportion of 
subjects achieving key categories 
in PGI-S/PGI-C.
Additional analyses added 
based on data previously 
specified for collection for 
proof-of-concept 
evaluation. 
Section 1.3 Schedule of Activities
Clarified text to indicate the 
preferred rather than specific 
order for performing 
assessments, that subject-
reported questionnaires and 
efficacy assessments must be 
performed before other 
assessments, and that 
Change was made to 
provide flexibility around 
assessments while still 
adhering to specific 
guidelines.  

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
Amendment 2
Protocol ANB019-207 
05 August 2021 
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
6 
Section # and Name 
Description of Change 
Brief Rationale 
photography may be performed 
any time predose provided it is 
before tape stripping.  
Section 1.3 Schedule of Activities; 
Section 8.2.1.1.1 Events Meeting 
the Adverse Event Definition 
Removed ECG assessments at 
Day 1 (Week 0), Week 4, and 
Week 24. Reduced the number 
of blood samples to be collected 
for PK evaluations. 
Revised text in section to read: 
“worsen from a prior 
assessment” instead of “Day 1”. 
Change was made to reduce 
number of assessments 
required of subjects. 
Alignment between 
timepoints captured on the 
Schedule of Activities and 
text within protocol.
Section 1.3 Schedule of Activities
Indicated that tape strips will be 
collected on Day 1, Day 57, and 
Day 113 from both nonlesional 
and lesional skin. Removed tape 
strip collection on Day 15. 
Change was made to allow 
comparison of lesional and 
nonlesional skin and reduce 
the number of visits for tape 
strip collection. 
Section 1.3 Schedule of Activities
Removed Week 1 and Week 6 
visits 
Change was made to reduce 
the number of visits.
Section 1.3 Schedule of Activities
Removed photography collection 
at Week 2 (Day 15), added Week 
4 (Day 29) for photography 
collection. 
Photography is not collected 
at Week 2 (Day15). 
Photography will also be 
collected at Week 4 (Day 
29).
Section 1.1 Synopsis; Section 1.2 
Schema; Section 1.3 Schedule of 
Activities; Section 4.1 Overall 
Design; Section 5.1 Inclusion 
Criteria, Inclusion Criterion 3 
Updated study design and 
inclusion criteria to allow 
screening of subjects prior to 
rash onset and modify the 
screening procedures for those 
subjects.  
Change was made in the 
inclusion criteria to allow 
screening of subjects prior 
to rash onset. The screening 
visit was updated and can 
be performed as one visit 
for subjects experiencing a 
rash or as two visits to 
follow subjects not 
experiencing a rash at the 
initial screening visit. 
Section 1.3 Schedule of Activities; 
Section 8.3.1 Fitzpatrick Skin Type 
Classification; Section 10.1.9.1 Data 
Collection and Management 
Responsibilities; Section 11 
References; Appendix 8 Fitzpatrick 
Skin Type Classification
Added the Fitzpatrick Skin Type 
Classification to the Screening 
activities.  
Change was made to further
classify skin type. 
Title Page; Investigator’s 
Agreement; Section 1.1 Synopsis; 
Section 2.1 Study Rationale; Section 
Indicated that subjects with a 
diagnosed neoplasm were to be 
included in the study. 
Change was made to be 
more inclusive of patients 
with different types of 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
Amendment 2
Protocol ANB019-207 
05 August 2021 
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
7 
Section # and Name 
Description of Change 
Brief Rationale 
4.1 Overall Design; Section 5.1 
Inclusion Criteria, Inclusion 
Criteria 2 and 8; Exclusion Criteria 7, 
10, 13j, and 21; Section 6.3
Measures to Minimize Bias: 
Randomization and Blinding; 
Section 6.5.2 Prohibited 
Medications or Procedures; 
Section 8.1.5 Systemic Therapy 
Induced Diarrhea Assessment Tool; 
Section 8.2.1 Adverse Events and 
Serious Adverse Events; 
Section 9.4.5.2 Statistical Analysis of 
Primary Endpoint
neoplasm (ie, 
malignant[cancer] and 
benign neoplasms). 
Section 5.1 Inclusion Criteria, 
Inclusion Criterion 7 
Revised body weight parameter.
Change was made to 
include body weight 40kg
Section 5.1 Inclusion Criteria, 
Inclusion Criterion 9 
Expanded on tuberculosis 
screening as inclusion criteria. 
Tuberculosis screening 
criteria added as inclusion 
criteria (previously 
exclusionary criteria).
Section 5.1 Inclusion Criteria, 
Inclusion Criterion 10 
Clarified childbearing potential.
Change was made to clarify 
the definition of 
childbearing potential.
Section 5.2 Exclusion Criteria, 
Exclusion Criterion 6 
Clarified possible therapies for 
active infection and adjusted 
time window. 
Added antifungal or antiviral 
therapy. 
Changed treatment window 
to 2 weeks of Day 1.
Section 5.2 Exclusion Criteria, 
Exclusion Criterion 8 
Reduced window for history of 
opportunistic infection or 
parasitic infections. 
Change was made from 6 
months prior to Screening 
to 3 months.
Section 5.2 Exclusion Criteria, 
Exclusion Criterion 13 q; Table 3
Added “other than used for 
treatment of neoplasm”. 
Clarified marketed biologic 
agent. 
Section 5.2 Exclusion Criteria, 
Exclusion Criterion 15 
Clarified periods of stable 
dosage. 
Change was made to reduce 
the duration from 26 weeks 
to 12 weeks. 
Section 5.2 Exclusion Criteria, 
Exclusion Criterion 13; Section 6.5.2 
Prohibited Medications or 
Procedures; Table 3 
Clarified the periods of washout 
for prohibited medications. 
Change was made to 
expand the period and use 
of prohibited medication 
prior to the study drug. 
Section 6.5 Concomitant Therapy
Added the following: “Nonlive-
attenuated vaccines, including 
those currently authorized for 
COVID-19 (eg, RNA-based 
vaccines, protein-based 
vaccines), are allowed during the 
Change was made to clarify 
which COVID-19 vaccines 
are allowed during the 
study. 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
Amendment 2
Protocol ANB019-207 
05 August 2021 
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
8 
Section # and Name 
Description of Change 
Brief Rationale 
study. The Medical Monitor 
should be consulted to confirm 
that the vaccine 
planned/received is allowed and 
that subject participation in the 
study should be continued. Of 
note, vaccines, including those 
for COVID-19, should be 
captured as a concomitant 
medication and any related 
symptoms documented as AEs.” 
Removed language around 
concomitant treatments for 
other indications
Defined in other sections. 
Section 7.1 Discontinuation of Study 
Treatment  
Removed definition of 
discontinuation from the study.  
Text was removed from this 
section and clarified in 
Section 7.2 Subject 
Discontinuation/ 
Withdrawal from the Study.
Section 7.2 Subject 
Discontinuation/Withdrawal from 
the Study 
Removed “Subjects withdrawing 
from the study prematurely for 
reasons other than a study 
treatment-related AE may be 
replaced at the discretion of the 
Sponsor.” 
To remove the possibility of 
subjects’ replacement 
during the study. 
Section 8.1.8 Facial Inflammatory 
Lesion Count 
Clarified assessment timepoints 
at final screening and Day 1 
visits. 
Added the following explanation: 
“Only for the facial inflammatory 
lesion count, papules and 
pustules should be counted 
separately to attain the total 
inflammatory lesion count.” 
Change was made to clarify 
assessments. 
Section 8.2.1.6.2 Reporting via 
Paper Case Report Form 
Removed facsimile as a means of 
transmitting SAEs. 
Facsimile is no longer being 
used.
Section 1.3, Section 8.2.7, Appendix 
7 
Updated the text to indicate that 
local laboratory tests will also be 
allowed at Screening for TB and 
viral serology testing 
Local laboratory tests will be 
allowed at TB screening and 
viral serology testing. 
Section 8.3.5 Biomarkers Analysis
Deleted word “tube” from 
description of test strip labeling.  
Tape strips are not collected 
in tubes. 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
Amendment 2
Protocol ANB019-207 
05 August 2021 
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
9 
Section # and Name 
Description of Change 
Brief Rationale 
Section 9.4.7 Analysis of the 
Exploratory Efficacy Endpoints 
Removed two duplicated 
endpoints. 
 Proportion of subjects 
achieving an IGA of clear 
(0) or almost clear (1) at 
each visit 
 Proportion of subjects 
achieving a facial IGA of 
clear (0) or almost clear (1) 
at each visit 
Change was made for 
clarity. 
Section 9.4.9.1 Derivation of 
Pharmacokinetic Parameters 
Due to minimal PK sampling, NCA 
will not be conducted. Updated 
text to reflect change.
Minimal PK sampling.
Section 9.4.12 Interim Analyses
Updated section header and text 
to indicate that interim analyses 
may be performed rather than 
interim analysis. 
There are planned to be at 
least 2 interim analyses.
Tables 4-9
Revised order of footer elements 
and added sources to table 
footers. 
Administrative change. 
 
Amendment 1  
Date: 11 February 2021 
Overall rationale for amendment: 
This amendment was prepared to address the following issues: 
 
Permit small editorial changes for correctness 
 
Clarify modifications to MESTT, use of CTCAE scoring and corresponding statistical analysis 
 
Permit (optional) home health visits during the COVID-19 pandemic, describe home nursing visit 
procedures, and acknowledge that COVID-19 measures only apply if they are in accordance with 
current, locally applicable recommendations/regulations  
 
Permit the use of remaining serum from samples collected for PK/immunogenicity endpoints to be 
retained for assay method development, troubleshooting, or validation 
 
Clarify timing for administration of live-attenuated vaccines after the subject completes the 12-
week standard safety follow-up period of the study or after 12 weeks following the last 
administration of the study drug for subjects who discontinued from the study early 
 
Clarify timing requirements for use of hormonal contraceptives prior to and during study 
participation and to identify which oral hormonal contraceptives are permissible 
 
Permit enrollment of subjects treated with any commercially available EGFRi or MEKi therapy  
 
Include a 30-minute observation period of study subjects after application of each dose of ANB019 
to identify any potential allergic/anaphylactic reaction  
 
Clarify timing of anti-drug antibody sample collection 
 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
Amendment 2
Protocol ANB019-207 
05 August 2021 
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
10 
Section # and Name 
Description of Change 
Brief Rationale 
Global
Small editorial changes and 
corrections. 
To add clarity and 
implement corrections to 
text.
Document Header/Footer; 
Document History  
Added amendment number and 
date in the header. Added 
amendment number and date to 
the Document History table. 
Administrative change for 
Amendment 1. 
Title Page; Investigator’s Agreement 
Added amendment number.
Administrative change for 
Amendment 1.
Section 1.1 Synopsis (Study 
Population); Section 4.1 Overall 
Design; Section 5.1 Inclusion 
Criteria; Section 5.2 Exclusion 
Criteria; Section 6.5.2 Prohibited 
Medications or Procedures, Table 3 
List of Prohibited Medications and 
Procedures
Updated text to clarify that
subjects are eligible if they are 
treated with oral or injectable 
commercially available EGFRi or 
MEKi therapy. 
Clarity of language for 
nonUS product 
usage/availability. 
Section 1.1 Synopsis Protocol 
Summary Exploratory Endpoints; 
Section 3 Objectives and Endpoints; 
Section 9 Statistical Considerations 
Updated secondary and 
exploratory endpoints; 
definitions of concomitant 
medications.
To add clarity and 
implement corrections to 
text.  
Section 1.1 Synopsis Section (Study 
Description); Section 4.1 Study 
Design; Section 8.3.2 
Pharmacokinetics; Section 8.3.3 
Immunogenicity Assessments; 
Section 10.1.4 Future of Stored 
Specimens and Data 
Updated text to clarify that 
remaining serum from samples 
collected for PK/immunogenicity 
endpoints may be retained for 
assay method development, 
troubleshooting, or validation. 
Samples will not be used for 
genetic analyses.
Alignment with AnaptysBio
practices. 
Section 1.3 Table 1 Schedule of 
Activities 
Updated SoA to correct minor 
discrepancies and align with 
changes mentioned in this 
amendment. 
To add clarity and 
implement corrections to 
text.  
Section 1.3 Schedule of Activities; 
Section 4.2 Modifications to Study 
Conduct Due to the Coronavirus 
Disease 2019 (COVID-19) Pandemic; 
Section 7.3 Lost to Follow-Up  
Updated text to:
Reflect that due to the COVID-19 
restrictions, conducting optional 
home visits is permissible when 
on-site study visits are not 
feasible.  
Clarified home nursing visit 
procedures. 
Clarified that such modifications 
always must be in accordance 
with local regulations.
The COVID-19 pandemic 
may impact the ability to 
adhere to certain study 
procedures due to center 
closures, travel restrictions, 
and quarantines.  
Section 2.3.1 Known Potential Risks; 
Section 6.1.2 Dosing and 
Clarified that subjects should stay 
on-site for a 30-minute 
Added clarity regarding 
observation of subject 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
Amendment 2
Protocol ANB019-207 
05 August 2021 
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
11 
Section # and Name 
Description of Change 
Brief Rationale 
Administration, Table 2 Study 
Treatment Details 
observation period to watch for a 
possible allergic/anaphylactic 
reaction after each dosing with 
ANB019.
following study drug 
administration.
Section 5.2 Exclusion Criteria; 
Section 6.5 Concomitant Therapy 
Clarified period of time 
permissible for administration of 
live-attenuated vaccine - 12 
weeks after the last 
administration of study drug. 
Also applies to subjects who 
terminate the study early. 
During the 12-week follow 
up period, no study drug is 
administered; 12 weeks 
allows for at least 3 half- 
lives of study drug and is 
estimated to be a sufficient 
period after the last dose 
administration when a live 
vaccine can be safely 
administered. 
Section 5.1 Inclusion Criteria; 
Section 12 Appendix 1, 
Contraceptive Guidance and 
Collection of Pregnancy Information 
Clarified that hormonal 
contraceptives must be used at a 
stable regimen throughout the 
study.  
Variability in hormonal 
contraceptive regimen may 
impact interpretation of 
possible exanthema. 
Section 5.1 Inclusion Criteria; 
Section 6.5.2 Prohibited 
Medications or Procedures, Table 3 
List of Prohibited Medications and 
Procedures; Section 12 Appendix 1, 
Contraceptive Guidance and 
Collection of Pregnancy Information 
Clarified that drospirenone, 
chlormadinone acetate, or 
cyproterone acetate must be 
initiated and used at a stable 
dosage for at least 12 weeks 
prior to Day 1. 
Alignment of prohibited 
medications and 
contraceptive guidance. 
Section 8.1.10; Section 8.1.10 Table 
8 Grading of Acneiform Rash 
According to Common Terminology 
Criteria for Adverse Events 
Clarified assessment timepoints 
at final screening and Day 1 
visits. 
Updated Table 8 to include:  
0 = No evidence of rash. 
To add clarity and 
implement corrections to 
text.  
Section 8.1.11 MASCC EGFRi Skin 
Toxicity Tool 
Use of ‘modified’ MESTT in lieu 
of standard MESTT to record skin 
changes in 4 different body 
regions vs total skin changes 
combined. 
To add clarity and 
implement corrections to 
text.  
Section 8.1.11 Table 9 Grading of 
Acneiform Rash According to the 
MASCC EGFRi Skin Toxicity Tool  
Updated Table 9 to include: 
0 = No evidence of papules or 
pustules. 
Updated Grade 1 definition to 
include presence of 5 papules 
and pustules (typographical error 
in the source document).
To clarify and implement 
corrections to text.  
Section 8.1.12 Table 10 Grading of 
Paronychia According to Common 
Updated Table 10 to include:  
0 = No evidence of paronychia.
To clarify and implement 
corrections to text. 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
Amendment 2
Protocol ANB019-207 
05 August 2021 
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12 
Section # and Name 
Description of Change 
Brief Rationale 
Terminology Criteria for Adverse 
Events 
Section 8.1.12 Table 11 Grading of 
Dry Skin According to Common 
Terminology Criteria for Adverse 
Events 
Updated Table 11 to include: 
0 = No evidence of dry skin. 
To add clarity and 
implement corrections to 
text.  
Section 8.1.12 Table 12 Grading of 
Alopecia According to Common 
Terminology Criteria for Adverse 
Events 
Updated Table 12 to include:  
0 = No evidence of alopecia. 
To add clarity and 
implement corrections to 
text.  
Section 8.1.12 Table 13 Grading of 
Pruritus According to Common 
Terminology Criteria for Adverse 
Events 
Updated Table 13 to include:  
0 = No evidence of pruritus. 
To add clarity and 
implement corrections to 
text  
Section 8.2.5 Vital Signs 
Clarified site methods for 
assessing body temperature (°C), 
pulse rate (bpm), blood pressure 
(mmHg), and respiratory rate 
(breaths/min) at the time points 
specified in SoA (Section 1.3).  
To implement consistent
methods for assessing vital 
signs across AnaptysBio 
protocols.  
Section 8.3.3 Table 16 Anti-Drug 
Antibodies Sample Collection and 
Time Points
Updated Table 16 to delete Anti-
Drug Antibody (ADA) sample 
collection times on Days 48 and 
85 as per SoA.
To implement corrections to 
text and to align with SoA. 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash 
Amendment 2 
Protocol ANB019-207 
05 August 2021 
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
13 
ABBREVIATIONS 
ADA 
anti-drug antibody 
ADL 
activities of daily living 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
BSA 
body surface area 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CK 
creatine kinase 
Cmax 
maximum observed concentration 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
Coronavirus Disease 2019 
CRO 
contract research organization 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CV 
coefficient of variation 
cyIL-36R 
cynomolgus monkey IL-36R 
D 
day 
EC 
Ethics Committee 
ECG 
electrocardiograms 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report forms 
EDC 
electronic data capture 
EGFR 
epidermal growth factor receptor 
EGFRi 
epidermal growth factor receptor inhibitor 
EOS 
end of study 
ERK 
extracellular signal-regulated kinase 
ET 
early termination 
EudraCT 
European Clinical Trials Database 
FACT-EGFRi-18 
Functional Assessment of Cancer Therapy - Epidermal Growth Factor Receptor 
Inhibitor 18 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GEE 
Generalized Estimating Equations 
GGT 
gamma glutamyl transferase 
GLP 
Good Laboratory Practice 
GMP 
Good Manufacturing Practices 
GPP 
generalized pustular psoriasis 
H0 
null hypothesis 
hCG 
human chorionic gonadotropin 
HHS 
Health and Human Services 
HIPAA 
Health Information Portability and Accountability Act 
HRT 
hormonal replacement therapy 
hsCRP 
high-sensitivity C-reactive protein 
IA 
interim analysis 
IB 
Investigator’s Brochure 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash 
Amendment 2 
Protocol ANB019-207 
05 August 2021 
Confidential and proprietary. Permission should be obtained before any reproduction.  
 
14 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IGA 
Investigator Global Assessment 
IgG4 
immunoglobulin G4 
IL 
interleukin 
IL-36R 
interleukin 36 receptor 
IL-36Ra 
IL-36R antagonist 
IND 
Investigational New Drug  
IRB 
Institutional Review Board 
ITT 
Intent-to-Treat 
IUD 
intrauterine device 
IUS 
intrauterine hormone-releasing system 
IV 
intravenous 
IWRS 
Interactive Web Response System 
KD 
dissociation constant 
LSM 
least squares means 
mAb 
monoclonal antibody 
MAD 
multiple ascending dose 
MAP 
mitogen-activated protein 
MAR 
missing at random 
MASCC 
Multinational Association for Supportive Care in Cancer 
MCH 
mean corpuscular hemoglobin 
MCHC 
mean corpuscular hemoglobin concentration 
MCV 
mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
MEK 
mitogen-activated protein/extracellular signal-regulated kinase kinase 
MEKi 
mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor 
MESTT 
MASCC EGFRi Skin Toxicity Tool 
min 
minute 
MMRM 
Mixed model of repeated measures 
MNAR 
Missing Not at Random 
NaCl 
sodium chloride 
NCA 
Noncompartmental analysis 
NOAEL 
no observed adverse effect level 
NRS 
Numeric Rating Scale 
OTC 
over-the-counter 
PBMC 
peripheral blood mononuclear cell 
PCV 
packed cell volume 
PGI-C 
Patient Global Impression of Change 
PGI-S 
Patient Global Impression of Severity 
PK 
pharmacokinetic 
PPP 
palmoplantar pustulosis 
PT 
preferred term 
QC 
quality control 
RBC 
red blood cell 
SAD 
single ascending dose 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
statistical analysis system 
SC 
subcutaneous/subcutaneously 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash 
Amendment 2 
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SD 
standard deviation 
SoA 
Schedule of Activities 
SOC 
system organ class 
SOP 
Standard Operating Procedure 
STIDAT 
Systemic Therapy Induced Diarrhea Assessment Tool 
t1/2 
terminal half-life 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 
TK 
toxicokinetic 
Tmax 
time to maximum observed concentration 
ULN 
upper limit of normal 
URTI 
upper respiratory tract infection 
W 
week 
WBC 
white blood cell  
WHO 
World Health Organization 
WOCBP 
woman of childbearing potential 
 
 
 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash 
Amendment 2 
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TABLE OF CONTENTS 
SPONSOR SIGNATURE PAGE ......................................................................................................................... 2 
INVESTIGATOR’S AGREEMENT ...................................................................................................................... 3 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE .......................................................................... 4 
ABBREVIATIONS .......................................................................................................................................... 13 
TABLE OF CONTENTS ................................................................................................................................... 16 
TABLE OF TABLES ........................................................................................................................................ 20 
TABLE OF FIGURES ...................................................................................................................................... 20 
STATEMENT OF COMPLIANCE .................................................................................................................... 21 
1 
PROTOCOL SUMMARY ........................................................................................................................ 22 
1.1 
Synopsis .................................................................................................................................... 22 
1.2 
Schema ...................................................................................................................................... 29 
1.3 
Schedule of Activities ................................................................................................................ 30 
2 
INTRODUCTION ................................................................................................................................... 35 
2.1 
Study Rationale ......................................................................................................................... 35 
2.1.1 
Acneiform Rash ............................................................................................................ 35 
2.1.2 
ANB019......................................................................................................................... 35 
2.1.3 
Study Rationale ............................................................................................................ 36 
2.2 
Background ............................................................................................................................... 36 
2.2.1 
Nonclinical Studies ....................................................................................................... 36 
2.2.2 
Clinical Studies ............................................................................................................. 37 
2.3 
Risk/Benefit Assessment ........................................................................................................... 37 
2.3.1 
Known Potential Risks .................................................................................................. 37 
2.3.2 
Known Potential Benefits ............................................................................................. 38 
2.3.3 
Assessment of Potential Risks and Benefits ................................................................. 38 
3 
OBJECTIVES AND ENDPOINTS ............................................................................................................. 39 
3.1 
Primary Objective and Endpoint ............................................................................................... 39 
3.2 
Secondary Objectives and Endpoints ........................................................................................ 39 
3.3 
Exploratory Objectives and Endpoints ...................................................................................... 40 
4 
STUDY DESIGN ..................................................................................................................................... 44 
4.1 
Overall Design ........................................................................................................................... 44 
4.2 
Modifications to Study Conduct due to the Coronavirus Disease 2019 (COVID-19) Pandemic 45 
4.3 
Scientific Rationale for Study Design ........................................................................................ 46 
4.4 
Justification for Dose ................................................................................................................ 46 
4.5 
End of Study Definition ............................................................................................................. 47 
5 
STUDY POPULATION ............................................................................................................................ 48 
5.1 
Inclusion Criteria ....................................................................................................................... 48 
5.2 
Exclusion Criteria....................................................................................................................... 49 
5.3 
Lifestyle Considerations ............................................................................................................ 52 
5.4 
Screen Failures .......................................................................................................................... 53 
5.5 
Strategies for Recruitment and Retention ................................................................................ 53 
6 
STUDY TREATMENT ............................................................................................................................. 54 
6.1 
Study Treatment Administration .............................................................................................. 54 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash 
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6.1.1 
Study Treatment Description ....................................................................................... 54 
6.1.2 
Dosing and Administration ........................................................................................... 54 
6.2 
Preparation/Handling/Storage/Accountability ......................................................................... 56 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................................................ 56 
6.4 
Study Treatment Compliance ................................................................................................... 57 
6.5 
Concomitant Therapy ............................................................................................................... 57 
6.5.1 
Permitted Therapies ..................................................................................................... 58 
6.5.2 
Prohibited Medications or Procedures ........................................................................ 58 
6.5.3 
Rescue Medication ....................................................................................................... 60 
6.6 
Dose Modification ..................................................................................................................... 60 
6.7 
Treatment After the End of the Study ...................................................................................... 60 
7 
STUDY TREATMENT DISCONTINUATION AND SUBJECT DISCONTINUATION/WITHDRAWAL ............. 61 
7.1 
Discontinuation of Study Treatment ........................................................................................ 61 
7.1.1 
Temporary Interruption ............................................................................................... 61 
7.1.2 
Re-Challenge ................................................................................................................ 61 
7.2 
Subject Discontinuation/Withdrawal from the Study .............................................................. 61 
7.3 
Lost to Follow-Up ...................................................................................................................... 62 
8 
STUDY ASSESSMENTS AND PROCEDURES ........................................................................................... 63 
8.1 
Efficacy Assessments ................................................................................................................ 63 
8.1.1 
Subject Assessments of Pruritus and Pain ................................................................... 63 
8.1.2 
Functional Assessment of Cancer Therapy - Epidermal Growth Factor Receptor 
Inhibitor 18 ................................................................................................................... 63 
8.1.3 
Patient Global Impression of Severity .......................................................................... 64 
8.1.4 
Patient Global Impression of Change ........................................................................... 64 
8.1.5 
Systemic Therapy Induced Diarrhea Assessment Tool ................................................ 64 
8.1.6 
Facial Investigator Global Assessment ......................................................................... 64 
8.1.7 
Investigator Global Assessment ................................................................................... 65 
8.1.8 
Facial Inflammatory Lesion Count ................................................................................ 65 
8.1.9 
Nail Folds with Paronychia ........................................................................................... 66 
8.1.10 Acneiform Rash – Common Terminology Criteria for Adverse Events ........................ 66 
8.1.11 MASCC EGFRi Skin Toxicity Tool ................................................................................... 67 
8.1.12 Paronychia, Dry Skin, Alopecia, and Pruritus COMMON TERMINOLOGY CRITERIA FOR 
ADVERSE EVENTS ......................................................................................................... 67 
8.1.13 Eastern Cooperative Oncology Group Performance STATUS ...................................... 69 
8.2 
Safety Assessments ................................................................................................................... 70 
8.2.1 
Adverse Events and Serious Adverse Events ............................................................... 70 
8.2.1.1 
Definition of Adverse Events ................................................. 70 
8.2.1.2 
Definition of Serious Adverse Events ..................................... 71 
8.2.1.3 
Classification of an Adverse Event ......................................... 72 
8.2.1.4 
Time Period and Frequency for Event Assessment and Follow-
Up ........................................................................................... 73 
8.2.1.5 
Adverse Event Reporting ....................................................... 74 
8.2.1.6 
Serious Adverse Event Reporting........................................... 74 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash 
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8.2.1.7 
Reporting Events to Subjects ................................................. 75 
8.2.1.8 
Reporting of Pregnancy ......................................................... 75 
8.2.1.9 
Treatment of Overdose ......................................................... 76 
8.2.2 
Height and Weight ....................................................................................................... 76 
8.2.3 
Chest X-ray ................................................................................................................... 76 
8.2.4 
Physical Examinations .................................................................................................. 77 
8.2.5 
Vital Signs ..................................................................................................................... 77 
8.2.6 
Electrocardiograms ...................................................................................................... 77 
8.2.7 
Clinical Safety Laboratory Assessments ....................................................................... 77 
8.3 
Other Assessments ................................................................................................................... 78 
8.3.1 
Photography ................................................................................................................. 78 
8.3.2 
Pharmacokinetics ......................................................................................................... 78 
8.3.3 
Immunogenicity Assessments ...................................................................................... 79 
8.3.4 
Biomarkers Analysis ..................................................................................................... 80 
9 
STATISTICAL CONSIDERATIONS ........................................................................................................... 81 
9.1 
Statistical Hypotheses ............................................................................................................... 81 
9.2 
Sample Size Determination ....................................................................................................... 81 
9.3 
Populations for Analyses ........................................................................................................... 81 
9.4 
Statistical Analyses .................................................................................................................... 82 
9.4.1 
General Approach ........................................................................................................ 82 
9.4.2 
Subject Disposition ....................................................................................................... 82 
9.4.3 
Baseline Descriptive Statistics ...................................................................................... 82 
9.4.4 
Concomitant Medication ............................................................................................. 83 
9.4.5 
Analysis of the Primary Efficacy Endpoint .................................................................... 83 
9.4.6 
Analysis of the Secondary Efficacy Endpoints .............................................................. 84 
9.4.6.1 
Continuous Endpoints ............................................................ 85 
9.4.6.2 
Categorical Endpoints ............................................................ 85 
9.4.7 
Analysis of the Exploratory Efficacy Endpoints ............................................................ 85 
9.4.8 
Safety Analyses ............................................................................................................ 87 
9.4.8.1 
Adverse Events and Serious Adverse Events ......................... 87 
9.4.8.2 
12-Lead Electrocardiogram, Vital Signs, and Clinical Safety 
Laboratory Tests .................................................................... 88 
9.4.9 
Pharmacokinetic Analyses ..................................................................................................... 88 
9.4.9.1 
Derivation of Pharmacokinetic Parameters ........................... 88 
9.4.9.2 
Pharmacokinetic Concentration Data Analysis ...................... 88 
9.4.9.3 
Pharmacokinetic Parameter Data Analysis ............................ 89 
9.4.9.4 
Population Pharmacokinetics Analysis .................................. 89 
9.4.10 Immunogenicity Analyses ............................................................................................ 89 
9.4.11 Biomarker Analyses ...................................................................................................... 89 
9.4.12 Planned Interim Analyses ............................................................................................. 89 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS .......................................... 90 
10.1 Regulatory, Ethical, and Study Oversight Considerations......................................................... 90 
10.1.1 Informed Consent Process ........................................................................................... 90 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash 
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10.1.1.1 
Consent/assent and Other Informational Documents Provided 
to subjects .............................................................................. 90 
10.1.1.2 
Consent Procedures and Documentation .............................. 90 
10.1.2 Study Discontinuation and Closure .............................................................................. 90 
10.1.3 Confidentiality and Privacy .......................................................................................... 91 
10.1.4 Future Use of Stored Specimens and Data .................................................................. 92 
10.1.5 Medical Monitor .......................................................................................................... 92 
10.1.6 Safety Oversight ........................................................................................................... 92 
10.1.7 Clinical Monitoring ....................................................................................................... 92 
10.1.8 Quality Assurance and Quality Control ........................................................................ 93 
10.1.9 Data Handling and Record Keeping.............................................................................. 93 
10.1.9.1 
Data Collection and Management Responsibilities ............... 93 
10.1.9.2 
Study Records Retention ....................................................... 95 
10.1.10 Protocol Deviations ...................................................................................................... 95 
10.1.11 Publication and Data Sharing Policy ............................................................................. 96 
10.1.12 Conflict of Interest Policy ............................................................................................. 96 
10.2 Additional Considerations ......................................................................................................... 96 
10.2.1 Ethics and Responsibility .............................................................................................. 96 
10.2.2 Amendment Policy ....................................................................................................... 96 
10.2.3 Insurance ...................................................................................................................... 97 
11 REFERENCES ........................................................................................................................................ 98 
12 APPENDICES ...................................................................................................................................... 100 
Appendix 1: Contraceptive Guidance and Collection of Pregnancy Information ............................. 100 
Appendix 2: Pruritus and Pain Numeric Rating Scales ...................................................................... 104 
Appendix 3: Functional Assessment of Cancer Therapy - Epidermal Growth Factor Receptor 
Inhibitor 18 .............................................................................................................................. 105 
Appendix 4: Patient-Global Impression of Severity .......................................................................... 106 
Appendix 5: Patient-Global Impression of Change ........................................................................... 107 
Appendix 6: Systemic Therapy Induced Diarrhea Assessment Tool ................................................. 108 
Appendix 7: Clinical Laboratory Tests ............................................................................................... 110 
 
 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash 
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TABLE OF TABLES 
Table 1: Schedule of Activities .................................................................................................................... 32 
Table 2: Study Treatment Details................................................................................................................ 54 
Table 3: List of Prohibited Medications and Procedures ............................................................................ 59 
Table 4: Facial Investigator Global Assessment Scale ................................................................................. 65 
Table 5: Investigator Global Assessment Scale ........................................................................................... 65 
Table 6: Definition of Inflammatory Lesions ............................................................................................... 66 
Table 7: Definition of Paronychia ................................................................................................................ 66 
Table 8: Grading of Acneiform Rash According to the Common Terminology Criteria for Adverse Events
 66 
Table 9: Grading of Acneiform Rash According to the MASCC EGFRi Skin Toxicity Tool ............................ 67 
Table 10: Grading of Paronychia According to Common Terminology Criteria for Adverse Events .......... 68 
Table 11: Grading of Dry Skin According to Common Terminology Criteria for Adverse Events ............... 68 
Table 12: Grading of Alopecia According to Common Terminology Criteria for Adverse Events .............. 68 
Table 13: Grading of Pruritus According to Common Terminology Criteria for Adverse Events ................ 68 
Table 14: Eastern Cooperative Oncology Group Performance Status ........................................................ 70 
Table 15: Pharmacokinetic Sample Collection and Time Points ................................................................. 79 
Table 16: Anti-Drug Antibodies Sample Collection and Time Points .......................................................... 80 
Table 17: Analysis Sets ................................................................................................................................ 81 
Table 18: Protocol-required Safety Laboratory Assessments by Central Laboratory ............................... 110 
 
TABLE OF FIGURES 
Figure 1: Study Schema ............................................................................................................................... 29 
 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
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STATEMENT OF COMPLIANCE 
The study will be conducted in accordance with the protocol, applicable International Council for 
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical 
Practice (GCP) guidelines, and applicable local laws and regulations. The investigator will assure that no 
planned deviation from, or changes to the protocol will take place without prior agreement from the 
IND Sponsor and documented approval from the Institutional Review Board (IRB)/Ethics Committee 
(EC), except where necessary to eliminate an immediate hazard(s) to the study subjects. All personnel 
involved in the conduct of this study have completed ICH GCP Training. 
The protocol, informed consent form(s) (ICFs), recruitment materials, and all subject materials will be 
submitted to the IRB/EC for review and approval. Approval of both the protocol and the consent form 
must be obtained before any subject is enrolled. Any amendment to the protocol will require review and 
approval by the IRB/EC before the changes are implemented to the study. In addition, all changes to the 
consent form will be IRB/EC-approved; a determination will be made regarding whether a new consent 
needs to be obtained from subjects who provided consent, using a previously approved consent form. 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
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1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS  
Title: 
A Phase 2a, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Efficacy and Safety of ANB019 in the Treatment of Acneiform 
Rash in Subjects with Neoplasm Receiving EGFRi or MEKi Therapy 
Short Title: 
Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated 
Acneiform Rash 
Study Description: 
This study is a Phase 2a, multicenter, randomized, double-blind, 
placebo-controlled study designed to evaluate the efficacy, safety, and 
tolerability of ANB019 in the treatment of acneiform rash in subjects with 
neoplasm receiving epidermal growth factor receptor inhibitor (EGFRi) or 
mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK) 
kinase inhibitor (MEKi). This study will also characterize the pharmacokinetic 
(PK) profile of ANB019 and explore the immune response to ANB019 in 
subjects with EGFRi/MEKi-associated acneiform rash. 
Written informed consent will be obtained from each subject prior to 
initiating any study-related procedures. 
Approximately 45 adult male and female subjects, aged 18 to 75 years, will 
be randomized in this study. To be eligible for the study, subjects must be 
receiving oral or injectable commercially available EGFRi or MEKi therapy at 
the Screening and Day 1 visits. Subjects can enter the initial screening 
regardless of their current acneiform rash status and severity (as described 
in Section 5.1). However, at the Screening Part 2 and at Day 1 visit, subjects 
must have 
lesions on the face. Randomization will be stratified based on acneiform 
rash CTCAE grade at Baseline and therapy the subject is receiving (EGFRi vs 
MEKi).  
Subjects who enter the screening period without an acneiform rash or with 
an acneiform rash severity that does not meet the requirements of Inclusion 
(refer to Section 5.1) may remain in screening for up to 6 months and be 
reevaluated if/when an acneiform rash develops or worsens as long as they 
remain on EGFRi or MEKi therapy. Once the acneiform rash severity meets 
the requirements of Inclusion Criterion 3, a last screening visit (Screening 
Part 2; refer to Section 1.3) must be performed, within 15 days prior to Day 
1, ideally within 1 week. 
During the treatment period, eligible subjects will be randomized (2:1) to 
receive either ANB019 or placebo, subcutaneously (SC) administered at 
4 time points. On Day 1, the subjects will receive a 400-mg dose of ANB019 
or placebo. On Days 29, 57, and 85, the subjects will receive a 200-mg dose 
of ANB019 or placebo.  

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
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For scheduled study visits, subjects will come to the study center on up to 
9 occasions to monitor changes in disease activity, PK (if applicable), safety, 
and tolerability: screening (depending on subject acneiform rash status, the 
screening visit may be planned either as 1 visit or 2 separate visits) and 
Days 1, 15, 29, 57, 85, 113 (end of treatment [EOT]/early termination [ET]), 
and 169 (end of study [EOS]). All procedures will be conducted in 
accordance with the Schedule of Activities (SoA) in Section 1.3. Of note, the 
primary endpoint will be evaluated on Day 57 (Week 8).  
Disease activity will be evaluated for all subjects using facial inflammatory 
lesion count, acneiform rash CTCAE grading, acneiform rash modified 
Multinational Association for Supportive Care in Cancer (MASCC) EGFRi Skin 
Toxicity Tool (MESTT) grading, Investigator Global Assessment (IGA), facial 
IGA, pruritus Numeric Rating Scale (NRS), pain NRS, Patient Global 
Impression of Severity (PGI-S), Patient Global Impression of Change (PGI-C), 
number of nail folds with paronychia, and paronychia, dry skin, alopecia, and 
pruritus CTCAE grading. The subject’s quality of life will be assessed using 
the Functional Assessment of Cancer Therapy - Epidermal Growth Factor 
Receptor Inhibitor 18 (FACT-EGFRi-18). Subject’s gastrointestinal 
inflammation will be evaluated using the Systemic Therapy Induced Diarrhea 
Assessment Tool (STIDAT). Subject’s level of functioning and daily living 
abilities will be evaluated to confirm eligibility using the Eastern Cooperative 
Oncology Group (ECOG) performance status. 
In addition, standardized photographs of the face will be taken at the time 
points specified in the SoA to record inflammatory lesions for lesion counts 
analysis as supporting information for efficacy analyses. 
Safety assessments will include adverse event (AE)/serious adverse event 
(SAE) monitoring, vital signs, physical examination, electrocardiograms 
(ECGs), and clinical laboratory tests (hematology, biochemistry, and 
urinalysis). 
Blood samples to determine PK and immunogenicity (presence of anti-drug 
antibodies [ADAs] to ANB019) will be collected on Day 1 before the 
administration of the study treatment and at the other time points specified 
in the SoA (see Section 1.3). Any remaining samples collected for PK and 
immunogenicity endpoints may be retained for assay method development, 
troubleshooting, or validation. The samples will not be used for any type of 
genetic analyses. Tape strips for biomarker analysis will be collected at the 
time points specified in the SoA.  
Interim analyses (IAs) may be performed during the treatment period for 
assessment of all primary and secondary efficacy endpoints, and evaluation 
of all safety data available. 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
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Objectives: 
Primary Objective:  
 To assess the efficacy of ANB019 compared with placebo in reduction of 
acneiform rash in subjects receiving EGFRi or MEKi therapy as measured 
by facial inflammatory lesion count  
 
Secondary Objectives:  
 To determine the effect of ANB019 compared with placebo on acneiform 
rash signs and symptoms, and quality of life in subjects receiving EGFRi 
or MEKi therapy 
 To assess the safety and tolerability of ANB019 in subjects with 
acneiform rash receiving EGFRi or MEKi therapy 
 
Exploratory Objectives: 
 To further evaluate the effect of ANB019 compared with placebo on 
acneiform rash signs and symptoms, and quality of life in subjects 
receiving EGFRi or MEKi therapy 
 To explore the effect of ANB019 on other EGFRi/MEKi adverse drug 
reactions (paronychia, dry skin, alopecia, and pruritus) 
 To assess the effect of ANB019 on gastrointestinal inflammation in 
subjects with acneiform rash receiving EGFRi or MEKi therapy 
 To explore the effect of ANB019 on cutaneous biomarkers 
 To explore the effect of ANB019 on acneiform rash as measured by facial 
inflammatory lesion count using standardized photographs 
 To describe the PK profile of ANB019 in subjects with acneiform rash 
receiving EGFRi or MEKi therapy 
 To test for immunogenicity to ANB019 
Endpoints: 
Primary Endpoint: 
 Change from Baseline in facial inflammatory lesion count (papules and 
pustules) at Week 8  
 
Secondary Endpoints:  
 Percent change from Baseline in facial inflammatory lesion count 
(papules and pustules) at Week 8 
 Proportion of subjects with an improvement of at least 1 grade from 
Baseline in acneiform rash CTCAE grading scale at Week 8 
 Time to first response of 1 grade improvement from Baseline on the 
acneiform rash CTCAE grading scale  
 Proportion of subjects with an improvement of at least 1 grade from 
Baseline in acneiform rash modified MESTT grading scale (total score) at 
Week 8 
 Time to first response of 1 grade improvement from Baseline on the 
acneiform rash modified MESTT grading scale (total score) 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
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25 
Proportion of subjects with an improvement of at least 1 grade from 
Baseline in acneiform rash modified MESTT grading scale (facial 
assessment) at Week 8 
 Time to first response of 1 grade improvement from Baseline on the 
acneiform rash modified MESTT grading scale (facial assessment) 
 Change from Baseline in pruritus NRS at Week 8 
 Percent change from Baseline in pruritus NRS at Week 8 
 Change from Baseline in pain NRS at Week 8 
 Percent change from Baseline in pain NRS at Week 8 
 Change from Baseline in FACT-EGFRi-18 at Week 8 
 Incidence of AEs, SAEs, and AEs leading to withdrawals, as well as 
changes in vital signs, clinical laboratory parameters (hematology, 
biochemistry, and urinalysis), and 12-lead ECGs 
 
Exploratory Endpoints:  
 Change from Baseline in facial inflammatory lesion count (papules and 
pustules) at each visit other than Week 8 
 Percent change from Baseline in facial inflammatory lesion count 
(papules and pustules) at each visit other than Week 8 
 Change from Baseline in facial papule count at each visit 
 Percent change from Baseline in facial papule count at each visit 
 Change from Baseline in facial pustule count at each visit 
 Percent change from Baseline in facial pustule count at each visit 
 Proportion of subjects with an improvement of at least 1 grade from 
Baseline in acneiform rash CTCAE grading scale at each visit other than 
Week 8 
 Proportion of subjects with an improvement of at least 1 grade from 
Baseline in acneiform rash modified MESTT grading scale (total score) at 
each visit other than Week 8 
 Change from Baseline in pruritus NRS at each visit other than Week 8
 Percent change from Baseline in pruritus NRS at each visit other than 
Week 8 
 Change from Baseline in pain NRS at each visit other than Week 8 
 Percent change from Baseline in pain NRS at each visit other than 
Week 8 
 Change from Baseline in FACT-EGFRi-18 at each visit other than Week 8  
 Proportion of subjects achieving an improvement of 50% from Baseline 
in facial inflammatory lesion count (papules and pustules) at each visit 
 Proportion of subjects achieving an improvement of 75% from Baseline 
in facial inflammatory facial lesion count (papules and pustules) at each 
visit 
 Change from Baseline in acneiform rash CTCAE grading scale at each visit 
 Change from Baseline in acneiform rash modified MESTT grading scale 
(total score) at each visit 
 Percent change from Baseline in acneiform rash modified MESTT grading 
scale (total score) at each visit

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
Amendment 2
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26 
Change from Baseline in acneiform rash modified MESTT grading scale 
(facial assessment) at each visit 
 Change from Baseline in acneiform rash modified MESTT grading scale 
(back assessment) at each visit 
 Change from Baseline in acneiform rash modified MESTT grading scale 
(scalp assessment) at each visit 
 Change from Baseline in acneiform rash modified MESTT grading scale 
(chest assessment) at each visit 
 Change from Baseline in IGA at each visit 
 Proportion of subjects achieving an IGA of clear (0) or almost clear (1) at 
each visit 
 Proportion of subjects with at least 2-point decrease in IGA at each visit 
 Change from Baseline in facial IGA at each visit 
 Proportion of subjects achieving a facial IGA of none (0) or minimal (1) at 
each visit 
 Proportion of subjects with at least 2-point decrease in facial IGA at each 
visit 
 Proportion of subjects with at least 3-point decrease in pruritus NRS at 
each visit for subjects with a Baseline pruritus NRS of at least 3  
 Proportion of subjects with at least 4-point decrease in pruritus NRS at 
each visit for subjects with a Baseline pruritus NRS of at least 4 
 Proportion of subjects with at least 3-point decrease in pain NRS at each 
visit for subjects with a Baseline pain NRS of at least 3  
 Proportion of subjects with at least 4-point decrease in pain NRS at each 
visit for subjects with a Baseline pain NRS of at least 4 
 Proportion of subjects in each response category for the PGI-S and PGI-C 
at each visit 
 Proportion of subjects achieving mild or clear skin according to the PGI-S 
at each visit 
 Proportion of subjects achieving improvement (a little better, much 
better or very much better) according to the PGI-C at each visit 
 Proportion of subjects receiving rescue medication from Week 4 through 
Week 24 
 Proportion of subjects that do not require a dose reduction of EGFRi or 
MEKi therapy due to acneiform rash at each visit 
 Proportion of subjects that do not require cessation of EGFRi or MEKi 
therapy due to acneiform rash at each visit 
 Change from Baseline in number of nail folds with paronychia at each 
visit 
 Proportion of subjects with paronychia, dry skin, alopecia, and pruritus of 
Grade 0 or 1 as per CTCAE grading scale at each visit 
 Proportion of subjects with an improvement of at least 1 grade from 
Baseline in acneiform rash modified MESTT grading scale (facial 
assessment) at each visit 
 Percent change from Baseline in facial inflammatory lesion count 
(papules and pustules) at each visit 

Efficacy and Safety of ANB019 in Subjects with EGFRi/MEKi-Associated Acneiform Rash
Amendment 2
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27 
Proportion of subjects with an improvement of at least 1 grade from 
Baseline in acneiform rash modified MESTT grading scale (back 
assessment) at each visit 
 Proportion of subjects with an improvement of at least 1 grade from 
Baseline in acneiform rash modified MESTT grading scale (scalp 
assessment) at each visit 
 Proportion of subjects with an improvement of at least 1 grade from 
Baseline in acneiform rash modified MESTT grading scale (chest 
assessment) at each visit 
 Time to first response of 1 grade improvement from Baseline on the 
acneiform rash modified MESTT grading scale (back assessment) 
 Time to first response of 1 grade improvement from Baseline on the 
acneiform rash modified MESTT grading scale (scalp assessment) 
 Time to first response of 1 grade improvement from Baseline on the 
acneiform rash modified MESTT grading scale (chest assessment) 
 Change from Baseline in STIDAT at each visit 
 Percent change from Baseline in STIDAT at each visit 
 Skin tape strip biomarkers analysis including, but not limited to, IL-36 and 
Th-17 
 Change from Baseline in inflammatory lesion counts as determined by 
standardized photographs at each visit 
 Percent change from Baseline in inflammatory lesion counts as 
determined by standardized photographs at each visit 
 Serum concentration following ANB019 administration and other 
parameters as appropriate will be determined to describe the PK profile 
of ANB019  
 Presence of ADA to ANB019 
Study Population: 
Approximately 45 adult male and female subjects, aged 18 to 75 years, will 
be randomized in this study. To be eligible for the study, subjects must be 
receiving oral or injectable commercially available EGFRi or MEKi therapy at 
the Screening and Day 1 visits. Subjects can enter the initial screening 
regardless of their current acneiform rash status and severity (as described 
in Section 5.1). However, at the Screening Part 2 and at Day 1 visit, subjects 
must have 
lesions on the face. Randomization will be stratified based on acneiform 
rash CTCAE grade at Baseline and the therapy the subject is receiving (EGFRi 
vs MEKi).  
Phase: 
2a 
Description of Study 
Sites Enrolling 
Subjects: 
Approximately 20 study centers located in North America and Europe are 
expected to participate in this study.  

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Description of Study 
Treatments: 
ANB019 will be provided in a glass vial as a sterile, colorless to yellow, and 
clear to slightly opalescent solution for injection. 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. 
During the treatment period, eligible subjects will be randomized (2:1) to 
receive either ANB019 or placebo, SC administered at 4 time points: 
 Day 1: 400-mg dose of ANB019 or placebo (administered as 2 SC 
injections of ANB019 at 200 mg each or placebo) 
 Days 29, 57, and 85: 200-mg dose of ANB019 or placebo 
Of note, the placebo will be administered via SC injection(s) on the same 
schedule and in the same volumes as ANB019. 
Rescue Medication: 
A subject who has worsening or no improvement in facial inflammatory 
lesion count (papules and pustules), and/or worsening or no improvement 
of pain and/or itch, per the pruritus and pain NRSs will be eligible to receive 
rescue medication (ie, systemic antibiotics and low/medium potency topical 
corticosteroids [eg, hydrocortisone > 1%, triamcinolone 0.1%]) starting at 
Day 29 (Week 4).  
Study Duration: 
The estimated study duration is approximately 20 months from first subject 
screened until database lock. 
Subject Duration: 
The expected study duration per subject is up to approximately 12 months 
from the screening to last visit. The screening period may last up to 
6 months depending on acneiform rash status and severity: an initial 
Screening will be planned for subjects without an acneiform rash or with an 
acneiform rash severity that does not meet the requirements of Inclusion 
Criterion 3 (refer to Section 5.1); once the acneiform rash severity meets the 
requirements of Inclusion Criterion 3, a last screening visit must be 
performed within 15 days prior to Day 1 (ideally within 1 week). The 
screening period will be followed by a 16-week treatment period and an 
8-week follow-up period). 

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1.2
SCHEMA
Figure 1: Study Schema
Abbreviations: D, day; SC, subcutaneously; W, week. 
a Depending on subject acneiform rash status, the screening visit may be planned either as 1 visit (for subjects who 
already have an acneiform rash) or as 2 separate visits (for subjects not having an acneiform rash at the initial 
screening visit): Screening Part 1 and Screening Part 2. Screening Part 2 will only be performed once subject is
having an acneiform rash. Screening Part 2 assessments must be performed within 15 days prior to Day 1 (ideally 
within 1 week) and safety evaluation results required to confirm eligibility must be obtained before randomization.
b During the treatment period, subjects will receive either ANB019 or placebo, SC administered at 4 time points: 
400-mg dose of ANB019 or placebo on Day 1; 200-mg dose of ANB019 or placebo on Days 29, 57, and 85.
c The primary endpoint will be evaluated on Day 57 (Week 8). 

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1.3 
SCHEDULE OF ACTIVITIES 
Written informed consent will be obtained from each subject prior to initiating any study-related 
procedures.  
To be eligible for the study, subjects must be receiving oral or injectable commercially available EGFRi or 
MEKi therapy at the Screening and Day 1 visits. Subjects can enter the initial screening regardless of 
their current acneiform rash status and severity (as described in Section 5.1). However, at the Screening 
Part 2 and at the Day 1 visit, subjects must have 
.  
The screening period may last up to 6 months depending on acneiform rash status and severity: an 
initial Screening will be planned for subjects without an acneiform rash or with an acneiform rash 
severity that does not meet the requirements of Inclusion Criterion 3 (refer to Section 5.1); once the 
acneiform rash severity meets the requirements of Inclusion Criterion 3, a last screening visit must be 
performed within 15 days prior to Day 1 (ideally within 1 week). The screening period will be followed by 
a 16-week treatment period and an 8-week follow-up period). The screening period must not last for 
more than 6 months. 
The screening evaluation will be performed according to the inclusion and exclusion criteria. If the 
subject fulfills all inclusion criteria and no exclusion criteria, he or she may be included in the study.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Table 1 provides a description of the procedures to be performed at each visit during the study.  
Of note, the primary endpoint will be evaluated on Day 57 (Week 8). 
Unless specified otherwise, the study assessments scheduled on Days 1, 15, 29, 57, and 85 must be 
performed before study treatment administration. The recommended order for performing the study 
assessments is as follows (applicable to all visits); however, subject-reported questionnaires and efficacy 
assessments must be conducted before other assessments:  
• Subject-reported questionnaires 
• Efficacy assessments (global assessments [eg, CTCAE, modified MESTT, IGA] should be performed 
before more quantitative assessments [eg, lesion count, nail folds with paronychia])  
• Vital signs 
• Physical examination 
• ECG 
• Photography (may be performed any time predose provided it is before tape stripping)
• Blood sample collections (for safety, PK, and ADA evaluations) do not have to follow a specific 
order, provided that they are performed after ECG 
• Tape stripping 
The Coronavirus Disease 2019 (COVID-19) pandemic may impact the ability to adhere to the study 
procedures described in Table 1 due to challenges that include, but are not limited to, subject 
preferences, center closures, travel restrictions, and quarantines. Please refer to Section 4.2 for more 
details on allowable, as necessary, modifications to the protocol due to COVID-19 restrictions, including 
conducting optional home visits when on-site study visits are considered not feasible. Such 
modifications in study conduct always must be in accordance with local regulations/mandates.  
 
 
 

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f Refer to Section 8.2.3 for details regarding the chest X-ray. A chest X-ray (both posterior-anterior and lateral views) must be done during the screening prior 
to Day 1 unless the report from a chest X-ray or a chest CT scan, done within 6 months before the first administration of study drug, and read by a qualified 
radiologist is already available.  
g Refer to Section 8.2.4 for details regarding the complete physical examination. 
h Refer to Section 8.2.5 for details and instructions regarding vital signs. 
i Refer to Section 8.2.6 for details and instructions regarding the ECG. In addition to the time points specified in the SoA, ECGs may be performed at any time 
during the study if, in the opinion of the investigator, it is clinically warranted. 
j The FSH testing is performed for postmenopausal women with at least 12 months of amenorrhea without an alternative medical cause to confirm they meet 
not of childbearing potential criteria. Additional pregnancy testing may be performed whenever a menstrual cycle is missed or when pregnancy is otherwise 
suspected. Local laboratory tests will also be allowed at Screening for TB and viral serology testing. Refer to Appendix 7 for details and instructions regarding 
clinical laboratory parameters and refer to Appendix 1 for the WOCBP definition. 
k Blood sample for PK will be collected prior to SC administration. In addition, samples for PK will also be collected on Days 15, 29, 57, 85, 113, and 169 (refer to 
Table 15). 
l Refer to Section 8.1 for details and instructions regarding ECOG, facial inflammatory lesion count, acneiform rash CTCAE, acneiform rash modified MESTT, IGA, 
facial IGA, pain and pruritus NRSs, FACT-EGFRi-18, PGI-S, PGI-C, nail folds with paronychia, paronychia, dry skin, alopecia, and pruritus CTCAE grading, and 
STIDAT. The IGA/facial IGA assessment must be performed prior to the facial lesion count assessment. PGI-C is not to be performed at Day 1. 
m Tape strips will be collected on Day 1, Day 57, and Day 113 from nonlesional and lesional skin. 
n During the treatment period, subjects will receive either ANB019 or placebo, SC administered at 4 time points: 400-mg dose of ANB019 or placebo on Day 1; 
200 mg dose of ANB019 or placebo on Days 29, 57, and 85. 
o At screening, prior medications should be reviewed and documented. Refer to Section 6.5. 

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2 
INTRODUCTION 
2.1 
STUDY RATIONALE  
This study is designed to evaluate the efficacy and safety of multiple doses of ANB019 in the treatment 
of acneiform rash in subjects with neoplasm who are currently receiving an EGFRi or MEKi therapy. 
2.1.1 
ACNEIFORM RASH  
Targeted drugs and biologics that inhibit the activity of the Epidermal Growth Factor Receptor (EGFR) 
and MAP/ERK kinase (MEK) are frequently used for the treatment of neoplasms, including solid tumors 
such as lung, head and neck, colon, and pancreatic cancers. They offer several advantages over less 
specific chemotherapy. However, they often induce cutaneous toxicities as EGFR and MEK are highly 
expressed in the skin (Yano 2003, Manousaridis 2013). One of the most frequently seen cutaneous AEs 
of EGFRi is an acneiform rash (also called papulopustular rash) that occurs in up to 85% of patients 
(Lacouture 2018, Segaert 2005). This dermatologic AE is also one of the most frequently observed 
following treatment with MEKi, likely because MEK is a downstream mediator of EGFR (Manousaridis 
2013). This eruption usually begins on the face a few weeks after initiation of EGFRi/MEKi therapy, can 
be extremely painful and pruritic, and can spread over to the entire body (Lacouture 2018, Manousaridis 
2013). The impact of targeted therapies, such as EGFRi/MEKi, on quality of life can be very important 
and has been reported to be higher than the impact of nontargeted therapies, such as chemotherapy 
(Rosen 2013). Moreover, the severity of the acneiform rash often requires modification of the neoplasm 
treatment regimen (Lacouture 2018). 
The pathophysiology of the EGFRi/MEKi-induced acneiform rash is not fully understood. Studies have 
shown that the inflammatory infiltrate of the skin rash induced by EGFRi is composed of T cells, dendritic 
cells, neutrophils, macrophages, and mast cells (Lichtenberger 2013). This is also accompanied by an 
increase in the expression of several proinflammatory chemokines such as CCL2, CCL5, CCL27, and 
CXCL14, and a decrease in antibacterial peptides that favors bacterial proliferation (Lichtenberger 2013). 
Recently, increased expression of interleukin (IL)-
-8 has been reported in lesions of acneiform 
eruption associated with EGFR/MEK inhibition (Satoh 2020).  
Current treatments for the acneiform rash induced by EGFRi/MEKi include topical and systemic 
antibiotics and corticosteroids, but the efficacy of these treatments is limited (Lacouture 2011, 
Farahnik 2016, Manousaridis 2013). In severe cases (eg, acneiform rash of Grade 2 or 3 as per CTCAE 
grading), dose reduction or cessation of EGFRi/MEKi may be required despite the use of antibiotics and 
corticosteroids (Boone 2007, Manousaridis 2013). There is a definite need for more efficacious and 
specific treatments for the management of acneiform rash induced by EGFRi/MEKi. 
2.1.2 
ANB019 
ANB019 is a high-affinity, humanized, immunoglobulin G4 (IgG4) monoclonal antibody (mAb) that 
specifically binds IL-36 receptor (IL-36R) and antagonizes IL-36 signaling. The IL-36 cytokines (IL-
IL-
-
-36R to initiate signaling events leading to proinflammatory responses. 
Interleukin 36 signaling is counter-balanced by IL-36R antagonist (IL-36Ra), an IL-36 receptor antagonist 
that binds to IL-36R and competes with activity of IL-36 cytokines. 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 IL-36 pathway activation.  
ANB019 is currently being studied as a potential first-in-class therapy for generalized pustular psoriasis 
(GPP), palmoplantar pustulosis (PPP), and other inflammatory diseases where the IL-36 pathway might 

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play a pathogenic role. Of note, generalized pustular psoriasis is characterized by a very extensive 
pustular rash.  
2.1.3 
STUDY RATIONALE  
It has recently been shown that IL-
and MEKi (Satoh 2020). 
Gene expression profiling using biopsies from patients presenting the acneiform rash has shown an 
increase in expression of IL-
and IL-8. Interleukin-36 is known to induce the production of IL-8, a 
potent chemotactic factor for neutrophils. This could explain the presence of pustules in the acneiform 
rash. Interestingly, administration of an anti-IL-8 antibody has been reported to suppress the acneiform 
rash induced by SC injection of an anti-EGFR monoclonal antibody in healthy volunteers 
(Bangsgaard 2012).  
The importance of the IL-36 pathway in the pathophysiology of the acneiform rash and the 
improvement induced by anti-IL-8 antibodies in the healthy volunteer model of acneiform eruption 
strongly suggest that ANB019 could improve or even suppress the acneiform rash induced by 
EGFRi/MEKi. Therefore, inhibition of IL-
-36R with ANB019 may provide a 
novel strategy to control the intense inflammatory reaction of acneiform rash induced by EGFRi/MEKi 
therapy in patients with neoplasms. 
2.2 
BACKGROUND  
2.2.1 
NONCLINICAL STUDIES  
ANB019 exhibits strong inhibitory activity for human as well as cynomolgus monkey IL-36R (cyIL-36R) 
cell populations. 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 cyIL-36R (dissociation constant [KD] of 67.9 ± 31.4 pM 
and 80.0 ± 49.6 pM, respectively), but not with mouse or rat IL-36R. 
 In primary human and cynomolgus monkey cell populations, keratinocytes, peripheral blood 
mononuclear cells (PBMCs), and human whole blood, ANB019 inhibited IL-36R mediated release 
of IL-8. 
 The terminal half-life (t1/2) of ANB019 in cynomolgus monkeys was 304 hours after single 
intravenous (IV) dose administration, and 310 hours after a single SC dose administration at 
10 mg/kg, with bioavailability approximately 76% consistent with the anticipated PK 
characteristics for a human IgG4 scaffold mAb in the cynomolgus monkey. 
 Repeat-dose, Good Laboratory Practice (GLP) toxicity and toxicokinetic (TK) 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 cynomolgus monkeys; the latter being consistent with the mechanism of action of an 
immune-modulator in cynomolgus monkeys (Dubey 2002). Weekly administrations of 
vehicle-control article, 30 mg/kg/dose ANB019 via SC injection, or 60 mg/kg/dose ANB019 via SC 
or IV bolus injection, to male and female sexually mature cynomolgus monkeys during the 
26-week toxicity and TK study was well tolerated. ANB019-related effects were limited to a low 
incidence of liquid feces not considered AEs for animals administered 60 mg/kg/dose IV. Thus, the 
no observed adverse effect level (NOAEL) is 60 mg/kg/dose administered by SC or IV injection. 

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These data provide a strong scientific rationale for advancing ANB019 through clinical development. 
A detailed description of the physical, chemical, and pharmaceutical properties of ANB019 and 
nonclinical studies is provided in the Investigator’s Brochure (IB). 
2.2.2 
CLINICAL STUDIES  
Currently, two clinical studies (ANB019-001 and ANB019-005) have been completed. Study ANB019-001 
was a Phase 1, first-in-human, single ascending dose (SAD) and multiple ascending dose (MAD) study in 
healthy volunteers and in subjects with psoriasis. Study ANB019-005 was a Phase 1, ethno-bridging 
study, a single-dose safety, tolerability, PK, and immunogenicity study of ANB019 in healthy Japanese 
and Caucasian subjects. A detailed description of the safety and tolerability, and PK/pharmacodynamic 
(PD) results of these two Phase 1 clinical studies is provided in the IB. 
In addition, two Phase 2a studies (ANB019-002 and ANB019-003) to evaluate clinical activity and safety 
of ANB019 in GPP and PPP are completed and ongoing, respectively. Study ANB019-002 was a single-
arm, multiple-dose study to be conducted in subjects with active GPP. Study ANB019-003 was a 
randomized, placebo-controlled, multiple-dose study to be conducted in subjects with PPP. 
2.3 
RISK/BENEFIT ASSESSMENT  
2.3.1 
KNOWN POTENTIAL RISKS  
No major toxicities were observed in the 4-week repeat-dose toxicity study in cynomolgus monkeys. The 
main finding consisted of minor, injection site reactions associated with the SC route of administration 
and not considered AEs. 
In cynomolgus monkeys, 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 observation 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. During the 26-week repeat-dose toxicity study, 
ANB019-related effects were limited to a low incidence of liquid feces. In the monkeys, the increased 
incidence of protozoa, nonformed feces, and prolapsed rectum were not considered AEs as they 
responded to veterinarian intervention. In humans, 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. 
In the ANB019-001 study in healthy adults, single doses of ANB019 up to 750 mg administered by IV 
infusion or SC injection to 32 healthy adults in the SAD part of the Phase 1 study were generally well 
tolerated with a similar number of treatment-emergent adverse events (TEAEs) reported in subjects 
receiving ANB019 or placebo, 29 subjects (81%) and 11 subjects (92%), respectively. The most frequently 
reported AEs were upper respiratory tract infection (URTI) (10 [28%] ANB019; 6 [50%] placebo), 

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headache (10 [28%] ANB019; 3 [25%] placebo), and viral URTI (4 [11%] ANB019; 1 [8%] placebo). 
Additionally, multiple doses of ANB019 up to 300 mg administered by IV infusion once weekly for 4 
weeks to 18 healthy adults were also well tolerated. Overall, TEAEs occurred in 16 subjects (89%) 
receiving ANB019 and in 3 subjects (50%) receiving the placebo. The most common AEs were headache 
(7 [39%] ANB019; 1 [17%] placebo) and URTI (3 [17%] ANB019; 1 [17%] placebo). 
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%]). 
To date, 1 SAE of sepsis was reported in the completed ANB019-002 study in subjects with GPP; the SAE 
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 subject recovery. Further details of ANB019 clinical studies are in the IB. 
As allergic or anaphylactic reactions may occur in any subjects treated with mAbs, subjects should be 
observed during study drug administration and for a period of 30 mins after each dose administration. 
Subjects with true allergic/anaphylactic reactions should not receive further doses of the monoclonal 
antibody. Symptoms of an apparent allergic reaction to the drug, also known as ‘cytokine release 
syndrome’, 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. 
2.3.2 
KNOWN POTENTIAL BENEFITS  
Subjects with EGFRi/MEKi-associated acneiform rash may or may not receive direct benefit from 
participating in this study. An improvement in the acneiform rash as a result of participating in the 
study, may be observed if subjects are randomized to the active study treatment.  
Participation in this study also may help generate future benefit for larger groups of patients with 
EGFRi/MEKi-associated acneiform rash if ANB019 proves to be successful in treating this manifestation.  
2.3.3 
ASSESSMENT OF POTENTIAL RISKS AND BENEFITS 
All quality, pharmacology and toxicology data, and satisfactory safety and tolerability data 
demonstrated in nonclinical and clinical studies are considered sufficient to expect a positive 
benefit/risk ratio for the treatment of EGFRi/MEKi-associated acneiform rash with ANB019, and 
therefore to initiate this study. 
The risk to subjects in this study will be minimized by compliance with the eligibility criteria, proper 
study design, and close monitoring. 

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Change from Baseline in acneiform rash modified MESTT 
grading scale (facial assessment) at each visit 
 
Change from Baseline in acneiform rash modified MESTT 
grading scale (back assessment) at each visit 
 
Change from Baseline in acneiform rash modified MESTT 
grading scale (scalp assessment) at each visit 
 
Change from Baseline in acneiform rash modified MESTT 
grading scale (chest assessment) at each visit 
 
Change from Baseline in IGA at each visit 
 
Proportion of subjects achieving an IGA of none (0) or 
almost minimal (1) at each visit 
 
Proportion of subjects with at least 2-point decrease in 
IGA at each visit 
 
Change from Baseline in facial IGA at each visit 
 
Proportion of subjects achieving a facial IGA of none (0) 
or minimal (1) at each visit 
 
Proportion of subjects with at least 2-point decrease in 
facial IGA at each visit  
 
Proportion of subjects with at least 3-point decrease in 
pruritus NRS at each visit for subjects with a Baseline 
pruritus NRS of at least 3  
 
Proportion of subjects with at least 4-point decrease in 
pruritus NRS at each visit for subjects with a Baseline 
pruritus NRS of at least 4 
 
Proportion of subjects with at least 3-point decrease in 
pain NRS at each visit for subjects with a Baseline pain 
NRS of at least 3  
 
Proportion of subjects with at least 4-point decrease in 
pain NRS at each visit for subjects with a Baseline pain 
NRS of at least 4 
 
Proportion of subjects in each response category for the 
PGI-S and PGI-C at each visit  
 
Proportion of subjects achieving mild or clear skin 
according to the PGI-S at each visit 
 
Proportion of subjects achieving improvement (a little 
better, much better, or very much better) according to 
the PGI-C at each visit 
 
Proportion of subjects receiving rescue medication from 
Week 4 through Week 24  
 
Proportion of subjects that do not require a dose 
reduction of EGFRi or MEKi therapy due to acneiform 
rash at each visit 
 
Proportion of subjects that do not require cessation of 
EGFRi or MEKi therapy due to acneiform rash at each 
visit 
 
Proportion of subjects with an improvement of at least 1 
grade from Baseline in acneiform rash modified MESTT 

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4 
STUDY DESIGN  
4.1 
OVERALL DESIGN 
This study is a Phase 2a, multicenter, randomized, double-blind, placebo-controlled study designed to 
evaluate the efficacy, safety, and tolerability of ANB019 in the treatment of acneiform rash in subjects 
with neoplasm receiving EGFRi or MEKi. This study will also characterize the PK profile of ANB019 and 
explore the immune response to ANB019 in subjects with EGFRi/MEKi-associated acneiform rash. 
Written informed consent will be obtained from each subject prior to initiating any study-related 
procedures.  
Approximately 45 adult male and female subjects, aged 18 to 75 years, will be randomized in this study. 
To be eligible for the study, subjects must be receiving oral or injectable commercially available EGFRi or 
MEKi therapy at the Screening and Day 1 visits. Subjects can enter the initial screening regardless of   
their current acneiform rash status and severity (as described in Section 5.1). However, at the Screening 
Part 2 and at Day 1, subjects must have an acneiform rash of Grade 
20 inflammatory lesions on the face. Randomization will be stratified based on acneiform rash CTCAE 
grade at Baseline and therapy the subject is receiving (EGFRi vs MEKi).  
The expected study duration per subject is up to approximately 12 months from the screening to last 
visit. Subjects who enter the screening period without an acneiform rash or with an acneiform rash 
severity that does not meet the requirements of Inclusion Criterion 3 (refer to Section 5.1) may remain 
in Screening for up to 6 months and be reevaluated if/when an acneiform rash develops or worsens as 
long as they remain on EGFRi or MEKi therapy. Once the acneiform rash severity meets the 
requirements of Inclusion Criterion 3, a last screening visit (Screening Part 2; refer to Section 1.3) must 
be performed, within 15 days prior to Day 1, ideally within 1 week. The screening period will be followed 
by a 16-week treatment period and an 8-week follow-up period. 
During the treatment period, eligible subjects will be randomized (2:1) to receive either ANB019 or 
placebo, SC administered at 4 time points. On Day 1, the subjects will receive a 400-mg dose of ANB019 
or placebo. On Days 29, 57, and 85, the subjects will receive a 200-mg dose of ANB019 or placebo. Refer 
to Section 6.1.2 for additional details on study treatment administration.  
For scheduled study visits, subjects will come to the study center up to 9 occasions to monitor changes 
in disease activity, PK (if applicable), safety, and tolerability: screening (depending on subject acneiform 
rash status, the screening visit may be planned either as 1 visit or 2 separate visits) and Days 1, 15, 29, 
57, 85, 113, and 169 (EOS/ET). All procedures will be conducted in accordance with the SoA in 
Section 1.3. Of note, the primary endpoint will be evaluated on Day 57 (Week 8).  
Disease activity will be evaluated for all subjects using facial inflammatory lesion count, acneiform rash 
CTCAE grading, acneiform rash modified MESTT grading, IGA, facial IGA, pruritus NRS, pain NRS, PGI-S, 
PGI-C, number of nail folds with paronychia, and paronychia, dry skin, alopecia, and pruritus CTCAE 
grading. The subject’s quality of life will be assessed using the FACT-EGFRi-18. Subject’s gastrointestinal 
inflammation will be evaluated using the STIDAT. Subject’s level of functioning and daily living abilities 
will be evaluated to confirm eligibility using the ECOG performance status. 
In addition, standardized photographs of the face will be taken at the time points specified in the SoA to 
record inflammatory lesions for lesion counts analysis as supporting information for efficacy analyses. 
Safety assessments will include AE/SAE monitoring, vital signs, physical examination, ECGs, and clinical 
laboratory tests (hematology, biochemistry, and urinalysis). 

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Blood samples to determine PK and immunogenicity (presence of ADA to ANB019) will be collected on 
Day 1 before the administration of the study treatment and at the other time points specified in the SoA 
(see Section 1.3). Any remaining samples collected for PK and immunogenicity endpoints may be 
retained for assay method development, troubleshooting, or validation. The samples will not be used for 
any type of genetic analyses. Tape strips for biomarker analysis will be collected at the time points 
specified in the SoA.  
Interim analyses (IAs) may be performed during the treatment period for assessment of all primary and 
secondary efficacy endpoints, and evaluation of all safety data available. 
4.2 
MODIFICATIONS TO STUDY CONDUCT DUE TO THE CORONAVIRUS DISEASE 2019 
(COVID-19) PANDEMIC 
As a consequence of the COVID-19 pandemic that has had a worldwide impact, including cases in North 
America and Europe, control measures in place in different regions may impact the ability to adhere to 
some of the study procedures described in this protocol. Due to challenges that include, but are not 
limited to, subject preferences, site closures, travel restrictions, and quarantines, some modifications to 
study conduct during the COVID-19 pandemic may be necessary to ensure study continuity, including 
conducting optional home visits when on-site study visits are considered not feasible. Such 
modifications in study conduct always must be in accordance with local regulations/mandates.  
The following are allowable, as necessary, modifications to study conduct during the COVID-19 
pandemic. 
 Prior to a study visit at the site, the subject may be contacted and screened for potential exposure 
or infection to COVID-19 per site, local, or federal requirements. If the subject is suspected to be 
exposed or infected with COVID-19, the on-site visit should either be re-scheduled or a virtual visit 
may be performed instead, as applicable.  
 In the event that a subject cannot attend their regularly scheduled study visits in person due to 
COVID-19 necessitating a limit on in-person contact, the investigator may perform safety and 
efficacy assessments by phone or video, with home nursing visit support for procedures that 
cannot be done virtually. The investigator may use the technology platform that is currently 
available to them. Suggested platforms include Apple FaceTime, Zoom for Healthcare, Facebook 
Messenger video chat, Microsoft Teams, Google Hangouts video, and Skype. Home nursing visit 
support may be used in addition to phone or video at visits that require procedures that cannot 
be done via phone or video alone, such as but not limited to, ECG, PK draws, clinical laboratory 
draws, study drug administration. The home nurse will collect the lab samples and perform all 
applicable study assessments that are possible during a home visit, including collection of adverse 
events and concomitant medications. During the COVID-19 period, if any data are collected at a 
home visit, it will be recorded by the home nurse in the source documents and the originals will 
be sent back to the site for data entry into the electronic data capture system for 
storage/archiving. 
 Clinical laboratory tests (chemistry and hematology) and pregnancy tests may be performed by 
local laboratory, if home nursing visits are not possible and sample collection cannot be 
performed at the study site due to COVID-19 related limitations, including but not limited to site 
closure. Abnormal laboratory results should be promptly communicated to the Medical Monitor. 
Subjects’ anonymity must be maintained when communicating results to the Medical Monitor.  
 At home investigational product administration by home health nurses may be done. 
 Source documentation should note that the visit was performed virtually (not face-to-face) and 
note the name of the local lab where laboratory tests were done. 

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 If certain study procedures or assessments cannot be completed per the schedule of events, the 
reason for the missed assessment (ie, laboratory tests, vital signs, physical examinations, etc) 
must be noted in the source documentation (eg, COVID-19), captured in the protocol deviations 
documentation, and reported to the IRB/EC, as applicable. 
A detailed assessment of COVID-19 related risk and mitigation measures will be documented in the 
appropriate study plans. 
4.3 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
The effective treatment of EGFRi/MEKi-associated acneiform rash remains an unmet medical need. The 
efficacy of available treatments (including topical and systemic antibiotics and corticosteroids) is limited 
and many patients with severe acneiform rash require dose reduction or cessation of EGFRi or MEKi 
therapy despite the use of these treatments. 
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 EGFRi/MEKi-associated acneiform rash, 
for whom increased lesional expression of IL-
.  
The proposed design is considered appropriate for assessing the efficacy, safety, and tolerability of 
ANB019 compared with placebo in subjects with EGFRi/MEKi-associated acneiform rash. 
In this study, randomization will ensure random allocation of subjects to treatment arms to reduce bias. 
Randomization will be stratified based on acneiform rash CTCAE grade at Baseline and therapy the 
subject is receiving (EGFRi vs MEKi). Because efficacy assessments of EGFRi/MEKi-associated acneiform 
rash have a high degree of subjectivity, the study will be double-blinded. The highest degree of subject 
and assessor (investigator or designee) blinding should be sought to achieve credible inference. A 
placebo-controlled period in this Phase 2a study will control for confounding factors, such as potential 
investigator bias, and ensure that the statistical procedures can be appropriately applied. In addition, 
the use of a placebo will help interpret the result of the study, because a spontaneous improvement of 
EGFRi/MEKi-associated acneiform rash is expected in several subjects. However, subjects with limited 
improvement of EGFRi/MEKi-associated acneiform rash will have access to rescue medication starting 
from Week 4, as judged by the investigator. 
4.4 
JUSTIFICATION FOR DOSE 
During the treatment period, ANB019 will be SC administered as a 400 mg dose on Day 1, followed by a 
200 mg dose on Days 29, 57, and 85. 
The doses selected for the study demonstrated a favorable safety and tolerability profile in a Phase 1 
study conducted in healthy volunteers. In addition, ANB019 demonstrated linear PK with an estimated 
terminal half-life (t1/2)of approximately 28 days at all doses tested with persistent pharmacodynamic 
activity. The loading dose of 400 mg SC administered on Day 1 was chosen to achieve maximum 
observed concentration (Cmax) soon after dosing in order to provide optimal potential benefit to subjects 
with EGFRi/MEKi-associated acneiform rash and to reach steady-state concentrations rapidly following 
200-mg SC dosing. The treatment period duration is expected to provide better clinical outcome, thus 
potentially benefiting subjects with EGFRi/MEKi-associated acneiform rash and further assessing the 
long-term efficacy and safety of ANB019. 

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4.5 
END OF STUDY DEFINITION 
A subject is considered to have completed the study if he or she has completed all periods of the study 
including the last specified visit (Day 169 [Week 24]/ET) shown in the SoA (see Section 1.3). 
The end of the study is defined as completion of the last visit or procedure shown in the SoA by the last 
subject included the study. 

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5 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, are not permitted. 
It is imperative that subjects fully meet all the inclusion criteria and none of the exclusion criteria. 
5.1 
INCLUSION CRITERIA 
To be eligible to participate in this study, a subject must meet all of the following criteria, either at the 
Screening and Day 1 visits, or only at one of the specified visits (Screening or Day 1) as noted in the 
criterion: 
1. Male and female subject aged 18 to 75 years (inclusive) at the time of signing the informed 
consent. 
2. Subject is treated with an oral or injectable commercially available EGFRi or MEKi therapy (alone 
or in combination) for a diagnosed neoplasm.  
3. Subject has EGFRi/MEKi-related acneiform rash of Grade 
 5.0, 
 20 
inflammatory lesions on the face at the Screening Part 2 visit and on Day 1. 
4. Subject has an ECOG performance score between 0 and 2 at Day 1. 
5. Subject has a life expectancy of 6 months at Day 1. 
6. Subject meets the following laboratory criteria at the Screening Part 2: 
a) 
 
 g/dL); 
b) 
 × 109
 × 103/µL); 
c) 
 × 109
 × 103/µL); 
d) Serum creatinine 
 × upper limit of normal (ULN) or creatinin
 50 mL/min; 
e) 
2.5 × ULN 
metastases; 
f) 
 × ULN. Subjects with known Gilbert’s disease who have serum 
bilirubin < 3 × ULN may be included; 
g) Absolute neutrophils count > 1.5 × 103/µL. 
7. Subject has a body weight  40kg.  
8. Subject has no clinically significant medical condition (other than neoplasm) or 
physical/laboratory/ECG/vital signs abnormality that would, in the opinion of the investigator, put 
the subject at undue risk or interfere with interpretation of study results. 
9. Subject meets the following tuberculosis (TB) screening criteria: 
a) Has no history of latent or active TB before screening, with an exception for subjects who have 
a history of latent TB that provide documentation of having completed appropriate treatment 
for latent TB before the first administration of study drug. The investigator must verify the 
adequacy of previous anti-TB treatment based on current local TB treatment guidelines and 
provide appropriate documentation. 
b) Has no signs or symptoms suggestive of active TB upon medical history and/or physical 
examination. 
c) Has had no recent close contact with a person with active TB, based on information provided 
by the subject. 
d) Has a negative QuantiFERON®-TB test result obtained during screening prior to Day 1.  
Note: a QuantiFERON®-TB test is not required at Screening for subjects with a history of latent 
TB who have previously completed appropriate TB treatment as described above in Inclusion 
Criterion 9a.  

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Note: A negative tuberculin skin test (as per local guidelines) may be required if the 
QuantiFERON®-TB test is not approved/registered in that country or the tuberculin skin test is 
mandated by local health authorities. If the tuberculin skin test is positive, but is suspected to 
be a false positive, a confirmation by a specialist will be required to exclude latent/active TB 
based on local guidelines. A subject whose first screening QuantiFERON-TB® test result is 
indeterminate may have the test repeated once. 
e) Has no more than 1 indeterminate QuantiFERON®-TB test result during screening. 
f) Has the report from a qualified radiologist of a chest X-ray performed within 6 months before 
Day 1 that shows no abnormalities suggestive of a current active infection, including TB. A 
chest CT scan is also acceptable if already available. If not performed with 6 months before 
Day 1, a chest X-ray must be performed at Screening. 
10. Contraceptive use by men and 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 who is sexually active with a female of childbearing potential and has not had a 
vasectomy must agree to use contraception as detailed in Appendix 1 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 last study treatment administration and 
refrain from donating sperm during this period. 
b) Female subjects: 
i) 
A woman of childbearing potential (WOCBP) 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 Day 1 (see Appendix 1), is not breastfeeding, and if heterosexually 
active agrees to follow the contraceptive guidance in Appendix 1 during the treatment 
period and for at least 6 months after receiving the study treatment, and refrains 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 at Day 1 (eg, hormonal contraception should be initiated at least 28 days 
before Day 1).  
ii) A woman not of childbearing potential is eligible to participate if she meets the criteria in 
Appendix 1. 
Note: If a female participant’s childbearing potential changes after start of the study (eg, a 
woman who is not heterosexually active becomes active, a premenarchal woman experiences 
menarche), she must begin practicing a highly effective method of birth control, as described 
above. 
11. Subject is willing to participate and is capable of giving written informed consent, which must be 
personally signed and dated by the subject and obtained prior to any study-related activities.  
12. Subject must be willing to comply with all study procedures and must be available for the duration 
of the study. 
5.2 
EXCLUSION CRITERIA 
A subject who meets any of the following criteria at the screening and/or Day 1 visits, as applicable, will 
be excluded from participation in this study: 
1. Subject has clinical evidence of an infection of their EGFRi/MEKi-associated acneiform rash (eg: 
cellulitis, impetigo), according to the investigator’s evaluation. 
2. Subject has other medical conditions which may interfere with the investigators’ ability to 
evaluate the subject’s response to therapy, as judged by the investigator. 

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3. Subject has significant skin disease other than EGFRi/MEKi-induced acneiform rash that, in the 
opinion of the investigator, would interfere with the study assessments. 
4. Subject has 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 that makes them unsuitable for the 
study. 
5. Subject has a 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 6 months prior to Screening. Note: A subject 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. 
6. Subject has a history or any evidence of active infection (eg, bronchopulmonary, urinary, or 
gastrointestinal) that required systemic antibiotic, antifungal or antiviral therapy within 2 weeks 
of Day 1, excluding localized oral or genital herpes simplex that, in the opinion of the investigator, 
is well-controlled. 
7. Subject has any factors (other than related to neoplasm) that would predispose the subject to 
develop an infection in the investigator’s opinion. 
8. Subject has a history of an opportunistic infection (eg, Pneumocystis carinii, aspergillosis, or 
mycobacteria other than tuberculosis [TB]) or parasitic infections (eg, helminths, protozoa, 
Trypanosoma cruzi) within 3 months prior to Screening. 
9. Subject has a history of a herpes zoster infection within 2 months prior to Screening. 
10. Subject has 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) not 
related to their neoplasm diagnosis or treatment. 
11. Subject had any major surgery within 2 weeks of Day 1. 
12. Subject has a history of any significant drug allergy or reaction (such as anaphylaxis or 
hepatotoxicity) to polysorbate 20, a component of ANB019 formulation, or the inactive 
ingredients (excipients). 
13. For subjects with prior use of the following therapies or procedures, the specified washouts 
between last dose of prohibited medication (or date of procedure) and Day 1 will apply: 
a) Over-the-counter (OTC) topical medication that can have an effect on acneiform rash, 
including topical anti-inflammatory medications, or antibacterial/antiseptic soap or wash:  
i) If used consistently without any alteration in dosage for at least 14 days prior to Day 1: 
subject may agree to either continue at current dosage over the entire course of the study 
OR discontinue the treatment at least 1 day prior Day 1. 
ii) If dosing initiated or dosage was changed less than 14 days prior to Day 1, the treatment 
must be discontinued at least 1 day prior to Day 1. 
b) Topical corticosteroids that can have an effect on acneiform rash:  
i) If used consistently without any alteration in dosage for at least 14 days prior to Day 1: 
subject may agree to either continue at current dosage over the entire course of the 
study OR discontinue the treatment at least 1 day prior to Day 1. 
ii) If dosing initiated or dosage was changed less than 14 days prior to Day 1, the treatment 
must be discontinued at least 1 day prior to Day 1. 
Note: Topical hydrocortisone 
 
c) Topical retinoids (eg: tretinoin, tazarotene, adapalene, dapsone) or other prescription topical 
medications that can have an effect on acneiform rash:  

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i) 
If used consistently without any alteration in dosage for at least 14 days prior to Day 1: 
subject may agree to either continue at current dosage over the entire course of the 
study OR discontinue the treatment at least 1 day prior to Day 1. 
ii) If dosing initiated or dosage was changed less than 14 days prior to Day 1, the treatment 
must be discontinued at least 1 day prior to Day 1. 
d) Topical antimicrobials (eg, clindamycin, erythromycin): 
i) 
If used consistently without any alteration in dosage for at least 14 days prior to Day 1: 
subject may agree to either continue at current dosage over the entire course of the 
study OR discontinue the treatment at least 1 day prior to Day 1. 
ii) 
If dosing initiated or dosage was changed less than 14 days prior to Day 1, the treatment 
must be discontinued at least 1 day prior to Day 1.  
e) Topical agents (on the regions affected by the rash) that could affect pruritus (eg, topical 
antipruritic agents):  
i) 
If used consistently without any alteration in dosage for at least 14 days prior to Day 1: 
subject may agree to either continue at current dosage over the entire course of the 
study OR discontinue the treatment at least 1 day prior to Day 1. 
ii) 
If dosing initiated or dosage was changed less than 14 days prior to Day 1, the treatment 
must be discontinued at least 1 day prior to Day 1. 
f) Systemic agents that could affect pruritus (such as oral antihistaminic, gabapentin, pregabalin, 
doxepin, and aprepitant):  
i) 
If used consistently without any alteration in dosage for at least 14 days prior to Day 1: 
subject may agree to either continue at current dosage over the entire course of the 
study OR discontinue the treatment at least 1 day prior to Day 1. 
ii) 
If dosing initiated or dosage was changed less than 14 days prior to Day 1, the treatment 
must be discontinued at least 1 day prior to Day 1.  
g) Oral antibiotic therapy for EGFRi/MEKi-associated acneiform rash: 
i) 
 If used consistently without any alteration in dosage for at least 14 days prior to Day 1: 
subject may elect to either remain on the therapy at current dosage for the entire 
duration of the study OR discontinue the treatment at least 1 day prior to Day 1.  
ii) If dosing initiated or dosage was changed less than 14 days prior to Day 1, a washout 
period of 1 day is required prior to Day 1.  
h) Other systemic antiacne drugs not mentioned in other exclusion criteria: 
i) 
If used consistently without any alteration in dosage for at least 14 days prior to Day 1: 
subject may agree to either continue at current dosage over the entire course of the 
study OR discontinue the treatment at least 1 day prior to Day 1. 
ii) If dosing initiated or dosage was changed less than 14 days prior to Day 1, the treatment 
must be discontinued at least 1 day prior to Day 1. 
i) 
Intramuscular corticosteroid injections: must be discontinued at least 28 days prior to Day 1. 
j) 
Oral corticosteroids: must be discontinued at least 7 days prior to Day 1. 
Note: Corticosteroids used to prevent nausea, vomiting, or hypersensitivity reactions related 
to treatment of neoplasm (eg, dexamethasone) are allowed. 
Note: Intranasal corticosteroids and inhaled corticosteroids are allowed.  
Note: Eye and ear drops containing corticosteroids are also allowed. 
k) Facial procedures (eg, chemical peel, laser, microdermabrasion): must be discontinued at least 
4 weeks prior to Day 1. 
l) 
Photodynamic therapy or phototherapy with blue or red light: must be discontinued at least 
14 days prior to Day 1. 

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m)  Androgen receptor blockers (such as spironolactone or flutamide): must be discontinued at 
least 14 days prior to Day 1. 
n) Oral retinoid (eg, isotretinoin) or vitamin A supplements > 10,000 U/d: must be discontinued 
at least 14 days prior to Day 1. 
o) Investigational nonbiologic drug: must be discontinued at least 14 days or 5 half-lives 
(whichever is longer) prior to Day 1. 
p) Investigational biologic agent: must be discontinued at least 12 weeks or 5 half-lives 
(whichever is longer) prior to Day 1. 
q) Marketed biologic agent (excluding any use for diagnosed neoplasm): must be discontinued at 
least 12 weeks or 5 half-lives (whichever is longer) prior to Day 1.  
14. Subject has had previous treatment with anti-IL-36R antibody.  
15. Subject has used drospirenone, chlormadinone acetate, or cyproterone acetate alone or as a 
component of an oral contraceptive, unless initiated and used at a stable dosage for at least 12 
weeks prior to Day 1. 
16. Subject has received live or live-attenuated vaccine within 12 weeks prior to Day 1.  
Note: Nonlive vaccines for currently authorized COVID-19 (eg, RNA-based vaccines, protein-based 
vaccines, and nonreplicating viral vector-based vaccines) are allowed during the study. 
17. Subject has had excessive sun exposure or has used tanning booths within 4 weeks prior to Day 1 
or is not willing to minimize natural and artificial sunlight exposure during the study. Use of 
sunscreen products and protective apparel are recommended when sun exposure cannot be 
avoided, except within 3 hours prior to the study visit. 
18. Subject has a known history of clinically significant drug or alcohol abuse in the last year prior to 
Day 1, or other factors limiting the ability to cooperate and to comply with the study protocol, as 
determined by the investigator. 
19. Subject is a pregnant or lactating woman, or a woman who intends to become pregnant during 
the study period. 
20. Subject has any other physical, mental, or medical conditions, which, in the opinion of the 
investigator, make study participation inadvisable or could confound study assessments. 
21. Subject has clinically significant abnormality on chest X-ray at screening, or on chest X-ray or any 
other chest imaging within 6 months prior to screening with the exception of the neoplasm 
(including primary or metastatic tumor, if applicable). 
22. Subject has any clinically significant abnormalities on 12-lead ECG at screening. 
23. Subject has a positive blood screen for hepatitis C antibody and hepatitis C RNA, antibodies to 
hepatitis B core antigens, hepatitis B surface antigen, or human immunodeficiency virus 1 and 2 
antibodies. 
24. Subject is not able to tolerate SC drug administration. 
5.3 
LIFESTYLE CONSIDERATIONS 
Subjects can apply an emollient of their choice (without pharmacological active ingredient) and topical 
hydrocortisone  1% on their skin, including on the acneiform eruption as desired throughout the study. 
For subjects who use make-up, facial moisturizers, creams, lotions, cleansers, and/or sunscreens, the 
same product brands/types should be used at the same frequency throughout the study. However, 
these products (including emollient and topical hydrocortisone) must not be applied within 3 hours prior 
to the study visits. Every effort should be made to keep the same products throughout the study. In case 
a subject applied these products on the face on a visit day, they will be instructed to wash their face at 
least 3 hours before the visit and not reapply these products on the face before the visit. 

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Subjects should continue with their regular facial skin care habits (including shaving) during the study 
but must not wash or shave their face within 3 hours prior to study the visit.  
The commercial name of the selected emollient(s) will be recorded in the source document and the 
electronic case report form (eCRF). No other products may be applied to the acneiform eruption during 
the study, unless deemed necessary by the investigator as described in Section 6.5.3. 
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 
(CONSORT) publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure reasons, eligibility criteria not met, and any SAE. 
Individuals who do not meet the eligibility criteria for participation in this study (screen failure) may be 
rescreened once after discussion with the Medical Monitor and if deemed appropriate. However, 
subjects without an acneiform rash or with an insufficient acneiform rash severity at the initial screening 
who are still not eligible after the 6-month screening period, will be considered screen failures and 
should not be rescreened. 
Rescreened subjects should not be assigned the same subject number as for the initial screening. All 
procedures planned at the screening visit, including signature of a new consent form, will be performed. 
5.5 
STRATEGIES FOR RECRUITMENT AND RETENTION 
The recruitment and retention strategies for the study will be covered in other study plans. 

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6 
STUDY TREATMENT 
Study treatment is defined as any investigational treatment or placebo intended to be administered to a 
clinical study subject according to the study protocol. 
6.1 
STUDY TREATMENT ADMINISTRATION 
6.1.1 
STUDY TREATMENT DESCRIPTION 
ANB019 is a humanized IgG4 (S228P)/kappa mAb that belongs in the class of anti-IL-36R mAb. 
ANB019 will be provided in a glass vial as a sterile, colorless to yellow, and clear to slightly opalescent 
solution for injection. 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. Detailed 
administration instructions will be provided in the Pharmacy Manual. 
During the treatment period, eligible subjects will be randomized (2:1) to receive either ANB019 or 
placebo, SC, administered at 4 time points: 
 Day 1: 400-mg dose of ANB019 or placebo (administered as 2 SC injections of ANB019 at 200 mg 
each or placebo) 
 Days 29, 57, and 85: 200-mg dose of ANB019 or placebo 
Of note, the placebo will be administered via SC injection(s) on the same schedule and in the same 
volumes as ANB019. Further information will be provided in the Pharmacy Manual. 
6.1.2 
DOSING AND ADMINISTRATION 
Study treatment dosing and administration details are provided in Table 2. 
Table 2: Study Treatment Details 
Study 
Treatment 
Name: 
ANB019 
Anti-interleukin 36 receptor monoclonal 
antibody 
Placebo 
 
Dosage Form: 
Solution for injection 
Solution for injection 
Source of 
procurement: 
AnaptysBio, Inc. 
AnaptysBio, Inc. 
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 1 mL. Each vial contains 100 mg of 
ANB019 at a concentration of 100 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 supplied in a single use, 
2R, Type I glass vial with a fill volume of 1 mL. 
Dosage 
Formulation: 
 
ANB019 study treatment is formulated as: 
100 mg/mL ANB019 in 25 mM histidine, 
60 mM NaCl, 145 mM sorbitol, and 
0.02% v/v polysorbate 20 at pH 6.0.  
The placebo is formulated as: 25 mM histidine, 
60 mM NaCl, 145 mM sorbitol, and 0.02% v/v 
polysorbate 20, at pH 6.0. 

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Table 2: Study Treatment Details (Continued) 
Unit Dose 
Strength(s)/ 
Dosage 
Level(s): 
Subjects assigned to ANB019 during the 
treatment period will receive the following 
doses: 
Day 1: 400-mg dose, administered as 2 mL 
× 2 SC injections of ANB019 at 200 mg 
each. 
Days 29, 57, and 85: 200-mg dose, 
administered as 2 mL × 1 SC injection of 
ANB019 at 200 mg. 
Subjects assigned to placebo during the 
treatment period will receive an equivalent 
volume of placebo SC administered on Days 1, 
29, 57, and 85. 
Day 1: 2 mL × 2 SC injections of placebo. 
Days 29, 57, and 85: 2 mL × 1 SC injection of 
placebo. 
Route of 
Administration:  
SC injection (4 doses during the treatment 
period) 
SC injection (4 doses during the treatment 
period) 
Dosing 
Instructions: 
ANB019 and placebo should be administered by clinic staff trained in best practices for SC 
administration of study treatments. 
For SC injections, ANB019 and 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. 
The preferred anatomical site of SC administration is the abdomen; however, the injection 
may be made in the upper arm, if needed.
An observation period of approximately 30 minutes after each dose should be included. 
The same anatomical site should be used throughout the entire study for a given subject (ie, 
do not administer one dose into the upper arm and at a subsequent visit or dose, administer 
the next dose into the abdomen). 
Subsequent doses should be rotated within an anatomical site (ie, if the upper left abdominal 
quadrant is used as the initial site of administration, then the next administration at a 
subsequent visit should be rotated to the upper right quadrant). Of note, on Day 1 the 2 SC 
injections should not be rotated within the anatomical site (ie, if the upper left abdominal 
quadrant is used for the first injection, then the second injection should be administered in 
the same quadrant). 
Subcutaneous injections should not be given into moles, scars, tattoos, or areas where the 
skin is tender, bruised, red, hard, or not intact. 
Prior to SC needle insertion, the skin will be pinched between the thumb and index finger to 
separate the subcutaneous layer from the muscle. 
The needle is to be injected at a 45 to 90-degree angle to the skin. 
The plunger will be pressed gently until the entire dose is delivered to the SC space and the 
needle will be held in place (fully depressed) for 10 seconds after the injection is 
administered.  
The needle will be removed and then the skin pinch released; any leakage or backflow of 
fluid from the administration site onto the surface of the skin will be noted and documented 
in the eCRF. 
The site of administration is NOT to be massaged by either the clinic staff or by the subject 
for at least 60 minutes after drug administration. 
Abbreviations: eCRF, electronic case report form; NaCl, sodium chloride; SC, subcutaneous; v/v, volume to 
volume. 
The contents of the label will be in accordance with all applicable regulatory requirements. 

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6.2 
PREPARATION/HANDLING/STORAGE/ACCOUNTABILITY 
The investigator or designee must confirm appropriate temperature conditions have been maintained 
during transit for all study treatments received, and any discrepancies are to be reported and resolved 
before use of the study treatment. 
Only subjects randomized in the study may receive study treatment and only authorized study site staff 
may supply or administer study treatment. Further guidance and information for the administration of 
the study treatment are provided in the Pharmacy Manual. 
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. 
ANB019 vials must be refrigerated at 2°C to 8°C (36°F to 46°F) until the day of use. ANB019 must not be 
used beyond the re-test or expiration date provided by the manufacturer. Vial contents should not be 
frozen, shaken, or diluted. ANB019 vials undiluted 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 not be used and should be discarded after study treatment accountability and reconciliation. 
The investigator is responsible for study treatment accountability, reconciliation, and record 
maintenance (ie, receipt, reconciliation, and final disposition records). 
Further guidance and information for the final disposition of unused study treatment are provided in the 
Pharmacy Manual. 
The investigator, a member of the study center staff, or a hospital pharmacist must maintain an 
adequate record of the receipt and distribution of all study 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 study is randomized, double-blind, and placebo-controlled. The blind will be maintained throughout 
the study with limited and controlled 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 
randomized in a 2:1 ratio to receive ANB019 or placebo. As subjects become eligible, they will be 
assigned unique randomization numbers, which will be used to assign the allocated treatment based on 
a randomization schedule. Randomization will be stratified based on acneiform rash CTCAE grade at 
Baseline and therapy the subject is receiving (EGFRi vs MEKi). Ideally, the study should include at least 
25% of subjects from each neoplasm therapy at Baseline (EGFRi and MEKi). 
The Sponsor, investigator, and subjects will be blinded to treatment assignment of ANB019 or placebo. 
An unblinded pharmacist will be responsible for study treatment dispensing. 
Once the subject has provided an informed consent and meets all inclusion and no exclusion criteria, the 
study site will request the treatment assignment using a central Interactive Web Response System 
(IWRS). 
The process for breaking the blind will be handled through the IWRS. Unblinding is undertaken by a 
predetermined process to ensure that participating subject and study team are not unblinded 
unnecessarily and the study results are not compromised. Unblinding of treatment assignment during 
the study should occur only if it is necessary to know what treatment the subject received during the 

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placebo-controlled period. Unblinding should occur 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 (emergency unblinding). 
In the event that emergency unblinding is necessary, the investigator must ensure that the unblinding of 
the treatment code is performed in a discreet manner and the treatment is disclosed only to those 
persons involved with the direct medical care of the subject. Subjects for whom the blind has been 
broken will be discontinued from treatment at the time of unblinding. After discontinuation from 
treatment, subjects should remain in the study but proceed directly into the safety follow-up period. 
The investigator must provide the reason for unblinding to the Sponsor’s Medical Monitor according to 
the Sponsor instructions following emergency unblinding. 
The Sponsor and the contract research organization (CRO) must be notified when a subject and/or 
investigator is unblinded during the study. The IWRS will create the blinded and/or unblinded 
notification when the blind is broken, which can be sent via email as per the user role of IWRS. The 
unblinding will be captured in the IWRS audit trail. Pertinent information regarding the circumstances of 
unblinding of a subject’s treatment code must be documented in the subject’s source documents.
6.4 
STUDY TREATMENT COMPLIANCE 
Study treatment compliance in this study will be under the direct control of the investigator; the study 
treatment will be administered on site. 
The prescribed dosage, timing, and mode of administration may not be changed. Any departures from 
the intended regimen must be recorded in the 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 OTC 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, route, and frequency 
In addition, all prior medications used to treat EGFRi/MEKi-associated acneiform rash and any other 
medications taken within 6 months prior to enrollment (Day 1) must be recorded in the eCRF. Live and 
live-attenuated vaccines may be utilized after subjects complete the safety follow-up period of the 
study. During the follow-up period, no study drug is administered and 12 weeks (at least three half-lives 
of study drug) is estimated to be a sufficient period after the last dose administration when a live or live-
attenuated vaccine can be safety administered. If a subject terminates the study early, live or live-
attenuated vaccines may be utilized 12 weeks after last dose of study drug administration. Nonlive and 
nonlive-attenuated vaccines, including those currently authorized for COVID-19 (eg, RNA-based 
vaccines, protein-based vaccines, and nonreplicating viral vector-based vaccines), are allowed during the 
study. The Medical Monitor should be consulted to confirm that the vaccine planned/received is allowed 
and that subject participation in the study should be continued. Of note, vaccines, including those for 
COVID-19, should be captured as a concomitant medication and any related symptoms documented as 
AEs. 

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The Medical Monitor should be contacted if there are any questions regarding concomitant or prior 
therapy. 
6.5.1 
PERMITTED THERAPIES 
Use of topical bland emollients (without pharmacological active ingredients) and topical 
hydrocortisone  1% on the skin, including on lesions, will be permitted throughout the study, except 
within 3 hours prior to the study visits.  
Use of make-up, facial moisturizers, creams, lotions, cleansers, and/or sunscreens will be permitted 
throughout the study, except within 3 hours prior to the study visits. 
Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and ear drops containing 
corticosteroids are also allowed. 
6.5.2 
PROHIBITED MEDICATIONS OR PROCEDURES 
Prohibited medications/therapy are listed below. The use of a prohibited medication/therapy (unless 
conditions for use of rescue medications have been met) is a protocol violation and must be recorded in 
the eCRF. 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 medications and procedures listed in Table 3 are prohibited from at least 1 day prior to Day 1 until 
the end of study, unless the specific requirements for continued use stated in the table were met. 

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7 
STUDY TREATMENT DISCONTINUATION 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 after enrollment, the investigator or qualified 
designee will determine if the subject can receive the study treatment and continue in the study and if 
any change in subject management is needed. 
7.1.1 
TEMPORARY INTERRUPTION 
Study treatment can be interrupted temporarily for any individual subject in case of an AE as per the 
investigator’s discretion. The Medical Monitor should be informed. Re-starting of study treatment can 
be done after discussion with the Medical Monitor. 
7.1.2 
RE-CHALLENGE 
In case the study drug was interrupted due to an AE that was deemed at least possibly related, 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 re-challenge, 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 or 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 discontinuation of study treatment, the subject will be required to attend an early 
termination ET (EOT/ET - Week 16) visit (see the SoA in Section 1.3). After completion of the ET visit, the 
subject should then return for a final follow-up visit (EOS - Week 24) 12 weeks after receiving their last 
dose of study treatment. Additional follow-up visit(s) may also be scheduled to follow any ongoing AE. 
Subjects must discontinue study treatment under the following circumstances: any SAE or significant AE, 
which, in the opinion of the investigator, warrants study discontinuation for safety reasons, or 
pregnancy occurring during the treatment period, which should be followed up until outcome. 
The following events are considered sufficient reasons for discontinuing a subject from the study 
treatment: 
 Pregnancy (refer to Appendix 1 and Section 8.2.1.8) 
 Significant deviation/lack of compliance with protocol 
 Any significant AE, laboratory abnormality, or other medical condition or situation occurs, such 
that continued participation in the study would not be in the best interest of the subject, in the 
opinion of the investigator  
 Disease progression which requires discontinuation of the study treatment 
 Discontinuation of use of EGFRi/MEKi therapy 
 Withdrawal of consent 
 Lost to follow-up 
 Use of any prohibited medication or treatment that, in the opinion of the investigator, 
necessitates the subject being withdrawn (refer to Section 6.5.2) 
 Termination of the subject participation by the investigator or Sponsor 

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The reason for subject discontinuation or withdrawal from the study will be recorded on the eCRF. 
If a subject withdraws from the study, he or she may request destruction of any samples taken and not 
tested, and the investigator must document this in the study center study records. 
See SoA (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. 
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 
(unless this is required by the COVID-19 restrictions and virtual visits are scheduled instead): 
 The study center must attempt to contact the subject and reschedule the missed visit as soon as 
possible and counsel the subject on the importance of maintaining the assigned visit schedule and 
ascertain whether or not the subject wishes to and/or should continue in the study. If the 
re-scheduled visit falls within the next visit’s window, then the visit should be considered a missed 
visit and the subject should come in for the next scheduled visit as planned. Missed visits must be 
captured in the eCRFs and will be recorded as a protocol deviation. 
 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 or study file. 
 Should the subject continue to be unreachable, he or she will be considered to have withdrawn 
from the study. 

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8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA (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. 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 SoA (Section 1.3) for instructions. 
Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the Medical Monitor 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 SoA, 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 purposes provided the procedures met 
the protocol-specified criteria and were performed within the time frame defined in the SoA (see 
Section 1.3). 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples. 
8.1 
EFFICACY ASSESSMENTS  
Clinical evaluations of EGFRi/MEKi-associated acneiform rash will be performed by an experienced and 
qualified dermatologist (board-certified or equivalent). To assure consistency and reduce variability, the 
same assessor should perform all assessments on a given subject, whenever possible (especially at Day 1 
and Day 57 [Week 8]). 
8.1.1 
SUBJECT ASSESSMENTS OF PRURITUS AND PAIN 
The intensity of pruritus and pain will be assessed at the visits specified in the SoA (see Section 1.3) 
using an NRS. This will be evaluated by asking subjects to assign a numerical score representing of the 
worst intensity over the last 24 hours of their symptoms (pruritus or pain) on a scale from 0 to 10, with 
0 indicating no symptoms and 10 indicating the worst imaginable symptoms (Phan 2012, 
Verweyen 2019, modified from Farrar 2001). 
These assessments will be completed by the subject on a worksheet prior to any efficacy and safety 
evaluations at every study visit. The 2 scales are presented in Appendix 2. 
8.1.2 
FUNCTIONAL ASSESSMENT OF CANCER THERAPY - EPIDERMAL GROWTH FACTOR 
RECEPTOR INHIBITOR 18 
The FACT-EGFRi-18 will be assessed at the visits specified in the SoA (see Section 1.3). The 
FACT-EGFRi-18 is a subject-reported outcomes questionnaire developed to assess the effect of 
EGFRi-induced dermatologic toxicities on health-related quality of life. It is an 18-item Likert-scaled 
questionnaire, arranged in three dimensions: physical (seven items), social/emotional (six items), and 
functional well-being (five items) (Wagner 2013). To provide a better fit for scale items, the item groups 

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are reorganized in skin, nail, and hair side effect domains. The response scores ranged from 0 (not at all) 
to 4 (very much).  
The FACT-EGFRi-18 will be completed by the subject on a worksheet prior to any efficacy and safety 
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 FACT-EGFRi-18 is presented in Appendix 3.  
8.1.3 
PATIENT GLOBAL IMPRESSION OF SEVERITY  
The PGI-S will be assessed at the visits specified in the SoA (see Section 1.3). It is a single-item question, 
which asks the subject to rate the current severity of the acneiform rash. The response options are 
“Clear skin”, “Mild”, “Moderate”, “Severe”.  
The PGI-S will be completed by the subject on a worksheet prior to any safety and 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 PGI-S (modified from Yalcin 2003) is presented in Appendix 4. 
8.1.4 
PATIENT GLOBAL IMPRESSION OF CHANGE 
The PGI-C will be assessed at the visits specified in the SoA (see Section 1.3). The PGI-C is a single-item, 
self-administered questionnaire, which asks the subject to rate the change in their symptom severity 
(“Very much better” to “Very much worse”). 
The PGI-C will be completed by the subject on a worksheet prior to any safety and 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 PGI-C (modified from Yalcin 2003) is presented in Appendix 5. 
8.1.5 
SYSTEMIC THERAPY INDUCED DIARRHEA ASSESSMENT TOOL 
The STIDAT will be assessed at the visits specified in the SoA (see Section 1.3). The STIDAT is a 
questionnaire that was developed to evaluate the severity of systemic therapy-induced diarrhea, a 
common side effect experienced by more than half of patients with neoplasm (Liu 2017; 
http://creativecommons.org/licenses/by/4.0/). The STIDAT will be used in the present study to assess 
the severity of gastrointestinal inflammation.  
The STIDAT assesses patient’s perception of having diarrhea, daily number of bowel movements, daily 
number of diarrhea episodes, antidiarrheal medication use, the presence of urgency, abdominal 
discomfort, fecal incontinence, patient’s perception of diarrhea severity, and quality of life.  
The STIDAT will be completed by the subject on a worksheet prior to any efficacy and safety evaluations. 
The questionnaire is self-explanatory and is first handed to the subject who is asked to fill in without the 
need for a detailed explanation. The STIDAT is presented in Appendix 6.  
8.1.6 
FACIAL INVESTIGATOR GLOBAL ASSESSMENT 
The facial IGAof the acneiform rash severity will be assessed at the visits specified in the SoA (see 
Section 1.3). The facial IGA will be used to evaluate the current state of the acneiform rash on the face 
only. It is a 5-point morphological assessment of facial acneiform rash severity. The facial IGA is a global 
evaluation that should be performed at arm’s length distance from the subject and must be performed 
before the facial inflammatory lesion count. A detailed description of the facial IGA scale (a modified IGA 
scale from ACZONE FDA guidance. https://www.fda.gov/media/104718/download) is provided in 
Table 4. 

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8.1.13 EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE STATUS 
Subject’s level of functioning will be assessed at the visits specified in the SoA (see Section 1.3) using the 
ECOG performance status (Oken 1982; ECOG-ACRIN Cancer Research Group). The ECOG performance 
scale is a 6-point scale ranging from 0 to 5.  
 
 

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clinical sequelae resulting from lack of efficacy will be reported as AE or SAE if they fulfill the definition 
of an AE or SAE. 
8.2.1.1.2 EVENTS NOT MEETING THE ADVERSE EVENT DEFINITION 
Events not meeting the AE definition include: 
 Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
which are associated with the underlying disease (acneiform rash and neoplasm), 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. 
8.2.1.2 DEFINITION OF SERIOUS ADVERSE EVENTS  
An AE or suspected adverse reaction is considered "serious" if, in the view of either the investigator or 
Sponsor, it results, at any dose, in any of the following outcomes:  
 Death 
 Life-threatening adverse event – 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. 
 Inpatient hospitalization or prolongation of existing hospitalization – In general, hospitalization 
signifies that the subject has been admitted (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 
(including neoplasm) that did not worsen from Baseline is not considered an AE. 
 Persistent or significant incapacity or substantial disruption of the ability to conduct normal life 
functions – 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. 
 Congenital anomaly/birth defect 
 Other important medical events – Events that may not result in death, be life-threatening, or 
require hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical intervention to 
prevent one of the outcomes listed in this definition.  

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Examples of such medical events include invasive or malignant cancers, allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions 
that do not result in inpatient hospitalization, or the development of drug dependency or drug 
abuse.  
8.2.1.3 CLASSIFICATION OF AN ADVERSE EVENT 
8.2.1.3.1 SEVERITY OF EVENT 
The intensity of an AE is an estimate of the relative severity of the event. The investigator will make an 
assessment of intensity for each AE and SAE reported during the study based on his or her clinical 
experience and familiarity with the literature. The following definitions are to be used to rate the 
severity of an AE: 
• Mild – Events require minimal or no treatment, are easily tolerated by the subject, causing 
minimal discomfort, and do not interfere with the subject’s daily activities.  
• Moderate – Events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with functioning and sufficient 
discomfort to the subject. 
• Severe – Events interrupt a subject’s usual daily activity and may require systemic drug therapy or 
other treatment. Severe events are usually potentially life-threatening or incapacitating. Of note, 
the term “severe” does not necessarily equate to “serious”. 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 
(Section 8.2.1.2), NOT when it is rated as severe. 
8.2.1.3.2 RELATIONSHIP TO STUDY TREATMENT 
All AEs must have their relationship to study treatment assessed by the investigator who examines and 
evaluates the subject based on temporal relationship and his or her clinical judgment. 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 or her assessment. The degree of certainty 
about causality will be graded using the categories below. In a clinical study, the study treatment must 
always be suspect.  
• Unrelated – Clinical event incontrovertibly not related to the study treatment. 
• Unlikely to be related – Clinical event with an incompatible time relationship to study treatment 
administration which makes a causal relationship improbable, and in which an underlying 
condition or other drugs or chemicals provides plausible explanations. 
• 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. 
• Related – Clinical event with plausible time relationship to study treatment administration and 
that cannot be explained by concurrent condition or other drugs or chemicals. 
For each AE/SAE, the investigator must document in the medical notes that he or she has reviewed the 
AE/SAE and has provided an assessment of causality.  
There may be situations in which an SAE has occurred, and the investigator has minimal information to 
include in the initial report to the pharmacovigilance unit. However, it is very important that the 

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investigator always make an assessment of causality for every event before the initial transmission of 
the SAE data to the pharmacovigilance unit within 24 hours of awareness of the event. 
The investigator may change his or her opinion of causality in light of follow-up information and send an 
SAE follow-up report with the updated causality assessment. 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
8.2.1.3.3 EXPECTEDNESS  
The pharmacovigilance unit will be responsible for determining whether an AE is expected or 
unexpected as interpreted through the IB. An AE will be considered unexpected if the nature, severity, 
or frequency of the event is not consistent with the risk information previously described for the study 
treatment. 
8.2.1.4 TIME PERIOD AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP 
The occurrence of an AE or SAE may come to the attention of study personnel during study visits and 
interviews of a study subject presenting for medical care, or upon review by a study monitor. 
All AEs including local and systemic reactions will be captured on the appropriate eCRF. Information to 
be collected includes event description, date of onset, clinician’s assessment of severity, seriousness, 
relationship to study treatment (assessed only by those with the training and authority to make a 
diagnosis), action taken, and outcome of the event. All AEs occurring while on study must be 
documented appropriately regardless of relationship (see Section 8.2.1.3.2). All AEs will be followed to 
adequate resolution or stabilization. 
Study site personnel will note the occurrence and nature of each subject’s medical condition(s) present 
prior to the informed consent signature in the appropriate section of the source document and eCRF. 
During the study, site personnel will note any change in the condition(s) and the occurrence and nature 
of any AE. Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the subject is the preferred method to inquire about AE occurrences. 
Should a subject experience an AE at any time after the informed consent signature until the end of 
participation in the study, the event will be recorded as an AE in the source document and eCRF. Any 
SAE related to the study participation (eg, screening procedure) will be recorded in the source document 
and eCRF from the time consent is given to participate in the study until the end of participation in the 
study (EOS/ET visit).  
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 or she considers the event to be reasonably related to the study 
treatment or study participation, the investigator must promptly notify the pharmacovigilance unit.  
Any medical condition that is present at the time that the subject is first screened will be considered as 
medical history and not reported as an AE. However, if the study subject’s condition deteriorates at any 
time during the study, it will be recorded as an AE.  
Changes in the severity of an AE/SAE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode. 
The investigator is responsible for appropriate medical care of subjects during the study. After the initial 
AE/SAE report, the investigator is required to proactively follow each subject at subsequent 

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visits/contacts. The investigator also remains responsible for following through with an appropriate 
health care option for all AEs that are ongoing at the end of the study. The subject should be followed 
until the event is resolved or stable. If an AE is ongoing at the end of study, the follow-up duration is left 
to the discretion of the investigator. Follow-up frequency will be performed at the discretion of the 
investigator.  
Whenever possible, clinically significant abnormal laboratory results are to be reported using the 
diagnostic that resulted in the clinically significant abnormal laboratory results and not the actual 
abnormal test. 
8.2.1.5 ADVERSE EVENT REPORTING  
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 nonserious) 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 the 
pharmacovigilance unit 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 the 
pharmacovigilance unit. 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 the pharmacovigilance unit. 
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. 
The investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the pharmacovigilance unit 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. 
New or updated information will be recorded in the originally completed eCRF. 
8.2.1.6 SERIOUS ADVERSE EVENT REPORTING  
Prompt notification by the investigator to the pharmacovigilance unit 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. All SAEs will be recorded and reported to the 
pharmacovigilance unit within 24 hours of awareness. The investigator will submit any updated SAE data 
to the pharmacovigilance unit within 24 hours of receipt of the information as outlined in the Safety 
Reporting Instructions that will be provided to the sites and in the study Safety Management Plan. 
The pharmacovigilance unit will inform the Medical Monitor, the Sponsor, and Innovaderm within 
1 business day of awareness of a new SAE. The pharmacovigilance unit will process and evaluate all SAEs 
as soon as the reports are received. For each SAE received, the pharmacovigilance unit, in consultation 
with the Sponsor if needed, will make a determination as to whether the criteria for expedited reporting 
to relevant regulatory authorities have been met. 
The Sponsor or designee 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 Sponsor or 

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designee will comply with country specific regulatory requirements relating to safety reporting to the 
regulatory authority, IRB/EC, and investigators. 
Investigator safety reports must be prepared for suspected unexpected SAEs according to local 
regulatory requirements and pharmacovigilance unit 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 pharmacovigilance will review and then file it 
along with the IB and will notify the IRB/EC, if appropriate according to local requirements.  
If a subject dies while participating in the study, the investigator will provide the pharmacovigilance unit 
with a copy of any postmortem findings.  
8.2.1.6.1 REPORTING VIA AN ELECTRONIC DATA COLLECTION TOOL  
The primary mechanism for reporting an SAE to the pharmacovigilance unit will be the electronic data 
capture (EDC) clinical database. 
If the electronic system is unavailable, then the study center will use the back-up paper SAE Report 
Form. The study center will then enter the SAE data into the EDC system as soon as it becomes available. 
After the study is completed and the database is locked, the tooled system 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 EDC system is locked, then the study center can report this information on a 
paper SAE form and email the form to the pharmacovigilance unit. 
Contacts for SAE reporting can be found in SAE form and Safety Reporting Instructions that will be 
provided to the sites. 
8.2.1.6.2 REPORTING VIA PAPER CASE REPORT FORM  
In rare circumstances, and in the absence of EDC or email, notification by telephone is acceptable for 
notifying the pharmacovigilance unit of an SAE. Once the EDC is available, the SAE must be reported in 
the system within 24 hours of it becoming available. 
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 Safety Reporting Instructions that will be provided to the 
sites. 
8.2.1.7 REPORTING EVENTS TO SUBJECTS  
Not applicable. 
8.2.1.8 REPORTING OF PREGNANCY  
If a female subject or a female partner of a male subject becomes pregnant during the study and up to 
28 days after the end of the subject participation, the subject should inform the study center as soon as 
possible. 
If a pregnancy is reported, the investigator should inform the pharmacovigilance unit within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 1. 

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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, where consent has been obtained to do so. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, 
and ectopic pregnancy) are considered SAEs and must be reported in 24 hours of awareness as 
described in Section 8.2.1.6. 
8.2.1.9 TREATMENT OF OVERDOSE  
For this study, any dose of ANB019 or placebo administered in a volume exceeding the planned dosing 
detailed in Table 2 (Dose Strength[s]/Dosage Level[s]) will be considered an overdose. For ANB019, this 
means a dose greater than 400 mg received within a 24-hour time period on Day 1 and greater than 
200 mg on Days 29, 57, and 85. 
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, creatine kinase (CK), and complete blood count) are to be 
performed and followed until all values return to Baseline levels and AEs subside, if applicable. 
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. 
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. 
4. Document the quantity of the excess dose as well as the duration of the overdose in the eCRF. 
Decisions regarding dose interruptions will be made by the investigator in consultation with the Medical 
Monitor based on the clinical evaluation of the subject. 
8.2.2 
HEIGHT AND WEIGHT
Height will be measured only at screening and weight will be measured at the time points specified in 
the SoA (see Section 1.3). 
8.2.3 
CHEST X-RAY 
Bidirectional posterior-anterior and lateral view chest X-ray will be performed during Screening 
(Section 1.3) unless the report from a qualified radiologist of a chest X-ray performed within 6 months 
before Day 1 shows no abnormalities suggestive of a current active infection, including TB, is available. A 
chest CT scan is also acceptable if already available. 

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8.2.4 
PHYSICAL EXAMINATIONS 
Complete physical examinations will be performed at the time points indicated in the SoA (see 
Section 1.3). 
A complete physical examination will include assessments of general appearance; skin; head/neck; 
pulmonary, cardiovascular, gastrointestinal, 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 SoA for the 
efficacy assessments. 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
8.2.5 
VITAL SIGNS 
Body temperature (°C), pulse rate (bpm), blood pressure (mmHg), and respiratory rate (breath/min) will 
be assessed at the time points specified in SoA (see Section 1.3). 
Blood pressure and pulse rate will be assessed in a seated position with a completely automated device. 
Manual techniques will be used only if an automated device is not available. 
Blood pressure and pulse rate measurements should be preceded by at least 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 at least 5 minutes rest) 
should be measured once. Arterial blood pressure should be measured twice (at intervals of at least 
5 minutes), using a validated device.  
8.2.6 
ELECTROCARDIOGRAMS 
A single 12-lead ECG will be obtained at the time points specified in the SoA (see Section 1.3) using a 
validated ECG machine that automatically calculates the heart rate and measures RR, PR, QRS, QT, QTcB, 
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. 
The investigator evaluation will take precedence over the central ECG laboratory for safety evaluation. 
The ECG individual data (with the exception of clinical significance that will be reported as AE) does not 
need to be entered into the EDC. 
8.2.7 
CLINICAL SAFETY LABORATORY ASSESSMENTS 
See Appendix 7 for the list of clinical laboratory tests to be performed and the SoA (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. 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. Local laboratory tests will also 
be allowed at Screening for TB and viral serology testing. If local laboratory is used for TB and viral 
serology, sample must be sent to central laboratory for analysis as well.  

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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 7, must be conducted in 
accordance with the Laboratory Manual and the SoA. 
If laboratory values from nonprotocol 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), then the results must be recorded in the eCRF. 
8.3 
OTHER ASSESSMENTS 
8.3.1 FITZPATRICK SKIN TYPE CLASSIFICATION 
The Fitzpatrick skin type (Fitzpatrick 1988; Attwa 2016; Wallace 2017; Zalaudek 2007) will be evaluated 
at Screening as described in Appendix 8. If not collected at Screening, the Fitzpatrick skin type may be 
collected at any visit thereafter. 
8.3.2 
PHOTOGRAPHY 
Standardized photographs of acneiform rash on the face will be performed at the time points 
mentioned in the SoA (see Section 1.3) for facial inflammatory lesion count analysis. Further guidance 
and information on the standardized photographs are provided in a separate manual and/or Statistical 
Analysis Plan (SAP). 
8.3.3 
PHARMACOKINETICS 
Whole blood will be obtained from each subject for the determination of ANB019 concentrations in 
human serum to enable modeling PK parameters. Samples will be collected according to the SoA (see 
Section 1.3) and Table 15. 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 as well as supportive analysis for dose justification. Any remaining serum 
from samples collected for PK endpoints may be retained for assay method development, 
troubleshooting, or validation. The samples will not be used for any type of genetic analyses.  
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 manual. 
The measurement of the concentrations of ANB019 will be performed using a validated assay method 
under the supervision of the Sponsor. The analytical methods used to measure concentrations of 
ANB019 will be described in a separate bioanalytical report. 

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Only samples within the stability window of the assay will be analyzed.  
While PK samples must be collected from subjects assigned to the placebo arm to maintain the blinding 
of treatment assignment, PK assay results for these subjects are not needed for the safe conduct or 
proper interpretation of this study. These samples may not be analyzed unless needed to investigate if a 
dosing error has occurred. Personnel at the bioanalytical laboratory performing PK assays will be 
unblinded, clinical study team members, and study center staff (with the exception of the unblinded 
pharmacist) will remain blinded to treatment for the duration of the study. Data may be de-identified 
for quality review. Additional details on de-identification or unblinding of the PK data, if applicable, will 
be described in a separate plan. 
Drug concentration information that may unblind the study will not be reported to study site or blinded 
personnel until the study has been unblinded. Any changes in the timing or addition of time points for 
any planned study assessments must be documented and approved by the relevant study team member 
and then archived in the Sponsor and study files but will not constitute a protocol amendment. The 
IRB/EC will be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICF. 
Table 15: Pharmacokinetic Sample Collection and Time Points 
Study Visit 
Pharmacokinetic Sample Time Point (Serum) 
Day 15
Anytime
Day 29
Predose 
Day 57
Predose 
Day 85
Predose 
Day 113 
Anytime
Day 169 
Anytime
8.3.4 
IMMUNOGENICITY ASSESSMENTS 
Anti-drug antibodies (ADAs) to ANB019 will be evaluated in serum samples collected from all subjects 
according to the SoA (see Section 1.3) and Table 16. Additionally, serum samples should 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). Any remaining serum from samples collected 
for immunogenicity endpoints may be retained for assay method development, troubleshooting, or 
validation. The samples will not be used for any type of genetic analyses. 
The detection and characterization of ADAs will be performed using a validated assay method by or 
under the supervision of the Sponsor.  
Serum samples will be tested in a multi-tiered approach. A validated screening assay for antibodies 
binding to ANB019 will be initially used to assess serum samples. Samples that are determined putative 
positive in the screening assay will then be subjected to a confirmatory assay to demonstrate that 
antibodies are specific to ANB019. Samples that are identified as positive in the confirmatory assay will 
be further characterized in a validated titer assay and the titer of confirmed positive samples will be 
reported. Other analyses may be performed to verify the stability of antibodies to study treatment 
and/or to further characterize the immunogenicity of study treatment.  
Samples that are confirmed positive for antibodies binding to ANB019 may be further characterized for 
their ability to neutralize the activity of the study treatment using a validated neutralizing antibody 
assay method and the presence and/or titer of ADAs may be correlated to safety and PK data.  

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Table 16: Anti-Drug Antibodies Sample Collection and Time Points 
Study Visit 
Anti-Drug Antibodies Sample Time Point (Serum) 
Day 1
Predose  
Day 29
Predose 
Day 57
Predose 
Day 113 
Anytime
Day 169 
Anytime
8.3.5 
BIOMARKERS ANALYSIS 
Tape strips samples will be collected from nonlesional and lesional skin according to the SoA (see 
Section 1.3) to measure cutaneous biomarkers including but not limited to IL-36R, Th-17 cytokines such 
as IL-17A, 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 
tape strips collection, sample labeling, sample preparation, storage, and shipping procedures will be 
described in a separate Laboratory Manual. 
The measurement of tape strips biomarkers may be performed by an additional third party (eg, a 
university investigator) designated by the Sponsor. 

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9 
STATISTICAL CONSIDERATIONS  
9.1 
STATISTICAL HYPOTHESES 
The primary analysis for this study is to compare the mean change from Baseline in facial inflammatory 
lesion count for ANB019 with placebo at Week 8 of the double-blind treatment period, at a two-sided 
alpha = 0.05 level. Any testing being performed for the secondary or exploratory endpoints will be 
considered exploratory in nature based on a two-sided alpha = 0.05.  
H0: µANB019 - µPlacebo = 0 vs. HA: µANB019 - µPlacebo
 
9.2 
SAMPLE SIZE DETERMINATION 
The primary efficacy endpoint is the change from Baseline in facial inflammatory lesion count at Week 8. 
The null hypothesis (H0) to be tested is that the mean change from Baseline in lesion count is the same 
for ANB019 and placebo. Treatment arm sample sizes of 30 (ANB019) and 15 (placebo) achieve 80% 
power to reject H0 of equal means if the population mean difference is -10.6 (ANB019 – placebo), with a 
common standard deviation (SD) within both groups of 11.7, and significance level (alpha) of 0.05 using 
a two-sided two-sample equal-variance t-test. 
9.3 
POPULATIONS FOR ANALYSES 
The analysis sets are defined in Table 17. 
Table 17: Analysis Sets 
Analysis Set 
Description 
Intent-to-Treat (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. ITT Analysis 
Set will be used for efficacy data analyses. 
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. If a subject receives 
both treatments, they will be analyzed in the ANB019 group. 
Per Protocol Analysis Set 
The Per Protocol analysis set will include all subjects in the ITT Analysis Set 
who do not have major protocol violations that would affect the evaluation 
of the primary efficacy endpoint. Per Protocol analysis set will be used for a 
sensitivity analysis of the primary endpoint and for some secondary 
endpoints. 
PK Analysis Set 
The PK Analysis Set will include all ANB019-treated subjects in the safety 
analysis set who have at least 1 quantifiable post-dose 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, pharmacokinetic 
 
 

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9.4 
STATISTICAL ANALYSES 
9.4.1 
GENERAL APPROACH 
The statistical analysis will be performed using statistical analysis system (SAS®) Version 9.4 or higher. All 
details regarding the statistical analysis will be described in the SAP. 
The default summary statistics for continuous variables include number of contributing observations, 
mean, SD, median, minimum, and maximum. For PK 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. 
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 transformations or nonparametric methods 
may be used for analysis. 
All data will be presented in by-subject listings. 
9.4.2 
SUBJECT DISPOSITION 
A tabular presentation of the subject disposition will be provided. It will include the number of subjects 
consented, 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 a 
dry run to categorize as major or minor with decisions of exclusion from analysis sets prior to unblinding. 
During the COVID-19 pandemic, protocol deviations related to COVID-19 will be documented and 
information on how they will be handled in the analyses will be detailed in the SAP. 
9.4.3 
BASELINE DESCRIPTIVE STATISTICS 
Subject characteristics obtained at Baseline will be summarized for all subjects taking ANB019 or 
placebo. 
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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9.4.4 
CONCOMITANT MEDICATION
All medications will be coded using the World Health Organization (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 descriptively with a by-subject listing. 
To handle the issue of rescue medication use, the efficacy data on and after the use rescue medication 
will be set to missing in the efficacy analysis. 
9.4.5 
ANALYSIS OF THE PRIMARY EFFICACY ENDPOINT 
The primary efficacy endpoint is the change from Baseline in facial inflammatory lesion count (papules 
and pustules) at Week 8.  
9.4.5.1 PRIMARY ESTIMAND 
The primary estimand, comprising of four components, is defined as follows: 
a) The target population is reflected by the patients that are eligible to be included in the clinical 
trial based on the inclusion/exclusion criteria in the protocol. The ITT Analysis Set will include all 
randomized subjects. For the analysis, treatment will be assigned based upon the treatment arm 
to which subjects were randomized regardless of which treatment they receive.  
b) The primary variable is the facial inflammatory lesion count (papules and pustules) of an 
individual subject at Week 8.  
c) To handle intercurrent events such as use of rescue medications, the hypothetical strategy for 
estimand will be used. Data collected following receipt of rescue medication (if any) will be 
considered missing in the analysis. 
d) The population-level summary measure for the primary endpoint is mean change from Baseline 
in facial inflammatory lesion count (papules and pustules) at Week 8. The estimator for 
between-group comparison of the primary endpoint will be the difference in the primary 
endpoint between ANB019 and placebo at Week 8. 
9.4.5.2 STATISTICAL ANALYSIS OF PRIMARY ENDPOINT 
A general linear mixed model repeated measures (MMRM) analysis will be used to estimate the least 
squares means (LSM) and associated standard errors for the change from Baseline in facial inflammatory 
lesion count (papules and pustules) at Week 8. The model will include change from Baseline in facial 
inflammatory lesion count (papules and pustules) at Week 8 as the dependent variable, fixed effects for 
treatment arm, visit, and the treatment by visit interaction, and the Baseline value of response, and the 
stratification factors (ie, acneiform rash CTCAE grade at Baseline and therapy the subject is receiving 
[EGFRi vs MEKi]) as covariates. An unstructured covariance structure will be used. The difference 
between LSMs (ANB019 – placebo) at Week 8 will be presented along with the associated 95% CI and p-
value. The ITT Analysis Set will be used for the primary efficacy analysis. 
 

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The possible effect of any covariates as well as investigation of subgroup analyses will be performed by 
minimally including the stratification factors of Baseline acneiform rash CTCAE grade (2 vs 3 or 4) and 
type of neoplasm therapy (EGFRi or MEKi).  
9.4.5.3 
HANDLING OF MISSING DATA 
The method for handling missing data for the primary variable will be MMRM, which is based on the 
statistical assumption of missing at random (MAR). Based on the hypothetical strategy for handling 
rescue medication use, data will be set to missing and will be considered missing in the analysis on or 
after the rescue medication use. All other missing values will be implicitly handled in MMRM. Sensitivity 
analysis under Missing Not at Random (MNAR) will be described in the next section.
9.4.5.4 
SENSITIVITY ANALYSIS 
As a sensitivity analysis of the primary analysis under MNAR, placebo Multiple Imputation (pMI) method 
will be conducted. The pMI assumes that the statistical behavior of ANB019-treated patients and 
placebo-treated patients after the occurrence of intercurrent events will be the same as if patients were 
treated with placebo. In the context of efficacy data, pMI is a specific form of a Missing Not at Random 
(MNAR) analysis and expected to yield a conservative estimate for efficacy. 
As an additional sensitivity analysis to assess the results from the ITT population, per protocol analysis of 
the primary efficacy endpoint will also be performed. 
9.4.6 
ANALYSIS OF THE SECONDARY EFFICACY ENDPOINTS 
Following are the secondary efficacy endpoints: 
 Percent change from Baseline in facial inflammatory lesion count (papules and pustules) at 
Week 8 
 Proportion of subjects with an improvement of at least 1 grade from Baseline in acneiform rash 
CTCAE grading scale at Week 8
 Time to first response of 1 grade improvement from Baseline on the acneiform rash CTCAE 
grading scale  
 Proportion of subjects with an improvement of at least 1 grade from Baseline in acneiform rash 
modified MESTT grading scale (total score) at Week 8 
 Proportion of subjects with an improvement of at least 1 grade from Baseline in acneiform rash 
modified MESTT grading scale (facial assessment) at Week 8 
 Time to first response of 1 grade improvement from Baseline on the acneiform rash modified 
MESTT grading scale (total score) 
 Time to first response of 1 grade improvement from Baseline on the acneiform rash modified 
MESTT grading scale (facial assessment) 
 Change from Baseline in pruritus NRS at Week 8 
 Percent change from Baseline in pruritus NRS at Week 8 
 Change from Baseline in pain NRS at Week 8 
 Percent change from Baseline in pain NRS at Week 8 
 Change from Baseline in FACT-EGFRi-18 at Week 8 
All secondary endpoints will be analyzed on the ITT Analysis Set. Between-treatment differences will 
be reported with corresponding 95% CIs and p-values. Secondary endpoints will be analyzed using 
the methods described in section 9.4.6.1 (continuous endpoints), section 9.4.6.2(categorical 
endpoints), and section 9.4.6.3 (time-to-event endpoints).  

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9.4.6.1 CONTINUOUS ENDPOINTS 
Summary statistics will be provided for absolute scores and change from Baseline to specified time 
points of facial inflammatory lesion count, acneiform rash CTCAE, acneiform rash modified MESTT (by 
body region), IGA, pruritus and pain NRS, and FACT-EGFRi-18; change and percent change from Baseline 
by visit and treatment arm also will be shown. A by-subject listing will be presented for each 
assessment, by visit.  
MMRM method for longitudinal continuous data will be used for testing, with treatment group as main 
effect, with visit and interaction of treatment by visit as factors, and with Baseline values of response 
and the stratification factors (ie, acneiform rash CTCAE grade at Baseline and therapy the subject is 
receiving [EGFRi vs MEKi]) as covariates. 
9.4.6.2 
CATEGORICAL ENDPOINTS 
Frequency and percentages for each response Yes/No for categorical endpoints related to inflammatory 
lesion count, acneiform rash CTCAE, acneiform rash modified MESTT (by body region and total score), 
IGA, pruritus and pain NRS, subjects that do not require dose reduction of EGFRi or MEKi therapy, and 
rescue medication will be presented separately by visit for both treatment arms. Subjects with missing 
scores, dose reduction data, or rescue medication data at a given visit will be considered to have not 
met the criteria of interest (ie, nonresponse). Estimates of the difference between treatments (ANB019 
and placebo) will be presented along with 95% CIs. 
Treatment arms will be compared using Cochran–Mantel–Haenszel chi-squared test, adjusted for 
stratification factors (ie, acneiform rash CTCAE grade at Baseline and therapy the subject is receiving 
[EGFRi vs MEKi]). Robustness analyses involving repeated measures Generalized Estimating Equations 
(GEE) may also be used. 
9.4.6.3 
TIME-TO-EVENT ENDPOINTS
Summary statistics such as median and 95% CI for time-to-event endpoints will be estimated using 
Kaplan-Meier Method. The statistical comparison of the time-to-event endpoints between treatment 
groups will be performed using Cox regression.  
9.4.7 
ANALYSIS OF THE EXPLORATORY EFFICACY ENDPOINTS 
Following are the exploratory efficacy endpoints: 
 Change from Baseline in facial inflammatory lesion count (papules and pustules) at each visit 
other than Week 8 
 Percent change from Baseline in facial inflammatory lesion count (papules and pustules) at each 
visit other than Week 8 
 Change from Baseline in facial papule count at each visit 
 Percent change from Baseline in facial papule count at each visit 
 Change from Baseline in facial pustule count at each visit 
 Percent change from Baseline in facial pustule count at each visit 
 Proportion of subjects with an improvement of at least 1 grade from Baseline in acneiform rash 
CTCAE grading at each visit other than Week 8 
 Proportion of subjects with an improvement of at least 1 grade from Baseline in modified MESTT 
grading scale (total score) at each visit other than Week 8  
 Proportion of subjects with an improvement of at least 1 grade from Baseline in modified MESTT 
grading scale (facial assessment) at each visit other than Week 8 

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 Proportion of subjects with an improvement of at least 1 grade from Baseline in modified MESTT 
grading scale (back assessment) at each visit 
 Proportion of subjects with an improvement of at least 1 grade from Baseline in modified MESTT 
grading scale (scalp assessment) at each visit 
 Proportion of subjects with an improvement of at least 1 grade from Baseline in modified MESTT 
grading scale (chest assessment) at each visit
 Time to first response of 1 grade improvement from Baseline on the acneiform rash modified 
MESTT grading scale (back assessment) 
 Time to first response of 1 grade improvement from Baseline on the acneiform rash modified 
MESTT grading scale (scalp assessment) 
 Time to first response of 1 grade improvement from Baseline on the acneiform rash modified 
MESTT grading scale (chest assessment) 
 Change from Baseline in pruritus NRS at each visit other than Week 8 
 Percent change from Baseline in pruritus NRS at each visit other than Week 8 
 Change from Baseline in pain NRS at each visit other than Week 8 
 Percent change from Baseline in pain NRS at each visit other than Week 8 
 Change from Baseline in FACT-EGFRi-18 at each visit other than Week 8 
 Proportion of subjects achieving an improvement of 50% from Baseline in facial inflammatory 
lesion count (papules and pustules) at each visit 
 Proportion of subjects achieving an improvement of 75% from Baseline in facial inflammatory 
lesion count (papules and pustules) at each visit 
 Change from Baseline in acneiform rash CTCAE grading scale at each visit 
 Change from Baseline in acneiform rash modified MESTT grading scale (total score) at each visit 
 Percent change from Baseline in acneiform rash modified MESTT grading scale (total score) at 
each visit  
 Change from Baseline in acneiform rash modified MESTT grading scale (facial assessment) at each 
visit 
 Change from Baseline in acneiform rash modified MESTT grading scale (back assessment) at each 
visit 
 Change from Baseline in acneiform rash modified MESTT grading scale (scalp assessment) at each 
visit 
 Change from Baseline in acneiform rash modified MESTT grading scale (chest assessment) at each 
visit 
 Change from Baseline in IGA at each visit 
 Proportion of subjects achieving an IGA of clear (0) or almost clear (1) at each visit 
 Proportion of subjects with at least 2-point decrease in IGA at each visit 
 Change from Baseline in facial IGA at each visit 
 Proportion of subjects achieving a facial IGA of none (0) or minimal (1) at each visit 
 Proportion of subjects with at least a 2-point decrease in facial IGA at each visit 
 Proportion of subjects with at least a 3-point decrease in pruritus NRS at each visit for subjects 
with a Baseline pruritus NRS of at least 3 
 Proportion of subjects with at least a 4-point decrease in pruritus NRS at each visit for subjects 
with a Baseline pruritus NRS of at least 4 
 Proportion of subjects with at least a 3-point decrease in pain NRS at each visit for subjects with a 
Baseline pain NRS of at least 3 

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 Proportion of subjects with at least a 4-point decrease in pain NRS at each visit for subjects with a 
Baseline pain NRS of at least 4 
 Proportion of subjects in each response category for the PGI-S and PGI-C at each visit 
 Proportion of subjects achieving mild or clear skin according to the PGI-S at each visit 
 Proportion of subjects achieving improvement (a little better, much better, or very much better) 
according to the PGI-C at each visit 
 Proportion of subjects receiving rescue medication from Week 4 through Week 24 
 Proportion of subjects that do not require a dose reduction of EGFRi or MEKi therapy due to 
acneiform rash at each visit 
 Proportion of subjects that do not require cessation of EGFRi or MEKi therapy due to acneiform 
rash at each visit 
 Change from Baseline in number of nail folds with paronychia at each visit 
 Proportion of subjects with paronychia, dry skin, alopecia, and pruritus of Grade 0 or 1 as per 
CTCAE grading scale at each visit 
 Change from Baseline in STIDAT at each visit 
 Percent change from Baseline in STIDAT at each visit 
 Change from Baseline in inflammatory lesion counts as determined by standardized photographs 
at each visit 
 Percent change from Baseline in inflammatory lesion counts as determined by standardized 
photographs at each visit 
Note: Reference to each visit in the exploratory endpoints excludes the visits covered by the primary 
and secondary endpoints. 
Methods for analyzing the above continuous and categorical efficacy endpoints will mirror the methods 
described in Section 9.4.6.1, 9.4.6.2, and 9.4.6.3, respectively. 
9.4.8 
SAFETY ANALYSES 
Following are the safety and tolerability endpoints: 
• Assessment of AEs, SAEs, AEs leading to study discontinuation, and AEs leading to study drug 
withdrawal 
• Vital signs 
• 12-lead ECG 
• Clinical safety laboratory tests (hematology, biochemistry, and urinalysis) 
All safety analyses will be performed on the safety analysis set. 
9.4.8.1 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
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. 
AEs 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 the subjects in the safety analysis set for the given treatment arm. 

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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, 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. 
9.4.8.2 12-LEAD ELECTROCARDIOGRAM, VITAL SIGNS, AND CLINICAL SAFETY LABORATORY 
TESTS 
Summaries and listings of data for 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 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 weight, 12-lead ECGs, vital 
signs, 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. 
9.4.9 
PHARMACOKINETIC ANALYSES 
ANB019 PK drug concentrations will be listed and summarized for each sampling time point using 
appropriate descriptive statistics and applied on the PK Analysis Set.  
9.4.9.1 DERIVATION OF PHARMACOKINETIC PARAMETERS 
Noncompartmental analysis (NCA) will not be conducted due to minimal PK sampling. However, 
observed PK parameters or other presentations PK information may be presented at the discretion of 
the PK scientist. Further details of PK analysis, data handling, analysis procedures, and data reporting 
will be detailed in a separate analysis plan. 
9.4.9.2 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. 
Mean trough (predose samples on Days 29) concentrations-time data will be graphically displayed for 
samples collected at the visits specified in the SoA (see Section 1.3) to visually assess time to attainment 
of steady state. Time to steady state may also be explored by using inferential statistics, if deemed 
appropriate.  

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9.4.9.3 PHARMACOKINETIC PARAMETER DATA ANALYSIS 
Noncompartmental analysis (NCA) will not be conducted due to minimal PK sampling.  
9.4.9.4 POPULATION PHARMACOKINETICS ANALYSIS 
Pharmacokinetic data from the study may also be used for population PK and exposure-response 
analyses. If done, a separate analysis plan will be prepared, and results will be reported separately from 
the Clinical Study Report (CSR). 
9.4.10 IMMUNOGENICITY ANALYSES 
Observed values for ADA levels/status will be listed by-subject and summarized with descriptive 
statistics based on the safety analysis set. 
The incidence of ADA positive, treatment-emergent, and treatment-boosted will be shown by treatment 
group. A treatment-emergent ADA result is one with any positive post-treatment ADA value when the 
Baseline ADA result is negative. A treatment-boosted ADA result is any post-Baseline positive ADA result 
that is at least four times greater than the Baseline value (when positive). If data permits, correlation 
will be analyzed between ADA levels and safety and efficacy endpoints, as well as ADA impact on 
ANB019 exposure. 
Frequency and percentage of ADA response will be presented and listed and correlated to safety and PK 
endpoints and correlated to safety and PK endpoints. 
9.4.11 BIOMARKER ANALYSES 
Tape strip biomarkers (including but not limited to IL-36R and Th-17 cytokine) analysis will be performed 
by a third party designated by the Sponsor. A separate analysis plan will be created for the biomarker 
analyses. 
9.4.12 PLANNED INTERIM ANALYSES  
Interim analyses may be performed during the treatment period for assessment of the primary and 
secondary efficacy endpoints, and evaluation of all safety data available.  
The rationale for IAs is to assist in making decisions for potential future development of this treatment. 
No adjustments to the current protocol are planned as a result of the IAs; therefore, overall alpha in the 
analysis of the primary analysis is expected to be maintained at 0.05, two-sided. 
Full details of the IAs, including procedures for maintaining the study blind for key personnel and the 
confidentiality of the results, will be described in the SAP. 

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10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1 REGULATORY, ETHICAL, AND STUDY OVERSIGHT CONSIDERATIONS 
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 site at which the 
investigator has not signed the protocol. 
10.1.1 INFORMED CONSENT PROCESS
10.1.1.1 CONSENT AND OTHER INFORMATIONAL DOCUMENTS PROVIDED TO SUBJECTS 
An ICF describing in detail the study treatments, study procedures, and risks will be given to the 
subjects, and written documentation of informed consent is required prior to starting any study-related 
procedures. The following materials will be submitted to the IRB/EC with this protocol: subject 
self-reported questionnaires, ICF, IB, and other relevant documents (eg, advertisements). 
10.1.1.2 CONSENT PROCEDURES AND DOCUMENTATION 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in the 
study and continues throughout the individual’s study participation. Each informed consent document 
must adhere to the ethical principles stated in the Declaration of Helsinki and will include the elements 
required by FDA regulations in 21 Code of Federal Regulations (CFR) Part 50, as well as the elements 
required by the ICH GCP guideline, and applicable federal and local regulatory requirements. The 
consent form will be IRB/EC-approved, and the subject will be asked to read and review the document.  
The investigator or his/her representative will explain the research study to the subject and answer any 
questions that may arise. A verbal explanation will be provided in terms suited to the subject’s 
comprehension of the purposes, procedures, and potential risks of the study and of their rights as 
research subjects. Subjects will have the opportunity to carefully review the written consent form and 
ask questions prior to signing. The subjects should have the opportunity to discuss the study with their 
family or surrogates or think about it prior to agreeing to participate. The subject will sign the informed 
consent document prior to any procedures being done specifically for the study.  
Subjects must be informed that participation is voluntary and that they may withdraw from the study at 
any time, without prejudice. A copy of the informed consent document will be given to the subjects for 
their records. The informed consent process will be conducted and documented in the source document 
(including the date), and the form signed, before the subject undergoes any study-specific procedures. 
The rights and welfare of the subjects will be protected by emphasizing to them that the quality of their 
medical care will not be adversely affected if they decline to participate in this study. 
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. Subjects who are rescreened are required to sign a new ICF. 
10.1.2 STUDY DISCONTINUATION AND CLOSURE 
This study may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for study suspension or termination, will be 
provided by the suspending or terminating party to study subjects, investigator, the IND Sponsor, and 

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regulatory authorities, as applicable. If the study is prematurely terminated or suspended, the 
investigator will promptly inform study subjects and the IRB/EC and will provide the reason(s) for the 
termination or suspension. Study subjects will be contacted, as applicable, and be informed of changes 
to study visit schedule.  
Circumstances that may warrant termination or suspension include, but are not limited to: 
 Determination of unexpected, significant, or unacceptable risk to subjects 
 Insufficient compliance to protocol requirements 
 Data that are not sufficiently complete and/or evaluable 
 Scientific or corporate reasons 
Study may resume once concerns about safety, protocol compliance, and data quality are addressed, 
and satisfy the Sponsor, IRB/EC and/or regulatory authorities. 
10.1.3 CONFIDENTIALITY AND PRIVACY  
Subject confidentiality and privacy are strictly held in trust by the participating investigators, their staff, 
and the Sponsor and their interventions. This confidentiality is extended to cover testing of biological 
samples and genetic tests in addition to the clinical information relating to subjects. Therefore, the study 
protocol, documentation, data, and all other information generated will be held in strict confidence. No 
information concerning the study or the data will be released to any unauthorized third party without 
prior written approval of the Sponsor.  
All research activities will be conducted in a setting as private as possible. The investigator must assure 
that the subjects’ anonymity will be maintained and that subjects’ identities are protected from 
unauthorized parties. On CRFs or other documents submitted to the Sponsor, subjects should not be 
identified by their names, but by an identification code. The investigator should keep a subject log 
relating codes with the names of subjects. The investigator should maintain in strict confidence 
documents not for submission to the Sponsor (eg, subjects’ written consent forms). 
The study monitor, other authorized representatives of the Sponsor, and representatives of the IRB/EC, 
regulatory agencies, or pharmaceutical company supplying study treatment may inspect all documents 
and records required to be maintained by the investigator, including but not limited to, medical records 
(office, clinic, or hospital) and pharmacy records for the subjects in this study. The clinical study site will 
permit access to such records. 
The study subject’s contact information will be securely stored at each clinical site for internal use 
during the study. At the end of the study, all records will continue to be kept in a secure location for as 
long a period as dictated by the applicable legal or regulatory requirements, the reviewing IRB/EC, 
Institutional policies, or Sponsor requirements. 
Study subject research data, which are for purposes of statistical analysis and scientific reporting, will be 
transmitted to and stored at the data management company responsible for data management, 
analysis, and reporting. This will not include the subject’s contact or identifying information. Rather, 
individual subjects and their research data will be identified by a unique study identification number. 
The study data entry and study management systems used by clinical study centers and by data 
management research staff will be secured and password protected. At the end of the study, all study 
databases will be de-identified and archived by the Sponsor.  
All information generated in this study must be considered highly confidential and must not be disclosed 
to any persons not directly concerned with the study without written prior permission from the 
Sponsor. Authorized regulatory officials and Sponsor personnel (or their representatives) will be allowed 

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full access to inspect and copy the records. All study investigational product, subject bodily fluids, and/or 
other materials collected shall be used solely in accordance with this protocol, unless otherwise agreed 
to in writing by the Sponsor. Subjects will only be identified by unique subject numbers on eCRFs. Every 
subject will be given a copy of each version of the ICF that he or she signs before and during the study. 
Each ICF may also include authorization allowing the institution, investigator, and Sponsor to use and 
disclose personal health information in compliance with the Health Information Portability and 
Accountability Act (HIPAA). 
10.1.4 FUTURE USE OF STORED SPECIMENS AND DATA  
With the subject’s approval and approval by IRB/EC, de-identified biological samples will be stored at a 
certified, licensed central laboratory. Remaining serum from samples collected for PK/immunogenicity 
endpoints may be retained for assay method development, troubleshooting, or validating. Samples will 
not be used for genetic analyses. During the conduct of the study, a subject may choose to withdraw 
consent to have biological specimens stored for future research. Those samples will be destroyed. In 
addition, once other samples (safety labs, tape strips) have been analyzed, specimens will be destroyed. 
If no analyses have been completed within 5 years following EOS, samples will be destroyed.  
10.1.5 MEDICAL MONITOR 
Medical monitoring will be conducted to ensure the early recognition, identification and reporting of 
issues impacting on subjects’ health and well-being throughout the study. Details of medical monitoring 
with contact information of the Medical Monitors will be documented in a Medical Monitoring Plan. 
10.1.6 SAFETY OVERSIGHT 
No Data and Safety Monitoring Board is required as part of this study. 
10.1.7 CLINICAL MONITORING 
All aspects of the study will be monitored by the Sponsor or authorized representatives of the Sponsor 
according to GCP and Standard Operating Procedures (SOPs) for compliance with applicable government 
regulations (ie, Informed Consent Regulations [US 21CFR, Part 50] and IRB regulations [US 21CFR, Part 
56.103]).  
Access to all records, both during the study and after study completion, should be made available to the 
Sponsor at any time for review and audit to ensure the integrity of the data. The investigator must notify 
Sponsor immediately if the responsible IRB/EC has been disqualified or if proceedings leading to 
disqualification have begun.  
The investigator must conduct the protocol in accordance with applicable GCP regulations and 
guidelines; applicable informed consent regulations (US 21CFR, Part 50); and in compliance with the 
Declaration of Helsinki. Every attempt must be made to follow the protocol and to obtain and record all 
data requested for each subject at the specified times. If data are not recorded per protocol, the reasons 
must be clearly documented on the eCRF/records.  
Before study initiation, at a study center initiation visit or at a meeting with the investigator(s), a 
representative from the Sponsor will review the protocol and study eCRFs with the investigator(s) and 
their staff. During the study, the study monitor will visit the study center regularly to check the 
completeness of subject records, the accuracy of entries on the eCRFs, the adherence to the protocol 
and to GCP, the progress of enrollment, and to ensure that consent is being sought and obtained in 
compliance with applicable regulations, and that the study drug is being stored, dispensed and 
accounted for according to specifications.  

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The investigator and key study personnel must be available to assist the monitor during these visits. The 
investigator must give the monitor access to relevant hospital or clinical records, to confirm their 
consistency with the eCRF entries. No information in these records about the identity of the subjects will 
leave the study center.  
Monitoring standards require full verification for the presence of informed consent, adherence to the 
inclusion/exclusion criteria, documentation of SAEs, and the recording of primary efficacy and safety 
variables. Additional checks of the consistency of the source data with the eCRFs will be performed 
according to the study-specific Monitoring Plan.  
The investigator must promptly complete the eCRFs after the subject’s visit. The monitor is responsible 
for reviewing them and clarifying and resolving any data queries. A copy of the eCRFs will be retained by 
the investigator who must ensure that it is stored in a secure place with other study documents, such as 
the protocol, the IB, and any protocol amendments.  
The investigator must provide the Sponsor and the responsible IRB/EC with a study summary shortly 
after study completion, or as designated by the Sponsor. 
10.1.8 QUALITY ASSURANCE AND QUALITY CONTROL 
Each clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation, and completion.  
Quality control (QC) procedures will be implemented beginning with the data entry system, and data QC 
checks, which will be run on the database, will be generated. Any missing data or data anomalies will be 
communicated to the site(s) for clarification/resolution. 
Following written SOPs, the monitors will verify that the clinical study is conducted and data are 
generated and biological specimens are collected, documented (recorded), and reported in compliance 
with the protocol, ICH GCP, and applicable regulatory requirements (eg, GLP, Good Manufacturing 
Practices [GMP]).  
The investigational site will provide direct access to all study-related sites, source data/documents, and 
reports for the purpose of monitoring and auditing by the Sponsor, and inspection by IRB/EC and local 
and regulatory authorities. 
10.1.9 DATA HANDLING AND RECORD KEEPING  
10.1.9.1 DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES  
All protocol-specified data will be recorded in site source documents. Study data will be entered within 
the clinical database eCRFs from the original source documents. Upon each subject’s completion of the 
study, the investigator is required to sign and affirm the data entered in the subject CRF along with a 
statement attesting that all pages of the subject’s case report have been reviewed. All investigator data 
attestation signatures will be made through the 21 CFR Part 11 compliant EDC system. Signature stamps 
and “per signatures” are not acceptable.  
It is the Sponsor’s policy that study data be verifiable with the source data which necessitates access to 
all original recordings, laboratory reports, and other records for each subject. The investigator must 
therefore agree to allow access to subjects’ records, and source data must be made available for all 
study data. Subjects (or their legal representatives) must also allow access to their medical records. 
Subjects will be informed of the importance of increased record access and permission granted by 
signature on the informed consent document prior to Screening.  

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Checks will be performed to ensure quality, consistency, and completeness of the data. Instances of 
missing or uninterpretable data will be resolved with the investigator or study coordinator. Data queries, 
documented within the clinical database, will be accessible to the research facility through the EDC 
system. Study center personnel will be responsible for providing resolutions to the data queries and for 
correcting the eCRFs, as appropriate. 
The investigator must keep written or electronic source documents for every subject participating in the 
clinical study for the appropriate document retention period. The subject file that identifies the study in 
which the subject is participating must include the subject’s available demographic and medical 
information, including:  
 Name 
 Contact information 
 Year of birth 
 Sex 
 Fitzpatrick skin type 
 Medical history 
 Concomitant therapies/medication 
 Study visit dates 
 Performed examinations, evaluations, and clinical findings 
 Investigational product administration 
 AEs, SAEs, or pregnancy (as applicable)  
Additionally, any other documents with source data, especially original printouts of data that were 
generated by technical equipment must be included in the subject’s source document (eg, laboratory 
value listings). All these documents must have at least the subject’s study number, and the date of the 
evaluation.  
The data recorded during the course of the study will be documented in the eCRF and/or the 
study-specific forms. Before or at study termination, all data must be forwarded to the Sponsor. The 
data will then be recorded, evaluated, and stored in anonymous or coded form in accordance with 
data-protection regulations.  
Subjects will authorize the use of their protected health information during the informed consent 
process in accordance with the applicable privacy requirements. Subjects who deny permission to use 
and disclose protected health information will not be eligible to participate in the study.  
The investigator will ensure that the study documents forwarded to the Sponsor, and any other 
documents, contain no mention of subject names. Any amendments and corrections necessary will be 
undertaken in both the source documents and eCRFs (as appropriate), and countersigned by the 
investigator, or documented designee, stating the date of the amendment/correction. Errors must 
remain legible and may not be deleted with correction aids. The investigator must state his/her reason 
for the correction of any data. In the case of missing data/remarks, the entry spaces provided in the 
eCRF should be cancelled out so as to avoid unnecessary follow-up inquiries.  
Electronic CRFs will be kept by the Sponsor or an authorized designee in a secured area. Clinical data will 
be recorded in a computer format for subsequent statistical analyses. Data files will be stored on 
electronic media with a final master data file kept by the Sponsor after descriptive and statistical 
analyses and reports have been generated and are complete.  

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It is the responsibility of the investigator to ensure that the study center file is maintained in accordance 
with the ICH Guidance for Industry E6(R2) GCP: Consolidated Guidance, Section 8 – Essential Documents 
for the Conduct of a Clinical Trial. 
10.1.9.2 STUDY RECORDS RETENTION  
Study documents should be retained for a minimum of 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 until at least 2 years have elapsed since the formal discontinuation of clinical 
development of the study treatment. These documents should be retained for a longer period, however, 
if required by local regulations or as specified in the study agreement, whichever retention period is 
longer.  
If the investigator withdraws from the study (eg, relocation, retirement), all study-related records should 
be transferred to a mutually agreed-upon designee. Notice of such transfer will be provided to the 
Sponsor in writing. No records will be destroyed without the written consent of the Sponsor, if 
applicable. It is the responsibility of the Sponsor to inform the investigator when these documents no 
longer need to be retained.  
10.1.10 PROTOCOL DEVIATIONS  
A protocol deviation is any noncompliance with the clinical study protocol or ICH GCP requirements. The 
noncompliance may be either on the part of the subject, the investigator, or the study site staff. As a 
result of deviations, corrective actions are to be developed by the site and implemented promptly. 
Protocol deviations related to COVID-19 pandemic will be identified and documented accordingly. 
These practices are consistent with ICH GCP:  
 4.5 Compliance with Protocol, Sections 4.5.1, 4.5.2, and 4.5.3  
 5.1 Quality Assurance and Quality Control, Section 5.1.1  
 5.20 Noncompliance, Sections 5.20.1, and 5.20.2.  
It is the responsibility of the investigator to use continuous vigilance to identify and report deviations as 
soon as possible. All deviations must be addressed in study source documents, and applicable deviations 
must be sent to the reviewing IRB/EC per their policies. The investigator is responsible for knowing and 
adhering to the reviewing IRB/EC requirements. Further details about the handling of protocol 
deviations will be included in the Protocol Deviation Plan, Data Management Plan, Medical Monitoring 
Plan, blind data review documentation, and SAP.  
This study will be conducted as described in this protocol, except for an emergency situation in which 
the protection, safety, and well-being of the subject requires immediate intervention, based on the 
judgment of the investigator (or a designee, appropriately trained professional designated by the 
investigator). In the event of a significant deviation from the protocol due to an emergency, accident, or 
mistake, the investigator or designee must contact the Medical Monitor and the Sponsor at the earliest 
possible time by telephone. This will allow an early joint decision regarding the subject’s continuation in 
the study. This decision will be documented by the investigator and the Medical Monitor. Please refer to 
Section 4.2 for allowable, as necessary, modifications to the protocol due to COVID-19 restrictions. 
The monitor must ensure that a prompt action is taken to secure compliance. If a noncompliance that 
significantly affects or has the potential to significantly affect human subject protection or reliability of 
study results is discovered, the CRO and the Sponsor should perform a root cause analysis and 
implement appropriate corrective and preventive actions. 

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10.1.11 PUBLICATION AND DATA SHARING POLICY 
This study will be conducted in accordance with the following publication and data sharing policies and 
regulations: It is understood by the investigator that the information generated in this study will be used 
by the Sponsor in connection with the development of the product. To allow for the use of information 
derived from the study, it is understood that the investigator is obliged to provide the Sponsor with 
complete test results, all study data, and access to all study records.  
Any results of medical investigations with Sponsor’s products and/or publications/lectures/manuscripts 
based thereon shall be exchanged and discussed by the investigator and Sponsor representative(s), 
30 days before submission for publication or presentation. Due regard shall be given to Sponsor’s 
legitimate interests for example, manuscript authorship, obtaining optimal patent protection, 
coordinating and maintaining the proprietary nature of submissions to health authorities, coordinating 
with other ongoing studies in the same field, and protecting confidential data and information. The 
Sponsor shall be furnished with a copy of any proposed publication. Comments shall be rendered 
without undue delay.  
In cases of publications or presentations of material arising from multicenter clinical investigations, the 
Sponsor is to serve as coordinator and referee. Individual investigators who are part of a multicenter 
investigation may not publish or present data that are considered common to a multicenter 
investigation without the consent of the other participating investigators and the prior review of the 
Sponsor.  
Results from investigations shall not be made available to any third party by the investigating team 
outside the publication procedure as outlined previously. The Sponsor will not quote from publications 
by investigators in its scientific information and/or promotional material without full acknowledgment 
of the source (ie, author and reference). 
10.1.12 CONFLICT OF INTEREST POLICY 
The independence of this study from any actual or perceived influence is critical. Therefore, any actual 
conflict of interest of persons who have a role in the design, conduct, analysis, publication, financial 
interest, or any aspect of this study will be disclosed and managed. Furthermore, persons who have a 
perceived conflict of interest will be required to have such conflicts managed in a way that is 
appropriate to their participation in the design and conduct of this study. The Sponsor has established 
policies and procedures for all study group members to disclose all conflicts of interest and will establish 
a mechanism for the management of all reported dualities of interest.
10.2 ADDITIONAL CONSIDERATIONS 
10.2.1 ETHICS AND RESPONSIBILITY  
This study must be conducted in compliance with the protocol, the ICH Guidance for Industry E6(R2) 
GCP: Consolidated Guidance, the Declaration of Helsinki, IRB/EC requirements, and all applicable 
national and local regulatory requirements. Investigators must submit all essential regulatory 
documentation, as required by local and national regulations (including approval of the protocol and ICF 
by a Health and Human Services [HHS]-registered IRB/EC) to the Sponsor before investigational product 
will be shipped to the respective study centers. 
10.2.2 AMENDMENT POLICY  
Only the Sponsor (or designee) may modify the protocol. Amendments must be approved by all 
applicable national and local committees including, but not limited to, the government regulatory 

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97 
authorities and/or regional IRB/EC before implementation. The only exception is when an investigator 
considers that a subject may be harmed, and immediate action is necessary. Under these circumstances, 
approval of the chairman of the IRB/EC, or an authorized designee, must be sought immediately. The 
investigator should inform the Sponsor, and the full IRB/EC, no later than 5 working days after the 
emergency occurs. Protocol-specified safety reporting requirements must be adhered to, independent 
of any other variables.  
10.2.3 INSURANCE  
Sponsor will provide insurance in accordance with local guidelines and requirements for the subjects in 
this study. The terms of the insurance will be kept in the study files. 

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11 REFERENCES  
Attwa E. Review of narrowband ultraviolet B radiation in vitiligo. World Journal of Dermatology. 
2016;5(2):93-108. 
Bangsgaard N, Houtkamp M, Schuurhuis D, et al. Neutralization of IL-8 prevents the induction of 
dermatologic adverse events associated with the inhibition of epidermal growth factor receptor. PLoS 
ONE. 2012;7(6):e39706. 
Boone SL, Rademaker A, Liu D, et al. Impact and management of skin toxicity associated with 
anti-epidermal growth factor receptor therapy: survey results. Oncology. 2007;72(3–4):152–159. 
Dubey JP, Markovits JE, Killary KA. Cryptosporidium muris-like infection in stomach of cynomolgus 
monkeys (Macaca Fascicularis). Vet Pathol. 2002;39(3):363-71. 
ECOG Performance Status. ECOG-ACRIN Cancer Research Group. 2020. https://ecog-
acrin.org/resources/ecog-performance-status 
Farahnik B, Kwong B, Murase J. General management strategy for epidermal growth factor receptor 
inhibitor-associated papulopustular eruption. J Am Acad Dermatol. 2016;75(5):e191. 
Farthing MJ. Treatment options for the eradication of intestinal protozoa. Nat Rev Gastroent Hepat. 
2006;3:436-445. 
Farrar JT, Young Jr. JP, LaMoreaux L, et al. Clinical importance of changes in chronic pain intensity 
measured on an 11-point numerical pain rating scale. Pain. 2001;94(2):149-58. 
Fitzpatrick, TB. 1988. The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol 
1988 Jun;124(6):869-71. doi: 10.1001/archderm.124.6.869. 
Lacouture ME, Anadkat MJ, Bensadoun RJ, et al. Clinical practice guidelines for the prevention and 
treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer. 2011; 19:1079–95. 
Lacouture ME, Maitland ML, Segaert S, et al. A proposed EGFR inhibitor dermatologic adverse event-
specific grading scale from the MASCC skin toxicity study group. Support Care Cancer. 2010;18:509–522. 
Lacouture ME, Sibaud V. Toxic Side Effects of Targeted Therapies and Immunotherapies Affecting the 
Skin, Oral Mucosa, Hair, and Nails. Am J Clin Dermatol. 2018; 19(Suppl 1): 31–39. 
Lichtenberger BM, Gerber PA, Holcmann M, et al. Epidermal EGFR controls cutaneous host defense and 
prevents inflammation. Sci Transl Med. 2013;5(199):199ra111. 
Lui M, Gallo-Hershberg D, DeAngelis C. Development and validation of a patient-reported questionnaire 
assessing systemic therapy induced diarrhea in oncology patients. Health and Quality of Life Outcomes. 
2017;15:249 
Oken MM, Creech RH, Torme, DC, et al. Toxicity and response criteria of the Eastern Cooperative 
Oncology Group. Am J Clin Oncol. 1982;5:649-655. 
Manousaridis I, Mavridou S, Goerdt S, et al. Cutaneous side effects of inhibitors of the 
RAS/RAF/MEK/ERK signalling pathway and their management. J Eur Acad Dermatol Venereol. 
2013;27(1):11-18. 
Pascoe VL, Enamandram M, Corey KC, et al. Using the Physician Global Assessment in a clinical setting to 
measure and track patient outcomes. JAMA Dermatol. 2015;151(4):375-381. 

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Phan NQ, Blome C, Fritz F, et al. Assessment of pruritus intensity: prospective study on validity and 
reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with 
chronic pruritus. Acta Derm Venereol. 2012;92(5):502-507. 
Rosen AC, Case EC, Dusza SW, et al. Impact of dermatologic adverse events on quality of life in 283 
cancer patients: a questionnaire study in a dermatology referral clinic. Am J Clin Dermatol. 
2013;14(4):327–33. 
Satoh TK, Mellett M, Meier-Schiesser B, et al. IL-36  drives skin toxicity induced by EGFR/MEK inhibition 
and commensal Cutibacterium acnes. J Clin Invest. 2020; 130(3): 1417–1430. 
Segaert S, Van Cutsem E. Clinical signs, pathophysiology and management of skin toxicity during therapy 
with epidermal growth factor receptor inhibitors. Ann Oncol. 2005;16(9):1425–1433. 
Verweyen E, Stander S, Kreitz K, et al. Validation of a Comprehensive Set of Pruritus Assessment 
Instruments: The Chronic Pruritus Tools Questionnaire PRURITOOLS. Acta Derm Venereol. 
2019;99(7):657-663. 
Wagner LI, Rosenbaum SE, Gandhi M, et al. The development of a Functional Assessment of Cancer 
Therapy (FACT) questionnaire to assess dermatologic symptoms associated with epidermal growth 
factor receptor inhibitors (FACT-EGFRI-18). Support Care Cancer. 2013;21(4):1033-41. 
Wallace HJ, Fear MW, Crowe MM, Martin LJ, Wood FM. Identification of factors predicting scar outcome 
after burn injury in children: a prospective case-control study. Burns Trauma. 2017;5:19. 
Yalcin I, Bump R. Validation of two global impression questionnaires for incontinence. Am J Obstet 
Gynecol. 2003;189:98-101. 
Yano S, Kondo K, Yamaguchi M, et al. Distribution and function of EGFR in human tissue and the effect of 
EGFR tyrosine kinase inhibition. Anticancer Res. 2003; 23:3639–50. 
Zalaudek I, Argenziano G, Mordente I, et al. Nevus type in dermoscopy is related to skin type in white 
persons. Arch Dermatol. 2007;143(3):351-356. 

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12 APPENDICES 
Appendix 1: 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 treatment, additional evaluation should be considered. 
Women in the following categories are not considered WOCBP (not of childbearing potential) 
1. Premenarchal 
2. Surgically sterilized based on meeting at least 1 of the following: 
a) Documented hysterectomy. 
b) Documented bilateral salpingectomy,  
c) Documented bilateral oophorectomy. 
Note: 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 FSH level in the postmenopausal range will 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 
nonestrogen 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 meet or 
agree to ONE of the following (during the protocol-defined time frame in Section 5.1):  
 Documented vasectomy with confirmed absence of sperm. 
 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 

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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 during the 
protocol-defined time frame in Section 5.1, and refrain from donating oocytes for assisted reproduction 
during this period. For WOCBP, hormonal contraceptives must be used without schedule changes and 
on a stable regimen during the study treatment. Starting hormonal contraceptives during the study is 
not permitted.  

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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) 
Implants inserted beneath the skin 
Tubal ligation or 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). 
Additional pregnancy testing should be performed as mentioned in the SoA (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 
pharmacovigilance unit 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.  
Any SAEs associated with the pregnancy in the male subject’s partner should also be reported to the 
pharmacovigilance unit within 24 hours of the event using the back-up paper SAE Report Form. 
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 Pregnancy Report form and submitted to 
the pharmacovigilance unit 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 poststudy pregnancy-related SAE considered reasonably related to the study treatment by the 
investigator will be reported to the Sponsor as described in Section 8.2.1.8. 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 4: Patient Global Impression of Severity 
Overall, how would you rate the severity of your rash now? 
1. 
 
Clear Skin 
2. 
 
Mild 
3. 
 
Moderate 
4. 
 
Severe 

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Appendix 5: Patient Global Impression of Change 
Overall, how would you rate the change in severity of your rash compared with how it was before you 
started taking the medication in this study? 
1. 
 
Very much better 
2. 
 
Much better 
3. 
 
A little better 
4. 
 
No change 
5. 
 
A little worse 
6. 
 
Much worse 
7. 
 
Very much worse 
 

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10) Rank how much your bowel habits in the last 7 days affect your mood. 
0 
no impact 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
extreme impact 
11) Rank how much your diarrhea has affected your family life. 
0 
no impact 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
extreme impact 
12) Rank how much your diarrhea has affected your social life. 
0 
no impact 
1 
 
2 
 
3 
 
4 
 
5 
 
6 
 
7 
 
8 
 
9 
 
10 
extreme impact 
Source: Lui 2017 
http://creativecommons.org/licenses/by/4.0/ 

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Appendix 7: Clinical Laboratory Tests  
The tests detailed in Table 18 will be performed by the central laboratory. The time points are specified 
in the SoA (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 make an immediate decision for any safety concerns. Local 
laboratory tests will also be allowed at Screening for TB and viral serology testing. If a local sample is 
collected, 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 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. 
Investigators must document their review of each laboratory safety report. 
Table 18: Protocol-required Safety Laboratory Assessments by Central Laboratory 
Laboratory Assessments
Parameters
Hematology 
Hemoglobin 
Red blood cell (RBC) count 
Hematocrit/ Packed cell volume 
(PCV) 
White blood cell (WBC) count with 
Differential: 
Neutrophils 
Mean corpuscular hemoglobin 
(MCH) 
Lymphocytes 
Mean corpuscular volume (MCV) 
Monocytes 
Mean corpuscular hemoglobin 
concentration (MCHC) 
Eosinophils 
Basophils
Platelet count 
Biochemistry 
Alanine aminotransferase (ALT)
Creatinine
Albumin 
Creatinine clearance
Alkaline phosphatase (ALP) 
Gamma glutamyl transferase (GGT) 
Aspartate aminotransferase (AST) 
Glucose
Bicarbonate 
Potassium
Bilirubin (Total)
Phosphate (Inorganic)
Bilirubin (Direct-only if total is 
elevated) 
Protein (Total) 
Sodium 
Calcium 
Blood urea nitrogen (urea)
Chloride
Creatine kinase (CK) 
Uric acid
Triglycerides 
Lactate dehydrogenase
high-sensitivity C-reactive protein (hsCRP)
Troponin 
Total cholesterol (fractions) 
Serum pregnancy 
Human chorionic gonadotropin (hCG) pregnancy test (as needed for women of 
childbearing potential)
Follicle-stimulating 
hormone (FSH) 
In women of nonchildbearing potential only (postmenopausal women with at least 
12 months of amenorrhea without an alternative medical cause)

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Laboratory Assessments
Parameters
Urinalysis 
Bilirubin 
pH 
Blood 
Protein 
Glucose
Specific gravity
Ketones 
Urobilinogen 
Leukocytes 
Nitrites
Microscopy (At discretion of the investigator 
based on urinalysis results) 
 
Viral serology 
Antibodies to hepatitis B core
antigens 
Hepatitis B surface antigen 
Hepatitis C antibody
Human immunodeficiency virus 
antibodies 
Tuberculosis (TB) 
screening
QuantiFERON-TB Gold®In-Tube, the third-generation test (If the test indeterminate 
it can be retested only once) 
NOTES: Please see SoA for laboratory tests time points. 
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.
 

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Appendix 8: Fitzpatrick Skin Type Classification  
Fitzpatrick Classification of Skin types 
Skin Type 
Hair 
Complexion 
Freckles 
Sun Reaction 
Tanning 
I 
Red or Blond 
Very Fair 
+++ 
Always burns 
Never tans 
II 
Blond 
Fair 
++ 
Often burns 
Tans lightly 
III 
Blond or Light 
Brown 
Fair to medium 
+ to 0 
Sometimes 
burns 
Tans 
progressively 
IV 
Brown 
Olive 
0 
Rarely burns 
Tans easily 
V 
Brown to Black 
Dark 
0 
Rarely burns 
Tans deeply 
VI 
Black 
Very dark 
0 
Never burns 
Tans deeply 
Source: Attwa 2016; Fitzpatrick 1988; Wallace 2017; Zalaudek 2007