A Phase 2A, Open Label, Proof of Concept Trial of Daxdilimab for the Treatment of Moderate To Severe Alopecia Areata
Phase: PHASE2
Conditions: Alopecia Areata
Sponsor: Amgen

DocuSign Envelope ID: 8998CE57-06B1-i241-B444-6584E6796BB8 
I 
HO·RIZON 
A PHASE 2A, OPEN LABEL, PROOF-OF-CONCEPT TRIAL OF 
DAXDILIMAB FOR THE TREATMENT OF MODERATE-TO-SEVERE 
ALOPECIA AREATA 
PROTOCOL HZNP-DAX-201 
lnvestigational New Drug (IND) Number: 158932 
Sponsor: 
Sponsor Medical 
Expe1t: 
Sponsor Signato1y: 
Clinical Research 
Organization: 
FINAL 
VERSION 2.0 
07 JAN 2022 
Horizon Therapeutics Ireland DAC 
70 St. Stephen's Green 
Dublin 2, Ireland 
D02 E2X4 
, MD 
Executive Medical Director 
Horizon Therapeutics 
1 Medimmune Way, Gaithersburg, MD, 20878 
Sr. Director, Biostatistics, Biometrics 
Horizon Therapeutics 
1 Medimmune Way, Gaithersburg, MD, 20878 
Innovade1m Research Inc. 
3530 Saint-Laurent boulevard, Suite 300 
Montreal, Quebec, Canada, H2X 2Vl 
Telephone: 514-521-4285 
PRIVATE AND CONFIDENTIAL INFORMATION OF HORIZON 1HERAPEUTICS IREIAND DAC 

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TABLE OF CONTENTS
TABLE OF CONTENTS................................................................................................................ 2
PROTOCOL VERSION HISTORY............................................................................................... 6
STATEMENT OF COMPLIANCE................................................................................................ 7
SIGNATURE PAGE ...................................................................................................................... 8
PRINCIPAL/QUALIFIED INVESTIGATOR SIGNATURE PAGE ............................................ 9
LIST OF ABBREVIATIONS....................................................................................................... 10
1
PROTOCOL SUMMARY............................................................................................ 13
1.1
Synopsis ........................................................................................................................ 13
1.2
Trial Diagram................................................................................................................ 23
1.3
Schedule of Assessments .............................................................................................. 23
2
INTRODUCTION ........................................................................................................ 27
2.1
Background................................................................................................................... 27
Alopecia Areata .................................................................................................... 27
Daxdilimab............................................................................................................ 27
Trial Rationale...................................................................................................... 28
2.2
Risk/Benefit Assessment............................................................................................... 29
Known Potential Risks.......................................................................................... 29
Known Potential Benefits...................................................................................... 30
Assessment of Risks and Benefits.......................................................................... 30
3
OBJECTIVES AND ENDPOINTS .............................................................................. 31
4
TRIAL DESIGN ........................................................................................................... 33
4.1
Overall Design .............................................................................................................. 33
4.2
Scientific Rationale for Trial Design ............................................................................ 34
4.3
Justification for Dose .................................................................................................... 34
4.4
End of Trial Definition.................................................................................................. 34
5
TRIAL POPULATION................................................................................................. 35
5.1
Inclusion Criteria........................................................................................................... 35
5.2
Exclusion Criteria ......................................................................................................... 36
5.3
Lifestyle Considerations ............................................................................................... 40
5.4
Screen Failures.............................................................................................................. 40
6
TREATMENT .............................................................................................................. 41
6.1
Trial Treatment Administered....................................................................................... 41

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6.2
Preparation/Handling/Storage/Accountability.............................................................. 41
Preparation/Storage/Handling ............................................................................. 41
Accountability ....................................................................................................... 41
6.3
Randomization .............................................................................................................. 42
Blinding................................................................................................................. 42
Trial Treatment Compliance................................................................................. 42
6.4
Concomitant Therapy.................................................................................................... 42
Permitted Therapies.............................................................................................. 42
Prohibited Therapies or Procedures .................................................................... 43
7
DISCONTINUATION AND LOST TO FOLLOW-UP............................................... 45
7.1
Discontinuation............................................................................................................. 45
Discontinuation of Investigational Product.......................................................... 45
Discontinuation from the Trial ............................................................................. 46
Withdrawal of Consent from the Trial.................................................................. 46
7.2
Lost to Follow-Up......................................................................................................... 46
8
TRIAL ASSESSMENTS AND PROCEDURES ......................................................... 48
8.1
Efficacy Assessments.................................................................................................... 48
Severity of Alopecia Tool (SALT) ......................................................................... 48
 
Medical Photography............................................................................................ 48
8.2
Pharmacokinetics .......................................................................................................... 49
8.3
Pharmacodynamics ....................................................................................................... 49
8.4
Immunogenicity ............................................................................................................ 49
8.5
Safety and Other Assessments ...................................................................................... 49
Vital Signs............................................................................................................. 49
Physical Examination ........................................................................................... 50
Clinical Laboratory Tests ..................................................................................... 50
Electrocardiogram................................................................................................ 51
Local Injection Tolerability Assessments.............................................................. 52
8.6
Adverse Events and Serious Adverse Events ............................................................... 52
Definition of Adverse Event .................................................................................. 52
Definition of Treatment-Emergent Adverse Event................................................ 52
Definition of Serious Adverse Event ..................................................................... 52
Definition of an Adverse Event of Special Interest (AESI) ................................... 53
Classification of an Adverse Event ....................................................................... 53
Time Period and Frequency for Event Assessment and Follow-Up..................... 54

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Adverse Event Reporting....................................................................................... 55
Serious Adverse Event Reporting.......................................................................... 55
Pregnancy Reporting ............................................................................................ 56
Overdose ........................................................................................................... 56
9
STATISTICAL CONSIDERATIONS.......................................................................... 57
9.1
Sample Size Determination........................................................................................... 57
9.2
Populations for Analyses .............................................................................................. 58
9.3
Statistical Analyses ....................................................................................................... 58
General Approach................................................................................................. 58
Efficacy Analyses .................................................................................................. 58
Safety Analyses...................................................................................................... 59
Pharmacokinetic Analyses.................................................................................... 59
Pharmacodynamic/Immunogenicity Analyses ...................................................... 59
Exploratory Analyses............................................................................................ 59
Planned Analyses.................................................................................................. 60
10
REGULATORY, ETHICAL, AND TRIAL OVERSIGHT CONSIDERATIONS...... 61
10.1
Local Regulations/Declaration of Helsinki................................................................... 61
10.2
Ethical Review.............................................................................................................. 61
10.3
Informed Consent Process ............................................................................................ 61
10.4
Trial Discontinuation and Closure ................................................................................ 62
10.5
Confidentiality and Privacy .......................................................................................... 62
10.6
Clinical Monitoring....................................................................................................... 63
10.7
Quality Assurance and Quality Control........................................................................ 63
10.8
Data Handling and Record Keeping ............................................................................. 63
10.9
Biological Specimens and Data .................................................................................... 64
10.10 Protocol Deviations....................................................................................................... 65
10.11 Publication Policy ......................................................................................................... 65
11
REFERENCES.............................................................................................................. 66
APPENDIX 1: Severity of Alopecia Tool (SALT)21.................................................................... 68
 
 
 
 
LIST OF TABLES
Table 1: Schedule of Assessments................................................................................................ 24
Table 2: Trial Treatment ............................................................................................................... 41

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Table 3: Prohibited Therapies or Procedures ................................................................................ 43 
Table 4: Clinical Laboratory Testing ............................................................................................ 51 
Table 5: CTCAE v5.0 General Guidelines ................................................................................... 54 
Table 6: Probability that true mean percent reduction from baseline in SALT score is above a 
cutoff for an observed mean. ........................................................................................................ 57 
Table 7: Probability that true proportion of participant
an observed response rate. ............................................................................................................ 57 
 
LIST OF FIGURES 
 
Figure 1: Trial Diagram ................................................................................................................ 23 
 
 
 

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STATEMENT OF COMPLIANCE 
The trial will be conducted in accordance with the protocol, International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP), and applicable local regulations. The 
principal investigator will assure that no planned deviation from, or changes to the protocol will 
take place without prior agreement from the sponsor and documented approval from the 
institutional review board (IRB)/research ethics board (REB), except where necessary to eliminate 
an immediate hazard(s) to the trial participants. All personnel involved in the conduct of this study 
have completed ICH GCP training. 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the IRB/REB for review and approval. Approval of both the protocol and the 
consent form must be obtained before any participant is enrolled. Any amendment to the protocol 
will require review and approval by the IRB/REB before the changes are implemented to the study. 
All changes to the consent form will be IRB/REB approved. 

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PRINCIPAL/QUALIFIED INVESTIGATOR SIGNATURE PAGE 
 
 
 
 
Investigator Name: 
 
 
 
Signature: 
 
Date: 
 
 
 
 
 
 
(DD-MMM-YYYY) 
 
Institution Name: 
 
 
 
 
By my signature, I agree to personally supervise the conduct of this study at my study site and 
to ensure its conduct in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki and in compliance with the protocol, informed consent, institutional 
review board/independent ethics committee procedures, instructions from 
 
representatives, ICH GCP guidelines, and applicable local regulations governing the conduct 
of clinical studies. 
 
 

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2
INTRODUCTION
2.1 Background
Alopecia Areata 
Alopecia areata (AA) is a common acute onset autoimmune disorder characterized by transient, 
non-scarring hair loss in well defined areas.1 It is the second most common form of Alopecia after 
the androgenetic type. The extent of hair loss defines the three main AA forms, namely Patchy AA, 
Alopecia Totalis (loss of all scalp hair) and Alopecia Universalis (loss of all body hair). Patchy AA 
is the most common form.
The risk of developing AA is estimated to be around 25% in adult-onset patients. Spontaneous 
regrowth can occur in 50-80% of the patchy AA cases within a year, however additional patches 
can also form, resulting in the formation of several patches that often coalesce eventually lead to 
alopecia totalis.2 Alopecia areata overall rate of relapse has been estimated to be around 86%.3,4
Patchy AA can also progress to alopecia universalis at any time.
Clinically, the patch of AA is usually completely bald, smooth and round or oval in shape. In the 
periphery of the lesions, short, less than 4 mm exclamation mark hairs and black dots are 
commonly observed, especially in acute stages of AA. The scalp, the beard area and the eyebrow 
are most commonly involved, however any hair-bearing area can be affected. One of the most 
important features of AA is that the disease process does not destroy hair follicles.
Alopecia areata is considered as a complex genetic disease influenced by environmental factors. 
Based on large epidemiologic studies from North America, Europe and Asia, and systematic 
meta-analysis, the lifetime incidence of AA is estimated to be around 2% of the population.5,6 The 
onset is most common in the third and fourth decades of life but it does occur at any age.7 When 
first onset is at an earlier age the risk for future extensive disease increases.8
No gender predilection has been identified, and while it was widely thought that there were no 
racial differences, a recent cross-sectional study of self-registered AA patients, showed higher 
odds of AA in African Americans and lower odds in Asians compared with whites.5,9
A number of comorbidities have been associated with AA, including depression, anxiety, and 
autoimmune diseases such as lupus erythematosus, vitiligo, psoriasis, rheumatoid arthritis, as well 
as asthma, thyroid disease, depression and anxiety .8,10,11
Daxdilimab
Daxdilimab (HZN7734 [previously known as MEDI7734 and VIB7734]) is a human 
immunoglobulin-like transcript 7 (ILT7), a cell-surface protein that is unique to plasmacytoid 
dendritic cells (pDCs) in human and the nonhuman primate. Daxdilimab binds to ILT7 on the 
surface of pDCs, which leads to recruitment of macrophages and natural killer (NK) cells, thus 
inducing apoptosis and depletion of pDCs in vivo. The afucosylation of daxdilimab is designed to 

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enhance the potency of daxdilimab for antibody-dependent cellular cytotoxicity (ADCC) against 
pDCs. Since pDCs are the major cell type that secretes type I interferons (IFNs) in response to 
nucleic acid-containing immune complexes, it is hypothesized that depletion of pDCs will reduce 
disease activity for patients with autoimmune diseases that are partially driven by abnormally high 
levels of type I IFNs.
Trial Rationale
The exclamation hair and the bald areas are caused by the inhibition of the hair follicle cycling 
which represents one of the end results of the AA pathophysiologic process, which starts with the 
loss of immune privilege of the hair follicle and a subsequent autoimmune attack of the bulbar 
region of anagen phase hair follicles by CD8+ T cells and Th1 cytokines.1,6,12
Genome-wide association studies have identified human leukocyte antigen (HLA) region genes 
and other immune function genes to be associated with AA. Interestingly some of these genes had 
not been previously implicated in other autoimmune diseases.6,13-15 These genes were the 
ULBP3/ULBP6 known to be ligands for the natural killer receptor D (NKG2D). 
The significance of this finding was later demonstrated in functional studies where 
CD8+NKG2D+T cells were shown to be major effectors of AA pathogenesis.16 Effector 
CD8 T cells can get activated by expression of MHC I and NKG2DL on epithelial cells and can 
exert their cytotoxic effects through IFNg. CD8 T cells are not the only immune cells involved 
in AA. CD4 T cells and NK cells are also present around the epithelial cells and secrete numerous 
pro-inflammatory cytokines, including IFNg. 
Critical to the recruitment and activation of the peri- and intra-lesional NK and T cells seems to be 
pDCs and Type I IFNs.17
In one study, alopecia developed in 19% of the treated patients, and it regressed soon after 
treatment completion.18 These observations led to studies that searched for direct histologic 
evidence of Type I interferons. 
Lesional scalp biopsies from patients with AA were assessed with immunohistochemistry for 
expression of the type 1 interferon-inducible myxovirus protein A (MxA), one of the most reliable 
surrogate markers of Type 1 interferons, and CXCR3, a chemokine receptor found on cytotoxic 
cells. Interestingly, MxA was expressed in the intradermal and subcutaneous compartments of the 
hair follicle including sebaceous glands in AA, but not in the epidermal compartment of AA. 
CXCR3 staining showed the same exact expression pattern, suggesting that Type 1 IFN attract the 
cytotoxic cells in the deeper areas of the skin, where the hair follicles are located.12
Another study using immunohistochemistry on AA biopsies, not only confirmed the expression of 
MxA in peribulbar areas, but also demonstrated the presence of pDCs through BDCA2 staining in 
the same areas. pDCs accounted for approximately 10% of the mononuclear cells, and the 
abundance of MxA expression suggested that the pDCs were in an active state producing 
Type I IFNs.19

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Using a dynamic model of AA development, the central role of pDCs in initiating AA was 
demonstrated.20 Induction of AA in mice, by intradermal injection of T cells derived from lymph 
nodes of AA-bearing syngeneic mice, revealed that densely infiltrated IFN-a-producing pDCs 
initiate the lesions in the affected hair follicle as well as in the proximity of these follicles. 
Additionally, intradermal injection of pDCs also induced AA.
2.2 Risk/Benefit Assessment
Known Potential Risks
Daxdilimab was tested in a first-in-human, single-ascending dose study (Study D6080C00001). 
The key objectives of the study were to evaluate the single dose safety, pharmacokinetics (PK), 
and pharmacodynamics (PD). The study enrolled 36 adult subjects with dermatomyositis (DM), 
polymyositis (PM), Sjo
sclerosis. Subjects received a single subcutaneous (SC) injection of daxdilimab
, or 
mg, or placebo. After single SC administration, serum peak concentrations were observed 5 to 
8 days post-dose. Daxdilimab PK exposures increased in an approximately dose-proportional 
manner. Apparent clearance (CL/F) ranged from 0.468 to 1.03 L/day. Apparent volume of 
distribution (Vz/F) ranged from 9.89 to 19.0 L. The estimated terminal elimination half-life (t1/2) 
ranged from 13 to 20 days across dose levels. No serious adverse events (SAEs) occurred that were 
considered related to the investigational product. Two subjects had treatment-emergent adverse 
events (TEAEs) considered related to the investigational product by the investigator: one subject
in the placebo group with nausea (Grade 1) and one subject in the daxdilimab
 mg group with 
tongue discolouration (Grade 1). The most common adverse events (AEs) reported in the 
daxdilimab-treated subjects were diarrhoea (11.5%) and upper respiratory tract infection (11.5%). 
There was no imbalance of AEs between the daxdilimab and placebo groups. No injection site 
reactions or hypersensitivity reactions were reported. No anti-drug antibodies (ADAs) occurred. 
Mean reductions of at least 50% in the pDC level of daxdilimab-treated subjects were evident at 
24 hours after dosing in all dose groups. Increasing doses were associated with a non-linear 
increase in pDC reduction. Increasing doses were generally associated with a longer duration of 
pDC reduction.
Study HZN7734.P1b.S1 evaluated the PK, PD, and safety of 3 monthly doses of daxdilimab. The 
study enrolled 31 subject
systemic sclerosis, PM, or DM. Subjects received placebo or daxdilimab at 
 mg by 
SC injection. Daxdilimab PK exposure was approximately dose proportional over the dose range 
investigated. Apparent steady-state clearance (CLss/F) values were similar across dose groups and 
ranged from 0.62 to 1.18 L/day. The t1/2 was 14.6 days for subjects receiving 
mg daxdilimab. 
Sixteen of 22 (72.7%) daxdilimab-treated subjects and 6 of 9 (66.7%) placebo treated subjects 
experienced at least one TEAE. There were no deaths in the trial. One placebo-treated subject and 
no daxdilimab-treated subjects experienced treatment emergent SAEs. No subject experienced an 
AE leading to treatment discontinuation. No treatment-emergent ADA was observed in subjects 
treated with daxdilimab. In subjects with CLE, Cutaneous Lupus Erythematosus Disease Area and 
Severity Index-Activity (CLASI-A) scores improved more in the daxdilimab
 mg group than 
the placebo group. After 3 monthly SC doses of daxdilimab
 mg or 
 mg, the median change 
in percent pDCs at Day 85 was -54.1% in the daxdilimab group, compared to a +9.8% in the 
placebo group. 

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To date, no adverse drug reactions (ADRs) for daxdilimab have been identified. Important 
potential risks for daxdilimab include viral infection and viral reactivation, opportunistic infection, 
malignancy (other than non-melanoma skin cancer), and hypersensitivity reactions including 
anaphylaxis. Other potential risks include injection site reactions, vaccine interaction, drug-drug 
interactions, and reproductive toxicity.
Known Potential Benefits
In this Phase 2a trial, it is hypothesized that participants moderate-to-severe alopecia areata may 
see an improvement in their condition as a result of participating in the trial.
Participation in this trial may help generate future benefit for larger groups of patients with AA if 
daxdilimab proves to be successful in treating this disease.
Assessment of Risks and Benefits
All quality, pharmacology and toxicology data, and satisfactory safety and tolerability data 
demonstrated in nonclinical studies are considered sufficient to expect a positive benefit/risk ratio 
for the treatment of patients with moderate-to-severe AA with daxdilimab, and therefore to initiate 
this trial.
The risk to participants in this trial will be minimized by compliance with the eligibility criteria, 
proper trial design, and close monitoring.

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4 TRIAL DESIGN 
4.1 Overall Design 
This is a Phase 2a, multicenter, open-label, proof-of-concept trial to assess the preliminary 
efficacy, safety, tolerability, PK, and PD of daxdilimab in participants with moderate-to-severe 
AA, with 
Severity of Alopecia Tool (SALT) 
score at Screening and Day 1. Participants will be between 18 and 65 years of age (inclusive), with 
a current episode of hair loss of 3 months but 7 
hair regrowth is possible and no evidence of active regrowth present at baseline, and no known 
history of significant regrowth during the last 6 months. Approximately 30 participants will be 
enrolled to receive daxdilimab 
 mg administered subcutaneously 
 
.  
 
All participants will read and sign an informed consent form (ICF) prior to any screening 
procedures being performed. Participants who meet all inclusion criteria and none of the exclusion 
criteria may be accepted into the trial. 
 
The trial will comprise of a screening period of up to 30 days with enrollment on Day 1.  
Participants will be treated with daxdilimab 
 mg 
  The primary endpoint 
assessment will occur during the Week 24 visit. All participants will have a follow-up period of 
16 weeks (through Week 48) to evaluate long-term safety and to observe the duration of efficacy 
following the treatment period. Participants who prematurely stop dosing will be followed through 
Week 48 unless participants withdraw consent of trial participation or are lost to follow-up. Any 
participant who discontinues from the trial prematurely and does not plan to participate in the 
post-treatment follow-up period will be requested to complete the ET visit. 
For scheduled trial visits, participants will come to the trial centers on 14 occasions: screening, 
 
Efficacy will be evaluated by assessment of SALT scores, 
 
 
 
 
. 
 
Blood samples will be collected from all participants to characterize the PK, PD, and 
immunogenicity of daxdilimab. 
Safety will be assessed by collecting AEs, SAEs, adverse events of special interest (AESIs), 
performing local injection tolerability assessment, recording vital signs, performing physical 
examinations and electrocardiograms (ECGs), and evaluating clinical laboratory results. 

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5 TRIAL POPULATION  
5.1 Inclusion Criteria 
All participants must meet all of the following criteria to be eligible for trial participation, either 
at the screening and Day 1 visits, or only at one of the specified visits (screening or Day 1) as noted 
in the criterion:  
1. Written informed consent and any locally required authorization (eg, Health Insurance 
Portability and Accountability Act in the United States,) obtained from the participant prior to 
performing any protocol-related procedures, including screening evaluations. 
2. Adult men and women, aged 18 to 65 years, inclusive, at the time of informed consent. 
3. Willing and able to comply with the prescribed treatment protocol and evaluations for the 
duration of the trial. 
4. Willing to keep the same hair style and color (eg, hair products, process, and timing for hair 
appointments) for the duration of the trial. 
5. Clinical diagnosis of moderate-to-severe AA - 
total scalp hair loss at screening and baseline (Day 1) defined by the SALT score. 
6. Duration of current episode of hair loss 3 months but 7 years at screening and Day 1, along 
with investig
since diagnosis of 
AA could be >7 years. 
7. No evidence of active regrowth present at baseline and no known history of significant 
regrowth
 over the last 6 months. 
8. Female of childbearing potential must have a negative serum pregnancy test at screening and 
negative urine pregnancy test at Day 1. 
9. For female participant of childbearing potential involved in any sexual intercourse that could 
lead to pregnancy: the participant must agree to use a highly effective contraceptive method 
from at least 4 weeks prior to Day 1 until at least 6 months (approximately 5 half-lives) after 
the last IP administration or the end of the trial, whichever is longer, and refrain from egg 
retrieval/egg donation during this period. 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) (provided his 
methods of contraception (e.g. male condom with cervical cap, male condom with diaphragm, 
and male condom with contraceptive sponge) in conjunction with spermicide.  
Note: For countries where double barrier methods are not accepted as highly effective 
contraception, this option must not be considered. 
Note: Participants must have been on a stable dose of hormonal contraceptives for at least 
4 weeks before Day 1.  
Note: The above list of contraceptive methods does not apply to participants who are abstinent 
for at least 4 weeks before Day 1 and will continue to be abstinent from penile-vaginal 
intercourse throughout the trial and for at least 6 months after the last IP administration or until 

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the end of the trial, whichever is longer.  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. Periodic abstinence (calendar, symptothermal, post-ovulation methods) is not 
acceptable. 
Note: A female participant of nonchildbearing potential is defined as follows:  
- 
Female participant who has had surgical sterilization (hysterectomy, bilateral 
oophorectomy, or bilateral salpingectomy). 
- 
Female participant 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). 
10. For male participant involved in any sexual intercourse that could lead to pregnancy, 
participant must agree to use one of the highly effective contraceptive methods listed in 
Inclusion Criterion #9, from Day 1 until at least 6 months (approximately 5 half-lives) after 
the last IP administration and refrain from donating sperm during this period. If the female 
partner of a male participant 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 Day 1 
until at least 6 months after the last administration of daxdilimab.  
5.2 Exclusion Criteria 
Participants will be ineligible for trial participation if they meet any of the following criteria at the 
Screening and/or Day 1 visits, as applicable: 
General Exclusion Criteria  
1. Individuals involved in the conduct of the trial, their employees, or immediate family members 
of such individuals. 
2. Any clinically significant medical condition or physical/laboratory/ECG/vital signs 
abnormality that would, in the opinion of the investigator, put the participant at undue risk or 
interfere with the evaluation of the IP or interpretation of trial results. 
3. History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP or to a 
previous mAb or Ig therapy. 
4. Participant has had excessive sun exposure, is planning a trip to a sunny climate, or has used 
tanning booths within 4 weeks prior to Day 1 or is not willing to minimize natural and artificial 
sunlight exposure during the trial. Use of sunscreen products and protective apparel are 
recommended when sun exposure cannot be avoided. 
5. Spontaneous or induced abortion or 
 
6. Breastfeeding or pregnant women or women who intend to become pregnant anytime from 
signing the ICF through 6 months after receiving the last dose of IP or until the end of the trial, 
whichever is longer. 

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7. History of drug or alcohol abuse that, in the opinion of the investigator, might affect participant 
safety or compliance with visits, or interfere with other trial assessments. 
8. Major surgery within 8 weeks prior to Screening or elective surgery planned during the trial. 
9. Known history of a primary immunodeficiency or an underlying condition such as known 
human immunodeficiency virus (HIV) infection, a positive result for HIV infection, 
splenectomy, or any underlying condition that in the opinion of the investigator significantly 
predisposes the participant to infection. 
10. At Screening, any of the following (tests may be repeated once within the same Screening 
period to confirm results prior to Day 1):  
 Aspartate aminotransferase (AST) > 2.5× upper limit of normal (ULN) 
 Alanine aminotransferase (ALT) > 2.5× ULN 
 
 
 Serum immunoglobulin G (IgG) < 600 mg/dL (or < 6 g/L) 
 
9/L)  
 
9/L) 
 Hemoglobin < 8 g/dL (or < 80 g/L) 
 Total lymphocyte count < 200 cells/mm3 
 Glomerular filtration rate (Modification of Diet in Renal Disease [MDRD]) 
< 30 mL/min/1.73 m2  
 Spot urine protein to creatinine ratio (UPCr) > 3 mg/mg 
11. Confirmed positive test for hepatitis B serology defined as: 
 Hepatitis B surface antigen (HBsAg), or  
 Hepatitis B core antibody (HBcAb or anti-HBc) 
12. Positive test for hepatitis C virus antibody.
13. Active tuberculosis (TB), or a positive TB test at Screening. Participant will be evaluated for 
latent TB infection with a purified protein derivative (PPD) test or a QuantiFERON-TB Gold 
test. Participant
induration or positive QuantiFERON-TB Gold test, irrespective of bacille Calmette-Guérin 
vaccination status will not be allowed to participate in the trial, unless documented history of 
appropriate treatment for active or latent TB. Participants with an indeterminate test result can 
repeat the test, but if the repeat test is also indeterminate, they are excluded. 
14. Any severe herpes virus family infection (including Epstein-Barr virus, cytomegalovirus 
[CMV]) at any time prior to Day 1, including, but not limited to, disseminated herpes, herpes 
encephalitis, recent recurrent herpes zoster (defined as 2 episodes within the last 2 years), or 
ophthalmic herpes. 
15. Any herpes zoster, CMV, or Epstein-Barr virus infection that was not completely resolved 
12 weeks prior to Day 1. 
16. Any of the following within 30 days prior to signing the ICF and though Day 1: 

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 Clinically significant active infection in the opinion of the investigator, including ongoing, 
and chronic infection requiring antibiotics or antiviral medication (chronic nail infections 
are allowed). Note: Participant with a limited recurrence of a cold sore or herpes genitalis 
between ICF signature and Day 1 could be eligible based on the investigator
 
 Any infection requiring hospitalization or treatment with intravenous (IV) anti-infectives. 
 A participant with a documented positive severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2) test may be rescreened at least 2 weeks after a positive test if the participant 
is asymptomatic and at least 3 weeks after resolution of symptomatic Coronavirus Disease 
2019 (COVID-19) illness. 
17. Opportunistic infection requiring hospitalization or parenteral antimicrobial treatment within 
2 years prior to Day 1. 
18. 
 38.0°C 
 100.5°F) on Day 1. 
19. History of clinically significant cardiac disease including unstable angina; myocardial 
infarction within 6 months prior to Day 1; congestive heart failure; arrhythmia requiring active 
therapy, except for clinically insignificant extra systoles, or minor conduction abnormalities; 
or presence of clinically significant abnormality on ECG if, in the opinion of the investigator, 
it would increase the risk of trial participation. 
20. History of cancer or lymphoproliferative disease within 5 years prior to Day 1, except as 
follows: 
 In situ carcinoma of the cervix treated with apparent success with curative therapy 
> 12 months prior to Screening, or 
 Nonmetastatic cutaneous basal cell or squamous cell carcinoma of the skin treated with 
apparent success with curative therapy. 
21. Receipt of a live or live-attenuated vaccine within 8 weeks prior to Day 1 or plans to receive a 
live or live attenuated vaccine during the trial and up to 4 weeks after the last IP administration.  
22. Nonlive and nonlive-attenuated vaccines for COVID-19 (eg, RNA-based vaccines, 
protein-based vaccines, and nonreplicating viral vector-based vaccines) are not allowed within 
4 weeks prior to Day 1 and within 2 weeks prior to each trial visit. 
23. Participant should be assessed for epidemiologic risk of COVID-19 (ie, recent exposure, 
high-risk housing) and for health-related risk of COVID-19 severity based on current 
understanding of risk factors for severe disease when making a decision regarding the 
individu
Participants who have COVID-19 or other significant 
infection, or in the judgment of the investigator, may be at a high risk of COVID-19 or its 
complications should not be enrolled. 
24. Participant who has given > 50 ml of blood or plasma within 30 days of Screening or > 499 mL 
of blood or plasma within 56 days of Screening (during a clinical trial or at a blood bank 
donation), or plans to give blood or plasma during their participation in the trial or up to 
6 months after the last IP administration, whichever is longer. 

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25. Transfusion with blood, packed red blood cells, platelets or treatment with plasmapheresis, or 
plasma exchange within 8 weeks prior to Day 1 and for the total duration of the trial 
participation. 
Disease-related Criteria 
26. Active forms of other inflammatory skin disease(s) or evidence of other skin conditions 
(eg, psoriasis, seborrheic dermatitis, lupus) at the time of the Screening and through Day 1, 
that in the opinion of the investigator might interfere with evaluation of AA and the assessment 
of the activity measures. 
27. Presence of another form of alopecia (except for androgenic alopecia). 
28. History of male or female pattern hair loss > Hamilton stage III or > Ludwig stage II. 
29. History or presence of hair transplants. 
30. History or presence of micropigmentation of the scalp (Note: microblading of the eyebrows is 
permitted). 
Prior and concomitant Therapy Criteria  
31. Use of steroids (systemic and intralesional), anthralin, squaric acid, diphenylcycloprophenone 
(DPCP), dinitrochlorobenzene (DCNB), protopic, minoxidil, or any other medication which in 
the opinion of the investigator may affect hair regrowth within 4 weeks of Day 1 visit.  
Note: Intranasal and inhaled corticosteroids are allowed, eye and ear drops containing 
corticosteroids are also allowed. 
32. Use of platelet-rich plasma injections in the last 12 weeks prior to Day 1. 
33. Topical medicated treatment that could affect AA including, but not limited to, topical 
corticosteroids, calcineurin inhibitors, antimicrobials, medical devices within 2 weeks of Day 1 
visit. 
Note: Topical corticosteroids are permitted outside of the scalp, eyebrows, and eyelids. 
34. Participants who have had previous treatment with any biologic B-cell-depleting therapy 
(eg, rituximab, ocrelizumab, or ofatumumab) or other B-cell targeting therapy (eg, belimumab) 
within 12 months before Day 1. 
35. Participants who have received previous treatment with pDC inhibiting therapies 
(eg, anti-ILT7, anti-blood dendritic cell antigen 2 [BDCA2]). 
36. Inadequate response to adequate trial of oral Janus Kinase (JAK) inhibitors. Previous exposure 
to topical JAK inhibitors is acceptable, regardless of response.  
37. Any biologic or conventional disease-modifying antirheumatic drugs (DMARD), 
immunosuppressant (eg, cyclosporine, methotrexate, or azathioprine), JAK-inhibitors, 
interferon (IFN) blocking therapies, or antiproliferative agents, if last dose was taken: 

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a. within 8 weeks prior to Day 1 or  
b. drug-specific 5 half-lives elimination period (if longer than 8 weeks). 
38. Participant has received any marketed or investigational biological agent within 12 weeks or 
5 half-lives (whichever is longer) prior to Day 1. 
39. Currently receiving a nonbiological IP or device or has received one within 4 weeks prior to 
Day 1 or within 5 published half-lives, whichever is longer. 
40. Participant has received any ultraviolet (UV)-B phototherapy (including tanning beds), has had 
psoralen-UV-A (PUVA) treatment, or excimer laser within 4 weeks prior to Day 1. 
5.3 Lifestyle Considerations 
Participants are expected to continue their usual scalp care routine without notable changes for the 
course of the treatment periods and follow-up period. Participants are prohibited from using 
tanning booths and sunbathing during the trial, and from shaving their scalp 2 weeks prior to visits. 
Participants are to keep the same hair style and color (eg, hair products, process, and timing for 
hair appointments) for the duration of the trial. 
5.4 Screen Failures 
Screen failures are defined as individuals who consent to participate in the clinical trial but are not 
subsequently enrolled in the trial. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants, 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. 
Individuals who do not meet the criteria for participation in this trial (screen failure) may be 
rescreened once, if deemed acceptable by the investigator. Rescreened participants should be 
assigned a different participant number than the initial screening. All procedures planned at the 
screening visit, including signature of a new consent form, will be performed. 
 
 

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containers should be reconciled and either destroyed on site or returned, as requested by the 
Sponsor.  
All IP accountability forms and treatment logs must be retained in the i
s. 
Product inventory and accountability records will be maintained, as per International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP). These records must be available for 
inspection at any time by the sponsor, its designees, or by regulatory agencies.
Further guidance and information for final disposition of IPs are provided in the study manual.
6.3 Randomization
At the trial site, each screened participant will be assigned a participant identifier number during 
screening that will be used on all participant documentation. The participant identifier number will 
contain the country ID, site number, and the participant number, and will be assigned in numerical 
order at the screening visit based on chronological order of screening dates (e.g., US-002-010 for 
the 10th participant screened at Site #002 in the United States).
No randomization scheme will be used, as all participants will receive the active IP only.
Blinding
This is an open-label trial. Participants and investigators are aware that the IP is daxdilimab. 
Trial Treatment Compliance
Trial treatment compliance in this trial will be under the direct control of the investigator; the IP
will always be administered on site. The date and time of each dose administered in the clinic will 
be recorded.
6.4 Concomitant Therapy
All medications (including over-the-counter drugs, vitamins, herbal/natural products, and 
antacids) taken within 4 weeks prior to screening and throughout the trial must be recorded. In 
addition, the use of any prohibited medications must be recorded within the timeframe described 
in the exclusion criteria. No rescue medications or treatments are permitted in this study.
Medication entries may be captured as generic or trade names. Trade names should be used for 
combination drugs. Entries should include as much as possible of the following information: the 
dose, unit, frequency of administration, route of administration, start date, end date, and indication. 
If the medication is stopped or the dosage is changed, these details must be recorded.
Permitted Therapies
The following therapies are permitted:
Intranasal corticosteroids and inhaled corticosteroids are allowed. Eye and ear drops containing 
corticosteroids are also allowed.  

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7
DISCONTINUATION AND LOST TO FOLLOW-UP
Participants have the right to withdraw from the trial at any time for any reason without penalty. 
The investigator also has the right to withdraw participants from treatment if he or she feels it is 
in the best interest of the participant or if the participant is uncooperative or noncompliant.
Should a participant decide to withdraw and does not plan to participate in the post-treatment 
follow-up period, all efforts will be made to complete and report the observations as thoroughly 
as possible, particularly the examinations outlined in the ET visit.
The investigator or one of his or her staff members should contact the participant to determine as 
accurately as possible the primary reason for the withdrawal. 
A complete final evaluation at the time of the participant
explanation of why the participant is withdrawing from the trial. If the reason for removal of a 
participant is an AE or an abnormal laboratory test result, the principal specific event or test will 
be recorded.
If a participant withdraws from the trial, he/she may request destruction of any samples taken and 
not tested, and the investigator must document this in the site trial records.
7.1 Discontinuation
Any participant who decides to discontinue from the trial prematurely and does not plan to 
participate in the post-treatment follow-up period will be requested to complete the ET visit.
Participants who discontinue will not be replaced.
Discontinuation of Investigational Product
An individual participant will not receive any further IP if any of the following occur in the 
participant:
Receipt of any medications that have been demonstrated to be effective for treatment of 
AA as described in Section 6.4.2.
A CTCAE Grade 3 or higher allergic reaction to the IP.
A CTCAE Grade 3 or higher infection considered related to the IP. 
Other AE that contraindicates further dosing in the opinion of the investigator and/or the 
Sponsor, or Medical Monitor.
Withdrawal of consent from further treatment with IP.
Participant is determined to have met one or more of the exclusion criteria or failed to 
meet all the inclusion criteria for study participation and there is a potential safety risk 
associated with continuation identified upon consultation with the Medical Monitor.
Pregnancy or a decision to become pregnant.
Any of the following liver function abnormalities:
ALT or AST 
8× ULN.

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ALT or AST 
5× ULN for more than 2 weeks.
ALT or AST 
3× ULN and total bilirubin 
2× ULN.
3× ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever,
5%).
Participants who are permanently discontinued from receiving IP will be followed for 
protocol-specified assessments including follow-up of any AEs through Week 48 unless consent 
is withdrawn specifically from further trial participation (Section 7.1.3), or the participant is lost 
to follow-up (Section 7.2). Site investigators will be trained about the importance of retention of 
participants through the completion of the study, and participants will be informed about the 
continued scientific importance of their data even if they discontinue study treatment early.
Discontinuation from the Trial
Reasons for discontinuation from the trial include the following:
The participant is lost to follow-up.
The sponsor or regulatory authorities, for any reason, stop the trial. In this case, all participants 
will be discontinued from the trial. The investigator will immediately, on discontinuance of 
the trial by the sponsor, in its entirety or at a clinical trial site, inform both the participants and 
the research ethics board of the discontinuance, provide them with the reasons for the 
discontinuance and advise them in writing of any potential risks to the health of participants or 
other persons.
Withdrawal of Consent from the Trial
Participants are free at any time to withdraw from the study (IP and assessments), without prejudice 
to further treatment (withdrawal of consent). Such participants will always be asked about the 
reason(s) for withdrawal and the presence of any AEs. If a participant withdraws participation in 
the study, then no further study visits or data collection should take place. Further details 
concerning use of samples collected during the study from a participant who withdraws consent 
are provided in Section 10.9.
7.2 Lost to Follow-Up
A participant 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 trial site staff. 
The following actions must be taken if a participant fails to return to the clinic for a required trial
visit:
The site will attempt to contact the participant and reschedule the missed visit. The site will 
then counsel the participant on the importance of maintaining the assigned visit schedule 
and ascertain if the participant wishes to or should continue in the trial.
Before a participant is deemed lost to follow-up, the investigator or designee will make 
every effort to regain contact with the participant (where possible, three telephone calls 
and, if necessary, a certified letter to the participant

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equivalent methods). These contact attempts should be documented in the participant
medical record or trial file. 
 
If all attempts to contact the participant fail, he or she will be considered to have withdrawn 
from the trial with a primary reason of lost to follow-up. 
 
 

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8
TRIAL ASSESSMENTS AND PROCEDURES
8.1 Efficacy Assessments
Clinical evaluations of AA will be performed by an experienced and qualified dermatologist (board 
certified or equivalent) or other suitably qualified and experienced designee. To assure consistency 
and reduce variability, the same assessor should perform all assessments on a given participant
whenever possible.
Severity of Alopecia Tool (SALT)
To participate in this trial, a participant must have moderate-to-severe AA as assessed by a SALT
score of
at screening and baseline (Day 1) as described in Section 5.1.
The SALT score is a well-validated metric and widely utilized tool for determining the degree of 
hair loss based on the percentage of scalp surface area involved on the top, back, and each side of 
the scalp for AA.  The investigator will determine the percent scalp hair loss in a given quadrant, 
multiply this by the total scalp area delineated by that quadrant, and sum the resultant numbers for 
each quadrant to give the total percent scalp hair loss with a maximum score of 100.21 The SALT 
assessment tool is provided in Appendix 1.
 
 
 
 
 
 
 
 
 
Medical Photography
Medical photographs of the full scalp for all participants, and of the eyebrows and eyelashes for 
participants who have hair loss in these areas at baseline, will be performed at the visits specified 
in Table 1. Care will be taken to use the same camera, the same magnification, and the same 
settings for each photograph at each visit in order to obtain comparable pictures. 
Additional information for the medical photograph will be provided in the corresponding study 
manual.

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8.2 Pharmacokinetics
Blood samples will be collected for analysis of daxdilimab concentrations for all participants who 
e of IP 2 hours (±5 minutes) after dosing on Day 1 and pre-dose at all other visits
specified in Table 1.
The actual date and time of each blood sample collection will be recorded in the electronic case 
report form (eCRF).
Details about the collection, processing, handling, storage, and shipping of PK samples will be 
provided in the laboratory manual. 
8.3 Pharmacodynamics
Blood samples will be collected for 
 of daxdilimab at the visits and timepoints specified 
in Table 1. 
 
 
The actual date and time of each blood sample collection will be recorded in the eCRF.
Details about the collection (including blood volume required for each sample collection), 
processing, handling, storage, and shipping of PD samples will be provided in the laboratory 
manual.
8.4 Immunogenicity
Blood samples will be collected for analysis of serum daxdilimab ADA.
The actual date and time of blood sample collection will be recorded in the eCRF.
Details about the collection (including blood volume required for sample collection), processing, 
handling, storage, and shipping will be provided in the laboratory manual.
8.5 Safety and Other Assessments
Vital Signs
The following vital signs will be recorded at the visits specified in Table 1 with the participant in 
a seated or supine position, after having sat calmly for at least 5 minutes: systolic and diastolic 
blood pressure (mmHg), pulse (bpm), body temperature (°C), and respiratory rate 
(breaths/minute).
Weight (kg) and height (cm) will be collected to calculate the BMI, and will be recorded at the 
visits specified in Table 1. The height will only be recorded once at the screening visit and the 
same value will be used for BMI calculation at other visits.

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If deemed appropriate by the investigator, clinically significant findings in the vital signs will
exclude a participant from trial participation. Any abnormal finding related to vital signs that the 
investigator considers to be clinically significant must be recorded as an AE. 
Physical Examination
The following sites/systems will at least be included in the focused physical examination, which 
will be performed at the visits specified in Table 1:
General appearance
Dermatological (except AA)
Head, eyes, ears, nose, throat (HEENT)
Respiratory
Cardiovascular
Abdominal
Neurological
Musculoskeletal
Lymphatic
Information for all physical examinations must be included in the source document. If deemed 
appropriate by the investigator, clinically significant findings in the physical examination will
exclude a participant from trial participation. Any significant change will be reported as an AE in 
the source document and eCRF.
Clinical Laboratory Tests
Laboratory tests will be performed at the visits specified in Table 1. The tests will include 
urinalysis, hematology with differential, a standard chemistry panel (chemistry includes liver 
function tests), and serum pregnancy test (screening) for women of childbearing potential 
(WOCBP). At the visit specified in Table 1, a urine pregnancy test will be performed for WOCBP
(conducted at the investigator site). The specific tests in these panels are listed in Table 4.

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deemed appropriate by the investigator). Any clinically significant value will be reported as an 
AE.
Local Injection Tolerability Assessments
Assessor local injection tolerability assessments will be performed approximately 30 minutes
post-dose (can be performed any time at Week 36 as no IP is administered), at the visits specified 
in Table 1. The investigator, or designee, will evaluate the injection sites at these visits, and will 
document the presence or absence of local intolerance/injection site reactions and will open an AE 
in case of local injection site intolerance. Additional follow-up after Week 36 can be performed 
for any ongoing injection site reactions.
8.6Adverse Events and Serious Adverse Events
Definition of Adverse Event
An AE is any untoward medical occurrence in a participant administered a pharmaceutical product 
and that does not necessarily have a causal relationship with this treatment. An AE can therefore 
be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of an IP, whether or not considered related to the IP.
Definition of Treatment-Emergent Adverse Event
A TEAE is any condition that was not present prior to treatment with the IP 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 Serious Adverse Event
A SAE or reaction is any untoward medical occurrence that, at any dose has any of the following 
consequences:
Results in death
Is life-threatening
Requires in-patient hospitalization or prolongation of existing hospitalization
Results in persistent or significant disability/incapacity
Is a congenital anomaly/birth defect
-
participant was at risk of death at the time of the event; it does not refer to an event that 
hypothetically might have caused death if it were more severe.
Medical and scientific judgment should be exercised in deciding whether expedited 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 participant or may 
require intervention to prevent one of the other outcomes listed in the definition above. These 
should also usually be considered serious.

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Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered serious when, based upon appropriate medical judgment, they may jeopardize 
the participant or participant and may require medical or surgical intervention to prevent one of 
the outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse.
Definition of an Adverse Event of Special Interest (AESI)
An AESI is an AE of scientific and medical interest specific to understanding of the IP and may 
require close monitoring and collection of additional information by the investigator. An AESI 
may be serious or nonserious.
The rapid reporting of AESIs allows ongoing surveillance of these events in order to characterize 
and understand them in association with the use of this IP.
The following AESIs will be particularly monitored in this trial:
Hypersensitivity reaction, including anaphylaxis.
Severe viral infection/reactivation (CTCAE Grade 3 or higher).
Opportunistic infection.
Malignancy (except non-melanoma skin cancer).
Classification of an Adverse Event
8.6.5.1 Relationship to Trial Treatment
The investigator is required to provide an assessment of the relationship of AEs and SAEs to the 
An unreasonable temporal relationship between administration of the IP and the onset of 
the event (eg, the event occurred either before, or too long after, administration of the IP 
for it to be considered IP related).
A causal relationship between the IP and the event is biologically implausible (eg, death as 
a passenger in an automobile accident).
A clearly more likely alternative explanation for the event is present (eg, typical adverse 
reaction to a concomitant drug and/or typical disease-related event).
are not met.
facts, evidence, or arguments to suggest possible causation).
8.6.5.2 Adverse Event Severity
The guidelines outlined in CTCAE v5.0 will be used for assessing the severity or intensity of the 

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event. The general guidelines for assessing the AE grade are provided in Table 5.
Table 5: CTCAE v5.0 General Guidelines
Grade
Description
Grade 1
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.
Grade 2
Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate 
instrumental ADL a. 
Grade 3
Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care ADL b.
Grade 4
Life-threatening consequences; urgent intervention indicated.
Grade 5
Death related to AE.
Abbreviations: ADL, activities of daily living; AE, adverse event; CTCAE, Common Terminology for Adverse
Events.
The CTCAE v5.0 is dated to 27 NOV 2017.
a Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc.
b Self-care ADL refers to bathing, dressing, and undressing, feeding self, using the toilet, taking medications, and 
not bedridden.
8.6.5.3 Expectedness
Horizon Therapeutics Ireland DAC will assess the expectedness of each SAE in relation to the IP.
Time Period and Frequency for Event Assessment and Follow-Up
The occurrence of an AE or SAE may come to the attention of trial personnel during trial visits 
and interviews of a trial participant presenting for medical care, or upon review by a trial monitor.
All AEs, including local and systemic reactions, will be captured on the appropriate eCRF. 
Information to be collected includes event description, date 
severity, relationship to IP (assessed only by those with the training and authority to make a 
diagnosis), and date of resolution/stabilization of the event. All AEs occurring while on trial must 
be documented appropriately regardless of relationship. 
Trial site personnel will note the occurrence and nature of each participant
present prior to the informed consent signature in the appropriate section of the source document 
and eCRF. During the trial, site personnel will note any change in the condition(s) and the 
occurrence and nature of any AE. 
Any medical condition that is present prior to informed consent signature will be considered as 
part of medical history and not reported as an AE. However, if the trial participant
deteriorates after the consent signature, it will be recorded as an AE.
Should a participant experience an AE at any time after the informed consent signature until the 
end of participation in the trial, the event will be recorded as an AE in the source document and 
eCRF. Any SAE related to the trial participation (e.g., screening procedure) will be recorded in 

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the source document and eCRF from the time consent is given to participate in the trial until the 
end of participation in the trial.
The investigator is responsible for appropriate medical care of participants during the trial. The 
investigator also remains responsible for following through with an appropriate health care option 
for all AEs that are ongoing at the end of the trial. The participant should be followed until the 
event is resolved or stable. If an AE is ongoing at the end of trial, the follow-up duration is left to 
the discretion of the investigator. Follow-up frequency will be performed at the discretion of the 
investigator.
Whenever possible, clinically significant abnormal laboratory results are to be reported using the 
diagnostic that resulted in the clinically significant abnormal laboratory results and not the actual 
abnormal test.
Adverse Event Reporting
Investigators are responsible for monitoring the safety of participants who are participating in this 
trial and for alerting the sponsor to any event that seems unusual, even if this event may be 
considered an unanticipated benefit to the participant. 
Serious Adverse Event Reporting
Horizon Therapeutics Ireland DAC will be the pharmacovigilance unit responsible for the overall 
pharmacovigilance process for this trial. All SAEs, related to the experimental treatment or not, 
occurring during the course of the trial must be reported by entering the information into the eCRF
within 24 hours of knowledge of the occurrence (this refers to any AE that meets one or more of 
the aforementioned serious criteria). The SAE reporting period ends at the end of the follow-up 
period or if the participant begins an alternative therapy.
If unable to access the eCRF, the event must be reported by submitting the completed SAE form 
to the following e-mail address (faxing can also be done as a second option in case e-mailing is 
not possible) within 24 hours after becoming aware that a participant has experienced an SAE.
Safety Contact Information:  Horizon Therapeutics 
E-mail:  clinicalsafety@horizontherapeutics.com
US Fax: (800) 860-7836
The pharmacovigilance unit will inform the medical monitor, the sponsor, and Innovaderm within 
1 business day of awareness of a new SAE. The pharmacovigilance unit will process and evaluate 
all SAEs as soon as the reports are received. For each SAE received, the pharmacovigilance unit, 
in consultation with the Sponsor if needed, will make a determination as to whether the criteria for 
expedited reporting to relevant regulatory authorities have been met. 
The expedited reporting of relevant safety information to concerned regulatory agencies and ethic 
committees will be performed in accordance with local laws and regulations and will be defined 
in the Safety Management Plan. 

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The trial sponsor will be responsible for notifying the Food and Drug Administration (FDA) of 
any unexpected fatal or life-threatening suspected adverse reactions as soon as possible, but in no 
case later than 7 calendar days after the sponsor's initial receipt of the information. In addition, the 
sponsor must notify the FDA and all participating investigators in an Investigational New Drug 
(IND) safety report of potential serious risks, from clinical trials or any other source, as soon as 
possible, but in no case later than 15 calendar days after the sponsor determines that the 
information qualifies for reporting.
Pregnancy Reporting
If a female participant becomes pregnant during the trial or up to 6 months after the last IP
administration, whichever is longer, the participant should inform the trial site as soon as possible. 
Upon confirmation of the pregnancy, the female participant will be discontinued from the trial. If 
a female partner of a male participant becomes pregnant up to 6 months after the last IP 
administration of the male subject, the participant should inform the trial site as soon as possible. 
The investigator must complete a trial-specific pregnancy form upon confirmation of a pregnancy 
and send it to the pharmacovigilance unit within 24 hours of confirmation of the pregnancy 
(contact information to be used is the same as for SAE reporting). The pharmacovigilance unit will 
report all cases of pregnancy to the medical monitor, the sponsor, and Innovaderm in a timely 
manner. Pregnancy is not itself an AE or SAE; however, maternal/fetal complications or 
abnormalities will be recorded as AEs or SAEs, as appropriate. The investigator will follow the 
pregnancy until completion or until pregnancy termination and, in the case of a live-born offspring, 
to 1 month of age in that infant. The investigator will notify the pharmacovigilance unit and 
Innovaderm of the outcome as a follow-up to the initial pregnancy form. All pregnancies should 
be reported to the sponsor and, when applicable, to the ethics committee.
Overdose
Investigational product overdose is any accidental or intentional use of IP in an amount higher than 
the dose indicated per protocol for a given participant. Trial treatment compliance (see 
Section 6.3.2) should be reviewed to detect potential instances of overdose (intentional or 
accidental).
Any IP overdose during the trial should be recorded on the source document and eCRF. In the 
event of overdose, the participant should be closely monitored for any potential AEs. All AEs 
associated with an overdose should be entered on the Adverse Event eCRF and reported using the 
procedures detailed in Section 8.6.8, Serious Adverse Events Reporting, even if the events do not 
meet seriousness criteria. If the AE associated with an overdose does not meet seriousness criteria, 
it must still be reported using the SAEs reporting procedures and in an expedited manner but should 
be noted as non-serious on the form and the Adverse Event eCRF. The excess quantity and duration 
of the overdose should be recorded.

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9 STATISTICAL CONSIDERATIONS  
9.1 Sample Size Determination 
A total of up to 30 participants will receive daxdilimab in the trial. The sample size was determined 
by the need to evaluate potential efficacy, safety and tolerability, and PK/PD. No formal power 
calculation was performed. 
The mean percent reduction from baseline in SALT score was 58% in 4 mg group at Week 36 in 
25. The lower bound of the 95% confidence interval was about 
42%. With 30 participants, if we observe a mean percent reduction from baseline in SALT score 
of 58% at Week 24, there is about 98% confidence that the mean percent reduction from baseline 
is at least 42%. The estimated probability that true mean percent reduction from baseline in SALT 
score is above a cutoff for an observed mean is provided in Table 6.  
Table 6: Probability that true mean percent reduction from baseline in SALT score is above 
a cutoff for an observed mean. 
  
Observed 
Probability that mean is 
n 
Mean %reduction 
 
 
 
30 
50% 
0.97 
0.85 
0.74 
 
55% 
>0.99 
0.95 
0.90 
 
58% 
>0.99 
0.98 
0.95 
 
The proportion of patients 
 in 4 mg group was 33% and 35% in 
. The lower bound of the 95% confidence interval was about 27%. 
The estimated probability that true proportion of participant
is above 27% 
and other cutoffs for an observed response rate is provided in Table 7. 
Table 7: Probability that true proportion of participant
 is above a 
cutoff for an observed response rate. 
  
Observed 
Probability that response rate is 
n 
response rate 
 
 
 
30 
9 (30%) 
0.87 
0.67 
0.58 
 
11(36.7%) 
0.97 
0.89 
0.84 
 
12(40%) 
0.99 
0.95 
0.92 
 
13(43.3%) 
0.99 
0.98 
0.96 
 
15(50%) 
0.99 
0.99 
0.99 
 

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9.2 Populations for Analyses
Safety analysis set: The safety analysis set is defined as participants who received any dose of 
daxdilimab. The efficacy, safety, PD and immunogenicity analyses will be based on the safety 
analysis set.
PK analysis set: The PK analysis set is defined as participants who received any dose of daxdilimab
and have at least 1 measurable PK concentration post dose. The PK analyses will be based on PK 
analysis set.
9.3 Statistical Analyses
General Approach
Continuous variables will be summarized in tables and will include the number of participants, 
mean, standard deviation (SD), median, minimum, and maximum. Categorical variables will be 
presented in tables as frequencies and percentages. Details of the statistical analysis will be 
specified in a separate statistical analysis plan (SAP).
Efficacy Analyses
9.3.2.1 Analysis of the Primary Efficacy Endpoint
The primary efficacy endpoint of percent change from baseline in SALT score at Week 24 will be 
summarized using descriptive statistics. A 2-sided 95% confidence interval will be calculated for 
the mean.
9.3.2.2 Analysis of the Secondary Efficacy Endpoints
The continuous secondary efficacy endpoints will be summarized similarly to the primary efficacy 
endpoint. The binary secondary efficacy endpoints will be summarized descriptively using 
frequencies and percentages. A 2-sided 95% confidence interval will be calculated for the 
percentage.
9.3.2.3 Handling Plan for Prohibited Medication Use 
For participants who take prohibited medications that are considered to be effective for treatment 
of AA, the result after administration of the prohibited medications will be imputed using the worst 
observation, including baseline for continuous endpoints. The participants will be considered 
non-responder after administration of the prohibited medications for binary endpoints.
9.3.2.4 Handling Plan for Treatment discontinuation
Participants who discontinue treatment early will be asked to come to scheduled evaluations until
the end of the study unless participants withdraw consent of trial participation or are lost to 
follow-up. The data collected after discontinuation of study treatment will be included in the 
analysis.

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9.3.2.5 Handling Plan for Missing Data
Missing visits, due to skipped visits or early dropout of study, will have the last observation carried 
forward for continuous endpoints. The participants will be considered non-responders after early 
dropout of study for binary endpoints.
Safety Analyses
AEs will be coded using the most recent version of Medical Dictionary for Regulatory Activities 
(MedDRA). Treatment emergent AEs will be summarized by the number of participants reporting 
the events, as well as by System Organ Class (SOC), Preferred Term (PT), severity, seriousness, 
and relationship to IP. For the summary of AEs by severity, each participant will be counted only 
once within a System Organ Class or a Preferred Term by using the AEs with the highest intensity 
within each category. For the summary of AEs by relationship to IP, each participant will be 
counted only once within a SOC or a PT by using the AEs with the greatest reported relationship 
within each category. The number and percentage of participants reporting treatment-emergent 
SAEs and treatment-emergent AESIs will also be summarized.
Clinically significant changes in laboratory analyses, vital signs, ECGs, and new findings on 
physical examination will be recorded as AEs or SAEs. Laboratory assessments, vital signs, and 
ECGs, as well as their changes from Baseline at each visit will also be summarized descriptively.
Concomitant medications will be coded with the World Health Organization-Drug Dictionary 
(WHO-DD). The number and percentage of participants who receive concomitant medications 
will be summarized by WHO-DD Anatomical Therapeutic Chemical category and PT. At each 
level of summarization, a participant is counted once if he/she reports one or more medications at 
that level.
Pharmacokinetic Analyses
Serum concentrations will be summarized descriptively by visit.
Individual serum concentration vs. actual time profiles for each participant, as well as the mean 
(±SD) serum concentration versus scheduled time profiles, will be presented graphically.
Pharmacodynamic/Immunogenicity Analyses
Descriptive summaries will be presented by visit for changes in pDC levels and ADA rate will be 
summarized descriptively. 
Exploratory Analyses
The exploratory analyses will be detailed in the SAP.

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Planned Analyses
The primary analysis will be performed when the last participant has completed Week 24 or 
withdraws prior to the scheduled Week 24 visit. All available data at the time of the data cut-off 
(including data collected after Week 24) will be included in the primary analysis.
The final analysis will be performed when all participants have completed trial.

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10 REGULATORY, ETHICAL, AND TRIAL OVERSIGHT 
CONSIDERATIONS 
10.1  Local Regulations/Declaration of Helsinki 
This trial will be conducted in accordance with the ethical principles that have their origin in the 
Declaration of Helsinki and that are consistent with ICH Tripartite Guideline for GCP and the 
applicable laws and regulations of the country in which the research is conducted, whichever 
affords the greater protection to the individual. 
10.2  Ethical Review  
It is the understanding of the sponsor that this protocol (and any amendments) as well as 
appropriate consent procedures, will be reviewed and approved by a research ethics board (REB)/ 
institutional review board (IRB). This board must operate in accordance with the current federal 
regulations. For sites with a local ethics committee, a letter or certification of approval will be sent 
by the investigator to the sponsor (or contract research organization [CRO]) before initiation of 
the trial and also whenever subsequent modifications to the protocol are made. 
10.3  Informed Consent Process 
An ICF describing in detail the trial treatment, trial procedures, and risks will be given to the 
participant, along with an assent form when required. 
It is the responsibility of the investigator, or a person designated by the investigator (if acceptable 
by local regulation), to obtain written informed consent from each individual participating in this 
trial, after adequate explanation of the aims, methods, objectives, and potential hazards of the trial. 
trial 
trial participation. Consent forms will be IRB/REB 
approved, and the participant will be asked to read and review the document. The investigator will 
explain the research trial to the participant and answer any questions that may arise. A verbal 
explanation will be provided in terms suited to the participant
procedures, and potential risks of the trial and of his or her rights as a research participant. 
Participants will have the opportunity to carefully review the written consent form and ask 
questions prior to signing. The participants should have the opportunity to discuss the trial with 
their family or surrogates or think about it prior to agreeing to participate. 
The participant will sign the informed consent document prior to any procedures being done 
specifically for the trial. Participants must be informed that participation is voluntary and that they 
may withdraw from the trial at any time for any reason, without prejudice. A copy of the signed 
informed consent document will be given to the participants for their records. The informed 
consent process will be conducted and documented in the source document (including the date), 
and the form signed, before the participant undergoes any trial-specific procedures. 

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The rights and welfare of the participants will be protected by emphasizing to them that the quality 
of their medical care will not be adversely affected if they decline to participate in this trial. 
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 participant to continue to 
participate, the consent form should, if necessary, be reviewed and updated by the IRB/REB. All 
participants (including those already being treated) should be informed of the new information, 
given a copy of the revised form, and asked to give their consent to continue in the trial. 
10.4  Trial Discontinuation and Closure 
This trial may be temporarily suspended or prematurely terminated if there is sufficient reasonable 
cause. Written notification, documenting the reason for trial suspension or termination, will be 
provided by the suspending or terminating party to trial participants, investigators, the sponsor, 
and regulatory authorities. If the trial is prematurely terminated or suspended, the principal 
investigators will promptly inform trial participants and the IRB/REB, and will provide the 
reason(s) for the termination or suspension. Trial participants will be contacted, as applicable, and 
be informed of changes to trial visit schedule. 
Circumstances that may warrant termination or suspension of the trial include, but are not limited 
to the following: 
 
Determination of unexpected, significant, or unacceptable risk to participants 
 
Insufficient compliance to protocol requirements 
 
Data that are not sufficiently complete or evaluable 
 
Scientific or corporate reasons 
The trial may resume once concerns about safety, protocol compliance, and data quality are 
addressed and satisfy the sponsor, IRB/REB, Health Canada, and/or FDA. 
10.5  Confidentiality and Privacy  
Participant confidentiality and privacy is strictly held in trust by the participating investigators, 
their staff, and the sponsor and their interventions. This confidentiality is extended to cover testing 
of biological samples in addition to the clinical information relating to participants. Therefore, the 
trial protocol, documentation, data, and all other information generated will be held in strict 
confidence. 
The investigator must assure that the participant
participant
case report form (CRF) or other 
documents submitted to the sponsor, participants should not be identified by their names, but by 
an identification code. The investigator should keep a participant log relating codes with the names 
of participants. The investigator should maintain in strict confidence documents not for submission 
to Horizon Therapeutics Ireland DAC (e.g., participant
 
All research activities will be conducted in a setting as private as possible. 
The trial monitor, other authorized representatives of the sponsor, and representatives of the IRB, 

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regulatory agencies, or pharmaceutical company supplying IP may inspect all documents and 
records required to be maintained by the investigator, including but not limited to, medical records 
(office, clinic, or hospital) and pharmacy records for the participants in this trial. The clinical trial 
site will permit access to such records. 
The trial participant
use during the trial. At the end of the trial, all records will continue to be kept in a secure location 
for as long a period as dictated by the applicable legal or regulatory requirements, the reviewing 
IRB, institutional policies, or sponsor requirements. 
10.6  Clinical Monitoring 
Clinical site monitoring will be conducted to ensure that the rights and well-being of trial 
participants are protected; that the reported trial data are accurate, complete, and verifiable; and 
that the conduct of the trial is in compliance with the currently approved protocol/amendment(s), 
ICH GCP guidelines, and with applicable regulatory requirement(s). Centralized monitoring, 
which consists of remote review of accumulating data from all sites, will be performed as detailed 
in the Centralized Monitoring Plan.  
10.7  Quality Assurance and Quality Control 
Each clinical site will perform internal quality management of trial conduct, data and biological 
specimen collection, documentation, and completion. 
Quality control (QC) procedures will be implemented beginning with the data entry system, and 
data QC checks, which will be run on the database, will be generated. Any missing data or data 
anomalies will be communicated to the site(s) for clarification/resolution. 
During the trial, the sponsor or its representative will conduct monitoring visits at regular intervals. 
The monitoring visits will be conducted to ensure protocol adherence, quality of data, accuracy of 
entries on the eCRFs, IP accountability, compliance with regulatory requirements, and continued 
adequacy of the trial site and its facilities. 
The site may be audited, monitored, or inspected by a quality assurance officer named by the 
sponsor, by the REB or IRB, and/or by the regulatory authorities. The investigator will be given 
notice before an audit occurs and will be expected to cooperate with any audit and provide 
assistance and documentation (including source data) as requested. The trial site will provide direct 
access to all trial-related sites, source data/documents, and reports for the purpose of monitoring 
and auditing by the sponsor and inspection by local and regulatory authorities. 
10.8 Data Handling and Record Keeping 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
site investigator. The investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 

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The investigator must maintain adequate and accurate records to enable the conduct of the trial to 
be fully documented and the trial data to be subsequently verified. These documents should be 
participant clinical source 
documents. 
The investigator must maintain source documents for each participant in the trial. These source 
documents will consist of case and visit notes (clinical medical records) containing demographic 
and medical information and the results of any tests or assessments. All information on the eCRFs 
must be traceable to the source documents in the participant
 or 
electronic record will be defined before trial start and will be recorded directly on the eCRFs, 
which will be documented as being the source data. 
The records should be retained by the investigator according to ICH guidelines, local regulations, 
or as specified in the Clinical Trial Agreement, whichever retention period is longer. 
Participant data will be entered by site personnel using Medidata Rave, a web-based electronic 
data capture (EDC) and reporting system. This application will be set up for remote entry. 
Medidata is the developer and owner of Rave EDC. The EDC software has been fully validated 
and conforms to Title 21 of the Code of Federal Regulations, Part 11 requirements. Investigator 
site staff will not be given access to the EDC system until they have been fully trained. Designated 
investigator staff will enter the data required by the protocol into the eCRFs using this web-based 
application. Automatic validation programs check for data discrepancies in the eCRFs and, by 
generating appropriate error messages, allow modification or verification of the entered data by 
the investigator staff before confirming the data. The investigator must certify that the data are 
complete and accurate by applying an electronic signature to the eCRFs. 
The data collected will be encoded and stored electronically in a database system. Validated data 
may subsequently be transferred to the sponsor. 
10.9 Biological Specimens and Data  
Study data are protected by the use of a sample identification (SID) number, which is a number 
specific to the participant. The investigator is in control of the information that is needed to connect 
a study sample to a participant; a participant may withdraw consent at any time by notifying the 
investigator. If consent is withdrawn, any samples collected prior to that time may still be given to 
and used by the Sponsor, but no new data or samples will be collected unless specifically required 
to monitor the safety of the participant.  
Leftover samples stored for future research with participant consent will be labeled with a sample 
identification number. If the participant consents to have his/her samples used for future research, 
this additional research may not start immediately and may start at any time during the storage 
15 years after the end of the 
study in which they were collected. If the participant chooses not to allow his/her study samples 
to be used for future research, the samples will be destroyed by the Sponsor once they are no longer 
required for the main study. If future use consent is withdrawn, the Sponsor and the investigator 

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sample has already been used for research, the Sponsor is not required to destroy the results of this 
research. In this case, only the remaining sample(s) will be destroyed. 
10.10 Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol requirements. The 
non-compliance may be either on the part of the participant, the investigator, or the trial site staff. 
As a result of deviations, corrective actions are to be developed by the site and implemented 
promptly. The CRA must ensure that a prompt action is taken to secure compliance. If a 
non-compliance that significantly affects or has the potential to significantly affect human 
participant protection or reliability of trial results is discovered, the CRO and the Sponsor should 
perform a root cause analysis and implement appropriate corrective and preventive actions 
Protocol deviations must be sent to the reviewing IRB per their policies. The investigator is 
responsible for knowing and adhering to the reviewing IRB requirements. 
10.11 Publication Policy 
The publication policy will be addressed in the Research and Financial Agreement, and all details 
outlined in the agreement will apply to this protocol. The trial will be registered on 
ClinicalTrials.Gov prior to the first participant being dosed. 
 

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