A Phase 2 Study to Evaluate the Efficacy and Safety of RPT193 as Monotherapy in Adults With Moderate-to-Severe Atopic Dermatitis
Phase: PHASE2
Conditions: Atopic Dermatitis
Sponsor: RAPT Therapeutics, Inc.

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
1 
 
 
 
TITLE PAGE 
Protocol Title: A Phase 2 Study to Evaluate the Efficacy and Safety of RPT193 as Monotherapy in 
Adults with Moderate-to-Severe Atopic Dermatitis 
Protocol Number: RPT193-02 
Amendment Number: 2.0 
Product: RPT193 
Short Title: An Efficacy and Safety Study of RPT193 in Adults with Atopic Dermatitis 
Study Phase: Phase 2 
Sponsor Name: RAPT Therapeutics, Inc. 
Legal Registered Address: 
561 Eccles Avenue 
South San Francisco, CA 94080 
United States 
 
 
 
Date of Protocol: 07 July 2023 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
2 
 
 
PROTOCOL AMENDMENT SUMMARY OF CHANGES 
 
 
DOCUMENT HISTORY 
Document 
Date 
Amendment 2.0 
07 July 2023 
Amendment 1 
31 May 2022 
Original Protocol 
22 November 2021 
 
Additions indicated with italicized text, deletions with strikethrough text. 
 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
PK parameters at Week 2, 4, 8, 12, 16, and 18. 
Correction for consistency 
with Section 3.0. 
1.1 Synopsis 
Approximately 60 80 sites in the US, Canada, and 
Poland are expected to participate in this study. 
Additional sites and 
countries were added. 
1.1 Synopsis; 
5.1 Inclusion Criteria 
6. 
Subject has a documented history of inadequate 
response to a ≥1 month treatment with topical 
medications, such as class I-V topical 
corticosteroids, topical phosphodiesterase 4 
(PDE4) inhibitor (e.g., crisaborole), and/or 
calcineurin inhibitors in the 6 months prior to the 
Screening visit or subjects for whom topical 
treatments are otherwise medically inadvisable. 
Clarification. 
1.1 Synopsis; 
5.1 Inclusion Criteria 
6. Subject has an EASI score ≥16 at Screening and 
at Baseline. 
• 
Subjects may be screened with an EASI 
score ≥12 if the subject is administering 
class I-V topical corticosteroids, topical 
PDE4 inhibitor (e.g., crisaborole), and/or 
topical calcineurin inhibitors or is using 
systemic immunosuppressants 
(e.g., methotrexate, cyclosporine A, 
mycophenolic acid, azathioprine, and/or 
systemic corticosteroids); eligibility for the 
study requires follow-up EASI score ≥16 at 
Baseline (after the relevant washout period 
for the index medication has been satisfied). 
Clarification. 
1.1 Synopsis; 
5.2 Exclusion Criteria 
6. Any of the following specific laboratory 
findings: 
• 
Alanine aminotransferase (ALT) 
>2.5× upper limit of normal (ULN) 
• 
Estimated glomerular filtration rate (eGFR) 
<60 mL/min/1.73m2 (Modification of Diet 
in Renal Disease [MDRD] equation) 
Note: For subjects between the ages of 50 to 
75 years old with an eGFR lower than 
60 mL/min/1.73 m2 but potentially within 
normal range for the subject’s age, please 
contact the Medical Monitor to discuss the 
subject’s eligibility 
Clarification. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
3 
 
 
 
Section # and Name 
Description of Change 
Brief Rationale 
 
• 
Platelet count <75,000 cells/mm3 
• 
Hemoglobin <10 g/dL 
• 
Absolute lymphocyte count <800 cells per 
mm3 
• 
Absolute neutrophil count <1500 cells per 
mm3 
1.1 Synopsis; 
5.2 Exclusion Criteria 
11. Subject has received treatment with systemic 
immunosuppressive/ immunomodulating drugs 
(e.g., methotrexate, cyclosporine A, systemic 
JAK inhibitors, mycophenolic acid, 
methotrexate, or azathioprine), 
immunoglobulins, blood products and/or 
systemic corticosteroids (e.g., oral, intravenous, 
intraarticular, rectal) within 4 weeks prior to the 
Baseline visit. 
Note: Intranasal corticosteroids and inhaled 
corticosteroids are allowed. Eye and ear drops 
containing corticosteroids are also allowed. 
The washout period for 
systemic JAK inhibitors is 
8 weeks per exclusion 
criterion 18. 
1.1 Synopsis; 
5.2 Exclusion Criteria 
12. Subject has used any topical medicated 
treatment that could affect AD within 2 weeks 
prior to the Baseline visit, including, but not 
limited to, topical corticosteroids, topical PDE4 
inhibitor (e.g., crisaborole), topical calcineurin 
inhibitors, topical JAK inhibitors 
(e.g., ruxolitinib), tars, topical antimicrobials, 
and medical devices. 
Clarification. 
1.2 Schema 
Figure 1 (Study Schema) was revised to remove 
inclusion criteria related to BMI. 
Correction for consistency 
with inclusion criteria. 
1.3 Schedule of Activities 
(footnotes) 
k. On Day 1, Day 15, Day 29, Day 57, and Day 85, 
the study drug will be administered at the study 
center after all other assessments are performed. 
All other daily drug intake will be 
self-administered by the subject, at home, at 
approximately the same time of the day through 
Day 112. 
l. 
PK blood sampling will be done pre-dose on 
Day 1, Day 15, Day 29 and Day 57. 
m. Tape stripping is only required for subjects in 
the US and Canada; tape stripping should not be 
performed for subjects in Poland. Tape strips 
will be collected from lesional and non-lesional 
skin pre-dose at Baseline. Tape strip samples 
will also be collected at the same sites sampled 
at Baseline on Day 29, Day 27 57, Day 113, and 
on Days 141 and 169, if applicable. 
Clarification that tape 
stripping will not be 
performed for subjects in 
Poland. Minor corrections. 
1.3 Schedule of Activities 
(footnotes) 
p. The immunophenotyping sample is only required 
for subjects in the US and Canada; 
immunophenotyping samples should not be collected 
from subjects in Poland. 
p. q. Blood sample will be collected from subjects 
who have consented to participate in the genetic 
analysis component of the study. Participation is 
optional. Please see Section 8.7 for further details. 
Clarification that 
immunophenotyping will 
not be performed for 
subjects in Poland. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
4 
 
 
 
Section # and Name 
Description of Change 
Brief Rationale 
2.2.1.2 Historical and 
Emerging Standard of 
Care 
There are 2 key recent developments within the AD 
treatment landscape: (1) dupilumab, the biologic 
agent approved for moderate-to-severe AD, and 
(2) recent approvals of oral Janus kinase (JAK) 
inhibitors, which have completed Phase 3 studies and 
are currently under review by the Food and Drug 
Administration (FDA). 
Revision to reflect the 
current regulatory status of 
JAK inhibitors. 
2.2.1.2 Historical and 
Emerging Standard of 
Care 
Additionally, the FDA has placed black box warnings 
for JAK inhibitors approved in other indications due 
to the potential for serious infections, malignancies, 
and thromboembolic events. Approved JAK 
inhibitors have been associated with serious side 
effects (including serious infection, malignancy, and 
thromboembolic events), which is reflected in the US, 
EU, and Canadian labeling. 
Revision to reflect the 
product labeling in Canada 
and Poland in addition to 
the US. 
5.4 Screen Failures 
Subjects may be rescreened once provided the 
disqualifying reason is considered transient and is not 
related to disease activity status (i.e., vIGA, BSA, or 
EASI), if deemed acceptable by the Investigator. The 
Investigator may consult with the and Medical 
Monitor on rescreening decisions if needed. 
Clarification. 
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding 
The randomization list will be stratified based on 
region (North America vs. rest of world), baseline 
vIGA scores (vIGA of 3 vs. 4), and prior dupilumab 
or tralokinumab use (yes or no). (Note: Enrollment of 
subjects with a prior history of dupilumab or 
tralokinumab use will be capped at approximately 
20%.) 
Revision to incorporate 
stratification by region. 
6.5 Prior Therapy 
Eligible subjects will need to have had a documented 
history of inadequate response to a ≥1-month 
treatment with topical medication, such as 
corticosteroids (class I to V), calcineurin inhibitors, 
and/or topical PDE4 inhibitor (e.g., crisaborole). 
Clarification. 
6.6.3 Prohibited Therapies 
or Procedures 
Table 3 (Prohibited Therapies or Procedures for 
Study Duration with Washout Periods) was revised to 
indicate that an 8-week washout period is required 
for systemic JAK inhibitors. 
Correction for consistency 
with exclusion criterion 18. 
6.6.4 Rescue Medications 
Permitted rescue medications include Mid potency, 
low-to-moderate potency (class IV-class VII), topical 
corticosteroids (Appendix 14) and should be applied 
only to problem areas. A topical calcineurin inhibitor, 
topical PDE4 inhibitor (e.g., crisaborole), or 
low-potency topical steroid may be used on the face 
if affected. 
Correction for consistency 
with Appendix 14 and 
clarification. 
8.1.5 Eczema Activity and 
Severity Index (EASI) 
To be eligible for this study, subjects must have an 
EASI score of ≥16 at the Screening and Baseline 
visit, except for subjects who are administering class 
I-V topical corticosteroids, topical PDE4 inhibitor 
(e.g., crisaborole), and/or calcineurin inhibitors or is 
using systemic immunosuppressants (e.g., 
methotrexate, cyclosporine A, mycophenolic acid, 
azathioprine, and/or systemic corticosteroids). 
Clarification. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
8 
 
 
TABLE OF CONTENTS 
1.0 
PROTOCOL SUMMARY ......................................................................................... 12 
1.1 
Synopsis ........................................................................................................... 12 
1.2 
Schema ............................................................................................................ 21 
1.3 
Schedule of Activities ..................................................................................... 22 
2.0 
INTRODUCTION ...................................................................................................... 26 
2.1 
Study Rationale .............................................................................................. 26 
2.2 
Background ..................................................................................................... 26 
2.2.1 
Atopic Dermatitis ............................................................................... 26 
2.2.2 
RPT193 .............................................................................................. 28 
2.3 
Benefit/Risk Assessment ................................................................................ 33 
2.3.1 
Known Potential Risks and Benefits.................................................. 33 
2.3.2 
Assessment of Risks and Benefits ..................................................... 33 
3.0 
OBJECTIVES AND ENDPOINTS ........................................................................... 34 
4.0 
STUDY DESIGN ........................................................................................................ 37 
4.1 
Overall Design ................................................................................................ 37 
4.2 
Scientific Rationale for Study Design ........................................................... 37 
4.3 
Justification for Dose ..................................................................................... 37 
4.4 
End of Study Definition ................................................................................. 38 
5.0 
STUDY POPULATION ............................................................................................. 39 
5.1 
Inclusion Criteria ........................................................................................... 39 
5.2 
Exclusion Criteria .......................................................................................... 41 
5.3 
Lifestyle Considerations ................................................................................. 44 
5.3.1 
Meals and Dietary Restrictions .......................................................... 44 
5.3.2 
Activity .............................................................................................. 44 
5.4 
Screen Failures ............................................................................................... 44 
5.5 
Replacement of Subjects ................................................................................ 44 
6.0 
STUDY TREATMENT .............................................................................................. 45 
6.1 
Study Treatment(s) Administered ................................................................ 45 
6.2 
Preparation/Handling/Storage/Accountability ............................................. 46 
6.3 
Measures to Minimize Bias: Randomization and Blinding ........................ 46 
6.4 
Study Treatment and e-Diary Compliance .................................................. 47 
6.5 
Prior Therapy ................................................................................................. 48 
6.6 
Concomitant Therapy .................................................................................... 48 
6.6.1 
Permitted Therapies ........................................................................... 48 
6.6.2 
Prior Use of Dupilumab, Tralokinumab, or an Oral JAK 
Inhibitor ............................................................................................. 49 
6.6.3 
Prohibited Therapies or Procedures ................................................... 50 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
11 
 
 
TABLE OF TABLES 
Table 1 
Study Objectives and Endpoints ......................................................................34 
Table 2 
Study Treatment Details ...................................................................................45 
Table 3 
Prohibited Therapies or Procedures for Study Duration with Washout 
Periods ..............................................................................................................51 
Table 4 
Severe Laboratory Abnormalities Requiring Permanent Withdrawal 
from RPT193-02 ..............................................................................................55 
Table 5 
Analysis Sets ....................................................................................................71 
Table 6 
Study Administrative Structure ........................................................................86 
Table 7 
Protocol-required Safety Laboratory Assessments ........................................106 
 
 
TABLE OF FIGURES 
Figure 1 
Study Schema ...................................................................................................21 
Figure 2 
Pruritus Numeric Rating Scale .........................................................................59 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
16 
 
 
5. Subject has AD covering ≥10% of the BSA. 
6. Subject has an EASI score ≥16 at Screening and at Baseline. 
• 
Subjects may be screened with an EASI score ≥12 if the subject is administering class I-V topical 
corticosteroids, topical PDE4 inhibitor (e.g., crisaborole), and/or topical calcineurin inhibitors or 
is using systemic immunosuppressants (e.g., methotrexate, cyclosporine A, mycophenolic acid, 
azathioprine, and/or systemic corticosteroids); eligibility for the study requires follow-up EASI 
score ≥16 at Baseline (after the relevant washout period for the index medication has been 
satisfied). 
7. Subject has a Validated Investigator Global Assessment (vIGA) score ≥3. 
8. Subject has been using one or more emollient(s) (except urea-containing emollients or medicated 
emollients that are regulated as a medical device) at least twice daily for 1 week prior to Baseline 
(except on visit day before the visit) and agrees to continue using the same emollient(s) daily at the 
same frequency (at least twice daily) throughout the study. 
Notes: On the day of scheduled visit, subjects cannot apply emollient before their scheduled visit, and 
every effort should be made to use the same emollient throughout the study for the same body region. 
However, the chosen emollient may differ depending on the body region (e.g., body vs face emollient 
may be different). 
9. Female subject of childbearing potential has had a negative serum pregnancy test at Screening and 
negative urine pregnancy test at Baseline. 
10. For female subject of childbearing potential involved in any sexual intercourse that could lead to 
pregnancy: the subject must agree to use a highly effective contraceptive method from at least 4 
weeks prior to Day 1 until at least 30 days after the last study drug administration. Highly effective 
contraceptive methods include hormonal contraceptives (e.g., combined oral contraceptive, patch, 
vaginal ring, injectable, or implant), intrauterine devices or intrauterine systems, vasectomized 
partner(s), tubal ligation or double barrier methods of contraception (e.g., male condom with cervical 
cap, male condom with diaphragm, and male condom with contraceptive sponge) in conjunction with 
spermicide. 
Notes: 
• 
For countries where double barrier methods are not accepted as highly effective contraception, 
then this option must not be considered. 
• 
A female subject of nonchildbearing potential is defined as follows: 
• 
Female subject who has had surgical sterilization (hysterectomy, bilateral oophorectomy, or 
bilateral salpingectomy) 
• 
Female subject who has had a cessation of menses for at least 12 months prior to the 
Screening visit without an alternative medical cause, and a follicle-stimulating hormone 
(FSH) test confirming nonchildbearing potential (refer to laboratory reference ranges for 
confirmatory levels). 
• 
Subjects must have been on a stable regimen of hormonal contraceptives for at least 4 weeks prior 
to Baseline. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
17 
 
 
• 
The above list of contraceptive methods does not apply to subjects who are abstinent for 
at least 4 weeks before Baseline (Day 1) and will continue to be abstinent from penile-vaginal 
intercourse throughout the study. The reliability of sexual abstinence needs to be evaluated in 
relation to the duration of the clinical trial and the preferred and usual lifestyle of the participant. 
11. Female subject agrees not to have egg retrieval during the study and for 30 days after the last study 
drug administration. 
12. For male subject involved in any sexual intercourse that could lead to pregnancy, subject must agree 
to use one of the highly effective contraceptive methods listed in Inclusion Criterion #10, from 
Baseline (Day 1) until at least 90 days after the last study drug administration. If the female partner of 
a male subject uses any of the hormonal contraceptive methods listed above, this contraceptive 
method should be used by the female partner from at least 4 weeks before Baseline (Day 1) until at 
least 90 days after the last study drug administration. 
13. Male agrees not to donate sperm during the study and for 90 days after the last study drug 
administration. 
14. Subject has negative COVID-19 results at screening. 
15. Subject is willing to comply with discontinuation of prohibited treatments for AD as described in 
Table 3 for the duration of the study, as directed by the Investigator. 
16. Subject is willing to participate and is capable of giving informed consent. 
Note: Consent must be obtained prior to any study-related procedures. 
17. Subject must be able and willing to comply with all study procedures and must be available for the 
duration of the study. 
Exclusion Criteria: 
Subjects are excluded from the study if any of the following criteria apply: 
 
1. Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant during the 
study. 
2. Employee of the study center or RAPT. 
3. Subject has any serious and/or uncontrolled medical condition (including cognitive impairment or 
signs/symptoms suspicious for a serious disease) or laboratory abnormality that would place subject’s 
safety at risk or interfere with study participation, as judged by the Investigator including but not 
limited to the following: 
• 
Moderate-to-severe asthma that is uncontrolled 
• 
Subjects with uncontrolled diabetes (hemoglobin A1c [HbA1c] ≥9%) 
• 
Stage III or IV cardiac failure according to the New York Heart Association classification 
• 
Severe renal conditions (e.g., subjects on dialysis) 
• 
Active autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, 
inflammatory bowel disease) 
4. Subject has had a major surgery in the past 8 weeks or has a major, elective surgery planned during 
the study. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
18 
 
 
5. Subject has any clinically significant medical condition or physical/laboratory/ECG (e.g., acute 
myocardial infarction, clinically significant arrythmia, or indications of serious underlying heart 
disease)/vital signs abnormality that would, in the opinion of the Investigator, be indicative of an 
underlying medical condition, put the subject at undue risk, and/or interfere with interpretation of 
study results. 
6. Any of the following specific laboratory findings: 
• 
Alanine aminotransferase (ALT) >2.5× upper limit of normal (ULN) 
• 
Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 (Modification of Diet in Renal 
Disease [MDRD] equation) 
Note: For subjects between the ages of 50 to 75 years old with an eGFR lower than 
60 mL/min/1.73 m2 but potentially within normal range for the subject’s age, please contact the 
Medical Monitor to discuss the subject’s eligibility 
• 
Platelet count <75,000 cells/mm3 
• 
Hemoglobin <10 g/dL 
• 
Absolute lymphocyte count <800 cells per mm3 
• 
Absolute neutrophil count <1500 cells per mm3 
7. Subject has a history of drug and/or alcohol abuse in the last 12 months. 
8. Subject has a history of skin disease or presence of skin condition that, in the opinion of the 
Investigator, would interfere with the study assessments. 
Note: Fungal infection of nail beds is allowed. 
9. Subject has any state of immunodeficiency due to primary or secondary immunodeficiency 
syndromes, organ transplant (except corneal transplant), previous opportunistic infections, or any 
other state of immunodeficiency, as judged by the Investigator. 
10. Subject has used tanning beds or phototherapy (narrowband ultraviolet B [NBUVB], UV-B, 
ultraviolet A1 [UVA1], or psoralen-UV-A [PUVA]) within 4 weeks prior to the Baseline visit. 
11. Subject has received treatment with systemic immunosuppressive/immunomodulating drugs 
(e.g., methotrexate, cyclosporine A, mycophenolic acid, or azathioprine), immunoglobulins, blood 
products and/or systemic corticosteroids (e.g., oral, intravenous, intraarticular, rectal) within 4 weeks 
prior to the Baseline visit. 
Note: Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and ear drops containing 
corticosteroids are also allowed. 
12. Subject has used any topical medicated treatment that could affect AD within 2 weeks prior to the 
Baseline visit, including, but not limited to, topical corticosteroids, topical PDE4 inhibitor 
(e.g., crisaborole), topical calcineurin inhibitors, topical JAK inhibitors (e.g., ruxolitinib), tars, topical 
antimicrobials, and medical devices. 
13. Subject has used medicated emollients (regulated as a medical device) within 7 days prior to the 
Baseline visit. 
14. Subject has received RPT193 in the past. 
15. Subject has received an investigational oral, systemic agent within 8 weeks or 5 half-lives (whichever 
is longer) prior to the Baseline visit. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
19 
 
 
16. Subject has received any marketed (other than dupilumab as described in exclusion criterion 17) or 
investigational biological therapeutic within 16 weeks or 5 half‑lives (whichever is longer) prior to 
the Baseline visit. 
17. Subject has used dupilumab within 12 weeks or tralokinumab within 16 weeks prior to the Baseline 
visit OR has received dupilumab or tralokinumab at any time in the past and was considered to have 
no clinical response within 4 months of initiating dupilumab or tralokinumab treatment. 
Note: Lack of clinical response to dupilumab or tralokinumab may be defined by subject history 
alone. 
18. Subject has used a systemic JAK inhibitor (e.g., tofacitinib, baricitinib, abrocitinib, upadacitinib) 
within 8 weeks prior to the Baseline visit OR has used a systemic JAK inhibitor at any time in the 
past and was considered to have no clinical response within 4 months of initiating JAK inhibitor 
treatment. 
Note: Lack of clinical response to a JAK inhibitor may be defined by subject history alone. 
19. Subject is receiving a concomitant medication for condition(s) other than AD that require a change in 
dosing regimen within 7 days prior to the Baseline (Day 1) visit. 
20. Subject has used a cell-depleting agent, including but not limited to rituximab within 6 months prior 
to the Baseline visit, or until lymphocyte counts return to normal, whichever is longer. 
21. Subject has begun an allergen-specific immunotherapy regimen or had a clinically relevant change to 
their immunotherapy within 4 weeks prior to the Baseline visit. 
22. Subject has used topical products containing urea within 1 week prior to the Baseline visit. 
23. Subject has used systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals 
within 2 weeks or topical antibiotics within 1 week prior to the Baseline visit. 
24. Subject has received a live or live-attenuated vaccine within 4 weeks prior to the Baseline visit or 
plans to receive a live or live-attenuated vaccine during the study and up to 4 weeks after the last 
study drug administration. 
25. Subject has a history of a clinically significant systemic infection or serious skin infection requiring 
parenteral antibiotic treatment within 4 weeks prior to the Baseline visit, or oral therapy 
within 2 weeks prior to the Baseline visit. 
26. Subject has a known active bacterial, viral, fungal, helminth, or mycobacterial, or any other infection 
at the Baseline visit (non-complicated recurrent muco-cutaneous infections such as cold sores, tinea 
pedis, or disto-lateral mild to moderate onychomycosis are not considered exclusionary). 
Note: Subjects for whom infections have resolved and otherwise meet eligibility criteria may be 
rescreened up to once. 
27. Active infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. 
28. Subject has a diagnosis of, is suspected of having, or is at high risk for an endoparasitic infection 
unless clinical and laboratory assessment have ruled out active endoparasitosis prior to the Baseline 
visit. 
29. Subject has a history of cancer or lymphoproliferative disease within 5 years prior to the Baseline 
visit. Subjects with treated and completely resolved cutaneous basal cell carcinoma and/or cutaneous 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
20 
 
 
squamous cell carcinoma in situ and/or cervical cancer in situ can be considered, as judged by the 
Investigator. 
30. Subject has a positive tuberculosis (TB) infection test at screening. Subject will be evaluated for 
latent TB infection with a purified protein derivative (PPD) test, a QuantiFERON-TB Gold test, or a 
T-spot test. Subjects who demonstrate evidence of latent TB infection (either PPD ≥5 mm of 
induration or positive QuantiFERON-TB Gold test, irrespective of bacilli Calmette-Guérin 
vaccination status) will not be allowed to participate in the study. 
31. Subject has a positive screen for hepatitis B surface antigen (HbsAg), hepatitis C (HCV) antibodies, 
or human immunodeficiency virus (HIV) antibodies. For HbsAg or HCV antibody positive screening, 
subjects may be enrolled if reflex testing (e.g., HBV-DNA or HCV-RNA) is negative and indicative 
that there is no active infection. 
32. Subject has a known hypersensitivity to RPT193 or its excipients. 
33. Subject 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. 
34. Subject is not willing to maintain their baseline skin care regimen (e.g., bathing) or use of herbals 
and/or supplements through the duration of the study. 
35. Subject who is still participating in a clinical trial or who has participated in a clinical trial 
within 1 month prior to the Screening visit. 
Note: Please also refer to Exclusion Criteria 15 and 16 regarding those who participated in an 
investigational clinical trial. 
Statistical methods: 
Continuous endpoints will be summarized using descriptive statistics (number of subjects [n], mean, 
standard deviation [SD], median, minimum, and maximum). Categorical endpoints will be summarized 
using frequency counts and percentages. All individual subject data will be present in listings. 
Analysis sets will include a Full Analysis Set, a Per-Protocol Analysis Set, and a Safety Analysis Set. 
The primary efficacy endpoint is the percent change from baseline in EASI score at Week 16. The 
primary analysis will be performed in FAS. The primary efficacy endpoint will be analyzed with analysis 
of covariance (ANCOVA) model. The model will include treatment group (each RPT193 dose vs. 
placebo), baseline vIGA scores, randomization stratification factors and study sites as factor, and baseline 
EASI score as a covariate. The least square (LS) mean and LS mean difference along with the 95% 
confidence interval (CI) and p-value will be reported. 
For continuous secondary endpoints, the same model as discussed for the primary analyses will be 
followed. For binary secondary endpoints, a logistic regression model with treatment group, baseline 
vIGA scores, randomization stratification factors, study sites as factors and baseline score as a covariate 
will be used. 
All safety analyses will be performed on the Safety Analysis Set. Adverse events will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA). Treatment-emergent adverse events (TEAEs) 
are defined as AEs that first occurred or worsened in severity after the first dose of study treatment. The 
AE summaries will be primarily based on TEAEs. Descriptive statistics for the number and percentage of 
subjects with TEAEs will be summarized by treatment arm, system organ class, and preferred term for all 
TEAEs, treatment-related TEAEs, serious TEAEs, and TEAEs leading to discontinuation of study 
treatment. All TEAEs will be further summarized by maximum severity and causality. All AEs will be 
present in a by-subject listing. Serious AEs, and TEAEs leading to discontinuation of study treatment will 
be present in separate listings. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
26 
 
 
 
2.0 INTRODUCTION 
2.1 
Study Rationale 
RPT193-02 is designed to assess the efficacy and safety of multiple dose levels of RPT193 in 
subjects with moderate-to-severe atopic dermatitis (AD). This randomized, double-blind, 
placebo-controlled study will compare 3 dose levels of RPT193 to placebo with a treatment 
duration of 16 weeks. Investigational product will be administered as monotherapy for AD in 
adult subjects who have had an inadequate response to topical medications for AD 
(e.g., corticosteroids) or who are otherwise unable to take topical medications. Maximum clinical 
benefit in the 4-week Phase 1b trial was observed 2 weeks after cessation of treatment and 
suggested that RPT193 may have therapeutic effects beyond the dosing period. Thus, after 
completion of treatment at 16 weeks, subjects will continue to be followed for an additional 
8 weeks to understand whether further improvement in clinical parameters and/or sustained 
responses are observed beyond the treatment period. 
The data generated during the current study will contribute to efficient and appropriate design of 
future clinical studies, including pivotal studies with RPT193 in subjects with AD. 
2.2 
Background 
2.2.1 
Atopic Dermatitis 
Atopic dermatitis is a common, chronic, relapsing, inflammatory skin disease. It is characterized 
by intense itch, xerosis and acute (erythematous papules, vesicles, edema, exudation, crusting), 
subacute and chronic (scaly, erythematous papules and plaques, lichenification, excoriations, 
fissuring) eczematous skin lesions.[Bieber 2010; Bieber 2017; Boguniewicz 2017; Eichenfield 
2014] Typically, AD presents with an age-related morphology and distribution.[Bieber 2017; 
Feldman 2019] 
The global prevalence of AD is estimated to be ׽15% to 30% in children and ׽2% to 10% in 
adults. In children with AD, onset occurs in 45% during the first 6 months of life, 60% during 
the first year, and 90% are affected before the age of 5. [Bieber 2010; Bieber 2017; Boguniewicz 
2017; Eichenfield 2014] Subjects can experience spontaneous disease remission later in 
adolescence but up to 50% will live with AD throughout adulthood. [Bieber 2010; Bieber 2017; 
Boguniewicz 2017; Feldman 2019] 
There are a number of extracutaneous comorbid health problems that occur in subjects with AD. 
Atopic dermatitis is associated with and may predispose to higher risk of other atopic disorders, 
including food allergies, allergic conjunctivitis/rhinitis, and asthma (atopic march). Chronic 
pruritus and inflammation/pain can lead to sleep disturbances and mental health symptoms. 
Subjects with AD are at higher risk for multiple neuropsychiatric disorders, including attention 
deficit (hyperactivity) disorder, depression and suicidal ideation, speech disorders in childhood, 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
27 
 
 
headaches, and seizures. [Patel 2019; Silverberg 2017; Silverberg 2018] There are also 
cardio-metabolic and musculoskeletal (osteoporosis, injuries, and fractures) comorbidities. 
[Silverberg 2017; Silverberg 2018; Ascott 2019] Each of these comorbidities negatively impacts 
subjects Quality of Life (QOL). In addition, AD, in particular moderate and severe AD, is 
associated with poor QOL independent of these comorbidities. [Silverberg 2018] 
2.2.1.1 
Pathophysiology of AD and the Role of Th2 Immune Cells 
AD has complex pathophysiology characterized by epidermal barrier dysfunction and 
immune‑mediated inflammation. It is driven by multiple interconnected genetic, environmental, 
and immunological factors. Damaged epidermal barrier allows penetration of allergens, followed 
by immunoglobulin E (IgE) and non-IgE mediated sensitization with predominant Type 2 helper 
T cell (Th2) response in the acute phase of AD. [Guttman 2017; Kim 2019] AD has a 
heterogeneous molecular fingerprint among different age groups and ethnicities, but with a 
dominant Th2/Th22 skewing and variable Th17/Th1 contributions. [Kim 2019; Renert-Yuval 
2019] 
Th2 cells express high levels of CCR4 and are clinically validated drivers of allergic diseases 
along the atopic march, which includes AD, food allergy, asthma, and allergic 
rhinitis/conjunctivitis. [Vestergaard 2003] When a pathogen comes into contact with the skin or 
mucosal lining of the nose or lungs, an immune response is triggered. It is believed that innate 
immune cells and antibodies that recognize the pathogen initiate a release of inflammatory 
cytokines, leading to the recruitment of other immune system components, including Th2 cells. 
Th2 cells secrete inflammatory cytokines, such as interleukin 4 (IL-4), IL-5, and IL-13. While 
this Th2 response may be highly effective against foreign pathogens, particularly parasites, 
sometimes the body overreacts to benign substances in this way, resulting in a significant and 
presumably unnecessary influx of Th2 cells, leading to conditions along the atopic march. 
At a cellular and molecular level, the Th2 response is initiated and sustained when Th2 cells are 
recruited to the site of inflammation by the binding of CCL17 and CCL22 to CCR4. Subjects 
suffering from AD and other allergic disorders have significantly elevated levels of both CCL17 
and CCL22. Additionally, elevated CCL17 in the blood is among the most tightly correlated 
biomarkers of AD severity and activity. All told, these data suggest that inhibiting the ability of 
these chemokines to bind to CCR4 may prevent migration of Th2 cells into these inflamed sites 
and promote clinical benefit. 
2.2.1.2 
Historical and Emerging Standard of Care 
Emollients and topical therapies (including corticosteroids, calcineurin inhibitors and 
phosphodiesterase-4 [PDE4] inhibitors) phototherapy or systemic anti‑inflammatory agents, are 
routinely used to manage skin inflammation in subjects with AD. Subjects who do not achieve 
sustained alleviation of symptoms with topical treatments are prescribed systemic steroids or 
other systemic immunosuppressive agents such as cyclosporine, azathioprine, methotrexate and 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
28 
 
 
mycophenolate mofetil. [Boguniewicz 2017; Eichenfield 2014] While these can be effective as 
temporary treatments of flare-ups, extended use has been associated with many potential side 
effects or adverse events (AEs). Systemic steroids, such as prednisone, can lead to temporary 
symptom relief but their use is not recommended to induce stable remission due to numerous 
side effects and the propensity of severe disease flares upon treatment cessation. Cyclosporine is 
also not suitable for long-term use as it has been associated with renal toxicity, hirsutism, nausea 
and lymphoma, and subjects must discontinue use after 1 to 2 years. Topical immunosuppressive 
agents inadequately address the systemic nature of AD. Furthermore, safety issues associated 
with systemic immunosuppressants such as steroids and cyclosporine make them inappropriate 
for chronic administration. The treatment paradigm in AD is evolving given the inadequacies of 
the historical standard of care agents. 
There are 2 key recent developments within the AD treatment landscape: (1) dupilumab, the 
biologic agent approved for moderate-to-severe AD, and (2) recent approvals of oral Janus 
kinase (JAK) inhibitors. [Traidl 2021] 
Dupilumab is a recently approved biologic for AD targeting the Th2 pathway. Dupilumab 
prevents T-cell activation and amplification of proinflammatory signaling pathways by blocking 
the interleukin 4 receptor (IL-4R), preventing IL-4 and IL-13 binding. Approximately 36% of 
subjects receiving weekly or biweekly injections of dupilumab achieved significant improvement 
in disease symptoms. [Simpson 2016] Among the orally administered JAK inhibitors in 
development for AD, there are 3 that have completed Phase 3 trials: upadacitinib, baricitinib, and 
abrocitinib. JAK inhibitors block the signaling pathway to multiple proinflammatory cytokines, 
including IL-4 and IL-13, thereby preventing the downstream signaling of Th2 cells at the sites 
of inflammation. While JAK inhibitors have demonstrated comparable clinical efficacy to 
dupilumab and offer the advantage of oral dosing, these inhibitors are broadly 
immunosuppressive and therefore may not be suitable for long-term dosing. Approved JAK 
inhibitors have been associated with serious side effects (including serious infection, 
malignancy, and thromboembolic events), which is reflected in the US, EU, and Canadian 
labeling. 
Despite the recent progress in the field, there is significant unmet medical need for a safe and 
efficacious agent for the treatment of AD. Inhibition of Th2 cell migration into inflamed tissues 
with an oral CCR4 antagonist represents a highly differentiated approach with the potential to 
compare favorably to dupilumab, which only blocks the downstream effects of 2 of the 
Th2‑produced cytokines. An oral agent with a favorable safety and efficacy profile offers an 
attractive alternative for subjects compared to the biweekly injections associated with dupilumab. 
2.2.2 
RPT193 
RPT193 is an antagonist of the CCR4 chemokine receptor that inhibits CCR4‑mediated 
chemotaxis toward both CCL22 and CCL17. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
29 
 
 
2.2.2.1 
Non-Clinical Pharmacology 
RPT193 potently inhibits CCL22- and CCL17-induced CCR4-mediated chemotaxis with 
excellent selectivity over other chemokine receptors. Daily oral dosing of RPT193 resulted in 
reduced Th2‑driven skin inflammation in multiple mouse models. In the ovalbumin 
(OVA)‑induced model, daily oral dosing of RPT193 resulted in more than 50% decrease in ear 
thickness and IL-4 levels in inflamed tissue. In a fluorescein isothiocyanate (FITC)-induced 
model, daily oral dosing of RPT193 resulted in a significant reduction of ear thickness (~25%) 
and significantly less IL-13 in inflamed tissue (~80%). Taken together, these data suggest that 
RPT193 may inhibit recruitment of Th2 cells to inflamed tissue and reduce the ongoing allergic 
inflammation. Furthermore, RPT193 may provide therapeutic efficacy equivalent to that of 
biologics such as anti-IL-13 modulating agents. For more details on non-clinical studies, refer to 
the RPT193 Investigator’s Brochure. 
Daily oral dosing of RPT193 in preclinical models of pulmonary inflammation also reduced 
accumulation of T cells, eosinophils, and neutrophils in bronchoalveolar lavage fluid (BALF) of 
allergically inflamed lungs in mice by approximately 50%. There was a corresponding reduction 
in Th2-inflammatory cytokines (IL-5, IL-13) and chemokines (CCL17 and CCL22) in BALF. 
Reduction in eosinophils, IL-13, CCL17, and CCL22 was similar to that observed for treatment 
with the anti-IL-13 antibody. Importantly, RPT193 resulted in the reduction in number of 
lymphocytes and neutrophils and in IL-5 levels in BALF whereas anti‑IL-13 treatment had no 
effect 24 hours after allergen challenge. 
Consistent with the observation that CCR4 is not associated with any direct immune activation, 
RPT193 did not stimulate secretion of cytokines (granulocyte-macrophage colony-stimulating 
factor [GM-CSF], interferon [IFN]-γ, tumor necrosis factor [TNF]-α, IL-1β, IL-2, IL-4, IL‑5, 
IL-6, IL-12p70, IL-13 or IL-18) from peripheral blood mononuclear cell (PBMC) in vitro at 
doses up to 5 µM. 
2.2.2.2 
Preclinical Pharmacokinetics 
 
 
 
 
 
 
 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
31 
 
 
2.2.2.4 
Clinical Pharmacokinetics and Pharmacodynamics 
Clinical pharmacokinetics (PK) and pharmacodynamics data have been obtained from a Phase 1 
study, RPT193-01, entitled: “A Phase 1, randomized, double-blind, placebo‑controlled, 
single-dose escalation, multiple‑dose escalation, and food effect study of RPT193 in healthy 
subjects and subjects with moderate-to-severe atopic dermatitis.” 
In the Phase 1 trial of heathy subjects, RPT193 has demonstrated increases in exposure following 
increasing single doses (5 to 400 mg) and up to approximately 2-fold accumulation following 
multiple doses (50 to 400 mg once daily [QD] for 7 doses), and minimal to no food effect, with a 
mean plasma half-life of approximately 24 hours. 
Following administration of multiple doses of 400 mg RPT193 QD for 28 days in subjects with 
AD in either a fasted or fed state, the median time to maximum concentration [tmax] of RPT193 
on Day 28 was ~6 hours. There was a substantial increase in Cmax and AUC on Day 28 when 
compared to Day 1. Overall, the data indicate similar PK parameters in both healthy volunteers 
and AD following multiple doses of 400 mg QD. 
 
 
 
 
 
 
 
 
 
 
 
 
Please refer to the Investigator’s Brochure for a detailed description of the clinical PK and 
pharmacodynamics of RPT193. 
2.2.2.5 
Clinical Safety Data to Date 
In RPT193-01, a first-in-human trial investigating RPT193 in healthy volunteers and subjects 
with AD, RPT193 was found to be well-tolerated at all tested doses (ranging from 5 to 400 mg) 
following single dose (Part A) and multiple-dose (Part B) administration to healthy subjects. 
RPT193 400 mg QD was also found to be well-tolerated following multiple-dose administration 
in subjects with AD (Part C). All treatment-emergent adverse events (TEAEs) were mild or 
moderate in severity and no severe TEAEs were reported in the study. Overall, TEAEs reported 
were generally equally represented across all treatment groups with no apparent relationship to 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
32 
 
 
dose or severity. No serious adverse events (SAEs) or TEAEs leading to study discontinuation 
were reported. There were minimal changes from baseline in biochemistry, hematology, and 
quantitative urinalysis parameters, with no specific trends observed, and the majority of 
abnormal laboratory values were not clinically significant. There were minimal changes from 
baseline in vital signs and electrocardiograms (ECGs), and the majority of abnormal values were 
not clinically significant. 
2.2.2.6 
Effects of RPT193 on Signs and Symptoms of AD in Subjects with 
Moderate-to-Severe Disease Subjects 
The effects of RPT193 as monotherapy on signs and symptoms of AD were explored in subjects 
with moderate-to-severe AD in the Phase 1 trial after a 4-week treatment period. Overall, the 
preliminary efficacy results and patient-reported outcomes (PROs) showed consistently higher 
improvement in the RPT193 400 mg QD group than the placebo group for most of the efficacy 
endpoints evaluated in this study during the treatment period up to Day 29. Only bland 
emollients were allowed with no rescue therapy during and after treatment discontinuation, and 
further improvements were observed up to Day 43 (which corresponded with the end of the 
study) for mean values of most efficacy parameters in the RPT193 group, whereas values were 
stable or decreased following cessation of treatment in the placebo group. Though the Phase 1b 
trial was signal-seeking and not powered for any specific endpoint, post-hoc statistical analyses 
conducted on Day 43 (2 weeks after the End-of-Treatment [ET]) revealed statistically significant 
differences between RPT193 and the placebo for several efficacy endpoints (% change in 
Eczema Activity and Severity Index [EASI], EASI-50, % change in SCORing Atopic Dermatitis 
[SCORAD], and % change in body surface area [BSA]). 
The proportion of responders with at least a 4-point reduction from baseline in single daily 
24-hour pruritus numerical rating scale (NRS) for subjects with a baseline ≥4 was numerically 
higher in the RPT193 400 mg QD group than placebo at all study visits. At Day 29, the 
proportion of responders was 45.0% in the RPT193 400 mg QD group, as compared to 22.2% in 
the group treated with placebo. 
Differences in improvement in QOL, as measured by the Dermatology Quality of Life Index 
(DLQI), between RPT193 and placebo groups were limited. Notably, this study was conducted 
during the coronavirus disease of 2019 (COVID-19) pandemic, during which time changes in 
work and leisure activities may have influenced how subjects responded to PRO questionnaires, 
including the DLQI. 
Despite the small sample size and short duration of treatment (4 weeks), clinically significant 
improvements in the signs and symptoms of AD were observed in this study following treatment 
with RPT193, with continued improvement even 2 weeks after the end of treatment. 
A detailed description of the chemistry, pharmacology, efficacy, and safety of RPT193 is 
provided in the current Investigator’s Brochure. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
33 
 
 
2.3 
Benefit/Risk Assessment 
2.3.1 
Known Potential Risks and Benefits 
RPT193 is under development and has not been marketed in any country. Clinical experience is 
limited to safety data from the Phase 1 study, RPT193-01. To date, review of laboratory, ECG, 
and clinical safety assessments has not identified any significant concerns. 
Based on the Phase 1 clinical data in subjects with moderate-to-severe AD, subjects treated with 
RPT193 as monotherapy showed signs of improvement for both signs and symptoms of AD after 
4 weeks of therapy compared to placebo-treated subjects. RPT193-treated subjects demonstrated 
continued improvement for 2 weeks after therapy suggesting unique kinetics of clinical 
improvement after CCR4 inhibition, which is an upstream mechanism to decrease the 
inflammatory response associated with AD. Subjects enrolled in this Phase 2 study may see 
benefit after treatment, particularly given the 16-week length of treatment in this study. 
Participation in this study will help generate future benefit for larger groups of subjects with AD 
and possibly other inflammatory skin diseases if RPT193 proves to be safe, well tolerated, and 
successful in treating this condition. 
2.3.2 
Assessment of Risks and Benefits 
The Phase 1 clinical and safety data in healthy volunteers and subjects with moderate-to-severe 
AD, the favorable safety and tolerability profile, convenience of an oral medication, PK, and 
preliminary efficacy results support further evaluation of RPT193 in studies with larger sample 
sizes and longer treatment periods for the development of RPT193 as a therapy for subjects with 
moderate-to-severe AD and other inflammatory diseases. 
All quality, pharmacology and toxicology data, and satisfactory safety results demonstrated in 
non-clinical studies are considered sufficient to expect a positive benefit/risk ratio for the 
treatment of subjects with moderate-to-severe AD and thus initiate the study. 
The risk to subjects in this trial will be minimized by compliance with the eligibility criteria, 
proper study design, and close monitoring. 
More detailed information about the known and expected benefits and risks and reasonably 
expected AEs of RPT193 may be found in the Investigator’s Brochure. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
37 
 
 
4.0 STUDY DESIGN 
4.1 
Overall Design 
This is a randomized, double-blind, dose-ranging study in adults with moderate-to-severe AD 
who have had an inadequate response to topical therapies or in whom topical therapies are 
contraindicated with a treatment duration of 16 weeks (112 days). 
This study will assess RPT193 as monotherapy for the treatment of AD. 
After the treatment period, there is a follow-up period ending at Day 169. 
4.2 
Scientific Rationale for Study Design 
The proposed design is considered appropriate for assessing the efficacy and safety of RPT193 in 
subjects with moderate-to-severe AD. 
This Phase 2 study will be randomized to ensure random allocation of subjects to treatment arms 
to reduce bias. Because efficacy assessments of AD can have a high degree of subjectivity, the 
study will be double-blinded. The highest degree of subject and assessor blinding should be 
sought to achieve credible inference. It is also important to have a placebo control to account for 
confounding factors, such as potential Investigator bias, and to ensure that the statistical 
procedures can be appropriately applied. The inclusion of 3 dose strengths of RPT193 across an 
8-fold dosing range is designed to identify a sub-efficacious as well as a minimally effective 
dose. 
4.3 
Justification for Dose 
RPT193-02 will investigate the efficacy and safety of RPT193 in subjects with moderate- 
to-severe AD. The study will assess 3 doses of RPT193 (50, 200, and 400 mg) taken orally QD 
for 16 weeks. 
 
 
 
 
 
 
 
 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
38 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4.4 
End of Study Definition 
A subject is considered to have completed the study if he/she has completed all phases of the 
study including a 35-day maximum screening period (Day -35 to Day -1), a 16-week 
double-blind treatment period (Day 1 to Day 113/Week 16) and an 8-week follow-up period 
(Day 113/Week 16 to Day 169/Week 24). 
 
The end of the study is defined as the completion of the last visit or procedure shown in the SoA 
for the last enrolled subject in the trial for all sites. 
CCI

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
39 
 
 
5.0 STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
Subjects are eligible to be included in the study only if all of the following criteria apply: 
1. Male or female subject aged 18 to 75 years, inclusive, at the time of consent. 
2. Subject has clinically confirmed diagnosis of active AD, according to the revised Hanifin and 
Rajka criteria. [Eichenfield 2014] 
3. Subject has at least a 12-month history of AD and had no significant flares in AD for at least 
4 weeks before Screening, as determined by the Investigator through subject interview at the 
Screening visit or information obtained from medical chart or subject’s physician. 
4. Subject has a documented history of inadequate response to a ≥1 month treatment with 
topical medications, such as class I-V topical corticosteroids, topical PDE4 inhibitor 
(e.g., crisaborole), and/or calcineurin inhibitors in the 6 months prior to the Screening visit or 
subjects for whom topical treatments are otherwise medically inadvisable. 
5. Subject has AD covering ≥10% of the BSA. 
6. Subject has an EASI score ≥16 at Screening and at Baseline. 
• Subjects may be screened with an EASI score ≥12 if the subject is administering class 
I-V topical corticosteroids, topical PDE4 inhibitor (e.g., crisaborole), and/or topical 
calcineurin inhibitors or is using systemic immunosuppressants (e.g., methotrexate, 
cyclosporine A, mycophenolic acid, azathioprine, and/or systemic corticosteroids); 
eligibility for the study requires follow-up EASI score ≥16 at Baseline (after the relevant 
washout period for the index medication has been satisfied). 
7. Subject has a Validated Investigator Global Assessment (vIGA) score ≥3. 
8. Subject has been using one or more emollient(s) (except urea-containing emollients or 
medicated emollients that are regulated as a medical device) at least twice daily for 1 week 
prior to Baseline (except on visit day before the visit) and agrees to continue using the same 
emollient(s) daily at the same frequency (at least twice daily) throughout the study. 
Notes: On the day of scheduled visit, subjects cannot apply emollient before their scheduled 
visit, and every effort should be made to use the same emollient throughout the study for the 
same body region. However, the chosen emollient may differ depending on the body region 
(e.g., body vs face emollient may be different). 
9. Female subject of childbearing potential has had a negative serum pregnancy test at 
Screening and negative urine pregnancy test at Baseline. 
10. For female subject of childbearing potential involved in any sexual intercourse that could 
lead to pregnancy: the subject must agree to use a highly effective contraceptive method from 
at least 4 weeks prior to Day 1 until at least 30 days after the last study drug administration. 
Highly effective contraceptive methods include hormonal contraceptives (e.g., combined oral 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
40 
 
 
contraceptive, patch, vaginal ring, injectable, or implant), intrauterine devices or intrauterine 
systems, vasectomized partner(s), tubal ligation or double barrier methods of contraception 
(e.g., male condom with cervical cap, male condom with diaphragm, and male condom with 
contraceptive sponge) in conjunction with spermicide. 
Notes: 
• For countries where double barrier methods are not accepted as highly effective 
contraception, then this option must not be considered. 
• A female subject of nonchildbearing potential is defined as follows: 
• 
Female subject who has had surgical sterilization (hysterectomy, bilateral 
oophorectomy, or bilateral salpingectomy) 
• 
Female subject who has had a cessation of menses for at least 12 months prior to the 
Screening visit without an alternative medical cause, and a follicle-stimulating 
hormone (FSH) test confirming nonchildbearing potential (refer to laboratory 
reference ranges for confirmatory levels). 
• Subjects must have been on a stable regimen of hormonal contraceptives for at least 
4 weeks prior to Baseline. 
• The above list of contraceptive methods does not apply to subjects who are abstinent for 
at least 4 weeks before Baseline (Day 1) and will continue to be abstinent from 
penile-vaginal intercourse throughout the study. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the clinical trial and the preferred and 
usual lifestyle of the participant. 
11. Female subject agrees not to have egg retrieval during the study and for 30 days after the last 
study drug administration. 
12. For male subject involved in any sexual intercourse that could lead to pregnancy, subject 
must agree to use one of the highly effective contraceptive methods listed in Inclusion 
Criterion #10, from Baseline (Day 1) until at least 90 days after the last study drug 
administration. If the female partner of a male subject uses any of the hormonal contraceptive 
methods listed above, this contraceptive method should be used by the female partner from at 
least 4 weeks before Baseline (Day 1) until at least 90 days after the last study drug 
administration. 
13. Male agrees not to donate sperm during the study and for 90 days after the last study drug 
administration. 
14. Subject has negative COVID-19 results at Screening. 
15. Subject is willing to comply with discontinuation of prohibited treatments for AD as 
described in Table 3 for the duration of the study, as directed by the Investigator. 
16. Subject is willing to participate and is capable of giving informed consent. 
Note: Consent must be obtained prior to any study-related procedures. 
17. Subject must be able and willing to comply with all study procedures and must be available 
for the duration of the study. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
41 
 
 
5.2 
Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria apply: 
1. Subject is a female who is breastfeeding, pregnant, or who is planning to become pregnant 
during the study. 
2. Employee of the study center or RAPT. 
3. Subject has any serious and/or uncontrolled medical condition (including cognitive 
impairment or signs/symptoms suspicious for a serious disease) or laboratory abnormality 
that would place subject’s safety at risk or interfere with study participation, as judged by the 
Investigator including but not limited to the following: 
• Moderate-to-severe asthma that is uncontrolled 
• Subjects with uncontrolled diabetes (hemoglobin A1c [HbA1c] ≥9%) 
• Stage III or IV cardiac failure according to the New York Heart Association classification 
• Severe renal conditions (e.g., subjects on dialysis) 
• Active autoimmune disease (e.g., systemic lupus erythematosus, rheumatoid arthritis, 
inflammatory bowel disease) 
4. Subject has had a major surgery in the past 8 weeks or has a major, elective surgery planned 
during the study. 
5. Subject has any clinically significant medical condition or physical/laboratory/ECG 
(e.g., acute myocardial infarction, clinically significant arrythmia, or indications of serious 
underlying heart disease)/vital signs abnormality that would, in the opinion of the 
Investigator, be indicative of an underlying medical condition, put the subject at undue risk, 
and/or interfere with interpretation of study results. 
6. Any of the following specific laboratory findings: 
• Alanine aminotransferase (ALT) >2.5× upper limit of normal (ULN) 
• Estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 (Modification of Diet in 
Renal Disease [MDRD] equation) 
Note: For subjects between the ages of 50 to 75 years old with an eGFR lower than 
60 mL/min/1.73 m2 but potentially within normal range for the subject’s age, please 
contact the Medical Monitor to discuss the subject’s eligibility 
• Platelet count <75,000 cells/mm3 
• Hemoglobin <10 g/dL 
• Absolute lymphocyte count <800 cells per mm3 
• Absolute neutrophil count <1500 cells per mm3 
7. Subject has a history of drug and/or alcohol abuse in the last 12 months. 
8. Subject has a history of skin disease or presence of skin condition that, in the opinion of the 
Investigator, would interfere with the study assessments. 
Note: Fungal infection of nail beds is allowed. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
42 
 
 
9. Subject has any state of immunodeficiency due to primary or secondary immunodeficiency 
syndromes, organ transplant (except corneal transplant), previous opportunistic infections, or 
any other state of immunodeficiency, as judged by the Investigator. 
10. Subject has used tanning beds or phototherapy (narrowband ultraviolet B [NBUVB], UV-B, 
ultraviolet A1 [UVA1], or psoralen-UV-A [PUVA]) within 4 weeks prior to the Baseline 
visit. 
11. Subject has received treatment with systemic immunosuppressive/immunomodulating drugs 
(e.g., methotrexate, cyclosporine A, mycophenolic acid, or azathioprine), immunoglobulins, 
blood products and/or systemic corticosteroids (e.g., oral, intravenous, intraarticular, rectal) 
within 4 weeks prior to the Baseline visit. 
Note: Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and ear drops 
containing corticosteroids are also allowed. 
12. Subject has used any topical medicated treatment that could affect AD within 2 weeks prior 
to the Baseline visit, including, but not limited to, topical corticosteroids, topical PDE4 
inhibitor (e.g., crisaborole), topical calcineurin inhibitors, topical JAK inhibitors 
(e.g., ruxolitinib), tars, topical antimicrobials, and medical devices. 
13. Subject has used medicated emollients (regulated as a medical device) within 7 days prior to 
the Baseline visit. 
14. Subject has received RPT193 in the past. 
15. Subject has received an investigational oral, systemic agent within 8 weeks or 5 half-lives 
(whichever is longer) prior to the Baseline visit. 
16. Subject has received any marketed (other than dupilumab as described in exclusion criterion 
17) or investigational biological therapeutic within 16 weeks or 5 half‑lives (whichever is 
longer) prior to the Baseline visit. 
17. Subject has used dupilumab within 12 weeks or tralokinumab within 16 weeks prior to the 
Baseline visit OR has received dupilumab or tralokinumab at any time in the past and was 
considered to have no clinical response within 4 months of initiating dupilumab or 
tralokinumab treatment. 
Note: Lack of clinical response to dupilumab or tralokinumab may be defined by subject 
history alone. 
18. Subject has used a systemic JAK inhibitor (e.g., tofacitinib, baricitinib, abrocitinib, 
upadacitinib) within 8 weeks prior to the Baseline visit OR has used a systemic JAK inhibitor 
at any time in the past and was considered to have no clinical response within 4 months of 
initiating JAK inhibitor treatment. 
Note: Lack of clinical response to a JAK inhibitor may be defined by subject history alone 
19. Subject is receiving a concomitant medication for condition(s) other than AD that require a 
change in dosing regimen within 7 days prior to the Baseline (Day 1) visit. 
20. Subject has used a cell-depleting agent, including but not limited to rituximab within 
6 months prior to the Baseline visit, or until lymphocyte counts return to normal, whichever 
is longer. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
43 
 
 
21. Subject has begun an allergen-specific immunotherapy regimen or had a clinically relevant 
change to their immunotherapy within 4 weeks prior to the Baseline visit. 
22. Subject has used topical products containing urea within 1 week prior to the Baseline visit. 
23. Subject has used systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals 
within 2 weeks or topical antibiotics within 1 week prior to the Baseline visit. 
24. Subject has received a live or live-attenuated vaccine within 4 weeks prior to the Baseline 
visit or plans to receive a live or live-attenuated vaccine during the study and up to 4 weeks 
after the last study drug administration. 
25. Subject has a history of a clinically significant systemic infection or serious skin infection 
requiring parenteral antibiotic treatment within 4 weeks prior to the Baseline visit, or oral 
therapy within 2 weeks prior to the Baseline visit. 
26. Subject has a known active bacterial, viral, fungal, helminth, or mycobacterial, or any other 
infection at the Baseline visit (non-complicated recurrent muco-cutaneous infections such as 
cold sores, tinea pedis, or disto-lateral mild to moderate onychomycosis are not considered 
exclusionary). 
Note: Subjects for whom infections have resolved and otherwise meet eligibility criteria may 
be rescreened up to once. 
27. Active infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. 
28. Subject has a diagnosis of, is suspected of having, or is at high risk for an endoparasitic 
infection unless clinical and laboratory assessment have ruled out active endoparasitosis prior 
to the Baseline visit. 
29. Subject has a history of cancer or lymphoproliferative disease within 5 years prior to the 
Baseline visit. Subjects with treated and completely resolved cutaneous basal cell carcinoma 
and/or cutaneous squamous cell carcinoma in situ and/or cervical cancer in situ can be 
considered, as judged by the Investigator. 
30. Subject has a positive tuberculosis (TB) infection test at screening. Subject will be evaluated 
for latent TB infection with a purified protein derivative (PPD) test, a QuantiFERON-TB 
Gold test, or a T-spot test. Subjects who demonstrate evidence of latent TB infection (either 
PPD ≥5 mm of induration or positive QuantiFERON-TB Gold test, irrespective of bacilli 
Calmette-Guérin vaccination status) will not be allowed to participate in the study. 
31. Subject has a positive screen for hepatitis B surface antigen (HbsAg), hepatitis C (HCV) 
antibodies, or human immunodeficiency virus (HIV) antibodies. For HbsAg or HCV 
antibody positive screening, subjects may be enrolled if reflex testing (e.g., HBV-DNA or 
HCV-RNA) is negative and indicative that there is no active infection. 
32. Subject has a known hypersensitivity to RPT193 or its excipients. 
33. Subject 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. 
34. Subject is not willing to maintain their baseline skin care regimen (e.g., bathing) or use of 
herbals and/or supplements through the duration of the study. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
44 
 
 
35. Subject who is still participating in a clinical trial or who has participated in a clinical trial 
within 1 month prior to the Screening visit. 
Note: Please also refer to Exclusion Criteria 15 and 16 regarding those who participated in an 
investigational clinical trial. 
5.3 
Lifestyle Considerations 
5.3.1 
Meals and Dietary Restrictions 
RPT193 has been demonstrated to have similar PK and tolerability properties whether taken in a 
fasted or fed state. Thus, no restrictions related to food and ingestion of investigational product 
have been put in place. Investigational product should be taken with approximately 240 mL 
(8 ounces) of water. Subjects may discuss the pros and cons of taking the investigational product 
with food with the Investigator of their site. 
5.3.2 
Activity 
Subjects should refrain from strenuous exercise or weightlifting within 96 hours (4 days) prior to 
screening and 48 hours prior to each subsequent visit as this could result in abnormal clinical 
laboratory values. 
Subjects should try to limit exposure to the sun for the duration of the trial, but the use of 
sunscreen products and protective apparel are permitted when sun exposure cannot be avoided. 
5.4 
Screen Failures 
Screen failures are defined as individuals who consent to participate in the clinical trial but are 
not subsequently randomly assigned to the study treatment. 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 details, eligibility criteria, and any SAEs. 
Subjects may be rescreened once provided the disqualifying reason is considered transient and is 
not related to disease activity status (i.e., vIGA, BSA, or EASI), if deemed acceptable by the 
Investigator. The Investigator may consult with the Medical Monitor on rescreening decisions if 
needed. Rescreened subjects should be assigned a different identification number than the initial 
screening. All procedures planned at the Screening visit, including signature of a new consent 
form, will be performed. 
5.5 
Replacement of Subjects 
The study assumes a drop-out rate of 10% with a goal of enrolling approximately 265 subjects 
and approximately 240 subjects completing the study. Thus, no replacement of subjects is 
anticipated. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
46 
 
 
6.2 
Preparation/Handling/Storage/Accountability 
1. The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study treatment received and any discrepancies are reported 
and resolved before use of the study drug. 
2. Only subjects enrolled in the study may receive study drug and only authorized study center 
staff may supply or administer study drug. All study drugs must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with 
the labeled storage conditions with access limited to the Investigator and authorized study 
center staff. 
3. The study drug will be dispensed by the study site to the subject at the visits specified in 
Table 1. 
4. Subjects are to return all study drug to the study site. The RPT193 tablets will be counted 
upon return, and the counts will be recorded in the source documents and electronic case 
report form (eCRF). 
5. Each subject will be instructed on the importance of returning the study drug at the next visit 
and on taking the product as prescribed. If a subject does not return study drug, he or she will 
be instructed to return it as soon as possible. 
6. The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study drug accountability reconciliation, and record maintenance (i.e., receipt, 
reconciliation, and final disposition records). 
7. The Investigator, a member of the study center staff, or a hospital pharmacist must maintain 
an adequate record of the receipt and distribution of all study drug using the Drug 
Accountability Form, as per International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP). 
These forms must be available for inspection at any time by the Sponsor, its designees, or by 
regulatory agencies. 
8. Further guidance and information for the final disposition of unused study drug are provided 
in the Study Reference Manual. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
At the study site, each screened subject will be assigned an identifier number during screening 
that will be used on all documentation. The identifier number will contain the site number 
(YYYY) and the subject number (SSSS) and will be assigned at the Screening visit 
(e.g., YYYY-4001). 
Randomization will occur prior to first dosing, at the Baseline (Day 1) visit. Approximately 
265 subjects will be randomized 1:1:1:1 to one of 4 groups (3 dose levels of RPT193 or placebo). 
In total and accounting for a dropout rate of 10%, approximately 67 subjects are anticipated to 
complete the study in each group. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
47 
 
 
A randomization list will be generated using a validated software. The randomization list will be 
kept secured until the study blind is broken at the end of study. 
The randomization list will be stratified based on region (North America vs. rest of world), 
baseline vIGA scores (vIGA of 3 vs. 4), and prior dupilumab or tralokinumab use (yes or no). 
(Note: Enrollment of subjects with a prior history of dupilumab or tralokinumab use will be 
capped at approximately 20%.) The list will be uploaded into an Interactive Web Response 
System (IWRS) and the Investigator or designee will be able to acquire a randomization number 
for eligible subjects by connecting to the IWRS. 
Further guidance and information can be obtained in the Study Reference Manual. 
This study will be double blind. At all times, treatment and randomization information will be 
kept confidential and will not be released to the Investigator, the study staff, the contract research 
organization (CRO), or the Sponsor study team until after the conclusion of the study. However, 
the laboratory where the PK samples will be analyzed will be provided with a copy of the 
randomization code since only samples of subjects who have received the active drug RPT193 
will be analyzed. 
The following controls will be employed to maintain the double-blind status of the study: 
• 
The oral tablets containing active drug or placebo will be indistinguishable in 
appearance and taste. 
Blinding codes should only be broken in emergency situations for reasons of subject safety. 
When the blind for a subject has been broken, the reason must be fully documented in the source 
document and eCRF. Whenever possible, the Investigator should contact the Sponsor or its 
designee before breaking the blind. If the blind is broken, the Investigator should promptly 
inform the Medical Monitor. Documentation of breaking the blind should be recorded with the 
date/time and reason why the blind was broken, and the names of the personnel involved. 
The subject for whom the blind has been broken will be discontinued from the study and undergo 
the End-of-Treatment (ET)/Discontinuation procedures. In cases where there are ethical reasons 
to have the subject remain in the study, the Investigator must obtain specific approval from the 
Sponsor or its designee for the subject to continue in the study. The primary reason for 
discontinuation (the event or condition which led to the unblinding) will be recorded. 
6.4 
Study Treatment and e-Diary Compliance 
Study treatment and Diary compliance will be monitored at the visits specified in the Schedule of 
Activities (SoA) (Section 1.3). Adherence to treatment will be assessed by direct questioning and 
by maintaining adequate study drug dispensing and return records. Any deviation from the 
prescribed dosage regimen will be recorded in the source document. Adherence to Diary 
completion will be assessed by a review of compliance reports by the site monitors prior to each 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
48 
 
 
site visit or contact. Subjects who are significantly noncompliant with e-Diary completion 
(i.e., missing >20% of Diary entries) will be counseled and could be discontinued from the study, 
at the discretion of the Investigator, following consultation with the Sponsor. 
On visit days, the date and time of study drug administration and the number of units 
administered will be recorded. In addition, subjects will capture the date and time of dosing in a 
daily e-Diary when the study drug will be taken at the site or at home. 
Subjects who are significantly noncompliant with treatment (i.e., missing >20% of doses) will be 
counseled and could be discontinued from the study, at the discretion of the Investigator, 
following consultation with the Sponsor. A subject will also be considered significantly 
noncompliant if he or she intentionally or repeatedly takes more than the prescribed amount of 
study drug in the same time frame, as judged by the Investigator. 
6.5 
Prior Therapy 
Eligible subjects will need to have had a documented history of inadequate response to a 
≥1-month treatment with topical medication, such as corticosteroids (class I to V), calcineurin 
inhibitors, and/or topical PDE4 inhibitor (e.g., crisaborole). Medical history is sufficient but the 
medication and duration of treatment should be documented. Inadequate response should also be 
documented to have occurred within 6 months prior to the Screening visit. Additionally, subjects 
for whom topical treatments are considered medically inadvisable will be considered to have 
satisfied the requirements related to prior therapy. 
6.6 
Concomitant Therapy 
6.6.1 
Permitted Therapies 
6.6.1.1 
Emollients 
Subjects must apply a basic, non-medicated emollient of their choice (except those containing 
urea) on their skin, including on AD lesions, at least twice a day. The emollient use must be 
initiated at least 7 days prior to Day 1 and subjects must continue using it at the same frequency 
(at least twice daily) throughout the study. However, on the day of scheduled visits, subjects 
should refrain from emollient use for at least 8 hours prior to each clinic visit. 
Every effort should be made to use the same emollient throughout the study for the same body 
region. However, the chosen emollient may differ depending on the body region (e.g., body vs 
face emollient may be different). The commercial name of the selected emollient(s) will be 
recorded in the source document and the eCRF. No other products may be applied to the lesions 
during the study. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
49 
 
 
6.6.2 
Prior Use of Dupilumab, Tralokinumab, or an Oral JAK Inhibitor 
Prior use of dupilumab, tralokinumab, or an oral JAK inhibitor for the treatment of atopic 
dermatitis will be assessed at screening. Per the eligibility criteria, subjects with a history of 
dupilumab, tralokinumab, or an oral JAK inhibitor will be allowed in the study provided that 
they have achieved the relevant washout period and a history of a clinical response. This clinical 
response may be assessed by interview of the subject by the PI. Enrollment of dupilumab- or 
tralokinumab-exposed subjects will be capped at approximately 20% and randomization will be 
stratified by prior use. 
6.6.2.1 
Skin Care 
Use of sunscreen products and protective apparel are permitted when sun exposure cannot be 
avoided. 
Regular skin care (e.g., cleansing and bathing) is permitted during the study. New skin care 
regimens that are not present at baseline (e.g., bleach baths) should not be introduced through the 
course of the study. 
6.6.2.2 
Anti-infectives 
Topical and systemic anti-infective medications are permitted during the study, independent of 
the location of the infection, should the Principal Investigator identify an acute infection 
requiring treatment. 
6.6.2.3 
Anti-histamines 
Non-sedating anti-histamines (e.g., loratadine, cetirizine, or fexofenadine) are permissible. 
Sedating anti-histamines (e.g., doxepin, diphenhydramine) are permissible so long as these 
medications were on a stable dosing regimen within 7 days prior to the Baseline (Day 1) visit 
and remain on the stable dosing regimen through the duration of the treatment period (Day 113). 
Dose adjustments must be discussed with the Investigator prior to change. 
6.6.2.4 
Medications for Conditions Unrelated to AD 
Subjects who are taking oral medications for conditions unrelated to AD should be on a stable 
dosing regimen within the 7 days prior to the Baseline (Day 1) visit. Adjustments to the regimen 
may be made after the Baseline visit if medically necessary. If a new medication is required to 
treat an emerging condition, these are allowable, provided the medication is not among the 
prohibited therapies. New concomitant medications should be discussed with the Medical 
Monitor prior to initiation. 
6.6.2.5 
Corticosteroids for Nose, Lungs, Eyes, and/or Ears 
Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and ear drops containing 
corticosteroids are also allowed when used as directed. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
50 
 
 
6.6.2.6 
Herbals and supplements 
Subjects may take herbals and/or supplements with the following conditions. First, subjects 
taking herbals and/or supplements at screening who wish to discontinue these may do so 
provided that they do the following for the duration of the study: 1) continue to refrain from 
taking the herbal/supplement and 2) do not introduce a new herbal and/or supplement. Second, 
subjects who intend to continue taking herbal products or supplements during the trial must agree 
to continue the regimen documented at Screening throughout the study unless discontinuation is 
considered medically necessary. 
6.6.3 
Prohibited Therapies or Procedures 
Female subject agrees not to have egg retrieval during the study and for 30 days after the last 
study drug administration. 
Male subject agrees not to donate sperm during the study and for 90 days after the last study drug 
administration. 
Table 3 lists prohibited medications that are not to be used from the defined washout periods 
before the first administration of study treatment at the Day 1 visit through the last study visit. 
Subjects who start prohibited medications or therapies as a treatment for AD or other reasons 
during the study may be withdrawn from study treatment for safety reasons. If in any doubt, 
Investigators are advised to discuss medications with the Medical Monitor. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
52 
 
 
6.6.4 
Rescue Medications 
Subjects who require topical corticosteroids, calcineurin inhibitors, or PDE4 inhibitor 
medications that could directly impact AD disease activity prior to Day 57 will be withdrawn 
from study drug and the study if requiring such topical therapies prior to Day 57. 
Starting at Day 57, rescue medications for persistent, intolerable AD activity may be considered 
by the Investigator. Investigators must document evidence of continued active AD with EASI 
unchanged from or greater than the Baseline EASI score over 2 consecutive visits before 
initiating therapy. All subjects requiring rescue therapy between Day 57 (Week 8) and Day 113 
(Week 16) will remain in the study and on study drug until Week 16. 
After the end of treatment at Day 113 and during the follow-up phase, subjects may also initiate 
rescue if either the subject or investigator feels that there is persistent, intolerable AD activity. 
Permitted rescue medications include low- to moderate-potency (class IV-class VII) topical 
corticosteroids (Appendix 14) and should be applied only to problem areas. A topical calcineurin 
inhibitor, topical PDE4 inhibitor (e.g., crisaborole), or low-potency topical steroid may be used 
on the face if affected. Subjects who require rescue therapy will be considered non-responders 
for all efficacy endpoints with data imputed for subsequent continuous endpoints for all time 
points as detailed in the Statistical Analysis Plan (SAP). Ideally, the specified medication for 
rescue treatment would be supplied by the clinic so that the tube could be weighed prior to 
administration. In addition, use of the specified medication should be recorded in the e-Diary, 
and the medication should be brought to clinic at subsequent visits to assess amount of 
medication used. 
6.7 
Dose Modification 
No dosing modifications are permitted. 
6.8 
Treatment after the End of the Study 
The Sponsor will not provide any additional care to subjects after they leave the study because 
such care should not differ from what is normally expected for subjects with moderate-to-severe 
AD. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
53 
 
 
7.0 DISCONTINUATION OF STUDY TREATMENT AND 
SUBJECT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Treatment 
See the SoA for data to be collected at the time of Early Termination/Treatment Discontinuation 
and follow-up and for any further evaluations that need to be completed. 
7.1.1 
Temporary Discontinuation 
In the event of an AE or clinically significant laboratory abnormality, study treatment of a 
subject may be temporarily discontinued based on the Investigator’s judgment and preferably 
following a discussion with the Medical Monitor in accordance with the guidelines described in 
this section. 
If during the course of treatment, a subject experiences a new (i.e., not existing at baseline) 
cardiovascular or hematologic AE (including laboratory abnormalities confirmed by repeat 
testing), consistent with Common Terminology Criteria for Adverse Events (CTCAE) 
Version 5.0 [CTCAE 2017] of Grade 2 or higher, then the study drug should be temporarily 
discontinued for that subject. Treatment may be re-initiated if the abnormality resolves 
within 2 weeks of the onset of the AE. 
In the event of a clinically significant laboratory abnormality, study treatment may be 
temporarily discontinued at the Investigator’s discretion. A decision to temporarily discontinue 
treatment with the study drug and/or to reinstitute study treatment should be discussed with the 
Medical Monitor. The Investigator may suspend study treatment at any time, even without 
consultation with the Medical Monitor if the urgency of the situation requires immediate action 
and if it is determined to be in the subject’s best interest. However, the Medical Monitor should 
be contacted as soon as possible for all cases of study drug discontinuation/interruption. 
Resumption of study treatment after temporary discontinuation should always be discussed with 
the Medical Monitor. Resumption of investigational product may occur so long as the laboratory 
finding has returned to Baseline or has only mild out-of-range levels less than or equal to 
2 weeks from onset of the laboratory abnormality. 
The information pertaining to interruption or discontinuation of study drug and the reasons for it 
must be recorded in the case report form (CRF). 
No dose reductions or modifications will be permitted in RPT193-02. 
7.2 
Subject Discontinuation/Withdrawal from the Study 
Subjects have the right to withdraw from the study at any time for any reason without penalty. 
The Investigator also has the right to withdraw subjects from the study if he or she feels it is in 
the best interest of the subject or if he or she is uncooperative or noncompliant. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
54 
 
 
Should a subject decide to withdraw, all efforts will be made to complete and report the 
observations as thoroughly as possible, particularly the examinations outlined in the Early 
Termination /Discontinuation (ET/Discon) visit. 
The Investigator or one of his or her staff members should contact the subject to determine as 
accurately as possible the primary reason for the withdrawal. 
A complete final evaluation at the time of withdrawal should be made with an explanation of 
why the subject is withdrawing from the study. If the reason for removal of a subject is an AE or 
an abnormal laboratory test result, the principal specific event or test will be recorded. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the Investigator must document this in the site study records. 
7.2.1 
Discontinuation 
Subjects who discontinue the study after the first dose will be asked, if they agree, to come for a 
last assessment (ET/Discon visit). Subjects who are discontinued for safety reasons may be asked 
to come for additional follow-up visits, at the Investigator’s discretion, after the ET/Discon visit 
to ensure appropriate medical care and AE follow-up. 
Reasons for discontinuation include the following: 
• The Investigator decides that the subject should be withdrawn for any of the following 
reasons, but not limited to: difficulties in obtaining blood samples, violation of the protocol, 
severe AEs or SAEs, or for any other reason relating to the subject’s safety or integrity of the 
study data. If this decision is made because of a SAE, the study drug is to be discontinued in 
that subject immediately and appropriate measures are to be taken. The Investigator will 
notify the Sponsor immediately. 
• The attending physician requests that the subject be withdrawn from the study. 
• The subject, for any reason, requires treatment with another systemic therapeutic agent that 
has been demonstrated to be effective for treatment of the study indication (e.g., oral 
corticosteroids, dupilumab, tralokinumab oral calcineurin inhibitor, oral 
immunosuppressive). In this case, discontinuation from the study occurs immediately upon 
introduction of the new agent. 
• The subject is lost to follow-up. In this case, a reasonable attempt to contact the subject and 
ascertain his or her status must be made, and these attempts must be documented. 
• The subject becomes pregnant at any time during the study. 
• A clinically significant change in a laboratory parameter occurs (See Table 4), 
• Onset of an opportunistic infection during the study. 
• Other: the subject may withdraw from the study for any other reason, including withdrawal 
of consent. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
56 
 
 
7.2.3 
Possible Case of Drug-Induced Liver Injury (DILI) 
Subjects who present with evidence of hepatocellular injury that may be caused by drug 
ingestion consistent with Hy’s Law with all of the following criteria acutely should be 
re-evaluated: 
• ALT or aspartate aminotransferase (AST) > 3× ULN 
• Total bilirubin > 2× ULN 
• No signs of cholestasis (alkaline phosphatase [ALP] < 2× ULN) 
• No other assignable cause such as liver metastases, pre-existing hepatic disease, viral 
hepatitis, alcohol abuse, ischemia, etc. 
Re-evaluation should include repeat of AST, ALT, total bilirubin and alkaline phosphatase along 
with additional laboratory assessments including: albumin, creatine kinase, direct bilirubin, 
gamma-glutamyl transferase (GGT), and prothrombin time (PT)/international normalize ratio 
(INR). Additional medical and/or laboratory investigation to investigate other potential causes 
(e.g., alcohol use, infectious hepatitis) should also be considered and assessed as appropriate by 
the Investigator. Potential cases satisfying Hy’s law should be reported as SAEs. If a subject 
satisfies Hy’s law, study drug should be discontinued for the subject. 
7.3 
Lost to Follow-up 
A subject will be considered lost to follow-up if he or she fails to return for scheduled visits and 
is unable to be contacted by the study site staff. 
The following actions must be taken if a subject fails to return to the clinic for a required study 
visit: 
• The site will attempt to contact the subject and reschedule the missed visit. The site will then 
counsel the subject on the importance of maintaining the assigned visit schedule and 
ascertain if the subject wishes to or should continue in the study. 
• Before a subject is deemed lost to follow-up, the Investigator or designee will make every 
effort to regain contact with the subject (where possible, 3 telephone calls and, if necessary, a 
certified letter to the last known mailing address of the subject, or local equivalent methods). 
These contact attempts should be documented in the medical record or study file of the 
subject. 
If all attempts to contact the subject fail, he or she will be considered to have withdrawn from the 
study with a primary reason of lost to follow-up. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
58 
 
 
licensed medical professional (e.g., Nurse Practitioner) who has previously had documented 
experience in such assessments in AD clinical trials may be designated by the primary site 
Investigator to perform such evaluations. As with other raters in the study, these raters must 
complete all protocol-associated training. 
Every effort should be made to have the same rater perform all AD efficacy assessments for an 
individual subject through the course of participation in the study. 
8.1.2 
Subject Questionnaires and Treatment Diaries 
Subject questionnaires and treatment diaries will be completed via an electronic application on 
their personal electronic device or via site provisioned device if they choose not to use their own. 
If they choose to use their own device, the site will provide clear instructions on how to 
download and set up the application. 
Subjects will complete daily e-Diaries including compliance with study drug and all 
questionnaires that are required listed in SoA. The e-Diary data will be reviewed regularly for 
compliance and queries by the monitors and study staff. Any queries identified will be managed 
by IQB and the clinical site. 
8.1.3 
Validated Investigator Global Assessment (vIGA) 
 
 
 
 
8.1.4 
Body Surface Area (BSA) of AD Affected Skin 
The overall BSA affected by AD will be evaluated (from 0% to 100%) at the visits specified in 
the SoA. The palmar surface of one hand represents ׽1% of a subject’s total BSA. To be 
eligible, subjects must have a BSA of ≥10% at the Screening and Baseline visits. 
8.1.5 
Eczema Activity and Severity Index (EASI) 
 
 
 
 
 
 
 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
59 
 
 
Numeric Rating Scale 
corticosteroids, topical PDE4 inhibitor (e.g., crisaborole), and/or calcineurin inhibitors or is using 
 
 
 
 
 
8.1.6 
SCORing Atopic Dermatitis (SCORAD) 
The SCORAD will be measured at the visits specified in the SoA. The SCORAD grading system 
 
 
 
 
 
 
 
 
 
 
8.1.7 
Pruritus Numerical Rating Score 
The intensity of pruritus will be recorded daily by the subject in an e-Diary using the pruritus 
NRS. At the visits specified in the SoA, the pruritus NRS will be completed by the subject at the 
study center using the e-Diary and should be assessed at about the same time each day. The 
pruritus NRS will ask subjects “On a scale of 0 to 10, with 0 being “no itch” and 10 being “worst 
itch imaginable”, how would you rate your itch at the worst moment during the previous 
24 hours?”. [Yosipovitch 2019] The daily (24-hour) pruritus NRS will be recorded and the 
weekly mean of the daily pruritus NRS will be calculated. The pruritus NRS is presented in 
Figure 2. Subjects should begin recording daily pruritus NRS scores starting at Day 1. 
Figure 2    Pruritus Numeric Rating Scale 
 
 
0 
1 
2  
3 
4  
5 
6  
7  
8 
9 
10 
No itch 
Worst itch imaginable 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
61 
 
 
8.1.14 
Atopic Dermatitis Sleep Scale 
The three-item ADSS captures the self-reported impact of itch on sleep disturbance each day, 
including: difficulty falling asleep (Item 1); number of night-time awakenings (Item 2), and 
difficulty falling back asleep after waking (Item 3) during the previous night [Silverberg 2021]. 
Each ADSS item is scored individually. For Items 1 and 3, subjects will be asked to select a 
score ranging from 0 (“not at all”) to 4 (“very difficult”). For Item 2, subjects select the number 
of times they woke up each night, ranging from 0 to 29 times. Subjects are only to answer Item 3 
if their answer to Item 2 is greater than 0. 
8.2 
Safety Assessments 
Planned time points for all safety assessments are provided in the SoA. 
8.2.1 
Physical Examinations 
• A complete physical examination will include, at a minimum, assessments of the 
[Cardiovascular, Respiratory, Gastrointestinal, and Neurological] systems. Height and weight 
will also be measured and recorded. At screening only, skin tone should be assessed using 
the Fitzpatrick skin type scale (I to VI). 
• A brief physical examination will include, at a minimum, assessments of the (skin, lungs, 
cardiovascular system, and abdomen [liver and spleen]). 
• Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
8.2.2 
Vital Signs 
• Vital signs will consist of body temperature, pulse rate, blood pressure, and respiratory rate. 
• Blood pressure and pulse measurements will be assessed with a completely automated 
device. Manual techniques will be used only if an automated device is not available. 
• Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest for 
the subject in a quiet setting without distractions (e.g., television, cell phones) and with the 
subject in a seated or supine position. 
• Vital signs (to be taken before blood collection for laboratory tests) will consist of 1 pulse 
and 1 blood pressure measurement with the subject in a seated or supine position. 
8.2.3 
Electrocardiograms 
• Triplicate 12-lead ECG will be obtained as outlined in the SoA (see Section 1.3) using an 
ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and 
QTc intervals. Refer to Section 7.0 for QTc withdrawal criteria and any additional QTc 
readings that may be necessary. 
• Triplicate 12-lead ECGs will be recorded with a maximum interval of 5 minutes between the 
first and the third ECG. The ECGs will be recorded after at least 10 minutes of rest in the 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
62 
 
 
supine position using an automated device equipped with computer-based interval 
measurements (with no/minimal disturbance by procedures). 
8.2.4 
Clinical Safety Laboratory Assessments 
• See Appendix 11 for the list of clinical laboratory tests to be performed and the SoA for the 
timing and frequency. 
• For the three visits requiring fasted labs (Baseline, Day 113, and Day 127), a subject should 
refrain from eating or drinking (except for water) for a period of at least 8 hours prior to the 
lab draw. 
• 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 CRF. 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 
participation in the study or within 30 days after the last dose of study treatment should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant 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 Medical 
Monitor and Sponsor notified. 
− All protocol-required laboratory assessments, as defined in Appendix 11, must be 
conducted in accordance with the laboratory manual and the SoA. 
− If laboratory values from non-protocol specified laboratory assessments performed at 
the institution’s local laboratory require a change in subject management or are 
considered clinically significant by the Investigator (e.g., SAE or AE or dose 
modification), then the results must be recorded in the CRF. 
8.3 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 12. 
AEs will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or the 
participant’s legally authorized representative). 
The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious, considered related to the study treatment or study procedures, or that caused the 
subject to discontinue the study treatment or the study (see Section 7.0). 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
63 
 
 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information 
Adverse events and SAEs will be collected from the signing of the ICF until Follow-up /Visit 10 
or 28 days after the last dose of study treatment if subject is terminated early. 
All SAEs will be recorded and reported to the Sponsor or designee within 24 hours of the 
Investigator’s awareness of the event, as indicated in Appendix 12. The Investigator will submit 
any updated SAE data to the Sponsor within 24 hours of receipt of the information. 
Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any time after 
a subject has been discharged from the study, and he/she considers the event to be reasonably 
related to the study treatment or study participation, the Investigator must promptly notify the 
Sponsor. 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Appendix 12. 
8.3.2 
Method of Detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the subject is the preferred method to inquire about 
AE occurrences. 
8.3.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. All SAEs will be followed until resolution, stabilization, the event is 
otherwise explained, or the subject is lost to follow-up (as defined in Section 7.3). Further 
information on follow-up procedures is given in Appendix 12. 
8.3.4 
Regulatory Reporting Requirements for SAEs 
• Prompt notification by the Investigator to the Sponsor 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. 
• The Sponsor 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 will comply with country-specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRBs/REBs/IECs, and Investigators. 
• Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and Sponsor policy and 
forwarded to Investigators as necessary. 
• An Investigator who receives an Investigator safety report describing an SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the Sponsor will review 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
64 
 
 
and then file it along with the Investigator’s Brochure and will notify the IRB/REB/IEC, if 
appropriate according to local requirements. 
8.3.5 
Adverse Events of Clinical Interest 
 
Events of clinical interest, whether serious or not, in the study include: 
• malignancy 
• major adverse cardiac events (MACE) 
• tuberculosis (TB) 
• inflammatory bowel disease (IBD) 
• depression and suicidal ideation and behavior 
• serious or opportunistic infection 
• hypersensitivity reactions 
RPT193 has not been associated with any of these events of clinical interest based on preclinical 
toxicology studies as well as clinical Phase 1 data from RPT193-01. These events of clinical 
interest will be evaluated on an ongoing basis. A separate analysis of these adverse events will 
also be performed at the end of the study. 
8.3.6 
Pregnancy 
 
• Details of all pregnancies in female subjects and, if indicated, female partners of male 
subjects, will be collected after the start of study treatment and until 30 days after the last 
administration of study treatment. 
• If a pregnancy is reported, the Investigator should inform the Sponsor within 24 hours of 
learning of the pregnancy and should follow the procedures outlined in Appendix 12. 
• If the outcome of the pregnancy meets the criteria for immediate classification as an SAE 
(i.e., spontaneous abortion, stillbirth, neonatal death, or congenital anomaly [including that in 
an aborted fetus, stillbirth, or neonatal death]), the Investigator will report according to the 
SAE reporting procedures described in Appendix 12. 
8.4 
Treatment of Overdose 
Study drug overdose is any accidental or intentional use of study drug in an amount at least 
2 times higher than the dose indicated per-protocol for a given subject. Study drug compliance 
(see Section 6.4) should be reviewed to detect potential instances of overdose (intentional or 
accidental). 
The Sponsor must be immediately notified of any instances of overdose and a protocol deviation 
must be thoroughly documented and reported per local regulations. Any study drug overdose 
during the study should be recorded on the source document and eCRF. The excess quantity and 
duration of the overdose should be recorded. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
65 
 
 
In the event of overdose, the subject should be closely monitored for any potential AEs. All AEs 
associated with an overdose should be entered on the Adverse Event eCRF. If the associated AE 
fulfills serious criteria, the event should be reported to the Sponsor or designee within 24 hours 
of awareness of the event. Any AEs or SAEs associated with an overdose will be reported using 
the procedures detailed in Appendix 12. 
8.5 
Pharmacokinetics 
Blood samples will be collected for PK analysis of RPT193 at the visits and time points specified 
in the SoA. 
The analysis of RPT193 in blood samples will be performed at 
 
 using (a) validated liquid chromatography-mass spectrometry/mass spectrometry method(s) 
(LC-MS/MS). The Bioanalytical Reports for the determinations will be included in the clinical 
study report (CSR). Exploratory analysis of RPT193 metabolites or related compounds in blood 
samples may be conducted at Sponsor laboratories. 
At the time points defined in the SoA, blood samples will be taken for the analysis of RPT193 
(and possibly for RPT193 metabolites or related compounds), in blood samples. The blood 
samples will be taken via an indwelling intravenous (IV) catheter or by direct venipuncture into 
K2 ethylenediaminetetraacetic acid [EDTA]-containing tubes. 
The actual date and time of each blood sample collection will be recorded in the eCRF. 
Details about the collection, processing, handling, storage, and shipping of PK samples will be 
provided in the laboratory manual. 
PK variables will be the plasma concentrations of RPT193 and their PK parameters. A complete 
list of PK parameters will be provided in the SAP. 
8.6 
Pharmacodynamics 
Blood samples will be collected for pharmacodynamic analysis of RPT193 at the visits and time 
points specified in the SoA. The pharmacodynamic analysis of RPT193 will include but may not 
be limited to the assessment of CCR4 occupancy by flow cytometry, measurement of serum 
cytokines/chemokines levels by immune-assay, and blood cell immunophenotyping by flow 
cytometry. Note: immunophenotyping will only be performed for subjects in the US and Canada; 
immunophenotyping will not be performed for subjects in Poland. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
66 
 
 
8.7 
Pharmacogenomics 
A blood sample for DNA isolation will be collected from subjects who have consented to 
participate in the genetic analysis component of the study. Participation is optional. Subjects who 
do not wish to participate in the genetic research may still participate in the study. 
In the event of DNA extraction failure, a replacement genetic blood sample may be requested 
from the subject. Signed informed consent will be required to obtain a replacement sample 
unless it was included in the original consent. 
Details on processes for collection and shipment and destruction of these samples can be found 
in the laboratory manual. 
8.8 
Biomarkers 
Collection of samples for biomarker research is also part of this study. The following samples for 
biomarker research are required and will be collected from all subjects in this study as specified 
in the SoA: 
− Whole blood 
− Serum 
− Plasma 
− Skin tape strips 
− Skin swabs 
Note: tape stripping is only required for subjects in the US and Canada; tape stripping should not 
be performed for subjects in Poland. 
Samples may be stored for a maximum of 25 years (or according to local regulations) following 
the last subject’s last visit for the study at a facility selected by the Sponsor to enable further 
analysis of biomarker responses to RPT193. 
8.8.1 
RNA Transcriptome Research 
Subjects in the US and Canada will have skin tape stripping samples collected at the visits 
specified in the SoA; tape stripping should not be performed for subjects in Poland. Tape strips 
will be collected from lesional and non-lesional skin at baseline. Tape strip samples will also be 
collected at the subsequent visits specified in SoA at the same sites sampled at baseline. For each 
sampled site, 16 tape-strip units will be placed and removed from the exact same site one after 
the other. All skin sampling (microbiome samples, and tape strips) should be collected from 
adjacent sites within the same lesion, whenever possible. Details about the collection, processing, 
handling, storage, and shipping of tape strip samples will be provided in the laboratory manual 
and/or the Study Reference Manual. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
67 
 
 
Transcriptome studies will be conducted using whole transcriptome RNA sequencing, which 
facilitates the simultaneous measurement of the relative abundances of thousands of ribonucleic 
acid (RNA) species resulting in a transcriptome profile for each skin sample. This will enable the 
evaluation of changes in transcriptome profiles that may correlate with biological response 
relating to AD or the action of RPT193. 
The same samples may also be used to confirm findings by application of alternative 
technologies. 
8.8.2 
Proteome Research 
Plasma and serum proteome studies will be performed by immunoassay for specific proteins of 
interest. Multiplexed or individual immunoassays may be used to determine relative and/or 
quantitative changes in protein level because of treatment. Proprietary algorithms and standard 
statistical techniques, such as analysis of variance (ANOVA) and analysis of covariance 
(ANCOVA), may be used to identify individual proteins exhibiting statistically significantly 
different changes in their levels between samples and/or between groups of samples. 
Alternatively, differentially expressed proteins may be identified by mass spectrometry or 
equivalent technology. This will enable the evaluation of changes in proteome profiles that may 
correlate with biological response relating to disease and medically related conditions or the 
results of treatment. Details about the collection, processing, handling, storage, and shipping of 
plasma and serum samples will be provided in the laboratory manual. 
The samples may also be used to confirm findings by application of alternative technologies. 
8.8.3 
Skin Microbiome Swab 
All subjects will have collection of skin microbiome samples at the visits specified in the SoA. 
Skin microbiome sampling is a non-invasive procedure that involves passing a swab along the 
skin. Two skin microbiome samples will be collected at baseline, one from lesional and one 
non‑lesional skin. A skin microbiome sample will also be collected at the subsequent visits 
specified in the SoA at the same lesional site sampled at Baseline. 
All skin sampling (microbiome samples and tape strips) should be collected from adjacent sites 
within the same lesion, whenever possible. 
Details about the collection, processing, handling, storage, and shipping of skin microbiome 
samples will be provided in the laboratory manual and/or the Study Reference Manual. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
68 
 
 
8.9 
Other Study Procedures 
8.9.1 
Medical Photography 
Medical photographs will be performed at selected sites at the visits specified in the SoA. One or 
more most affected body regions, per Investigator’s judgment, may be photographed. 
Photographs will be identified with the following information: study number, subject number, 
and visit name and date. Digital images will be uploaded 
 via the secure website for 
Sponsor review. 
Details about the medical photography will be provided in the Study Reference Manual. 
8.9.2 
COVID-19-Related Considerations 
COVID-19 Vaccination Guidance 
Investigators and subjects should consider the schedule of their COVID-19 booster vaccine (if 
applicable) when planning the timing of their study participation. Where possible, the timing of 
vaccination should be planned so that a booster vaccination is not administered during the study 
treatment period. Ideally, administration of a COVID-19 booster vaccine (if applicable) should 
be given at least 4 weeks prior to the first dose of study treatment for live, attenuated vaccines 
and 2 weeks prior to the first dose of study treatment for mRNA vaccines. If unavoidable, 
vaccination with mRNA-based vaccines can proceed during the study, but every effort should be 
made to avoid administration during the final month of the treatment period, if possible. These 
events will not be considered major protocol deviations, but are considered prohibited therapies. 
It should be noted that the effect of RPT193 on the response to COVID-19 vaccination is 
unknown. The COVID-19 vaccine may lead to AEs (fever, chills, etc.), which will need to be 
captured and distinguished as related to the vaccine versus RPT193. 
COVID-19 Testing Guidance 
At the Screening visit (Visit 1) and Baseline visit (Visit 2) prior to the first dose of study 
treatment, all subjects must have a nasopharyngeal swab, or oropharyngeal swab, nasal swab, or 
saliva sample collected to test for the presence of the SARS-CoV-2 virus. The sample will be 
sent to the study’s central laboratory or local laboratory, if necessary, for analysis by an 
acceptable diagnostic assay. Subjects with positive test results at Screening (Visit 1) will be 
considered screen failures and will not be allowed to enroll per the exclusion criteria for the 
study. Such screen failed subjects may be considered for rescreening at a later date following 
consultation with the study Medical Monitor. If results from the COVID-screening at the 
Baseline visit are immediately available and positive, the subject should be screen failed and 
may be considered for rescreening at a later date following consultation with the study Medical 
Monitor. If results from COVID-screening at the Baseline visit are not immediately available at 
the time of randomization, subjects are allowed to dose with study treatment at the Baseline visit 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
69 
 
 
(Visit 2) provided the Screening test was negative and as long as there is no clinical suspicion of 
COVID-19 infection or subject recent exposure to an individual with a confirmed, active 
infection at the time of the Baseline visit. 
If the subject’s results are positive for SARS-CoV-2 following sample collection at Baseline 
(Visit 2), the subject will need to be notified immediately upon receipt of the results. The subject 
should be advised to begin self-isolation and self-monitoring procedures according to any 
applicable local, state, and/or country-specific health recommendations. Referral to an 
appropriate health care provider for management of the subject’s COVID-19 diagnosis should 
also be made. The subject’s COVID-19 diagnosis will be reported as medical history unless the 
subject’s clinical course progresses such that criterion for SAE reporting is met 
(see Appendix 12), in which case, all applicable safety reporting procedures will be followed by 
the site. Sites will also have the option to perform an unscheduled test for the SARS-CoV-2 virus 
at any time during the treatment phase of the study should a subject’s clinical presentation 
necessitate it, in the Investigator’s opinion. The same notification and referral procedures, as 
outlined in the preceding paragraphs, should be followed by the site. However, it is expected that 
any COVID-19 diagnosis made from a sample collected after the initiation of study treatment 
administration be reported as an AE per the requirements of Appendix 12 of this protocol. In the 
event that a subject tests positive for the SARS-CoV-2 virus at or after Baseline (Visit 2), the 
Investigator must consult with the study Medical Monitor to determine if the subject should 
continue with study drug treatment or discontinue from treatment. Determinations will be made 
on a case-by-case basis with the intent to minimize any increased risk for the subject. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
70 
 
 
9.0 STATISTICAL CONSIDERATIONS 
9.1 
General Considerations 
The comprehensive SAP with detailed description of all statistical analyses will be developed 
and finalized before database lock. 
All statistical analyses, including summary tables and data listings will be performed using SAS® 
software (version 9.4 or higher). Continuous endpoints will be summarized using descriptive 
statistics (number of subjects [n], mean, standard deviation [SD], median, minimum, and 
maximum). Categorical endpoints will be summarized using frequency counts and percentages. 
All individual subject data will be present in listings. 
9.2 
Sample Size Determination 
 
 
 
 
 
 
 
 
 
 
 
Based on the assumptions above and using a two-sample t-test, a sample size of 60 subjects per 
treatment group is needed to detect the treatment effect on the primary endpoint between 
RPT193 and placebo. Assuming a 10% drop out rate, a total sample size of approximately 
265 subjects (approximately 67 per treatment group) will be needed. 
9.3 
Populations for Analyses 
For purposes of analysis, the analysis sets in Table 5 are defined. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
71 
 
 
Table 5 
Analysis Sets 
 
Analysis Set 
Description 
Full Analysis Set (FAS) 
All subjects who have been randomized to a study treatment group. FAS will 
be the primary analysis set for all efficacy analyses. Subjects will be analyzed 
according to their randomized treatment. 
Per-Protocol (PP) Analysis Set 
All subjects in FAS with no major protocol deviation that would have an 
impact on the primary and key secondary efficacy assessments. Major 
protocol deviations will be reviewed and determined prior to database lock. 
Subjects to be excluded from the PP analysis set will be determined based on a 
blinded data review meeting prior to database lock. Subjects will be analyzed 
according to their randomized treatment. 
Safety Analysis Set 
All randomized subjects who receive at least 1 dose of study treatment. This 
analysis set will be used for all safety analyses. Subjects will be analyzed 
according to the treatment they received. 
9.4 
Statistical Analyses 
9.4.1 
Subject Disposition and Demographics 
Subject disposition events as well as the number of subjects in each analysis sets will be 
summarized using frequency counts and percentages by treatment arms. 
Demographic and baseline characteristic will be summarized as appropriate. 
9.4.2 
Primary Efficacy Analysis 
The primary efficacy endpoint is the percent change from baseline in EASI score at Week 16. 
The primary estimand is defined as 
• 
Population of interest: adult subjects with moderate-to-severe AD as defined by the 
inclusion/exclusion criteria 
• 
Variable/endpoint of interest: percent change from baseline in EASI score at 
Week 16. 
• 
Intercurrent event handling strategy: 
• 
Early termination of study treatment: subjects who discontinue from the study 
treatment prior to Week 16 will be analyzed by the treatment policy strategy, i.e., all 
data collected will be included in analysis. 
• 
Use of rescue medications: subjects who use rescue medication during the 16-week 
treatment period will be analyzed by the hypothetical strategy. All EASI scores 
collected after the start of rescue medication will be set to missing and imputed. 
• 
Population-level summary measure: difference in mean percent change from baseline 
in EASI score between RPT193 and placebo. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
72 
 
 
The primary analysis will be performed in FAS. The primary efficacy endpoint will be analyzed 
with ANCOVA model. The model will include treatment group (each RPT193 dose vs. placebo), 
baseline vIGA scores, randomization stratification factors and study sites as factor, and baseline 
EASI score as a covariate. The least square (LS) mean and LS mean difference along with the 
95% confidence interval (CI) and p-value will be reported. 
The following sensitivity analysis will be planned for the primary estimand: 
• 
In FAS, including only the observed data regardless of rescue medication uses and 
without missing data imputation. 
• 
In PP analysis set, following the same model as described for the primary estimand. 
9.4.2.1 
Secondary Efficacy Analysis 
For continuous secondary endpoints, the same model as discussed for the primary analyses will 
be followed. For binary secondary endpoints, a logistic regression model with treatment group, 
baseline vIGA scores, randomization stratification factors, study sites as factors and baseline 
score as a covariate will be used. 
9.4.2.2 
Multiplicity 
For the primary efficacy endpoint, to preserve the Type I error at 0.05, a serial gatekeeping 
strategy will be employed to address the multiplicity of the pairwise comparison of each RPT193 
dose vs. placebo. The order of the testing will be performed from the highest RPT193 dose to the 
lowest dose. Testing will stop if non-significance (2-sided p-value ≥ 0.05) is observed. 
9.4.3 
Safety Analyses 
All safety analyses will be performed on the Safety Analysis Set. 
Adverse events will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA). A TEAE is any condition that was not present prior to treatment with the study drug 
but appeared following treatment, was present at treatment initiation but worsened during 
treatment, or was present at treatment initiation but resolved and then reappeared while the 
individual was on treatment (regardless of the intensity of the AE when the treatment was 
initiated). 
The AE summaries will be primarily based on TEAEs. Descriptive statistics for the number and 
percentage of subjects with TEAEs will be summarized by treatment arm, system organ class, 
and preferred term for all TEAEs, treatment-related TEAEs, serious TEAEs, and TEAEs leading 
to discontinuation of study treatment. All TEAEs will be further summarized by maximum 
severity and causality. 
All AEs will be present in a by-subject listing. Serious AEs, and TEAEs leading to 
discontinuation of study treatment will be present in separate listings. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
73 
 
 
Adverse Events of Clinical Interest 
A separate analysis focused on the following events of clinical interest will also be performed: 
malignancy, major adverse cardiac events (MACE), tuberculosis (TB), inflammatory bowel 
disease (IBD), depression and suicidal ideation and behavior, serious or opportunistic infection 
(e.g., infection resulting in hospitalization, requiring IV antibiotics, or considered 
life-threatening), and hypersensitivity reactions. 
Clinical Laboratory Tests 
Laboratory data will be summarized using descriptive statistics for each parameter, including 
change baseline at each assessment time by treatment arm. Frequency tables or shift tables will 
be used to present the number and percentages of subjects with laboratory values within/outside 
normal reference ranges. All laboratory data will be present in the listings. A by-subjects listing 
will also be provided for subjects with abnormal laboratory results. 
12-Lead Electrocardiogram (ECG) and Vital Signs 
Descriptive statistics will be used to summarize the observed and change from baseline values of 
the ECG and vital signs parameters at each assessment time point by treatment group. All ECG 
and vital signs data will be present in listings. 
9.4.4 
Other Analyses 
Pharmacokinetic (PK), pharmacodynamic, exploratory endpoints and skin microbiome analyses 
will be summarized using descriptive statistics and will be listed and summarized in a tabular 
and/or graphical form. 
9.4.5 
Missing Data 
For the primary and key secondary efficacy endpoints, the efficacy data collected 
after the start of rescue medication will be set to missing. All missing data up to 
Week 16 will be imputed using a multiple imputation (MI) technique as follows: 
• Intermittent missing data will first be imputed using the Markov Chain 
Monte Carlo (MCMC) method implemented with the SAS PROC MI 
procedure and imputed datasets with monotone missing pattern will be 
generated. This applies to intermittent missing data prior to the intercurrent 
events including early termination of the study treatment as well as initiation 
of rescue medications. 
• The monotone missing values will then be imputed with the imputation 
model estimated from subjects in the placebo group using the SAS PROC 
MI procedure with MNAR statement. This approach is based on the missing 
not at random (MNAR) assumption. This assumes that the missing data in 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
75 
 
 
10.0 REFERENCES 
Ascott A, Mulick A, Yu AM, et al. Atopic eczema and major cardiovascular outcomes: A 
systematic review and meta-analysis of population-based studies. J Allergy Clin Immunol. 
2019;143(5):1821-1829. 
Bieber T. Atopic dermatitis. Ann Dermatol. 2010;22(2):125-137. 
Bieber T, D’Erme AM, Akdis CA, et al. Clinical phenotypes and endophenotypes of atopic 
dermatitis: Where are we, and where should we go? J Allergy Clin Immunol. 
2017;139(4S):S58-S64. 
Boguniewicz M, Alexis AF, Beck LA, et al. Expert perspectives on management of 
moderate-to-severe atopic dermatitis: a multidisciplinary consensus addressing current and 
emerging therapies. J Allergy Clin Immunol Pract. 2017;5(6):1519-1531. 
Charman CR, Venn AJ, Williams HC. The patient-oriented eczema measure: development and 
initial validation of a new tool for measuring atopic eczema severity from the patients’ 
perspective. Arch Dermatol. 2004;140(12):1513-1519. 
Damsch S, Eichenbaum G, Tonelli A, et al. Gavage-related reflux in rats: identification, 
pathogenesis, and toxicological implications (review). Toxicol Pathol. 2011;39:348–360. 
Eichenfield LF, Tom WL, Berger TG, et al. Guidelines of care for the management of atopic 
dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. 
J Am Acad Dermatol. 2014;71(1):116-132. 
Eli Lilly and Company. Validated investigator global assessment scale for atopic dermatitis. 
2017. 
Feldman SR, Cox LS, Strowd LC, et al. The challenge of managing atopic dermatitis in the 
United States. Am Health Drug Benefits. 2019;12(2):83-93. 
Finlay AY, Khan GK. Dermatology life quality index (DLQI)—a simple practical measure for 
routine clinical use. Clin Exp Dermatol. 1994;19(3):210-216. 
Fitzpatrick T. The validity and practicality of sun-reactive skin types I through VI. Arch 
Dermatol. 1988;124:869-871. 
Guttman-Yassky E, Waldman A, Ahluwalia J, Ong PY, Eichenfield LF. Atopic dermatitis: 
pathogenesis. Semin Cutan Med Surg. 2017;36(3):100-103. 
Hanifin JM, Thurston M, Omoto M, et al. The eczema area and severity index (EASI): 
assessment of reliability in atopic dermatitis. Exp Dermatol. 2001;10(1):11-18. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
78 
 
 
11.0 APPENDICES 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
79 
 
 
Appendix 1 
Abbreviations 
 
Abbreviation 
Definition 
ACQ 
Asthma Control Questionnaire 
AE 
Adverse event 
AD 
Atopic dermatitis 
ADSS 
Atopic Dermatitis Sleep Scale 
ALC 
Absolute lymphocyte count 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
ANCOVA 
Analysis of covariance 
ANOVA 
Analysis of variance 
AST 
Aspartate aminotransferase 
AUC0-24 
Area under the plasma concentration-time curve 
at 0 to 24 hours 
BALF 
Bronchoalveolar lavage fluid 
BSA 
Body surface area 
CI 
Confidence interval 
Cmax 
Maximum concentration 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
Coronavirus disease of 2019 
CRF 
Case report form 
CRO 
Contract research organization 
CSR 
Clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP450 
Cytochrome P450 
DLQI 
Dermatology Quality of Life Index 
EASI 
Eczema Activity and Severity Index 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
e-Diary 
Electronic Diary 
EDTA 
Ethylenediaminetetraacetic acid 
eGFR 
Glomerular filtration rate 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
80 
 
 
 
Abbreviation 
Definition 
ET 
Early Termination 
FAS 
Full Analysis Set 
FCS 
Full conditional specification 
FDA 
Food and Drug Administration 
FITC 
Fluorescein isothiocyanate 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transferase 
GM-CSF 
Granulocyte-macrophage colony-stimulating factor 
HbA1c 
Hemoglobin A1c 
HbsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C 
HIV 
Human immunodeficiency virus 
IC90 
Concentration of an inhibitor where the response is 
reduced by 90% 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IFN 
Interferon 
IgE 
Immunoglobulin E 
IL 
Interleukin 
IL-4R 
Interleukin 4 receptor 
INR 
International normalized ratio 
IRB 
Institutional Review Board 
IV 
Intravenous 
IWRS 
Interactive Web Response System 
JAK 
Janus kinase 
LC-MS/MS 
Liquid chromatography-mass spectrometry/mass spectrometry 
LOCF 
Last observation carried forward 
LS 
Least square 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
82 
 
 
 
Abbreviation 
Definition 
Th2 
Type 2 helper T cell 
tmax 
Time to maximum concentration 
TNF 
Tumor necrosis factor 
ULN 
Upper limit of normal 
UVA1 
Ultraviolet A1 
VAS 
Visual analog scale 
vIGA 
Validated Investigator Global Assessment 
vIGA-AD 
Validated Investigator Global Assessment for atopic dermatitis 
WOCBP 
Women of childbearing potential 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
83 
 
 
Appendix 2 
Regulatory, Ethical, and Study Oversight Considerations 
Regulatory and Ethical Considerations 
• This study will be conducted in accordance with the protocol and with the following: 
− Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines. 
− Applicable ICH Good Clinical Practice (GCP) Guidelines. 
− Applicable laws and regulations. 
• The protocol, protocol amendments, ICF, Investigator Brochure, and other relevant 
documents (e.g., advertisements) must be submitted to an IRB/REB/IEC by the Investigator 
and reviewed and approved by the IRB/REB/IEC before the study is initiated. 
• Any amendments to the protocol will require IRB/REB/IEC and regulatory authority 
approval, when applicable, before implementation of changes made to the study design, 
except for changes necessary to eliminate an immediate hazard to subjects. 
• The Investigator will be responsible for the following: 
− Providing written summaries of the status of the study to the IRB/REB/IEC annually 
or more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/REB/IEC. 
− Notifying the IRB/REB/IEC of SAEs or other significant safety findings as required 
by IRB/REB/IEC procedures. 
− Providing oversight of the conduct of the study at the study center and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/REB/IEC, European regulation 
536/2014 for clinical studies, other country-specific requirements, as applicable, and 
all other applicable local regulations. 
• After reading the protocol, each Investigator will sign the protocol signature page and send a 
copy of the signed page to the Sponsor or representative (Appendix 15). The study will not 
start at any study center at which the Investigator has not signed the protocol. 
Protocol Adherence and Deviations 
The Investigator and site personnel should conduct the study in compliance with the protocol and 
should use continuous vigilance to identify and report protocol deviations. A protocol deviation 
is any change, divergence, or departure from the study design or procedures defined in the 
protocol that may be on the part of the Investigator, site personnel, or the subject. Important 
protocol deviations are a subset of protocol deviations that may significantly impact the 
completeness, accuracy, and/or reliability of the study data or that may significantly affect a 
subject’s rights, safety, or well-being. For example, important protocol deviations may include 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
84 
 
 
enrolling subjects in violation of key eligibility criteria designed to ensure a specific subject 
population or failing to collect data necessary to interpret primary endpoints, as this may 
compromise the scientific value of the study. The Investigator should not implement any 
deviation from the protocol without agreement from the Sponsor and prior review and approval 
from the IRB/REB/IEC of an amendment, except where necessary to eliminate an immediate 
hazard to a study subject, or when the change involves only logistical or administrative aspects 
of the study, such as a change in a monitor or telephone number. If a large number of protocol 
deviations are noted at a site, the Investigator shall implement corrective actions and evaluate the 
effectiveness of the corrective actions as they pertain to protocol deviations. Issues of non- 
compliance with the study protocol (repeated protocol deviations) may result in a corrective 
action plan or non-use of study data (depending on the quantity and content of protocol 
deviations). In the event of an important protocol deviation, the Investigator will discuss the 
deviation with the Sponsor’s medical monitor and will come to an agreement as to whether the 
subject should be withdrawn from the study due to the important protocol deviation. 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate financial 
information as requested to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study. 
Insurance 
The Sponsor has obtained liability insurance, which covers this study as required by local law 
and/or national regulations and/or ICH guidelines, whichever is applicable. The terms of the 
insurance will be kept in the Sponsor files. 
Informed Consent Process 
• The Investigator or a person designated by the Investigator (if acceptable by local 
regulation), will explain the nature of the study (i.e., purposes, procedures, potential risk, and 
his or her rights as a research subject) to the subject or his/her legally authorized 
representative and answer all questions regarding the study. In addition, insurance coverage 
provided during the study will be explained. 
• Subjects must be informed that their participation is voluntary and that they may withdraw 
from the study at any time for any reason, without prejudice. Subjects or their legally 
authorized representative will be required to sign a statement of informed consent that meets 
the requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance 
Portability and Accountability Act (HIPAA) requirements, where applicable, and the 
IRB/REB/IEC or study center. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
85 
 
 
• 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 
specially for the study. The study source 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. 
• A copy of the ICF(s) must be provided to the subject or the subject’s legally authorized 
representative for their records. 
• If new safety information results in significant changes in the risk benefit assessment, or if 
any new information becomes available that may affect the willingness of a subject to 
continue to participate the consent form should, if necessary, be reviewed and updated by the 
Sponsor and approved by the IRB/REB/IEC. All subjects should be informed of the new 
information, given a copy of the revised form and asked to give their consent to continue in 
the study. When the ICF is revised, re-consent is required for subjects to continue on study. 
• Subjects who are rescreened are required to sign a new ICF. 
Clinical Monitoring and Inspections 
The CRO monitor is responsible for visiting sites at regular intervals throughout the study to 
verify adherence to the protocol; completeness, accuracy, and consistency of the data; and 
adherence to ICH Good Clinical Practice (GCP) and local regulations on the conduct of clinical 
research. The monitor is responsible for inspecting the eCRFs and ensuring completeness of the 
study essential documents. The monitor should have access to subject medical records and other 
study-related records needed to verify the entries on the eCRFs. 
The monitor will communicate deviations from the protocol, SOPs, GCP, and applicable 
regulations to the Investigator and will ensure that appropriate action designed to prevent 
recurrence of the detected deviations is taken and documented. 
The Investigator agrees to cooperate with the monitor to ensure that any problems detected in the 
course of these monitoring visits are addressed and documented. 
In accordance with ICH GCP and the Sponsor’s audit plans, the study may be selected for audit 
by representatives from the Sponsor. Inspection of site facilities (e.g., pharmacy, drug storage 
areas, laboratories etc.) and review of study-related records (e.g., eCRFs, source data, and other 
pertinent documents) will occur in order to evaluate the study conduct and compliance with the 
protocol, ICH GCP, and applicable regulatory requirements. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
86 
 
 
Data Protection 
• Subjects will be assigned a unique identifier by the Sponsor. Any subject records or datasets 
that are transferred to the Sponsor will contain the identifier only; subject names or any 
information which would make the subject identifiable will not be transferred. 
• The subject must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the subject. 
• The subject must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/REB/IEC members, and by inspectors from regulatory authorities. 
• The ICF will incorporate (or, in some cases, be accompanied by a separate document 
incorporating) wording that complies with relevant data protection and privacy legislation. 
Administrative Structure 
Table 6 
Study Administrative Structure 
 
Function 
Responsible Organization 
Study Operations Management 
Medical Monitoring 
CRO 
Study Master File 
CRO 
Randomization Code 
Sponsor/CRO 
Data Management 
CRO 
Clinical Supply Management 
Sponsor/CRO 
Quality Assurance Auditing 
CRO 
Biostatistics 
Medical Writing 
Sponsor/CRO 
Laboratory Assessments 
Sponsor/ICON 
Electrocardiogram Collection, Review, and Analysis 
 
Pharmacokinetic Sample Testing 
 
Management of Event Adjudication 
Not applicable 
Adjudication Committee 
Not applicable 
Steering Committee 
Not applicable 
Safety Monitoring Committee (see Section 9.6) 
Sponsor/CRO 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
88 
 
 
source data should be traceable, should not obscure the original entry, and should be explained if 
necessary (e.g., via an audit trail). 
• Source documents provide evidence for the existence of the subject and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s study center. 
• Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
Investigator may need to request previous medical records or transfer records, depending on 
the study. Also, current medical records must be available. 
Study and Study Center Closure 
The Sponsor/ designee reserves the right to close the study center or terminate the study at any 
time for any reason at the sole discretion of the Sponsor. Study centers will be closed upon study 
completion. A study center is considered closed when all required documents and study supplies 
have been collected and a study center closure visit has been performed. 
The Investigator may initiate study center closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study center by the Sponsor or Investigator may include but 
are not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/REB/IEC or local health authorities, the Sponsor’s procedures, or GCP guidelines. 
• Inadequate recruitment of subjects by the Investigator. 
• Discontinuation of further study treatment development. 
Publication Policy 
The data generated by this study are confidential information of the Sponsor. The Sponsor will 
make the results of the study publicly available. The publication policy with respect to the 
Investigator and study center will be set forth in the Clinical Trial Agreement. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
90 
 
 
Appendix 4 
Eczema Activity and Severity Index (EASI) 
 
 
 
 
EASI guidance December 14 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
91 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
EASI guidance December 14 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
96 
 
 
 
 
 
EASI guidance December 14 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
97 
 
 
 
 
 
EASI guidance December 14 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
103 
 
 
Appendix 8 
Patient Global Assessment (PtGA) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
104 
 
 
Appendix 9 
Asthma Control Questionnaire (ACQ) 
 
 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
106 
 
 
Appendix 11 
Clinical Laboratory Tests 
• The tests detailed in Table 7 will be performed by the central laboratory. 
• Protocol-specific requirements for inclusion or exclusion of subjects are detailed in 
Section 5.0 of the protocol. 
• Additional tests may be performed at any time during the study as determined necessary by 
the Investigator or required by local regulations. 
Table 7 
Protocol-required Safety Laboratory Assessments 
 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count 
RBC Indices: 
White Blood Cell Count 
with Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
 
Red Blood Cell (RBC) 
Count 
Mean corpuscular volume 
(MCV) 
 
Hemoglobin 
Mean corpuscular 
hemoglobin (MCH) 
Hematocrit 
 
%Reticulocytes 
 
White Blood Cell Count 
Clinical 
Chemistrya 
Blood Urea 
Nitrogen 
Potassium 
Aspartate 
Aminotransferase 
Total and direct 
bilirubin 
 
 
 
(AST)/ Serum 
Glutamic- 
Oxaloacetic 
Transaminase 
(SGOT) 
 
 
Creatinine 
Sodium 
Alanine 
Aminotransferase 
Total Protein 
 
 
 
(ALT)/ Serum 
Glutamic-Pyruvic 
Transaminase 
(SGPT) 
 
 
Glucose [fasting] 
Calcium 
Alkaline 
phosphatase 
Cholesterol (Total, 
HDL, LDL)1 
 
Albumin 
Chloride 
GGT 
LDH 
 
Triglycerides 
Uric Acid 
Coagulation panel 
 
Routine 
Urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase 
by dipstick 
• 
Microscopic examination (if blood or protein is abnormal) 
Other Screening 
Tests 
• 
Follicle-stimulating hormone and estradiol (as needed in women of non-childbearing 
potential only) 
• 
Serum human chorionic gonadotropin (hCG) pregnancy test at screening and urine at 
baseline and during study (as needed for women of childbearing potential)b 
• 
Serology (HIV antibody, hepatitis B surface antigen [HBsAg], and hepatitis C virus 
antibody or specify other tests) 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
107 
 
 
 
Laboratory 
Assessments 
Parameters 
 
• 
Tuberculosis test (PPD or QuantiFERON-TB Gold or T-spot) 
The results of each test must be entered into the (e)CRF. 
NOTES: 
a Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in Section 7.1. All events of ALT ≥3 × upper limit of normal (ULN) and 
bilirubin ≥2 × ULN (>35% direct bilirubin) or ALT ≥3 × ULN and international normalized ratio (INR) >1.5, 
if INR measured, which may indicate severe liver injury (possible Hy’s Law), must be reported as an SAE 
(excluding studies of hepatic impairment or cirrhosis). 
b Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/REB/IEC. 
1 Fasting required for labs at Baseline, Day 113 (Week 16), and Day 127/ET/Discon (Week 18). A subject 
should refrain from eating or drinking (except for water) for a period of at least 8 hours prior to the lab draw. 
Investigators must document their review of each laboratory safety report. 
Pharmacokinetics results that could unblind the study will not be reported to study centers or 
other blinded personnel. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
108 
 
 
Appendix 12 
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
 
Definition of AE 
 
AE Definition 
• 
An AE is any untoward medical occurrence in a subject administered a medicinal product and which 
does not necessarily have a causal relationship with that product. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding, for example), symptom, or disease (new or exacerbated) temporally associated with 
the use of study treatment, whether or not considered related to the study treatment. 
 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety 
assessments (e.g., ECG, radiological scans, vital signs measurements), including those that worsen 
from baseline, considered clinically significant in the medical and scientific judgment of the 
Investigator (i.e., not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study treatment administration even though it may have 
been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study treatment or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an intentional 
overdose taken with possible suicidal/self-harming intent. Such overdoses should be reported 
regardless of sequelae. 
• 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be reported as an AE 
or SAE. Such instances will be captured in the efficacy assessments. However, the signs, symptoms, 
and/or clinical sequelae resulting from lack of efficacy will be reported as AE or SAE if they fulfil the 
definition of an AE or SAE. 
 
 
Events NOT Meeting the AE Definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments which are 
associated with the underlying disease, unless judged by the Investigator to be more severe than 
expected for the subject’s condition. 
• 
Because worsening of AD is captured by efficacy assessments, it will not be recorded as an AE, unless 
more severe than expected for the subject’s condition. 
• 
Medical or surgical procedure (e.g., 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. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
109 
 
 
Definition of TEAE 
 
TEAE Definition 
• 
A TEAE is any condition that was not present prior to treatment with the study product but appeared 
following treatment, was present at treatment initiation but worsened during treatment, or was present 
at treatment initiation but resolved and then reappeared while the individual was on treatment 
(regardless of the intensity of the AE when the treatment was initiated). 
 
 
Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (e.g., hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
 
An SAE is defined as any untoward medical occurrence that, at any dose: 
a)  Results in death 
b)  Is life-threatening 
The term ‘life-threatening’ in the definition of “serious” refers to an event in which the subject was at risk 
of death at the time of the event. It does not refer to an event, which hypothetically might have caused 
death, if it were more severe. 
c) 
Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the subject has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, the 
event is serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE should 
be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is not 
considered an AE. 
d) Results in persistent or significant disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance such as 
uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (e.g., sprained 
ankle) which may interfere with or prevent everyday life functions but do not constitute a substantial 
disruption. 
e) 
Is a congenital anomaly/birth defect 
f) 
Other medically important serious event: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is appropriate 
in other situations such as important medical events that may not be immediately life-threatening or 
result in death or hospitalization but may jeopardize the subject or may require medical or surgical 
intervention to prevent 1 of the other outcomes listed in the above definition. These events should 
usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment in an emergency 
room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that do not result in 
hospitalization, or development of drug dependency or drug abuse. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
110 
 
 
 
 
Recording and Follow-up of AE and/or SAE 
 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation (e.g., 
hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
• 
The Investigator will then record all relevant AE/SAE information in the CRF. Each event must be 
recorded separately. 
• 
It is not acceptable for the Investigator to send photocopies of the subject’s medical records to the 
Sponsor and/or designee in lieu of completion of the applicable AE/SAE CRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by the Sponsor 
and/or designee. 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 Sponsor and/or designee. 
• 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, and/or 
other clinical information. Whenever possible, the diagnosis (not the individual signs/symptoms) will 
be documented as the AE/SAE. 
Assessment of Intensity 
The intensity of an AE is an estimate of the relative severity of the event made by the Investigator 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: The symptom is barely noticeable to the subject and does not influence performance of daily 
activities. Treatment is not ordinarily indicated. 
• 
Moderate: The symptom is sufficiently severe to make the subject uncomfortable, and performance of 
daily activities is influenced. Treatment may be necessary. 
• 
Severe: The symptom causes severe discomfort, and daily activities are significantly impaired or 
prevented. Treatment may be necessary. 
Please note that the severity of cardiovascular and hematologic adverse events only will also be graded 
according to the CTCAE Version 5.0. 
 
 
Assessment of Causality 
The Investigator will establish causality of the AE to the experimental treatment. The Investigator should 
take into account the history of the subject, most recent physical examination findings, and concomitant 
medications. 
The following definitions will be used to determine causality of an AE: 
• 
Definitely Related: There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out. The clinical event, including an abnormal laboratory test result, 
occurs in a plausible time relationship to study intervention administration and cannot be explained by 
concurrent disease or other drugs or chemicals. The response to withdrawal of the study intervention 
(dechallenge) should be clinically plausible. The event must be pharmacologically or 
phenomenologically definitive, with use of a satisfactory rechallenge procedure if necessary. 
• 
Probably Related: There is evidence to suggest a causal relationship, and the influence of other factors 
is unlikely. The clinical event, including an abnormal laboratory test result, occurs within a reasonable 
time after administration of the study intervention, is unlikely to be attributed to concurrent disease or 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
111 
 
 
 
other drugs or chemicals, and follows a clinically reasonable response on withdrawal (dechallenge). 
Rechallenge information is not required to fulfill this definition. 
• 
Potentially Related: There is some evidence to suggest a causal relationship (e.g., the event occurred 
within a reasonable time after administration of the trial medication). However, other factors may have 
contributed to the event (e.g., the participant’s clinical condition, other concomitant events). Although 
an AE may rate only as “possibly related” soon after discovery, it can be flagged as requiring more 
information and later be upgraded to “probably related” or “definitely related”, as appropriate. 
• 
Unlikely to be Related: A clinical event, including an abnormal laboratory test result, whose temporal 
relationship to study intervention administration makes a causal relationship improbable (e.g., the 
event did not occur within a reasonable time after administration of the study intervention) and in 
which other drugs or chemicals or underlying disease provides plausible explanations (e.g., the 
participant’s clinical condition, other concomitant treatments). 
• 
Not Related: The AE is completely independent of study intervention administration, and/or evidence 
exists that the event is definitely related to another etiology. There must be an alternative, definitive 
etiology documented by the clinician. 
For regulatory reporting purposes, AEs assessed as ‘Unlikely Related’ will map to ‘Not Related.’ 
Events assessed as ‘Definitely Related’, ’Probably Related’, and ‘Potentially Related’ will map to 
‘Related.’ 
• 
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 Investigator’s Brochure (IB) and/or Product Information, for 
marketed products, in his/her assessment. 
• 
For each AE/SAE, the Investigator must document in the medical notes that he/she has reviewed the 
AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the Investigator has minimal information to 
include in the initial report to the Sponsor or designee. However, it is very important that the 
Investigator always make an assessment of causality for every event before the initial transmission of 
the SAE data to the Sponsor or designee. 
• 
The Investigator may change his/her opinion of causality in light of follow-up information and send a 
SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
 
Follow-up of AEs and SAEs 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental measurements 
and/or evaluations as medically indicated or as requested by the Sponsor and/or designee to elucidate 
the nature and/or causality of the AE or SAE as fully as possible. This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other health 
care professionals. 
• 
If a subject dies during participation in the study or during a recognized follow-up period, the 
Investigator will provide the Sponsor and/or designee with a copy of any postmortem findings 
including histopathology. 
• 
New or updated information will be recorded in the originally completed CRF. 
• 
The Investigator will submit any updated SAE data to the Sponsor and/or designee within 24 hours of 
receipt of the information. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
113 
 
 
Appendix 13 
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). 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with one of the following: 
a) Documented hysterectomy. 
b) Documented bilateral salpingectomy. 
c) Documented bilateral oophorectomy. 
Note: Documentation can come from the study center personnel’s: review of the subject’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female: 
a) A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient. 
b) Females on HRT and whose menopausal status is in doubt will be required to use 1 of the 
non-estrogen hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow confirmation 
of postmenopausal status before study enrollment. 
Contraception Guidance 
Male subjects 
• Male subjects with female partners of childbearing potential are eligible to participate if they 
agree to ONE of the following [during the protocol-defined time frame in Section 5.1]: 
− 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 as described in the table below when having penile-vaginal 
intercourse with a woman of childbearing potential who is not currently pregnant. 
• In addition, male subjects must refrain from donating sperm for the duration of the study and 
for 90 days after the last dose of study treatment. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
114 
 
 
• Male subjects with a pregnant or breastfeeding partner must agree to remain abstinent from 
penile-vaginal intercourse or use a male condom during each episode of penile penetration 
for the duration of the study and 90 days after the last dose of study treatment. 
Female subjects 
Female subjects of childbearing potential are eligible to participate if they agree to use a highly 
effective method of contraception consistently and correctly as described in the table below. 
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 ovulationb 
• 
Oral. 
• 
Intravaginal. 
• 
Transdermal. 
Progestogen only hormonal contraception associated with inhibition of ovulationb 
• 
Oral. 
• 
Injectable. 
Highly Effective Methods That Are User Independent a 
Implantable progestogen only hormonal contraception associated with inhibition of ovulationb 
• 
Intrauterine device (IUD). 
• 
Intrauterine hormone-releasing system (IUS). 
• 
Bilateral tubal occlusion. 
Vasectomized partner 
A vasectomized partner is a highly effective birth control method provided that the partner is the sole male sexual 
partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly effective method 
of contraception should be used. 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study treatment. The reliability of sexual abstinence 
needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of the subject. 
NOTES: 
a Use should be consistent with local regulations regarding the use of contraceptive methods for subjects 
participating in clinical studies. 
b Female study participants who are women of childbearing potential using one of the highly effective, hormonal 
contraceptives described above (either birth control pills or implantable devices) will be required to also employ 
a barrier method of contraception (e.g., condom use by a male partner, diaphragm, or cervical cap) for a 
minimum of 30 days following the last dose of study drug. 
Male study participants with partners who are women of childbearing potential using one of the highly effective, 
hormonal contraceptives described above (either birth control pills or implantable devices) will be required to 
also employ a barrier method of contraception (e.g., condom use by a male partner, diaphragm, or cervical cap) 
for a minimum of 90 days following the last dose of study drug. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
115 
 
 
 
 
Pregnancy Testing: 
• WOCBP should only be included after a negative highly sensitive serum pregnancy test. 
• Additional pregnancy testing should be performed at the times specified in the SoA during 
the study period after the last dose of study treatment and as required locally. 
• Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected. 
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 RPT193. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor or designee within 24 hours of learning of the partner’s pregnancy. 
The female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to the Sponsor. 
Generally, the follow-up will be no longer than 6 to 8 weeks following the estimated delivery 
date. Any termination of the pregnancy will be reported regardless of fetal status (presence or 
absence of anomalies) or indication for the procedure. 
Female Subjects who become pregnant 
• The Investigator will collect pregnancy information on any female subject who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the Sponsor or designee 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 or designee. Generally, follow-up will not be 
required for longer than 6 to 8 weeks beyond the estimated 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 
will be reported as an AE or SAE. If the outcome of the pregnancy meets the criteria for 
immediate classification as an SAE (i.e., spontaneous abortion, stillbirth, neonatal death, or 
congenital anomaly [including that in an aborted fetus, stillbirth, or neonatal death]), the 
investigator will report according to the SAE reporting procedures described in Appendix 12. 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
117 
 
 
Appendix 14 
Table of Topical Corticosteroid Potencies 
 
 
Category 
Drug 
Formulation 
Ultra High (I) 
Clobetasol proprionate 
Cream 0.05% 
Ointment 0.05% 
Lotion 0.05% 
Fluocinonide 
Cream 0.1% 
Diflorasone diacetate 
Ointment 0.05% 
Halobetasol proprionate 
Cream 0.05% 
Ointment 0.05% 
High (II) 
Amcinonide 
Ointment 0.1% 
Betamethasone diproprionate 
Ointment 0.05% 
Desoximetasone 
Cream 0.05% 
Ointment 0.05% 
Fluocinonide 
Cream 0.05% 
Ointment 0.05% 
Halcinonide 
Cream 0.1% 
Ointment 0.1% 
High (III) 
Betamethasone diproprionate 
Cream 0.05% 
Betamethasone valerate 
Ointment 0.1% 
Dicflorasone diacetate 
Cream 0.05% 
Triamcinolone acetonide 
Ointment 0.1% 
Moderate (IV 
and V) 
Betamethasone dipropionate 
Lotion 0.02% 
Betamethasone valerate 
Cream 0.1% 
Lotion 0.1% 
Desoximetasone 
Cream 0.05% 
Fluocinolone acetonide 
Cream 0.025% 
Ointment 0.025% 
Fluticasone proprionate 
Cream 0.05% 
Fludroxycortide 
Ointment 0.05% 
Hydrocortisone butyrate 
Ointment 0.1% 
Cream 0.1% 
Hydrocortisone probutyrate 
Cream 0.1% 
Hydroxycortisone valerate 
Cream 0.2% 
Ointment 0.2% 
Mometasone furoate 
Cream 0.1% 
Ointment 0.1% 
Triamcinolone acetonide 
Cream 0.025% 
Lotion 0.025% 
Cream 0.1% 
Lotion 0.1% 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
118 
 
 
 
Category 
Drug 
Formulation 
Low (VI) 
Betamethasone valerate 
Lotion 0.05% 
Desonide 
Cream 0.05% 
Ointment 0.05% 
Lotion 0.05% 
Fluocinolone acetonide 
Cream 0.01% 
Low (VII) 
Dexamethasone sodium phosphate 
Cream 0.1% 
Hydrocortisone 
Cream 1% 
Lotion 1% 
Ointment 1% 
Cream 2.5% 
Lotion 2.5% 
Ointment 2.5% 
Hydrocortisone acetate 
Cream 1% 
Methylprednisolone acetate 
Cream 0.25% 

CONFIDENTIAL 
Protocol RPT193-02 – Amendment 2 
119 
 
 
Instructions to the Investigator: Please SIGN and DATE this signature page. PRINT your name, title, and the name of the study 
center in which the study will be conducted. Return the signed copy to the CRO. 
Appendix 15 Signature of Principal Investigator 
PROTOCOL TITLE: A Phase 2 study to evaluate the efficacy and safety of RPT193 as 
monotherapy in adults with moderate-to-severe atopic dermatitis 
PROTOCOL NO: 
RPT193-02 
VERSION: 
Amendment 2.0 
This protocol is a confidential communication of RAPT Therapeutics, Inc. 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 Good Clinical Practices 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. 
 
 
 
 
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: