A Phase 2a, Multicenter, Proof-of-Concept Clinical Trial to Evaluate Efficacy and Safety of BSI-045B mAb Injection in Patients With Moderate to Severe Atopic Dermatitis
Phase: PHASE2
Conditions: Atopic Dermatitis
Sponsor: Biosion, Inc.

Biosion, Inc. 
Protocol BSI-045B-002 
V4.0_8 Jul 2024 
Page 1 of 68 
Protocol Number: 
BSI-045B-002 
Protocol Title: 
A Phase 2a, Multicenter, Proof-of-Concept Clinical Trial to 
Evaluate Efficacy and Safety of BSI-045B mAb Injection as 
Monotherapy in Patients with Moderate to Severe Atopic 
Dermatitis 
Indication: 
Atopic dermatitis 
Phase: 
2a 
Investigational 
Product: 
BSI-045B 
Sponsor: 
Biosion, Inc. 
5th Floor, Building D 
3-1 Zhongdan Unit
South Longshan Road
Jiangbei New District, Nanjing
Key Sponsor 
Contacts: 
 
, Biosion, Inc. & 
President, Biosion USA, Inc. 
 
Date and Version: 
Version 4.0, 8 Jul 2024 
Confidentiality Statement 
This document contains confidential and/or proprietary information of Biosion Inc. and use of this 
information is strictly limited to the conduct of this study. Acceptance of this document constitutes 
agreement by the recipient that the contents will not be copied, distributed, or otherwise disclosed 
to third parties, and will not be used in any way, except as expressly authorized by Biosion, Inc 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
NCT # NCT05932654

Biosion, Inc. 
Protocol BSI-045B-002 
V4.0_8 Jul 2024 
Page 2 of 68 
 
I have read the protocol version 4.0 
Proof-of-Concept 
Clinical Trial to Evaluate Efficacy and Safety of BSI-045B mAb Injection as Monotherapy in 
forth therein. 
I agree to comply with the International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) 
Guidelines and all locally applicable regulations. 
 
 
 Biosion, Inc. & President, 
Biosion USA, Inc. 
Date (DD Month YYYY) 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
SPONSOR'S AGREEMENT 
entitled "A Phase 2a, Multicenter, 
Patients with Moderate to Severe Atopic Dermatitis" and agree to abide by all provisions set 
7/8/2024 

Biosion, Inc. 
Protocol BSI-045B-002 
V4.0_8 Jul 2024 
Page 3 of 68 
TABLE OF CONTENTS 
1 SCHEMA  ............................................................................................................................. 7 
2 PROTOCOL SYNOPSIS ....................................................................................................... 8 
3 SCHEDULE OF ACTIVITIES ............................................................................................ 17 
4 LIST OF ABBREVIATION ................................................................................................ 22 
5 INTRODUCTION AND BACKGROUND ........................................................................ 25 
5.1 Disease Overview ....................................................................................................... 25 
5.2 Development of BSI-045B ......................................................................................... 25 
5.2.1 Mechanism of Action ......................................................................................... 25 
5.2.2 Preclinical Findings ........................................................................................... 26 
5.2.3 Phase 1 Study (BSI-045B-001) .......................................................................... 26 
5.2.4 Design of Phase 2 Studies .................................................................................. 31 
5.3 Product Name.............................................................................................................. 32 
5.4 Study Rationale ........................................................................................................... 32 
5.5 Proposed Strengths and Dose Justification ................................................................. 33 
5.6 Risks and Benefits of BSI-045B in Human Volunteers Patients with Atopic 
Dermatitis ........................................................................................................ 35 
6 STUDY OBJECTIVES AND ENDPOINTS ....................................................................... 38 
7 INVESTIGATIONAL PLAN .............................................................................................. 40 
7.1 Study Dosing ............................................................................................................... 40 
7.2 Washout Period ........................................................................................................... 40 
7.3 Replacement of Patients who Withdraw from Treatment ........................................... 40 
7.4 Monitoring by Safety Steering Committee ................................................................. 41 
7.5 Assessment of Primary Efficacy Endpoint ................................................................. 41 
7.6 Other Efficacy and Safety Assessments ..................................................................... 41 
7.7 Follow-up Period ........................................................................................................ 41 
7.8 Study Drug Administration ......................................................................................... 41 
7.9 Enrollment and Study Procedures ............................................................................... 42 
7.9.1 General Considerations ...................................................................................... 42 
7.9.2 Assessments at Screening .................................................................................. 42 
7.9.3 Efficacy .............................................................................................................. 43 
7.9.4 Safety ................................................................................................................. 44 
7.9.5 Stopping Criteria ................................................................................................ 45 
7.9.6 Pharmacokinetic Assessments ........................................................................... 46 
7.9.7 Immunogenicity ................................................................................................. 47 
7.9.8 Pharmacodynamic Biomarker Assessments ...................................................... 47 
7.10 Criteria for end of Study ........................................................................................... 47 
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Protocol BSI-045B-002 
V4.0_8 Jul 2024 
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7.11 Criteria for Early Discontinuation of Study Drug..................................................... 47 
7.12 Criteria for Withdrawal from the Study .................................................................... 48 
7.13 Data Handling for Patients who do not Complete the Study .................................... 48 
7.14 Compliance/Adherence ............................................................................................. 49 
7.15 Randomization and Blinding .................................................................................... 49 
8 STUDY POPULATION ...................................................................................................... 50 
8.1 Inclusion Criteria ........................................................................................................ 50 
8.2 Exclusion Criteria ....................................................................................................... 50 
8.3 Contraception Requirements ....................................................................................... 53 
9 STUDY DRUG SUPPLIES, DOSING, AND CONCOMITANT MEDICATIONS .......... 54 
9.1 BSI-045B .................................................................................................................... 54 
9.2 Receipt, Dispensing, Storage, and Return of Investigational Product ........................ 54 
9.3 Concomitant Medications ........................................................................................... 54 
9.4 Rescue Medications for Exacerbations of Atopic Dermatitis ..................................... 54 
9.5 Prohibited Concomitant Medications ......................................................................... 54 
9.6 Drug Compliance ........................................................................................................ 55 
10 ADVERSE EVENT REPORTING ................................................................................... 56 
10.1 Definitions, Acquisition, and Recording of Adverse Events .................................... 56 
10.2 Definition of Serious Adverse Event ........................................................................ 56 
10.3 Assessment of Causal Relationship of Adverse Events and Serious Adverse Events
 ......................................................................................................................... 56 
10.4 Assessment of Severity of Adverse Events and Serious Adverse Events ................ 57 
10.5 Adverse Event and Serious Adverse Event Reporting ............................................. 57 
10.6 Procedures for Reporting Serious Adverse Events ................................................... 58 
10.7 Follow-up of SAEs and AEs ..................................................................................... 60 
10.8 Special Situations ...................................................................................................... 60 
10.9 Pregnancy Reporting ................................................................................................. 60 
11 STATISTICAL METHODS .............................................................................................. 61 
11.1 Sample Size ............................................................................................................... 61 
11.2 Statistical Approach .................................................................................................. 61 
11.3 Study Population ....................................................................................................... 61 
11.3.1 Patient Disposition ........................................................................................... 61 
11.3.2 Protocol Deviations .......................................................................................... 61 
11.3.3 Baseline Characteristics ................................................................................... 62 
11.4 Efficacy Assessments................................................................................................ 62 
11.5 Safety Assessments ................................................................................................... 62 
11.6 Pharmacokinetic Data Analysis ................................................................................ 62 
11.6.1 Analysis of Serum Drug Concentration versus Time Data .............................. 62 
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Protocol BSI-045B-002 
V4.0_8 Jul 2024 
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11.7 Immunogenicity Analysis ......................................................................................... 62 
11.8 Pharmacodynamic Biomarker Analysis .................................................................... 63 
12 INVESTIGATOR AND ADMINISTRATIVE REQUIREMENTS ................................. 64 
12.1 Institutional Review Board ....................................................................................... 64 
12.2 Informed Consent...................................................................................................... 64 
12.3 Data Reporting and Case Report Forms ................................................................... 64 
12.4 Retention of Data ...................................................................................................... 64 
12.5 Deviations from the Protocol .................................................................................... 65 
12.6 Study Monitoring ...................................................................................................... 65 
12.7 Disclosure of Data..................................................................................................... 65 
13 REFERENCES .................................................................................................................. 66 
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Biosion, Inc. 
Protocol BSI-045B-002 
V4.0_8 Jul 2024 
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LIST OF TABLES 
Table 1. Screening and Treatment .......................................................................................... 17 
Table 2. Follow-up, End of Study, and Early Withdrawal ..................................................... 20 
Table 3. Objectives and Endpoints, Phase 1 Study (BSI-045B-001) ..................................... 26 
Table 4. Treatments Administered per Cohort in Study BSI-045B-001 ................................ 28 
Table 5. Objectives and Endpoints in BSI-045B-002 Study .................................................. 38 
Table 6. Washout Durations Required Before Initial Dose of BSI-045B, by Therapy .......... 40 
Table 7. Clinical Laboratory Assessments, BSI-045B-002 .................................................... 43 
Table 8. Toxicity with the Potential to Cause Study Treatment Discontinuation .................. 45 
Table 9. Grading scale for injection site reactions .................................................................. 46 
Table 10. Assessment of Severity of an Adverse Event ......................................................... 57 
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Biosion, Inc. 
Protocol BSI-045B-002 
V4.0_8 Jul 2024 
Page 7 of 68 
1 SCHEMA 
BSI-045B-002 Study Design 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
Weekl 
Day 1 
II 
Week4 
Dayl 
Week 24 
Week 26 
Day 1 
(2 weeks 
after last dose) 
1 
Primary endpoint analysis 
12 weeks 
after last dose 

Biosion, Inc. 
Protocol BSI-045B-002 
V4.0_8 Jul 2024 
Page 8 of 68 
2 PROTOCOL SYNOPSIS 
Protocol No. 
BSI-045B-002 
Title 
A Phase 2a, Multicenter, Proof-of-Concept Clinical Trial to Evaluate Efficacy 
and Safety of BSI-045B mAb Injection as Monotherapy in Patients with 
Moderate to Severe Atopic Dermatitis 
Version No. and 
Date 
V 4.0, 8 Jul 2024 
Sponsor 
Biosion, Inc 
Clinical Phase 
2a 
Study Drug 
Investigational Product 
BSI-045B, anti-thymic stromal lymphopoietin (TSLP) mAb injection 
Objectives 
Primary Objectives 
To evaluate the efficacy of BSI-045B as monotherapy in patients with 
moderate to severe atopic dermatitis (AD) 
To evaluate the safety and tolerability of BSI-045B as monotherapy in 
patients with moderate to severe AD 
Secondary Objectives 
To evaluate the pharmacokinetics (PK) of BSI-045B 
To evaluate the immunogenicity of BSI-045B 
Exploratory Objectives 
To assess additional efficacy and safety outcomes of BSI-045B as 
monotherapy 
To evaluate the pharmacodynamic (PD) biomarkers of BSI-045B 
Study Design 
The study design is presented in the Schema. The study is a multicenter clinical 
trial and is designed as a proof-of-concept study to evaluate the efficacy, safety, 
tolerability, PK, immunogenicity, and PD of BSI-045B following SC injections. 
The present study, which is intended to assess the efficacy and safety of BSI-
045B in moderate to severe AD patients, is being conducted as a proof-of-
concept study prior to performing a more traditional Phase 2 trial. If this study is 
successful, the Sponsor plans to conduct a future Phase 2b, randomized, blinded, 
dose-finding trial that will formally compare BSI-045B with placebo and/or other 
treatments for AD. 
The study will enroll patients with moderate to severe AD. Eligible patients will 
receive BSI-045B 300 mg treatment, firstly at every week (QW) during Week 1 
to Week 4, and then every 2 weeks (Q2W) to Week 24. 
Patients will start with a washout period for anti-AD treatment prior to study 
treatment, including systemic and topical agents and phototherapy. The duration 
of the washout period varies by therapy and the Investigator should consult 
section 7.2. Eligible patients who complete the washout period for previous 
therapies for AD will be treated with BSI-045B as described above. 
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Biosion, Inc. 
Protocol BSI-045B-002 
V4.0_8 Jul 2024 
Page 9 of 68 
Monitoring by Safety Steering Committee (SSC) 
The SSC will monitor the study and will be composed of representatives from the 
Sponsor, the National Principal Investigator, and independent physicians, as 
indicated in the SSC charter. 
The SSC will formally assess safety findings when 20 patients complete dosing 
at Week 12. The SSC will assess all events, especially treatment-related SAEs 
that might prompt a change to the study. 
Assessment of Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of patients with EASI75 at 
Week 26 (2 weeks after last dose at Week 24). 
Follow-up Period 
After the Treatment Period, there will be a 12 -week Follow-up Period. 
Methodology 
This study is a Phase 2a, proof-of-concept clinical study designed to evaluate the 
efficacy, safety, tolerability, PK, immunogenicity, and PD of BSI-045B injection, 
in patients with moderate to severe AD. The study will be unblinded. 
BSI-045B treatment will be initiated with a loading dose of 300 mg SC QW for 
4 weeks. After that, patients will be treated Q2W to Week 24. After treatment, 
there will be a 12-week Follow-up Period. 
The preferred SC injection site is the abdomen. The thigh can be used as an 
alternative site for SC injections. A 2.5-mL injection of 120 mg/mL (300 mg total 
dose) will be administered at a single injection site. After injections, all patients 
should be monitored at the study sites for at least 30 mins to observe body 
reactions, including injection site reactions. Any injection site reactions observed 
after each site visit should be reported to the Investigators by the patients. 
The total number of evaluable patients with AD of the study is approximately 20 
to 24, patients who do not complete the first 5 doses will be replaced. 
The SSC will monitor the study to identify questions concerning safety. 
The primary efficacy endpoint is the proportion of patients with EASI75 at 
Week 26 (2 weeks after last dose at Week 24), compared with baseline (Day 1). 
Additional efficacy outcomes also include 
Global Assessment (IGA), Facial IGA, and Peak Pruritus Numerical Rating Scale 
(PP-NRS). Efficacy assessments will be conducted at Screening, within the first 
hour prior to dosing on Day 1, at all subsequent visits, and at the time of early 
withdrawal from the study. 
Adverse events (AEs) will be collected after signing the Informed Consent Form 
(ICF) and throughout the Treatment Period and the Follow-Up Period. After 
injections, all patients should be monitored at the study sites for at least 30 mins 
to observe body reactions, including injection site reactions. Any injection site 
reactions observed after each site visit should be reported to the Investigators by 
the patients.   
Concomitant medications will be recorded after signing the ICF and throughout 
the Treatment Period and Follow-Up Period. 
No rescue medications will be allowed in this study. 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
> 
-
> 
-
other scores on EASI, Investigator's 

Biosion, Inc. 
Protocol BSI-045B-002 
V4.0_8 Jul 2024 
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During the Treatment and Follow-up Periods, PK, PD, and immunogenicity 
samples will be collected for analysis. 
Follow-up assessments will occur during subsequent visits to the study sites. At 
study sites at other times 
for re-evaluation. 
Number of 
evaluable Patients 
Approximately 20 to 24 evaluable patients 
Inclusion Criteria 
Patients must meet the following criteria for study entry: 
1)
In the opinion of the Investigator, the patient is capable of understanding and
complying with this protocol requirements. 
2)
The patient signs and dates a written ICF prior to the initiation of any study
procedures. 
3)
The patient has a diagnosis of AD (according to the criteria established by
Hanifin and Rajka, 1980). The diagnosis of AD must have been present for at 
least 6 months. 
4)
The patient is aged 18 to 65 years, inclusive at the time of consent. Patients
of any gender are eligible. 
5)
A female patient weighs at least 45 kg and a male patient weighs at least
50 kg. The patient has a body mass index (BMI) between 18.0 and 32.0 
kg/m2 inclusive at Screening. 
6) 
 and on Day 1. 
7) 
Screening and on Day 1. 
8) 
the physical examination at Screening and on Day 1. 
9)
The patient has:
(a) not received prior treatment with topical or systemic medications OR
(b) the patient has active disease despite topical or systemic treatment as per
the Investigator at the time of screening 
Prescription moisturizers or moisturizers containing additives such as 
ceramide, hyaluronic acid, urea, or filaggrin degradation products can be 
allowed if the patient agrees to continue using at the current dose during the 
study. 
10) A male patient who is non-sterilized and sexually active with a female
partner of childbearing potential agrees to use highly effective contraception 
from the time of signing the ICF throughout the duration of the study 
treatment and for 90 days (~5 half-lives) after the last dose of study drug 
(See Section 8.3). 
11) A female patient of childbearing potential who is sexually active with a non-
sterilized male partner agrees to routinely use highly effective contraception 
from the time of signing the ICF throughout the duration of the study 
treatment and for 90 days after the last dose of study drug (See Section 8.3). 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
the Investigator's discretion, patients may return to the 
The EASI is ~12 at Screening 
The score on the IGA is ~3 (scale ofO to 4) at 
The total body surface area (BSA) affected by AD is ~10% as assessed by 

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Protocol BSI-045B-002 
V4.0_8 Jul 2024 
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12) The patient has a negative urine/blood result for drugs of abuse (if there are
concerns in the opinion of the Investigator regarding the use of illicit drugs, 
including cannabinoid products) at Screening. 
Exclusion Criteria 
Any patient who meets any of the following criteria will be excluded from the 
study: 
1) The patient has received any of the following treatments but did not finish the
required washout as stated in the following table. After the washout period, the 
patients can be considered for study treatment.  
Therapy 
Washout Duration Required 
before First Dose of BSI-045B 
Tralokinumab 
12 weeks 
Dupilumab 
12 weeks 
Phototherapy 
4 weeks 
Abrocitinib 
4 weeks 
Upadacitinib 
4 weeks 
Topical corticosteroids 
1 week 
Topical calcineurin inhibitors 
1 week 
Investigational Products 
4 weeks 
All Other Therapies prescribed for therapeutic 
immunosuppression or immunomodulation 
3 weeks or 4 half-lives, whichever 
is longer 
2) The patient has another dermatologic condition that might confound a
diagnosis of AD or a treatment assessment. 
3) The patient has any clinically significant illness that may affect the safety,
increase the risk for seizure or lower the seizure threshold, or potentially 
confound the study results, such as cardiovascular, neurologic, pulmonary, 
hepatic, renal, metabolic, gastrointestinal, immunologic, endocrine, or 
psychiatric disease or disorder, or other abnormality. It is the responsibility of 
the Investigator to assess the clinical significance of a patient
however, consultation with the 
 Medical Monitor may be warranted. 
4) The patient has abnormal laboratory values during the Screening Period:
alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) > 1.5 
estimated 
glomerular filtration rate (GFR) < 60 mL/min (based on Cockcroft-Gault 
calculation)
 150 ×103/µL. 
Individual exceptions may be granted with the agreement of the Sponsor and 
the Investigator. 
5) The patient has a history of anaphylaxis following biologic therapy.
6) The patient has a history of allergy to corticosteroids, diphenhydramine,
hydroxyzine, cetirizine, or fexofenadine. 
7) The patient has a history of a clinically significant infection within 4 weeks
prior to Screening. 
8) The patient has been diagnosed with a helminthic parasitic infection within 6
months prior to Screening. 
9) The patient has a history of drug abuse (defined as any illicit drug use) or a
history of alcohol abuse within 1 year prior to Screening or is unwilling to 
agree to abstain from excessive alcohol consumption and drugs (including 
cannabinoids) throughout the study. 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
's condition; 
Sponsor's 
times the upper limit of normal (ULN), total bilirubin 
1.5 mg/dL, 
, hemoglobin (Hgb) :'.S 10 g/dL, platelet count :'.S 

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Protocol BSI-045B-002 
V4.0_8 Jul 2024 
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10) The patient had a major surgical or major dental procedure within 8 weeks
prior to Screening. 
11) The patient is pregnant or lactating or intends to donate ova before, during, or
within 90 days (~ 5 half-lives) since the last dose of study drug. 
12) If male, the patient intends to donate sperm during this study or within 90
days (~ 5 half-lives) since the last dose of study drug. 
13) The patient has a history of neurologic abnormalities including abnormal
electroencephalography, brain injury including traumatic injury, perinatal 
cerebropathy, postnatal brain damage, blood-brain barrier abnormality, and 
cavernous angioma. 
14) The patient has a history of cerebral arteriosclerosis.
15) The patient has a history of cancer, except for adequately treated basal or
squamous cell skin cancer or in situ cancers; or any other cancer from which 
the patient has been disease free for at least 5 years prior to the first dose of 
study drug. 
16) The patient has a positive test result for hepatitis B surface antigen (HbsAg),
antihepatitis C virus (HCV), a history of active tuberculosis, a positive test 
result for human immunodeficiency virus (HIV), or a known history of HIV 
infection at Screening. 
17) The patient has poor peripheral venous access.
18) The patient 
 450 mL of blood (including 
plasmapheresis) or had a transfusion of any blood product within 90 days 
prior to the first dose of study drug. 
19) The patient has an abnormal (clinically significant) electrocardiogram (ECG)
at Screening and/or on Day 1. Entry of any patient with an abnormal (not 
clinically significant) ECG must be approved and documented by signature 
of the Investigator. In the case of a corrected QT interval (Fridericia) 
(QTcF) > 450 ms or > 470 ms (patients with bundle branch block) or PR 
interval outside the range of 115 to 220 ms, assessment may be repeated once 
for eligibility determination at Screening and/or on Day 1. 
20) The patient has poorly controlled hypertension and is not considered suitable
for participation in this study in the judgement of the Investigators at 
Screening and/or on Day 1. 
21) The patient has abnormal resting heart rate and is not considered suitable for
participation in this study in the judgement of the Investigator at Screening 
and/or on Day1. Assessment is allowed to be repeated once for eligibility 
determination at Screening and/or on Day 1 if deemed necessary. 
22) The patient plans to use any other prohibited medication or undergo any
prohibited procedure during the study. Oral antibiotics are permitted. Bleach 
baths are not permitted. 
23) The patient has a risk of suicide on the Patient Health Questionnaire-2 (PH-2)
or in the judgment of the Investigator, or the patient has made a suicide 
attempt or has a history of deliberate self-harm within 6 months prior to 
Screening. 
24) The patient is compulsorily detained for a medical or psychiatric illness.
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
has donated or lost~ 

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Protocol BSI-045B-002 
V4.0_8 Jul 2024 
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25) The patient or their immediate family are personnel at the study site.
26) The patient is unable to comply with restrictions and prohibited
activities/treatments as listed in the study protocol. 
Study Endpoints 
Primary Efficacy Endpoint: 
Proportion of patients with EASI75 at Week 26 (2 weeks after last dose at 
Week 24) 
Primary Safety Endpoint: 
Safety and tolerability as evidenced by the incidence of AEs, anti-BSI-045B 
antidrug antibody (ADA) formation, clinical laboratory evaluations, 12-lead 
ECGs, vital signs, physical examinations. The relationships between study drugs 
and AEs will be evaluated by Investigators. 
Secondary Endpoints: 
Pharmacokinetics listings will be provided. PK parameters might be estimated 
through compartmental modeling. Additionally, the PK/Efficacy relationship 
might be explored. 
Immunogenicity: Anti-BSI-045B ADA during and post BSI-045B treatment. 
PD biomarkers: Serum levels of thymus and activation related chemokine/C-C 
chemokine ligand 17 [TARC/CCL-17], periostin, and IgE during and post BSI-
045B treatment. 
Exploratory Endpoints: 
Proportion of patients with EASI90 at Week 26 (2 weeks after last dose at 
Week 24) 
Proportion of patients with EASI50 at Week 26 (2 weeks after last dose at 
Week 24) 
Percent change from baseline in EASI at each visit 
Proportion of patients achieving IGA 0 or 1 at Week 26 (2 weeks after last 
dose at Week 24) 
Percent changes in PP-NRS scores at Week 26 (2 weeks after last dose at 
Week 24) 
Proportion of patients achieving facial IGA 0/1 at Week 26 (2 weeks after 
last dose at Week 24) 
Occurrence of conjunctivitis 
Stopping Criteria 
-
organ class of Cardiac Disorders) according to Common Terminology Criteria 
for Adverse Events (CTCAE v5), then: 1) BSI-045B treatment may be continued 
if the AE is considered to be unrelated to BSI-045B; 2) BSI-045B treatment will 
be withheld if the AE is considered to be related to BSI-045B, until the toxicity 
-045B will be permanently discontinued if the AE
-045B treatment resumed and is considered to be
BSI-045B related. Treatment discontinuation decisions will be made by 
Investigators after a discussion with Sponsor. These AEs include hepatotoxicity, 
injection site reactions, allergic conjunctivitis and hypersensitivity (see Table 8). 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
> 
-
• 
• 
• 
• 
• 
• 
• 
If a patient experiences an AE assessed as 
Grade 3 
Grade 2 for the system 
returns to 
Grade 2; 3) BSI 
recurs to~ Grade 3 after BSI 

Biosion, Inc. 
Protocol BSI-045B-002 
V4.0_8 Jul 2024 
Page 14 of 68 
Patients who experience such AEs will be followed until the adverse events 
resolves or stabilizes. Study drug administration will not be discontinued. 
 
for the system-organ classes of Cardiac Disorders) per CTCAE v5, the study 
should be suspended for an evaluation from SSC. 
Screening 
Assessments 
Screening assessments will be performed after the patients signed the ICF. After 
all screening results are obtained, eligible patients who require no washout will 
be enrolled to the study directly; eligible patients who require washout will start 
washout and repeat some screening assessments during Day -14 to Day -1. 
A complete history will be recorded at Screening and will include medical 
history, surgical history, smoking history, alcohol use history, drug abuse history, 
prior and current medication, blood donation history, allergy history, and other 
demographic information. 
Physical examinations at Screening will include weight, height, BMI, as well as a 
complete examination. Symptom-driven examinations will be performed at other 
time points. 
Other screening assessments will include 12-lead ECG, blood pregnancy test 
(females of childbearing potential only), and vital signs (blood pressure, pulse, 
temperature, and respiratory rate). A subset of these tests will be completed at 
other time points, as detailed in the Schedule of Activities. 
A screening for drugs of abuse is optional (per the discretion of the Investigator). 
Clinical laboratory assessments at Screening will include the following: 
-
Hematology: Hgb, hematocrit, white blood cell (WBC) count and
differential, red blood cell (RBC) count and indices, platelet count 
-
Chemistry: Sodium, potassium, chloride, bicarbonate, calcium, phosphorus,
magnesium, glucose, BUN, creatinine, uric acid, ALT, AST, gamma 
glutamyl transferase (GGT), alkaline phosphatase, total protein, albumin, 
globulin, total bilirubin, lactate dehydrogenase (LDH), total cholesterol, 
triglycerides 
-
Coagulation: Prothrombin time (PT), activated partial thromboplastin time
(aPTT), fibrinogen, international normalized ratio (INR) 
-
Virology (performed only at Screening): HbsAg, anti-HCV, HIV
-
Urinalysis: Protein, glucose, ketones, occult blood, urobilinogen, urine
sediment microscopy (if other parameters abnormal) 
Efficacy 
Assessments 
Patients will be assessed to determine an EASI score at Screening, within the first 
hour prior to dosing on Day 1 (baseline), at subsequent visits, and at the time of 
early withdrawal from the study. 
The EASI score is a composite index that measures the severity of AD based on 
the average intensity of four clinical signs (erythema, edema/papulation, 
excoriations, and lichenification) at four body areas (head, neck, upper 
extremities, and trunk and lower extremities), and the percentage of affected area 
for each of the four body areas (Hanifin and Rajka, 1980). The primary efficacy 
endpoint is the proportion of patients with EASI75 at Week 26 (2 weeks after 
last dose at Week 24). 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
If 2/3 of patients experience any adverse event assessed as 
Grade 3 (2: Grade 2 
> 
-

Biosion, Inc. 
Protocol BSI-045B-002 
V4.0_8 Jul 2024 
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The IGA and facial IGA requires the Investigator to rate the severity of AD on a 
scale from 0 (clear) to 4 (severe). Assessments will be made on Day 1 and at 
subsequent visits, and at the time of early withdrawal from the study. 
The assessment tool for itching is the PP-NRS, on which the patient rates the 
maximum severity of the itch from AD on a scale from 0 (no itch) to 10 (worst 
itch imaginable) over a 24-hour period. The baseline PP-NRS score is based on 
the average of daily PP-NRS scores for the 7 days immediately preceding Day 1. 
Patients will complete the rating scale daily using the patient diary beginning on 
Day -8, throughout the last study visit, and at the time of early withdrawal from 
the study. In order to calculate an average for the score, the patient must have 
completed the diary for a minimum of 4 days during the previous 7 days. 
At each visit, the percentage of patients who achieve 50%, 75%, and 90% 
improvement in the EASI score from Day 1 and the change in EASI score from 
Day 1 will be calculated. Detailed assessment of additional exploratory efficacy 
endpoints is described in the Statistical Analysis Plan (SAP). 
Safety Assessments 
The safety of BSI-045B will be assessed by the incidence of AEs, anti-BSI-045B
antibody formation, clinical laboratory evaluations, 12-lead ECGs, vital signs, 
and physical examinations, as well as occurrence of conjunctivitis. The 
relationships between study medication and AEs will be evaluated by the 
Investigators. 
Pharmacokinetic 
Assessments 
Serial blood samples (4 mL) for PK assessments will be collected at the 
following time points relative to the SC injection of BSI-045B: within 1 h before 
each dose during the Treatment Period, on each visit during the Follow-up 
Period, and at the time of early withdrawal from the study drug. 
Immunogenicity 
Blood samples (4 mL) will be drawn from patients to determine anti-BSI-045B 
ADA status (negative or positive with titer). Blood samples will be collected at 
the following time points relative to SC injection of BSI-045B: W1D1, W2, W3, 
W4, W8, W12, W16, W20, and W24 within 1 h before dose during the Treatment 
Period, at FU2, FU4, and FU6 during the Follow-up Period, and at the time of 
early withdrawal from the study drug. 
Pharmacodynamic / 
Biomarker 
Assessments 
Blood samples (4 mL) for serum TARC/CCL 17, periostin, and IgE 
concentrations will be collected at W1D1, W2, W3, W4, W8, W12, W16, W20, 
and W24 within 1h before dose during the Treatment Period, at FU2, FU4, and 
FU6 during the Follow-up Period, and at the time of early withdrawal from the 
study drug. 
Enrollment, 
Randomization, and 
Blinding 
The study will not be randomized and will be unblinded. 
Statistical Methods 
Sample size calculations: 
With a minimum sample size of 20 patients, the maximum one-sided 95% 
confidence interval width for the proportion achieving EASI75 equals 21%. 
With a maximum sample size of 24 patients, the maximum one-sided 95% 
confidence interval width for the proportion achieving EASI75 equals 19%. 
Statistical approach: 
Statistical analyses will be descriptive in nature, with frequencies and 
percentages generated for categorical variables and mean, standard deviation, 
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median, minimum, and maximum values generated for continuous variables. 
Exact one-sided 95% confidence intervals will be generated for primary and 
select secondary efficacy endpoints based on proportions. 
Additional details regarding the statistical analyses will be presented in the SAP. 
Sample Handling 
Samples for serum PK, ADA, and biomarker assessments will be collected for 
PK and ADA assessments using Good Laboratory Practice (GLP)-validated 
assays and for PD biomarker assessments using fit-for-purpose qualified assays 
with commercial kits. Refer to the laboratory manual for additional details on 
laboratory assessment and sample processing. 
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3 SCHEDULE OF ACTIVITIES 
The Schedule of Activities is divided into two tables: 
Table 1. Screening and Treatment 
Table 2. Follow-up, End of Study, and Early Withdrawal 
Table 1. Screening and Treatment 
Study Procedure 
Screening
1
Treatment Period 
QW Loading Dose 
W4 
(±3d) 
W6 
(±3d) 
W8 
(±3d) 
W10 
(±3d) 
W12 
(±3d) 
W14 
(±3d) 
W16 
(±3d) 
W18 
(±3d) 
W20 
(±3d) 
W22 
(±3d) 
W24 
(±3d) 
W1 D1 
W1 
D2 
W2 
(±1d) 
W3 
(±1d) 
Predosing2 
Dosing 
and after 
Sign ICF 
X 
Inclusion/exclusion criteria 
X 
X 
Medical history, 
demographics 
X 
Assessment of suicidality 
(PH-2) 
X 
AD medication washout
X 
BSI-045B administration 
X 
X 
X 
X3 
12-lead ECG4
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Clinical labs4,6 
X7 
X 
X 
X 
X 
X 
X 
X 
X 
Blood pregnancy test 
(females of childbearing 
potential only) 
X 
Urine pregnancy testing 
(females of childbearing 
potential only) 
X 
X 
X 
X 
X 
X 
X 
Urine toxicology for drugs of 
abuse (optional)8 
X7 
Virology screen4,8 
X 
Assess for injection site 
reaction 10 
X 
X 
X 
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Study Procedure 
Screening
1
Treatment Period 
QW Loading Dose 
W4 
(±3d) 
W6 
(±3d) 
W8 
(±3d) 
W10 
(±3d) 
W12 
(±3d) 
W14 
(±3d) 
W16 
(±3d) 
W18 
(±3d) 
W20 
(±3d) 
W22 
(±3d) 
W24 
(±3d) 
W1 D1 
W1 
D2 
W2 
(±1d) 
W3 
(±1d) 
Predosing2 
Dosing 
and after 
Efficacy and safety 
assessments and patient diary 
(EASI, IGA, facial IGA, PP-
NRS, assessment of 
conjunctivitis)11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK sample collection4,11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity sample 
collection4,13 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PD Biomarker sample 
collection4,14 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess concomitant 
medications 
X 
Monitor and document AEs 
X 
AD = atopic dermatitis; AE = adverse event; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; CCL-17 = C-C chemokine ligand 17; D = day; EASI = Eczema and Severity Index; ECG = electrocardiography; GGT = gamma glutamyl 
transferase; HbsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; ICF = Informed 
Consent Form; IGA = 
; IgE = immunoglobulin E; IL = interleukin; INR = international normalized ratio; LDH = lactate 
dehydrogenase; PD = pharmacodynamic; PH-2 = Patient Health Questionnaire-2; PK = pharmacokinetic; PP-NRS = Peak Pruritus Numerical Rating Scale; PT 
= prothrombin time; Q2W = every 2 weeks; QW = every week; RBC = red blood cell; SC = subcutaneous; TARC = thymus and activation regulated 
chemokine; W = week; WBC = white blood cell. 
1. Screening duration varies by prior AD treatment and the Investigator should consult Section 7.2 for required washout duration.
For patients not requiring washout, screening assessments should be conducted after ICF been signed and the screening period will take up to 2 weeks;
once they complete their screening assessments and meet all study inclusions/exclusions, the patients will advance directly to W1D1.
For patients requiring washout, screening assessments should be conducted after ICF been signed, if all inclusion/exclusions are met, they will be
notified by the study sites to start the washout for prior AD treatment. Screening assessments should be repeated if they are performed 14 days before
W1D1.
2. W1D1 pre-dosing is set to confirm the eligibility of patients.
3. BSI-045B administration after W4 (4 loading doses) at Q2W interval to Week 24.
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4. Order of assessments: When collecting PK, immunogenicity, biomarker, and clinical laboratory samples, vital signs, and/or ECG assessments are
scheduled to occur at the same time point, ECG and vital signs testing will be performed prior to blood collections. The preferred order of assessments
is: 1) ECG, 2) vital signs, 3) PK, immunogenicity, and biomarker sampling, 4) clinical laboratory sampling.
5. Height and weight, and BSA affected by AD should be determined at the Screening physical examination. BSA affected by AD should also be
determined at W1D1 pre-dosing. Symptom-driven examinations will be performed at other time points beyond screening.
6. Clinical laboratory assessments:
-
Hematology: Hemoglobin, hematocrit, WBC count and differential, RBC count and indices, platelet count
-
Chemistry: Sodium, potassium, chloride, bicarbonate, calcium, phosphorus, magnesium, glucose, BUN, creatinine, uric acid, ALT, AST, GGT,
alkaline phosphatase, total protein, albumin, globulin, total bilirubin, LDH, total cholesterol, triglycerides
-
Coagulation: PT, aPTT, fibrinogen, INR
-
Urinalysis: Protein, glucose, ketones, occult blood, urobilinogen, urine sediment microscopy (if other parameters abnormal)
7. For patients requiring washout, clinical laboratory assessments and urine toxicology test should be repeated to make sure the tests are conducted
within 14 days prior to W1D1.
8. Urine toxicology: Urine toxicology testing is optional. If the PI has no concerns about the use of illicit drugs by a patient, testing for drugs of abuse is
not required. If the PI has concerns, a negative urine/blood result for drugs of abuse is required at Screening. Screening assessment on urine toxicology
9. Virology screening: HbsAg, anti-HCV, HIV.
10. All patients should be monitored in the study sites for at least 30 mins after each dose to observe body reactions, including injection site reactions.
Any injection site reactions observed after each site visit should be reported to the Investigators by the patients.
11. Efficacy assessments: EASI, IGA, facial IGA and PP-NRS. For PP-NRS: Patients will complete the PP-NRS daily in a patient diary beginning on
Day -8, throughout the last study visit, and at the time of early withdrawal from the study, and scores for each timepoint will be the average of scores
over the past 7 days. In order to calculate an average for the score, the patient must have completed the diary for a minimum of 4 days during the
previous 7 days. Investigator should also assess Facial IGA. For the assessment of conjunctivitis, diagnosis history with severity will be recorded at
screening, and at every visit during the treatment period, all patients will be asked if they had been diagnosed as conjunctivitis since last visit.
Conjunctivitis severity grade includes:  0 = no conjunctivitis; 1 = mild conjunctivitis; 2 = moderate conjunctivitis requiring treatment; 3 = severe
conjunctivitis that may require an ophthalmic exam. 
12. PK blood sample collection: Within 1 h before each dose during the Treatment Period.
13. Immunogenicity blood sampling: Blood samples are to be collected at W1D1, W2, W3, W4, W8, W12, W16, W20, and W24 within 1 h before each
dose during the Treatment Period.
14. Biomarker blood sample collection: Assessments are TARC/CCL-17, periostin, and IgE. Samples are to be obtained at W1D1, W2, W3, W4, W8,
W12, W16, W20, and W24 within 1 h before each dose during the Treatment Period.
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Table 2. Follow-up, End of Study, and Early Withdrawal 
Study Procedure 
Follow-up Period 
Early 
Withdrawal1 
FU1  
(2 weeks after 
last dose±3d) 
 FU2 
 (4 weeks after 
last dose±3d) 
 FU3 
(6 weeks after 
last dose±3d) 
FU4 
 (8 weeks after 
last dose±3d) 
 FU5  
(10 weeks after 
last dose±3d) 
 FU6 
 (12 weeks after 
last dose±3d) 
(+7d) 
12-lead ECG2
X 
X 
Vital signs2 
X 
X 
X 
X 
X 
X 
X 
Physical examination (system 
driven) 
X 
X 
X 
X 
Clinical labs2,3 
X 
X 
X 
X 
Blood pregnancy test (females of 
childbearing potential only) 
X 
Urine pregnancy testing (females 
of childbearing potential only) 
X 
X 
X 
Efficacy assessments and patient 
diary (EASI, IGA, facial IGA, PP-
NRS)4 
X 
X 
X 
X 
X 
X 
X 
PK sample collection2,5 
X 
X 
X 
X 
X 
X 
X 
Immunogenicity sample 
collection2,6 
X 
X 
X 
X 
PD Biomarker sample collection2,7 
X 
X 
X 
X 
Assess concomitant medications 
X 
Monitor and document AEs 
X 
AE = adverse event; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate aminotransferase; CCL-17 = 
C-C chemokine ligand 17; EASI = Eczema and Severity Index; ECG = electrocardiography; GGT = gamma glutamyl transferase; 
Assessment; IgE = immunoglobulin E; IL = interleukin; INR = international normalized ratio; LDH = lactate dehydrogenase; PD = pharmacodynamic; PK = 
pharmacokinetic; PP-NRS = Peak Pruritus Numerical Rating Scale; PT = prothrombin time; RBC = red blood cell; TARC = thymus and activation regulated 
chemokine; W = week; WBC = white blood cell 
1.
Early withdrawal: Early withdrawal assessments must be completed within 7 days after the last treatment with BSI-045B or within 7 days after the
discontinue study treatment, whichever occurs first. When medically feasible, the Medical Monitor should be consulted prior
to study drug discontinuation.
2.
Order of assessments: When collecting PK, immunogenicity, biomarker, and clinical laboratory samples, vital signs, and/or ECG assessments are
scheduled to occur at the same time point, ECG and vital signs testing will be performed prior to blood collections. The preferred order of
assessments is: 1) ECG, 2) vital signs, 3) PK, immunogenicity, and PD/biomarker sampling, 4) clinical laboratory sampling.
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3.
Clinical laboratory assessments:
-
Hematology: Hemoglobin, hematocrit, WBC count and differential, RBC count and indices, platelet count
-
Chemistry: Sodium, potassium, chloride, bicarbonate, calcium, phosphorus, magnesium, glucose, BUN, creatinine, uric acid, ALT, AST, GGT,
alkaline phosphatase, total protein, albumin, globulin, total bilirubin, LDH, total cholesterol, triglycerides, CK, CK isoenzymes
-
Coagulation: PT, aPTT, fibrinogen, INR
-
Urinalysis: Protein, glucose, ketones, occult blood, urobilinogen, urine sediment microscopy (if other parameters abnormal)
4.
Efficacy assessments: EASI, IGA, facial IGA, and PP-NRS. Patients will complete the PP-NRS daily throughout the last study visit, and at the
time of early withdrawal from the study, and scores for each timepoint will be the average of scores over the past 7 days. In order to calculate an
average for the score, the patient must have completed the diary for a minimum of 4 days during the previous 7 days. Investigator should also
assess Facial IGA.
5.
PK blood sample collection: At each visit during the Follow-up Period, and at the time of early withdrawal from the study drug.
6.
Immunogenicity blood sampling: Blood samples are to be collected at FU2, FU4, and FU6 during the Follow-up Period, and at the time of early
withdrawal from the study drug.
7.
Biomarker blood sample collection: Assessments are TARC/CCL-17, periostin, and IgE. Samples are to be obtained at FU2, FU4, and FU6 during
the Follow-up Period, and at the time of early withdrawal from the study drug.
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4 LIST OF ABBREVIATION 
Abbreviation 
Definition 
AD 
atopic dermatitis 
ADA 
antidrug antibody 
ADL 
activity of daily living 
AE
adverse event
ALT 
alanine aminotransferase 
AMIT 
Acumen Medical Information & Technology Co., Ltd. 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
AUC0-7 
area under the serum drug concentration-time curve from time 0 to 7 days 
AUCinf 
area under the serum drug concentration-time curve from last dose extrapolated to 
infinity 
AUClast 
area under the serum drug concentration-time curve from last dose to the last quantifiable 
drug concentration 
 
area under the serum drug concentration-time curve 
BMI 
body mass index 
BSA 
body surface area 
CCL-17
C-C chemokine ligand 17
CI 
confidence interval 
Cave 
average serum drug concentration 
Cmin 
minimum observed serum drug concentration  
Cmax 
maximum observed serum drug concentration 
CRF 
Case Report Form 
CRO 
contract research organization 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTTQ 
ChiaTai Tianqing Pharmaceutical Group Co., Ltd 
D 
day 
EASI 
Eczema Area and Severity Index 
ECG
electrocardiography
EOS 
end of study 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
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GFR 
glomerular filtration rate 
GGT 
gamma glutamyl transferase 
GLP 
Good Laboratory Practices 
HbsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HED 
human equivalent dose 
Hgb 
hemoglobin 
HIV
human immunodeficiency virus
HV 
healthy volunteer 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals 
for Human Use 
IGA 
 
IgE
immunoglobulin E
IL
interleukin
INR 
international normalized ratio 
IP 
investigational product 
IRB 
Institutional Review Board 
IV 
intravenous 
LDH 
lactate dehydrogenase 
mAb 
monoclonal antibody 
MAD 
multiple ascending dose 
NOAEL 
no observed adverse effect level 
NRS 
Numerical Rating Scale 
PCR 
polymerase chain reaction 
PD 
pharmacodynamic 
PH-2 
Patient Health Questionnaire-2 
PI 
Principal Investigator 
PK 
pharmacokinetic 
PP-NRS 
Peak Pruritus Numerical Rating Scale 
PT 
prothrombin time 
Q2W 
every other week 
Q7D 
every 7 days (weekly) 
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QTcF 
corrected QT interval, Fridericia 
QW 
every week 
Rauc 
ratio of 
 at last dose / AUC0-7 
RBC
red blood cell
RCmax 
ratio of Cmax at last dose / Cmax 
SAD 
single ascending dose 
SAE
serious adverse event
SAP 
Statistical Analysis Plan 
SC
subcutaneous
SD 
standard deviation 
SOC 
system organ class 
SSC 
Safety Steering Committee 
SUSAR 
suspected unexpected serious adverse reaction 
t½
apparent terminal elimination half-life
TARC 
thymus and activation regulated chemokine 
TCS 
topical corticosteroids 
TEAE 
treatment-emergent adverse event 
Th2 
helper T cell 2 
Tmax
time to maximum serum drug concentration
TRPA1 
transient receptor potential ankyrin 1 
Tss,max 
time to maximum serum drug concentration at steady state 
TSLP
thymic stromal lymphopoietin
TSLPR 
thymic stromal lymphopoietin receptor 
ULN 
upper limit of normal 
W 
week 
WBC
white blood cell
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5 INTRODUCTION AND BACKGROUND 
5.1 Disease Overview 
Atopic dermatitis (AD) is a chronic inflammatory pruritic skin disease and is the most 
common type of eczema, affecting more than 9.6 million children and about 16.5 million 
adults in the United States. Worldwide prevalence ranges from 0.2% to 24.6%, with the 
highest rates of AD seen in children in Africa and Latin America (Odhiambo et al, 2009). 
Atopic dermatitis is a chronic relapsing and remitting condition that may overlap with other 
types of eczema and may progress through a process called atopic march to food allergies, 
asthma (up to 70%), and rhinitis (He and Geha, 2010; Locksley et al, 2010). Thymic stromal 
lymphopoietin (TSLP) plays a key role in the triad of atopic diseases: asthma, allergic 
rhinitis, and AD (Ziegler et al, 2013). 
5.2 Development of BSI-045B 
5.2.1 Mechanism of Action 
BSI-045B (the investigational product [IP]) is a humanized IgG1 subtype mAb that targets 
TSLP. It is being co-developed by ChiaTai Tianqing Pharmaceutical Group Co., Ltd (CTTQ) 
and Biosion, Inc., China. 
TSLP protein is one of the key molecules that mediate allergic reactions. The TSLP protein 
belongs to the interleukin-2 (IL-2) cytokine family, which has actions similar to IL-7. TSLP 
is mainly derived from the barrier surface of epithelial cells in skin, intestine, and lung 
tissues, and responds to danger signals by regulating type 2 inflammatory responses at 
mucosal barriers in allergic inflammation (Han et al, 2020). The protein acts on a variety of 
immune cells (eg, dendritic cells) by forming complexes with the TSLP receptor (TSLPR) 
and IL-7 receptor on the cell surface to drive downstream helper T cell 2 (Th2) cytokine 
release. It also activates cells involved in non-Th2-driven inflammation and promotes the 
expression of inflammatory cytokines such as IL-4, IL-5, and IL-13. Abnormally high TSLP 
protein expression is related to a variety of atopic diseases including asthma, AD, allergic 
rhinitis, eosinophilic esophagitis, cancer, arthritis, intestinal parasites, and other diseases 
(Nakajima et al, 2020). 
BSI-045B specifically binds to human TSLP, blocking its interaction with the receptor 
complex and interrupting signal transduction, thereby preventing immune cells targeted by 
TSLP from releasing proinflammatory cytokines. BSI-045B has good in vitro binding 
affinity to HuTSLP (KD(mol/L) <1.08E-12) and to cynoTSLP (KD (mol/L) <7.14E-13), and has 
a higher affinity than tezepelumab (KD(mol/L) =6±2E-11) (Verstraete et al, 2017). In vivo 
efficacy of BSI-045B showed a significant dose-dependent therapeutic effect in a 
cynomolgus asthma model. Other studies determined that BSI-045B can significantly reduce 
the level of eosinophils in alveolar lavage fluid, reducing lung resistance and improving lung 
compliance. The effectiveness of BSI-045B in this model appeared equivalent to the 
reference drug tezepelumab at the same dose (BSI-
). 
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5.2.2 Preclinical Findings 
In preclinical studies, BSI-045B exhibited good absorption characteristics after subcutaneous 
(SC) injection and exposure was proportional to the increase in dose. There was no 
difference between sexes in drug exposure (BSI-
). 
5.2.3 Phase 1 Study (BSI-045B-001) 
A Phase 1 study is being conducted by the Sponsor to evaluate the safety, tolerability, 
immunogenicity, pharmacokinetic (PK) profile, and activity of BSI-045B injection after 
single and multiple doses in adult healthy volunteers (HVs) and patients with AD. 
5.2.3.1 Study Design 
The Phase 1 study employs a randomized, double-blind, placebo-controlled design. The study 
consists of 3 parts: a single -ascending dose (SAD) study in HVs, a single-dose study in patients 
with AD, and a multiple -ascending dose study (MAD) study in HVs. The study is ongoing, 
and an interim analysis was conducted to analyze the safety and PK data. In this interim 
analysis, all subjects enrolled in Part A (SAD) and in the lowest dose level cohort (5 doses, 
240 mg weekly [Q7D]) in Part C (MAD) had completed the study and data was analyzed up 
to end of study (EOS). Subjects enrolled in the second dose level cohort (3 doses, 480 mg Q7D) 
in Part C (MAD) had completed the study up to Day 84 (final dose administered on Day 15, 
EOS Day 104) and data was analyzed up to Day 84. Serum BSI-045B concentrations versus 
time data are available up to Day 56. All subjects enrolled in Part B (patients with AD) had 
completed the study up to Day 43 (single dose administered on Day 1, EOS Day 113) and data 
was analyzed up Day 43. Serum BSI-045B concentrations versus time data are available up to 
Day 15. 
All study objectives and endpoints shown in Table 3 are as stated in the BSI-045B-001 study 
protocol version 4.0, dated 20 September 2022. 
Table 3. Objectives and Endpoints, Phase 1 Study (BSI-045B-001) 
Objectives 
Endpoints 
Primary 
To evaluate the safety and tolerability 
of BSI-045B 
AEs, clinical laboratory assessments, vital signs, 
ECGs, physical examinations 
Secondary 
To evaluate the pharmacokinetics (PK) 
of BSI-045B 
Primary: Cmax, Tmax, t1/2, AUCinf, AUClast 
(Other PK parameters may also be included) 
To evaluate the activity of BSI-045B 
in patients with moderate to severe AD 
over one dosing interval
50% and 75% improvement from Day 1 in EASI 
scores 
Pruritus NRS (daily) 
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To evaluate the immunogenicity of 
BSI-045B 
ADA at Day 1 and post BSI-045B treatment 
To collect serum samples for possible 
future evaluation of PD biomarkers of 
BSI-045B target engagement 
IL-4, IL-5, IL-13, IL-17, TARC/CCL-17, 
periostin, and IgE at Day 1 prior and post 
BSI- 045B treatment to be evaluated in patients 
with AD 
ABBREVIATIONS: AD = atopic dermatitis; ADA = antidrug antibodies; AE = adverse event; AUCinf = area 
under the serum drug concentration-time curve from last dose extrapolated to infinity; AUClast = area under 
the serum drug concentration-time curve from time last dose to the last quantifiable drug concentration; CCL-
17 = C-C chemokine ligand 17; Cmax = maximum observed serum drug concentration; EASI = Eczema Area 
and Severity Index; ECG = electrocardiography; IgE = immunoglobulin E; IL = interleukin; NRS = Numerical 
Rating Scale; PD = pharmacodynamic; PK = pharmacokinetic; t1/2 = apparent terminal elimination half-life; 
TARC = thymus and activation regulated chemokine; Tmax = time to maximum serum drug concentration 
In detail the 3 parts of the study are: 
Part A SAD cohorts: To evaluate the safety, tolerability, PK, and immunogenicity of 
single ascending doses of BSI-045B administered as an SC injection of 120, 240, 480, 
and 720 mg to HVs. Eight (8) (6 Active:2 Placebo) subjects were enrolled in each 
dose level cohort (total 32 subjects) as outlined in Table 4. 
Part B single dose cohort: To evaluate the safety, tolerability, PK, activity (as 
measured by the Eczema Area and Severity Index [EASI] score), and 
immunogenicity of a single dose of BSI-045B administered as a SC injection of 480 
mg to patients with AD. A total of 12 subjects (9 Active:3 Placebo) were planned to 
be enrolled in the cohort as outlined in Table 4. However, due to difficulties in 
identifying and enrolling AD patients into Part B, a total of 5 AD patients (4 Active: 1 
Placebo) are participating in this ongoing study. 
Part C MAD cohorts: To evaluate the safety, tolerability, PK, and immunogenicity of 
multiple ascending doses of BSI-045B administered as SC injections Q7D to HVs for 
5 cycles at the 240 mg dose level and for 3 cycles at the 480 mg dose level. Eight (8) 
(6 Active:2 Placebo) subjects were planned for each dose level cohort. Due to one 
withdrawal in the 240 mg Q7D cohort, an additional subject was enrolled and treated 
with BSI-045B. A total of 17 subjects were enrolled (240 mg Q7D cohort: [7 BSI-
045B:2 Placebo]; 480 mg Q7D cohort: [6 BSI-045B:2 Placebo]) as outlined in Table 
4. 
In total, 55 subjects (49 HVs, 5 patients with AD, and 1 withdrawal) were enrolled at the 
time of the interim analysis. 
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Table 4. Treatments Administered per Cohort in Study BSI-045B-001 
Cohort 
Number
Dose 
Level 
(mg) 
Total 
Number 
of Doses
# SC injections 
Volume 
administered 
(mL) 
Number of Participants 
BSI-
045B 
Placebo 
Randomized 
to BSI-045B
Randomized 
to Placebo 
Total 
Part A  SAD, HVs 
1 
120 
1 
1 
1 
1 
6 
2 
8 
2 
240 
1 
1 
1 
2 
6 
2 
8 
3 
480 
1 
2 
2 
4 
6 
2 
8 
4 
720 
1 
3 
3 
6 
6 
2 
8 
Part B  Single dose, patients with AD 
1 
480 
1 
2 
2 
4 
4 
1 
5 
Part C  MAD, HVs 
1 
240 Q7D
5 
1 
1 
2 
71 
2 
91 
2 
480 Q7D
3 
2 
2 
4 
6 
2 
8 
1.
One subject in Cohort C1 withdrew from the study after the first dose and was replaced.
AD = atopic dermatitis; HV = healthy volunteer; MAD = multiple ascending dose; Q7D = every 7 days; SAD 
= single ascending dose; SC = subcutaneous. 
Part C of the study was originally planned to consist of 3 MAD cohorts: 240 mg, 480 mg, 
and 600 mg. In each cohort, subjects were to receive a total of 5 doses, administered once 
Q7D. Following a Safety Review Committee meeting conducted on 30 August 2022, during 
which the committee reviewed safety, tolerability, and PK data from the Part A cohorts and 
Part C first MAD cohort, a decision was made to reduce the dosing schedule for the second 
MAD cohort (480 mg dose level) from 5 cycles to 3 cycles and not conduct the third cohort 
(600 mg Q7D). The basis for this decision was the apparent accumulation of BSI-045B based 
on the mean maximum observed serum drug concentration (Cmax). The mean Cmax 
determined in the MAD Cohort 1 (240-mg dose level after 5 weekly SC injections) slightly 
exceeded the mean Cmax determined from the 720-mg dose level in SAD Cohort 4. 
5.2.3.2 Safety of BSI-045B 
Per the interim report for this Phase 1 study, there were no serious treatment-emergent 
adverse events (TEAEs), TEAEs leading to death or any deaths in any part of the study. 
There was one (1; 12.5% of group) severe TEAE (transaminases increased), reported by a 
subject in the 240-mg dose level cohort in Part A. One (1; 11.1% of group) subject (Part 
C; 240-mg Q7D cohort) who experienced increased aspartate aminotransferase (AST) and 
increased alanine aminotransferase (ALT) withdrew from the study. 
Among HVs in the study, TEAEs were similarly frequent across all single and multiple dose 
levels, with most or all subjects in each cohort in Part A (SAD) and Part C (MAD) reporting 
at least one TEAE. In Part A, the frequency of study drug related TEAEs increased with dose 
level, indicating a potential relationship. In Part C, there was no increase in the frequency of 
study drug related TEAEs increasing with dose level. 
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Treatment-emergent AEs in system organ class (SOC) General Disorders and Administration 
Site Conditions, most or all of which were injection site reactions, were the most common 
TEAEs by SOC. 
In the single-dose cohort (480 mg) in AD patients, no TEAE by Preferred Term was reported 
by greater than 1 (20.0%) of subjects. The frequency of TEAEs (2 [40.0%]) in the single 
dose- (480 mg) cohort in patients with AD was lower than the frequency of TEAEs 
(7 [87.5%]) in the 480 mg single-dose cohort in HVs. 
No deaths or other serious adverse events (SAEs) were reported in the study. 
5.2.3.3 Pharmacokinetics of BSI-045B 
In addition to the safety and tolerability assessment, a PK interim evaluation included results 
from the SAD, MAD, and antidrug antibody (ADA) cohorts. Due to ongoing PK sample 
analysis, limited results are available from the AD patient cohort. In general, the PK results 
show BSI-045B is well behaved over the dose range used in this study for the SAD, MAD 
and AD patient cohorts. 
For the SAD cohort, mean semilogarithmic plots of serum BSI-045B concentration (ng/mL) 
versus time (days) profiles for 6 subjects at 4 dose levels showed a typical absorption pattern 
for an IgG monoclonal antibody. BSI-045B has a mono-exponential decline and an apparent 
linear disposition following a 120, 240, 480, and 720 mg SC single injection. In general, the 
variability was typical of an IgG monoclonal antibody and given the low number of subjects. 
A box plot analysis clearly determined dose proportionality and a linear disposition for both 
Cmax and the area under the serum drug concentration-time curve from last dose extrapolated 
to infinity (AUCinf) over the dose range. Cmax values from the lowest single dose (120 mg) to 
the highest single dose (720 mg) ranged from 10.2 to 53.8 µg/mL, respectively. Time to 
maximum serum drug concentration (Tmax) values ranged from 128 to 164 hours. The mean 
AUCinf values increased in a dose -proportional manner between the 120 mg and the 720 mg 
dose and mean values ranged from a low of 362.8 to 2066 day*µg/mL. The mean apparent 
terminal elimination half-life (t½) values were consistent and varied between 24.3 and 29.5 
days, which is a typical half-life for an IgG monoclonal antibody. 
In the MAD cohort, the mean semilogarithmic plots of serum BSI-045B concentrations 
(ng/mL) versus time (days) profiles were constructed for subjects receiving active drug 
(N=6) following the 240 mg SC dose Q7D for 5 doses and the 480 mg SC doses Q7D for 3 
doses. The mean profile for the 240 mg multiple doses showed a typical PK profile for an 
IgG monoclonal antibody administered Q7D for 5 doses, with the mean trough serum BSI-
045B concentrations continuing to rise over the dosing period in the expected manner. 
Steady-state conditions were not attained since only 5 doses were administered. Following 
peak drug concentrations, BSI-045B followed a mono-exponential decline over time. For the 
480 mg SC dose, Q7D dosing for 3 doses showed a similar and a typical rise in serum BSI-
045B concentration versus time profile. Following the third dose and after attainment of 
Cmax, there was an apparent mono-exponential decline. 
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5.2.3.3.1 Part C1: 240 mg Q7D SC Dose 
Nine subjects completed Cohort C1: first dose and 7 subjects had serum drug concentration 
vs time data that were used for PK analysis. Following the first dose of 240 mg, the mean 
Cmax value was 17.6 µg/mL which was close to the Cmax mean value (19.9 µg/mL) 
determined in the SAD cohort at the same SC dose level.  The Tmax mean value was 147 
hours which compares favorably with the mean value of 164 hours determined in the SAD 
cohort. The mean area under the serum drug concentration-time curve (AUC ) value was 
93.5 day*µg/mL.
Following Q7D dosing for 5 consecutive doses in 6 subjects, the mean Cmax was 76 µg/mL 
and occurred at 776 hours. The mean Cmax value was close to the expected mean value of 
88 µg/mL (mean Cmax from first dose * 5 doses), confirming a linear disposition of BSI-045. 
The mean Cmin value was 54.9 µg/mL and the mean average serum drug concentration (Cave) 
was 65.6 µg/mL. The mean AUC  value was 458.9 day*µg/mL and was very close to the 
expected mean value of 468 day*µg/ml (mean AUC  from first dose * 5 doses), again 
confirming a linear disposition of BSI-045. The mean AUClast was 2455 day*µg/mL. The 
mean t1/2 was 23.8 days and is similar to the half-lives determined in the SAD cohort. The 
mean value for RCmax (Cmax of fifth dose/Cmax) was 5.1 and the mean value for Rauc (AUC  of 
fifth dose/AUC0-7) was 6.1. The RCmax and Rauc would be expected to be 5.  The mean values 
from the two parameters further support the linear disposition of BSI-045B. 
5.2.3.3.2 Part C2: 480 mg Q7D SC Dose 
Eight subjects completed Cohort C2: first dose and 6 subjects had serum drug concentration 
vs time data used for PK analysis. Following the first dose of 480 mg, the mean Cmax value 
was 37.5 µg/mL which was very close to the Cmax mean value (42.0 µg/mL) determined in 
the SAD cohort at the same dose level. The mean Tmax value was 124 hours which compares 
favorably with the mean value of 128 hours determined in the SAD cohort. The mean AUCtau 
value was 214.3 day*µg/mL. 
Mean (± standard deviation [SD]) PK parameters were determined following Q7D dosing for 
3 consecutive doses in 6 subjects. The mean Cmax was 98.6 µg/mL and occurred at 432 hours 
(Tmax). The mean Cmax value was slightly below the expected mean value of 112.5 µg/mL 
(mean Cmax from first dose * 3 doses), but still supports the linear disposition of BSI-045. 
The mean minimum observed serum drug concentration (Cmin) value was 65.2 µg/mL and the 
mean Cave (AUC / ) concentration was 89.2 µg/mL. The mean AUC  value was 624.2 
day*µg/mL which was very close to the expected mean value of 643 day*µg/mL (mean 
AUC  from first dose * 3 doses), again confirming a linear disposition of BSI-045. The mean 
AUClast was 2454 day*µg/mL. The mean t1/2 was 22.1 days and is similar to the half-life 
determined in the SAD and MAD C1cohorts. The mean value for RCmax (Cmax of the third 
dose/Cmax) is 2.7 and the mean value for Rauc (AUC  of third dose / AUC 0-7) is 3.1. The 
RCmax and Rauc would be expected to be 3.  The mean values further support the linear 
disposition of BSI-045B. 
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5.2.3.3.3 Part B: 480 mg SC Dose 
Five AD patients are enrolled in the ongoing Part B of the study. Four of the 5 patients had 
serum drug concentration vs time data up to Day 15. Patients received a single SC dose of 
480 mg of BSI-045B. Cmax and Tmax were determined over this time period. The mean Cmax 
of BSI-045B from 4 patients was 41.0 µg/mL and was nearly identical to the mean Cmax 
value of 42.0 µg/mL determined in the SAD cohort and is close to the mean Cmax value of 
37.5 µg/mL determined in the 480 mg first dose in the MAD cohort. The Tmax mean value 
was 108 hours, shorter than the mean half-life of 128 hours and 124 hours reported in healthy 
volunteers following a 480 mg dose in the SAD cohort and following the first 480 mg SC 
dose in the MAD cohort. 
5.2.3.4 Anti-drug Antibodies 
The presence of ADAs in patients with AD enrolled in Part B have not been evaluated at the 
present time. In Part A (SAD), ADA was detected in 1 subject at the 120 mg, 240 mg and 
720 mg dose levels. There were no occurrences of ADA at the 480 mg dose. In total, 3 
subjects out of 24 subjects in Part A had ADA present and in 2 out of 3 occurrences, ADA 
appeared late in the study. In Part C, 2 out of 6 subjects developed ADA at the last scheduled 
PK sampling on Day 124 following administration of 5 doses of 240- mg Q7D. Following 
administration of 480 mg SC Q7D for 3 doses, no ADA was detected over the 124-day study 
period. The results suggest a low incidence of ADA following single and multiple dosing. 
In general, the PK analysis has shown BSI-045B is well behaved following single and 
multiple doses in subjects. While there were minor apparent differences among various 
cohorts in their PK parameters, given the sample sizes and individual variances, the 
assessment of dose proportionality clearly showed a linear disposition of BSI-045B over the 
dose range from 120 mg to 720 mg in the SAD cohort and dose proportionality was also 
confirmed in the MAD cohort. A single SC dose of 480 mg in the SAD and AD patient 
cohorts exhibited nearly identical mean Cmax values. In general, the t1/2 is approximately 25 
days for subjects in the SAD and MAD cohorts. Results from the ADA assessment show a 
low incidence of ADA in both the SAD and MAD cohorts. The consistent and reliable PK 
profiles of BSI-045B observed in the SAD and MAD cohorts has provided a basis for 
designing a dose regimen in the proposed proof-of-concept Phase 2 study. 
5.2.4 Design of Phase 2 Studies 
This IND-enabling Phase 2a study is specifically designed to be a small, simpler study to 
give the Sponsor early insights into the activity of this molecule in a patient population after 
multiple dosing. This study is not intended to take the place of or to be a definitive Phase 2b 
study. A definitive Phase 2b study, using multiple doses and dosing regimens, will be 
conducted after we have more information about the product s effects in the AD patient 
population from the Phase 2a study. Prior to proceeding to Phase 3, the Sponsor will conduct 
both this Phase 2a study as well as a Phase 2b study. 
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5.3 Product Name 
Generic name: BSI-045B 
Molecular formula: C6470H9968N1708O2020S46 (no post-translational modifications) 
Molecular weight: 145,183 Da (N-terminal cyclization of heavy chain, excision of 
C-terminal lysine of heavy chain, aglycosylated)
Active ingredient: BSI-045B protein 
Dosage form: Injection, 300 mg/vial (2.5-mL/vial, 120 mg/mL) 
Excipients: histidine, acetic acid, proline, polysorbate 80 (for injection), water for injection 
Note: The product pH is 5.8 ± 0.5. 
5.4 Study Rationale 
AD is a common inflammatory skin disorder characterized by recurrent eczematous lesions 
and intense itch. It is a major non-communicable disease that affects both children and adults 
and is the leading cause of the global burden from skin disease (Langan et al, 2020). It is 
estimated that 1 in 10 individuals will develop eczema during their lifetime. Eczema impacts 
people of all skin colors, races, and ethnicities (range 10 to 13%) (National Eczema 
Association). 
AD involves a complex interplay of inflammatory pathways with multiple cytokines and 
inflammatory and epithelial cells implicated, with AD lesions always associated with 
underlying immune activation. Alarmins, which include TSLP, are endogenous, 
constitutively expressed chemotactic and immune activating peptides that are released 
following degranulation, cell injury or upon immune induction (Yang et al, 2017). TSLP is 
an IL-7-like cytokine expressed by epithelial cells and keratinocytes, and a key instigator of 
the immune response to environmental insults, initiating a range of downstream 
inflammatory pathways (Gauvreau et al, 2020). A common symptom of pruritis observed in 
AD can be attributed to TSLP signalling indirectly via the aforementioned inflammatory 
cascade but also via direct activation by TSLP of a specific subset of sensory neurons 
expressing TSLPR and the ion-channel transient receptor potential ankyrin 1 (TRPA1), 
further validating the targeting of TSLP in AD therapies (Wilson et al 2013). BSI-045B is 
designed to inhibit TSLP binding to the TSLP receptor, thereby inhibiting the inflammatory 
cascade and direct activation by TSLP of a specific subset of sensory neurons expressing 
TSLPR and the ion-channel TRPA1 associated with atopic dermatitis. 
Anti-TSLP therapy has been clinically validated and is an effective treatment for allergic 
inflammatory diseases such as severe asthma (Menzies-Gow et al, 2021) and has shown 
clinical activity in patients with moderate to severe atopic dermatitis (Parnes et al, 2019). In 
vitro studies with BSI-045B demonstrated that the IP inhibits the TSLP pathway and 
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production of downstream cytokines. BSI-045B is an anti-TSLP mAb being investigated to 
treat moderate to severe AD. 
In animal models, BSI-045B reduced levels of inflammatory factors and eosinophil 
production in a dose-dependent manner. In preclinical studies, BSI-045B was safe and well 
tolerated, and no treatment-related abnormal changes were observed during administration 
and recovery. BSI-045B is not associated with irritation at the injection site and has a low 
incidence of immunogenicity. 
This study is a Phase 2a, multicenter, proof-of-concept clinical trial to evaluate efficacy and 
safety of BSI-045B mAb injection in patients with moderate to severe atopic dermatitis. The 
study will also evaluate the tolerability, PK, immunogenicity, and PD/biomarker of BSI-
045B following SC injections. The findings from this proof-of-concept study will be used to 
design a follow-on Phase 2b study. 
5.5 Proposed Strengths and Dose Justification 
Good Laboratory Practice (GLP) toxicity studies conducted with BSI-045B in cynomolgus 
monkeys showed that the IP is well tolerated 
 (more than 16-fold the human 
equivalent dose for the maximum single dose (720 mg) administered in the Phase 1 clinical 
study) when administered as a single dose by SC injection. Further evaluation of the toxicity 
of BSI-045B was performed through a GLP repeat dose study (TQC-TOX-01) in which 5 
doses of BSI-045B were administered SC to cynomolgus monkeys with a 1-week interval 
between administrations, followed by a 4-week recovery period. Doses of 30, 100 and 300 
mg/kg were administered, with the high dose administered giving a human equivalent 
dose 19.4-fold higher than the clinical dose (300
) to be administered in the Phase 2a 
clinical trial. As in the single-dose study, no relevant toxicity findings were observed that 
were attributable to BSI-045B and the no observed adverse effect level (NOAEL) was 
considered to be 300 mg/kg for repeat dose administration up to 5 cycles. No significant 
toxicity findings were observed following weekly SC administration of BSI-045B to 
cynomolgus monkeys at 15, 50, and 150 mg/kg for 26 consecutive weeks. The NOAEL of 
BSI-045B was considered to be 150 mg/kg over 26 consecutive weeks, with an HED of 
2,903 mg for a 60-kg subject, resulting in a safety margin of 9.7-fold above the clinical dose 
(300 mg) to be administered in the Phase 2a clinical study. 
Local tolerance assessment revealed no BSI-045B related abnormalities on clinical or 
microscopic evaluation of the injection site, and immunotoxicity evaluation revealed no 
noteworthy findings. 
No sex-related effect in the toxicity of BSI-045B after SC administration was evident in the 
nonclinical studies performed in monkeys (BSI-
). Nonclinical 
pharmacology studies have demonstrated BSI-
manner, to human TSLP in vitro. BSI-045B was also shown to inhibit the ability of TSLP to 
bind to its target receptor in an in vitro cell based model, using TSLPR expressing HEK293 
cells. (BSI-
). Like BSI-045B, tezepelumab is a monoclonal 
antibody that specifically binds to human TSLP and acts on the same target as BSI-045B. 
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up to 600 mg/kg 
mg 
045B Investigator's Brochure 
045B' s efficacy in binding, in a highly specific 
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Parnes et al (2019) reported results from a Phase 1 study in which tezepelumab was 
administered as a single SC dose (2.1, 7, 21, 70, 210, or 420 mg) or an intravenous (IV) dose 
(210 or 700 mg) to healthy subjects and following SC injections in multiple dose regimens of 
35, 105, 210 mg or IV injections of 700 mg over a 3-month period. Parnes also reported 
results from a single IV injection of 700 mg in AD patients. In addition, Parnes and 
Sakamoto et al (2020) conducted independent phase 1 PK studies and determined that 
tezepelumab followed a linear disposition over various SC dosing levels and dosing intervals 
(including Q7D) up to 3 months. 
Parnes et al (2019) reported mean PK parameter values for Cmax and AUC over the dosing 
interval following an IV dose of 700 mg of tezepelumab administered Q28D over 3 months. 
The reported Cmax was 370 µg/mL and the AUC was 4050 day*µg/mL. Following a single 
highest SC dose of 420 mg, the mean Cmax was 58 µg/mL and AUCinf was 2140 day*µg/mL 
or 51360 h*µg/mL Parnes also reported no differences between HVs and AD patients in 
mean values of various PK parameters. Zheng et al (2021) reported that although PK 
parameter values were slightly lower following SC injection into the arm, and there were no 
clinically significant differences between arm, abdomen, and thigh injections following an 
SC vial and syringe injection of 210 mg tezepelumab. 
Simpson et al (2018) reported results from a Phase 2a, randomized, double-blind, placebo-
controlled study at 26 centers in Australia, Canada, Germany, Hungary, New Zealand, and 
the United States. The 12-week study evaluated the efficacy and safety of tezepelumab in 
patients with moderate to severe AD who were treated with continuous concomitant class 3 
topical corticosteroids (TCS). The effects of tezepelumab in patient-reported outcomes and 
impact of serum biomarkers on treatment responses were also reported. Following SC 
injections of 280 mg of tezepelumab every 2 weeks plus TCS, patients with moderate to 
severe AD achieved numerical improvements over placebo in the percent achieving 50% 
improvement on the EASI at week 12; however, these improvements were not statistically 
significant. In a safety analysis of the as-treated population (N=111), TEAEs were mild or 
moderate in severity (grade 1-2) and no deaths were reported. The most frequent TEAE that 
was considered by the investigators to be possibly treatment related was injection site 
erythema, which was reported in 3 (5.4%) of patients receiving tezepelumab and none in the 
placebo group. Numerical improvements were seen across several clinical and patient-
reported endpoints, and greater efficacy in biomarker-defined subgroups suggested potential 
benefits in TSLP blockade. Simpson et al (2018) postulated that limitations of their study 
may have been confounded by the patient population selected (only 10% of patients had 
severe disease); patients were not required to be refractory to TCS at baseline, patients 
applied high-strength TCS during the 2-week run-in period, and the dose selected may not 
have provided a complete inhibition of TSLP. This study will investigate the safety, 
tolerability, PK, biomarkers, and impact of using higher SC doses of BSI-045B in AD 
patients than previously used with tezepelumab. Higher doses may increase receptor 
occupancy, leading to a more pronounced biomarker and clinical response. The study results 
will provide additional information that will be used to better design future studies 
investigating whether BSI-045B is associated with significant clinical effects. 
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For Study BSI-045B-002, the proposed SC doses of 300 mg administered weekly (QW) for 3 
doses (loading dose) or twice weekly (Q2W) (maintenance dose) fall within the dose range of 
SC administration of 240 mg and 480 mg previously evaluated in a Phase 1 MAD study.  
The dosing intervals proposed for Study BSI-045B-002, including QW/Q2W, are designed to 
meet or exceed the weekly (Q7D) interval investigated in the Phase 1 MAD study. In that 
study, BSI-045B was observed by a mono-exponential reduction in concentration after 
reaching peak levels. According to the principle of superposition, which is generally 
applicable in such cases, the concentration levels following each dose are expected to be 
superimposed on the levels after the prior dose. With these proposed dosing intervals being 
equal to or longer than those in the MAD study, the peak concentrations of the drug in Study 
BSI-045B-002 are anticipated to be similar to or lower than those in the MAD study. This 
implies that, if peak drug concentration is a key factor in toxicity, the safety profile of the 
proposed dosing regimen in Study BSI-045B-002 should be comparable to, or more 
favorable than, what was observed in the Phase 1 MAD study. A detailed evaluation of the 
PK characterization from Study BSI-045B-001 is presented in Section 5.2.3.3. 
5.6 Risks and Benefits of BSI-045B in Human Volunteers Patients with Atopic 
Dermatitis 
Good Laboratory Practices (GLP) toxicity studies conducted with BSI-045B in cynomolgus 
monkeys showed that the drug is well tolerated up to 600 mg/kg (more than 16-fold the 
human equivalent dose (HED) for the maximum single dose (720 mg) administered in the 
Phase 1 clinical study) when administered as a single dose by SC injection. Further 
evaluation of BSI-
(TQC-TOX-01) in which 5 doses of BSI-045B were administered SC to cynomolgus 
monkeys with a 1-week interval between administrations, followed by a 4-week recovery 
period. Doses of 30, 100 and 300 mg/kg were administered, with the high dose administered 
giving an HED 19.4-fold higher than the clinical dose (300 mg) to be administered in the 
Phase 2a clinical trial. As in the single dose study, no relevant toxicity findings were 
observed that were attributable to BSI-045B and the NOAEL was considered to be 300 
mg/kg for repeat dose administration up to 5 cycles. Additionally, a 26-week GLP toxicity 
study with an 8-week recovery period in sexually mature cynomolgus monkeys was 
conducted. Monkeys were dosed with BSI-045B SC at 0, 15, 50 or 150 mg/kg/week. No 
significant toxicity findings were observed following weekly SC administration of BSI-045B 
to cynomolgus monkeys at 15, 50, and 150 mg/kg for 26 consecutive weeks. The NOAEL of 
BSI-045B was considered to be 150 mg/kg over 26 consecutive weeks, with an HED of 
2,903 mg for a 60-kg subject, resulting in a safety margin of 9.7-fold above the clinical dose 
(300 mg) to be administered in the Phase 2a clinical study. 
Local tolerance assessment revealed no abnormalities attributable to BSI-045B on clinical or 
microscopic evaluation of the injection site, and immunotoxicity evaluation revealed no 
noteworthy findings.  
Biosion Australia Pty Ltd is currently completing a Phase 1 study in Australia. The study 
consists of 3 parts: Part A, a SAD study in HVs; Part B, a single-dose study in patients with 
AD; and Part C, a MAD study in HVs. An interim analysis was conducted to analyze the 
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safety and PK data. In the interim analysis, a total of 54 participants, including 28 (51.9%) 
men and 26 (48.1%) women, were assessed. The actual numbers of subjects in Part A 
Cohort 1 (120 mg), Cohort 2 (240 mg), Cohort 3 (480 mg), and Cohort 4 (720 mg) were 8, 8, 
8, and 8; the actual number of patients in Part B was 5; the actual number of subjects in 
Part C Cohort 1 (240 mg Q7D) was 9, and Cohort 2 (480 mg Q7D) was 8. 
According to the interim analysis for this Phase 1 study, there were no serious TEAEs, 
TEAEs leading to death, or any deaths in any part of the study. There was 1 (1; 12.5% of 
group) severe TEAE (transaminases increased), reported by a subject in the 240-mg dose 
level Cohort in Part A. One subject (1; 11.1% of group in Part C; 240-mg Q7D Cohort) was 
withdrawn from the study due to TEAEs (increased AST and increased ALT). 
Overall, the frequency of TEAEs was similar across all single and multiple dose levels, with 
most or all subjects in each cohort in Part A (SAD) and Part C (MAD) reporting at least 1 
TEAE. In Part A, the frequency of study drug related TEAEs increased with dose level, 
indicating a potential relationship. In Part C, there was no increase in the frequency of study 
drug related TEAEs increasing with dose level. The frequency of TEAEs in Part B (patients 
with AD; 2 [40.4%]) was lower than the frequency of TEAEs at the same dose level in 
healthy volunteers in Part A (480 mg; 7 [87.5%]). 
Treatment-emergent AEs in SOC General Disorders and Administration Site Conditions, 
most or all of which were injection site reactions, were the most common TEAEs by SOC in 
both Part A and Part C. A relationship between increasing dose level and the events injection 
site erythema and injection site pain was observed in Part A, and a relationship between 
increasing dose level and injection site swelling was observed in Part C. In Part B, no TEAE 
by Preferred Term was reported by greater than 1 (20.0%) of subjects. Except for the severe 
TEAE in Part A, all TEAEs in the study were mild or moderate. 
Overall, injection site reactions were common in Part A and Part C of the study, although 
variances in the frequency and nature of reactions across dose levels were observed. 
Remarkably, in Part B no patients with AD reported injection site reactions on the day of 
study drug administration; 1 subject (20.0%) reported an injection site reaction (mild 
tenderness) on Day 2. Based on the clinical safety information of similar targeted drugs, 
injection site reactions are common adverse reactions, which could be regarded as potential 
risks for receiving BSI-045B treatment (Adbry® prescribing information, 2022). 
Another Phase 1 study was conducted by an independent licensee (CTTQ) for BSI-045B 
(named as TQC2731 by CTTQ) in healthy adults to evaluate the safety, tolerability, PK, and 
immunogenicity of TQC2731. As listed in the study abstract submitted to the American 
Academy of Allergy Asthma and Immunology meeting 2023, 54 participants were enrolled. 
TQC2731/placebo-related AEs were mild or moderate in severity across all dosing groups. 
The incidence of AEs observed was not dose dependent. No drug-related SAEs were 
reported. In summary, TQC2731 was safe and well-tolerated (Liu et al, 2023). 
Thus, based on both nonclinical and clinical data obtained with BSI-045B, this new 
monoclonal antibody is expected to be well tolerated in the proposed Phase 2a study. Up to 
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this amendment to the study protocol, no specific safety signals have been observed in this 
study, indicating a safety profile of 300 mg monotherapy in AD patients. 
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6 STUDY OBJECTIVES AND ENDPOINTS 
Table 5. Objectives and Endpoints in BSI-045B-002 Study 
Objectives 
Endpoints 
Primary 
Primary Efficacy Objective: 
To evaluate the efficacy of 
BSI-045B in patients with 
moderate to severe atopic 
dermatitis (AD)  
Primary Efficacy Endpoint: 
Proportion of patients with Eczema Area and Severity 
Index (EASI)75 at Week 26 (2 weeks after last dose at 
Week 24) 
Primary Safety Objective: 
To evaluate the safety and 
tolerability of BSI-045B in 
patients with moderate to 
severe AD 
Primary Safety Endpoint: 
Safety and tolerability as evidenced by the incidence of 
adverse events (AEs), anti-BSI-045B antidrug antibody 
(ADA) formation, clinical laboratory evaluations, 12-
lead electrocardiography (ECGs), vital signs, and 
physical examinations. The relationships between study 
drugs and AEs will be evaluated by the Investigators. 
Secondary 
To evaluate the 
pharmacokinetics (PK) of BSI-
045B 
Pharmacokinetics listings will be provided. PK 
parameters might be estimated through compartmental 
modeling. Additionally, the PK/Efficacy relationship 
might be explored. 
To evaluate the 
immunogenicity of BSI-045B 
Anti-BSI-045B ADA during and post BSI-045B 
treatment 
Exploratory 
To assess additional efficacy 
and safety outcomes of BSI-
045B  
 Proportion of patients with EASI90 at Week 26 (2 
weeks after last dose at Week 24) 
Proportion of patients with EASI50 at Week 26 (2 
weeks after last dose at Week 24) 
 Percent change from baseline in EASI at each visit 
Proportion of patients achieving 
Global Assessment (IGA) 0 or 1 at 26 (2 weeks after 
last dose at Week 24) 
 Percent changes in PP-NRS scores at Week 26 (2 
weeks after last dose at Week 24)  
 Proportion of patients achieving Facial IGA 0/1 at 
Week 26 (2 weeks after last dose at Week 24) 
 Occurrence of conjunctivitis 
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Objectives 
Endpoints 
To evaluate the PD biomarkers 
of BSI-045B  
Serum levels of thymus and activation regulated 
chemokine/C-C chemokine ligand 17 (TARC/CCL-17), 
periostin, and IgE during and post BSI-045B treatment 
AD = atopic dermatitis; ADA = antidrug antibody; AE = adverse event; CCL-17 = C-C chemokine ligand 
17; EASI = Eczema Area and Severity Index; ECG = electrocardiography; 
Assessment; IgE = immunoglobulin E; ; PD = pharmacodynamic; PK = pharmacokinetic; PP-NRS = Peak 
Pruritus Numerical Rating Scale; TARC = thymus and activation regulated chemokine 
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7 INVESTIGATIONAL PLAN 
This study is a multicenter clinical trial and is designed as a proof-of-concept study to 
evaluate the efficacy, safety, tolerability, PK, immunogenicity, and PD/biomarker of BSI-
045B following SC injections. 
The present study, which is intended to assess the efficacy and safety of BSI-045B in 
moderate to severe AD patients, is being conducted as a proof-of-concept study prior to 
performing a more traditional Phase 2 trial. If this study is successful, the Sponsor plans to 
conduct a future Phase 2b, randomized, blinded, dose-finding trial that will formally compare 
BSI-045B with placebo and/or other treatments for AD. 
7.1 Study Dosing 
The total number of evaluable patients with AD will be approximately 20 to 24. 
Patients will initially be treated with a loading dose of BSI-045B given QW for 4 weeks. 
Thereafter, BSI-045B will be given at Q2W interval to Week 24.  
7.2 Washout Period  
Patients will start with a washout period for anti-AD treatment prior to study treatment, 
including systemic and topical agents and phototherapy. The duration of the washout period 
varies by therapy and the Investigator should consult Table 6. Eligible patients who complete 
the washout period for previous therapies for AD will be treated with BSI-045B.  
Washout period is required for patients already on treatment for AD. Washout duration 
requirements is described in Table 6. 
Table 6. Washout Durations Required Before Initial Dose of BSI-045B, by Therapy 
Therapy 
Washout Duration Required before 
First Dose of BSI-045B 
Tralokinumab
12 weeks
Dupilumab
12 weeks
Phototherapy
4 weeks
Abrocitinib
4 weeks
Upadacitinib
4 weeks
Topical corticosteroids
1 week
Topical calcineurin inhibitors
1 week
Investigational Products
4 weeks
All Other Therapies prescribed for therapeutic 
immunosuppression or immunomodulation
3 weeks or 4 half-lives, whichever is 
longer
7.3 Replacement of Patients who Withdraw from Treatment 
Patients who do not complete the first 5 doses of BSI-045B will be replaced. 
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7.4 Monitoring by Safety Steering Committee 
The Safety Steering Committee (SSC) will monitor the study and will be composed of 
representatives from the Sponsor, the National Principal Investigator, and independent 
physicians, as indicated in the SSC charter. 
The SSC will formally assess safety findings when 20 patients complete dosing at Week 12. 
The SSC will assess all events, especially treatment-related serious adverse events (SAEs) 
that might prompt a change to the study.  
7.5 Assessment of Primary Efficacy Endpoint 
The primary efficacy endpoint is the proportion of patients with EASI75 at Week 26 (2 
weeks after last dose at Week 24), compared with baseline (Day 1). 
7.6 Other Efficacy and Safety Assessments 
Assessment (IGA), Facial IGA, assessment of conjunctivitis, and Peak Pruritus Numerical 
Rating Scale (PP-NRS). Efficacy assessments will be conducted prior to dosing on Day 1, at 
all subsequent visits, and at the time of early withdrawal from the study. 
Adverse events (AEs) will be collected after signing the ICF and throughout the Treatment 
Period and the Follow-Up Period. After injections, all patients should be monitored at the 
study sites for at least 30 mins to observe body reactions, including injection site reactions. 
Any injection site reactions observed after each site visit should be reported to the 
Investigators by the patients.   
Concomitant medications will be recorded after signing the ICF and throughout the 
Treatment Period and Follow-Up Period. 
During the Treatment and Follow-up Periods, PK and PD samples will be collected for 
analysis. Immunogenicity will be assessed throughout the Treatment Period and Follow-up 
Period. 
Follow-up assessments will occur during subsequent visits to the study sites. At the 
study sites at other times for re-
evaluation. 
7.7 Follow-up Period 
After the Treatment Period, there will be a 12-week Follow-up Period. 
7.8 Study Drug Administration 
The preferred SC injection site is the abdomen. The thigh can be used as an alternative site 
for SC injections. A 2.5 mL injection of 120 mg/mL (300 mg total dose) will be administered 
at a single injection site.   
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7.9 Enrollment and Study Procedures 
7.9.1 General Considerations 
Patients will be assigned a screening identification number once they have signed the ICF 
and will then be considered enrolled into the study if they have been determined to satisfy all 
inclusion and exclusion criteria (and after washout if requiring washout).  
When collecting PK samples, immunogenicity, PD/biomarker, and clinical laboratory 
samples, vital signs, and/or ECG assessments are scheduled to occur at the same time point, 
ECG and vital signs testing will be performed prior to blood collections. The preferred order 
of assessments is: 
1) ECG
2) Vital signs
3) PK, Immunogenicity, PD/biomarker sampling
4) Clinical laboratory sampling
Samples for serum PK (collected at nominal times), ADA, and PD/biomarker assessments 
will be collected for PK and ADA assessments using GLP validated assays and for 
PD/biomarker assessments using fit-for-purpose, qualified assays with commercial kits. 
Refer to the laboratory manual for additional details on laboratory assessment and sample 
processing. 
7.9.2 Assessments at Screening 
Screening assessments will be performed after the patients signed the ICF. After all screening 
results are obtained, eligible patients who require no washout will be enrolled to the study 
directly; eligible patients who require washout will start washout and repeat some screening 
assessments during Day-14 to Day-1. 
Rescreening is allowed after a delay of at least 4 weeks from the initial screening assessment. 
Any rescreening should be approved by the Sponsor. 
A complete history will be recorded at Screening and will include medical history, surgical 
history, smoking history, alcohol use history, drug abuse history, prior and current 
medication, blood donation history, allergy history, and other demographic information. 
Physical examinations at Screening will include weight, height, and body mass index (BMI), 
as well as a complete examination. Symptom-driven examinations will be performed at other 
time points. 
Other screening assessments will include 12-lead ECG, blood pregnancy test (females of 
childbearing potential only), and vital signs (blood pressure, pulse, temperature, and 
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respiratory rate). A subset of these tests will be completed at other time points, as detailed in 
the Schedule of Activities. 
A screening for drugs of abuse is optional (per the discretion of the Investigator). 
Clinical laboratory assessments at Screening will include those listed in Table 7 and will be 
conducted as site policy requires. 
Table 7. Clinical Laboratory Assessments, BSI-045B-002 
Type of Test 
Laboratory Parameters 
Hematology  
Hemoglobin, hematocrit, WBC count and differential, RBC count 
and indices, platelet count 
Chemistry 
Sodium, potassium, chloride, bicarbonate, calcium, phosphorus, 
magnesium, glucose, BUN, creatinine, uric acid, ALT, AST, 
GGT, alkaline phosphatase, total protein, albumin, globulin, total 
bilirubin, LDH, total cholesterol, triglycerides 
Coagulation 
PT, aPTT, fibrinogen, INR 
Virology (performed 
only at Screening) 
HbsAg, anti-HCV, HIV 
Urinalysis 
Protein, glucose, ketones, occult blood, urobilinogen, urine 
sediment microscopy (if other parameters abnormal) 
ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate 
aminotransferase; DNA = deoxyribonucleic acid; ECG = electrocardiography; GGT = gamma glutamyl 
transferase; HbsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV 
= human immunodeficiency virus; INR = international normalized ratio; LDH = lactate dehydrogenase; 
PCR = polymerase chain reaction; PT = prothrombin time; RBC = red blood cell; WBC = white blood cell 
7.9.3 Efficacy 
Patients will be assessed to determine an EASI score at Screening, prior to dosing on Day 1 
(baseline), at subsequent visits, and at the time of early withdrawal from the study. 
The EASI score is a composite index that measures the severity of AD based on the average 
intensity of four clinical signs (erythema, edema/papulation, excoriations, and 
lichenification) at four body areas (head, neck, upper extremities, and trunk and lower 
extremities), and the percentage of affected area for each of the four body areas (Hanifin and 
Rajka, 1980). The primary efficacy endpoint is the proportion of patients with EASI75 at 
Week 26 (2 weeks after last dose at Week 24). 
The IGA and facial IGA require the Investigator to rate the severity of AD on a scale from 0 
(clear) to 4 (severe).  
The assessment tool for itching is the PP-NRS, on which the patient rates the maximum 
severity of the itch from AD on a scale from 0 (no itch) to 10 (worst itch imaginable) over a 
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24-hour period. The baseline PP-NRS score is based on the average of daily PP-NRS scores
for the 7 days immediately preceding Day 1. Patients will complete the rating scale daily
using the patient diary beginning on Day -8, throughout the last study visit, and at the time of
early withdrawal from the study. In order to calculate an average for the score, the patient
must have completed the diary for a minimum of 4 days during the previous 7 days.
Exploratory efficacy and safety assessments will include the following. At each visit, the 
percentage of patients who achieve 50%, 75%, and 90% improvement in the EASI score 
from Day 1) and the change in EASI score from Day 1 will be calculated. Detailed analysis 
of all exploratory endpoint is described in the Statistical Analysis Plan (SAP). 
Proportion of patients with EASI90 at Week 26 (2 weeks after last dose at Week 24) 
Proportion of patients with EASI50 at Week 26 (2 weeks after last dose at Week 24) 
Percent change from baseline in EASI at each visit 
Proportion of patients achieving IGA 0 or 1 Week 26 (2 weeks after last dose at Week 
24) 
Percent changes in PP-NRS scores at Week 26 (2 weeks after last dose at Week 24) 
Proportion of patients achieving Facial IGA 0/1 at Week 26 (2 weeks after last dose 
at Week 24)  
Occurrence of conjunctivitis 
7.9.4 Safety 
The safety of BSI-045B will be assessed by the incidence of AEs, anti-BSI-045B ADA 
formation, clinical laboratory evaluations, 12-lead ECGs, vital signs, physical examinations, 
occurrence of conjunctivitis, as well as injection site reactions. The relationships between 
study medication and AEs will be evaluated by the Investigators. 
Assessments will occur during visits to the study sites or via videoconference or telephone 
conference. Adverse events will be collected throughout the Treatment Period and the 
Follow-Up Period to determine whether there are ongoing AEs, SAEs, worsening of AEs or 
SAEs, or development of new AEs or SAEs. Follow-up of AEs and SAEs will occur during 
clinic visits and whenever abnormal, clinically significant findings are observed. 
Concomitant medications taken after the final dose of BSI-045B will be recorded throughout 
the Follow-
 patients may be brought back to the 
study sites at other times for re-evaluation. 
For the assessment of conjunctivitis, conjunctivitis history will be asked at screening visit, 
and all patients will be asked if they had been diagnosed as conjunctivitis at every visit 
during study treatment period. For patients who have been diagnosed as conjunctivitis, the 
conjunctivitis severity will be asked, and the severity grades include: 0 = no conjunctivitis; 1 
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= mild conjunctivitis; 2 = moderate conjunctivitis requiring treatment; 3 = severe 
conjunctivitis that may require an ophthalmic exam. Investigators should also check the 
 
7.9.5 Stopping Criteria 
-organ class 
of Cardiac Disorders) according to Common Terminology Criteria for Adverse Events 
(CTCAE v5), then: 1) BSI-045B treatment may be continued if the AE is considered to be 
unrelated to BSI-045B; 2) BSI-045B treatment will be withheld if the AE is considered to 
be related to BSI-045B, until the toxicity returns to 
 Grade 2; 3) BSI-045B will be 
permanently discontinued if the AE recurs to 
 Grade 3 after BSI-045B treatment resumed 
and is considered to be BSI-045B related. Treatment discontinuation decisions will be made 
by Investigators after a discussion with Sponsor. These AEs include hepatotoxicity, 
injection site reactions, allergic conjunctivitis and hypersensitivity (see Table 8). Patients 
who experience such AEs will be followed until the adverse events resolves or stabilizes. 
Study drug administration will not be discontinued.  
If 2/3 of patients experience any adverse event assessed as  Grade 3 (
Grade 2 for the 
system-organ classes of Cardiac Disorders) per Common Terminology Criteria for Adverse 
Events (CTCAE v5), the study should be suspended for an evaluation from SSC. 
Table 8. Toxicity with the Potential to Cause Study Treatment Discontinuation 
Toxicity 
Criteria 
Hepatotoxicity 
 
AST/ALT >5×ULN and/or Bilirubin >3×ULN 
Hepatic failure 
 
Recurrence of a severe or life-threatening event, or any of the 
laboratory abnormalities listed above, that are presumed to be study 
treatment related. 
Injection site 
reactions 
Ulceration or necrosis; severe tissue damage; operative intervention 
indicated 
 
Severe reactions lasting more than 24 hours 
Conjunctivitis* 
Symptomatic with marked decrease in visual acuity (best corrected 
visual acuity worse than 20/40 or more than 3 lines of decreased 
vision from known baseline, up to 20/200); limiting self-care 
Activities of Daily Living (ADL); if infectious is the etiology, 
intravenous antibiotic, antifungal, or antiviral intervention indicated
 
Urgent intervention indicated or life-threatening. 
Hypersensitivity
Anaphylaxis: Symptomatic bronchospasm, with or without urticaria; 
parenteral 
intervention 
indicated; 
allergy-related 
edema/angioedema; hypotension 
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If a patient experiences an AE assessed as 
Grade 3 (~ Grade 2 for the system 
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Toxicity 
Criteria 
 
Serum sickness: Severe arthralgia or arthritis; extensive rash; 
steroids or IV fluids indicated 
Allergic reaction: Bronchospasm; hospitalization indicated for 
clinical sequelae; intravenous intervention indicated 
 
Urgent intervention indicated or life-threatening. 
* Definition of Conjunctivitis: a disorder characterized by inflammation, swelling and redness of the
conjunctiva of the eye.
For the evaluation of injection site reactions, the following scale (Table 9) which is a part of 
FDA toxicity grading scale will be used.  
Table 9. Grading scale for injection site reactions 
Local 
reactions 
Mild (Grade 1) 
Moderate (Grade 
2) 
Severe (Grade 
3) 
Potentially life 
threatening 
(Grade 4) 
Pain 
Dose not interfere 
with activity 
Repeated use of 
non-narcotic pain 
reliever > 24 
hours or 
interferes with 
activity 
Any use of 
narcotic pain 
reliever or 
prevents daily 
activity 
Emergency 
room (ER) visit 
or 
hospitalization 
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant 
discomfort at 
rest
ER visit or 
hospitalization  
Erythema/ 
Redness* 
2.5-5 cm 
5.1-10 cm 
>10 cm
Necrosis or 
exfoliative 
dermatitis
Induration/ 
Swelling ** 
2.5-5 cm and dose 
not interfere with 
activity
5.1-10 cm or 
interferes with 
activity
>10 cm or
prevents daily
activity
Necrosis 
* In addition to grading the measured local reaction at the greatest single diameter, the measurement should be
recorded as a continuous variable.
** Induration/Swelling should be evaluated and graded using the functional scale as well as the actual
measurement.
7.9.6 Pharmacokinetic Assessments 
Assessments of the PK of BSI-045B will be evaluated throughout the Treatment Period and 
Follow-up Period as outlined in the Schedule of Activities in Section 3.  Blood sample for the 
analysis of the PK of BSI-045B will be collected at the time points indicated in the PK 
Sample Collection in Table 1 and Table 2. Refer to the laboratory manual for additional 
details on laboratory assessment and sample processing. 
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7.9.7 Immunogenicity 
Assessments of the ADA status (negative or positive with titer) of BSI-045B will be 
evaluated throughout the Treatment Period and Follow-up Period as outlined in the Schedule 
of Activities in Section 3.  Blood sample for the analysis of the ADA of BSI-045B will be 
collected at the time points indicated in the Immunogenicity Sample Collection in Table 1 
and Table 2. Refer to the laboratory manual for additional details on laboratory assessment 
and sample processing. 
7.9.8 Pharmacodynamic Biomarker Assessments 
Blood samples (4 mL) for TARC/CCL-17, periostin, and IgE concentrations will be collected 
at W1D1, W2, W3, W4, W8, W12, W16, W20, and W24 within 1 h before each dose during the 
Treatment Period, on every visit during the Follow-up Period, and at the time of early 
withdrawal from the study drug. 
7.10 Criteria for end of Study 
A patient is considered to have completed the study when study and follow-up procedures 
have been completed as per the Schedule of Activities. 
The end of this study is defined as the date when the last patient, last visit occurs or when last 
patient finished the safety follow-up, whichever occurs first. 
7.11 Criteria for Early Discontinuation of Study Drug 
A patient has the right to withdraw from treatment at any time at his/her request and this 
decision will not affect the treatment provided by clinicians or research institutions in the 
future. Moreover, the patients may be withdrawn at any time at the discretion of the 
Investigators for safety, behavioral, compliance, or administrative reasons. When medically 
feasible, the Medical Monitor should be consulted prior to study drug discontinuation. Study 
drug treatment will be permanently discontinued if one of the following criteria applies: 
Withdrawal of consent 
Patient or guardian requests to discontinue the study drug 
Start of new anti-AD treatment 
Lost to follow-up 
Death 
Intolerable safety issues 
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AE, abnormal laboratory tests, or other medical condition (including pregnancy) 
occurred, and the Investigator judges that the study drug should be terminated based 
on the best interests of the patient 
Major noncompliance with the study protocol and in the Investigator s judgment, 
treatment should be discontinued 
Other conditions that the Investigator considers inappropriate for continue treatment 
Study terminated by the Sponsor 
If a patient withdraws from study treatment after receiving study treatment, a safety 
examination is required within 7 days after the patient's withdrawal. Additional follow-up 
assessments should be completed.  
7.12 Criteria for Withdrawal from the Study 
The primary reason for withdrawal from the study will be recorded as one of the following: 
Death 
Lost to follow-up 
The patient has poor compliance and serious deviation from study protocol 
Withdrawal of consent by patient 
Study terminated by Sponsor or regulatory agency 
Other conditions as per Investigators 
The Investigator or designee must make appropriate efforts to contact any patient who is lost 
to follow-up, with at least 3 telephone contacts. If a patient who has received study drug 
withdraws from the study early, a safety examination is required within 7 days after the 
patient's withdrawal if the patient consents to this visit. 
7.13 Data Handling for Patients who do not Complete the Study 
Before descriptive statistical analysis of data, the Investigator and the Sponsor will determine 
whether individual patients are to be included in a per-protocol analysis for the analysis of 
the primary efficacy endpoint. Patients who receive any amount of study drug will be 
included in safety analyses. 
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7.14 Compliance/Adherence 
In select cases, the Investigator may need to discuss with the patient whether they should 
continue the study and make relevant explanations in certain situations, including but not 
limited to the following: 
1) The Investigator considers it advisable for the patient to stop the study from the
perspective of medical ethics, or believes that withdrawal from the study may be in
the best interest of the patient.
2) During the study, the patient does not comply with the study plan and shows poor
compliance (eg, failure to take the study drug or failure to obtain samples for PK and
safety evaluation as required by the protocol).
3) The patient evidences behavioral issues during the study that may affect study
assessments
7.15 Randomization and Blinding 
The study will not be randomized and will be unblinded.
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8 STUDY POPULATION 
8.1 Inclusion Criteria 
Patients must meet the following criteria for study entry: 
1) In the opinion of the Investigator, the patient is capable of understanding and complying
with protocol requirements.
2) The patient signs and dates a written ICF prior to the initiation of any study procedures.
3) The patient has a diagnosis of AD (according to the criteria established by Hanifin and
Rajka, 1980). The diagnosis of AD must have been present for at least 6 months.
4) The patient is aged 18 to 65 years, inclusive at the time of consent. Patients of any gender
are eligible.
5) A female patient weighs at least 45 kg and a male patient weighs at least 50 kg. The
patient has a BMI between 18.0 and 32.0 kg/m2 inclusive at Screening.
6) 
on Day 1. 
7) The score on the IGA 
on Day 1. 
8) The total body surface area (BSA) affected by AD is 
10% as assessed by the physical
examination at Screening and on Day 1.
9) The patient has:
(a) not received prior treatment with topical or systemic medications OR
(b) the patient has active disease despite topical or systemic treatment as per the
Investigator at the time of screening.
Prescription moisturizers or moisturizers containing additives such as ceramide, 
hyaluronic acid, urea, or filaggrin degradation products can be allowed if the patient 
agrees to continue using at the current dose during the study. 
10) A male patient who is non-sterilized and sexually active with a female partner of
childbearing potential agrees to use highly effective contraception from the time of
signing the ICF throughout the duration of the study treatment and for 90 days
(~5 half-lives) after the last dose of study drug (See Section 8.3).
11) A female patient of childbearing potential who is sexually active with a non-sterilized
male partner agrees to use highly effective contraception from the time of signing the ICF
throughout the duration of the study treatment and for 90 days after the last dose of study
drug (See Section 8.3).
12) The patient has a negative urine/blood result for drugs of abuse (if there are concerns in
the opinion of the Investigators regarding the use of illicit drugs, including cannabinoid
products).
8.2 Exclusion Criteria 
Any patient who meets any of the following criteria will be excluded from the study: 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
The EASI is ~12 at Screening and 
is ~3 (scale of Oto 4) at Screening and 

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1) The patient has received any of the following treatments but did not finish the required
washout period as stated in the following table. After the washout period, the patients
can be considered for study treatment.
Therapy 
Washout Duration Required before First 
Dose of BSI-045B 
Tralokinumab 
12 weeks 
Dupilumab 
12 weeks 
Phototherapy 
4 weeks 
Abrocitinib 
4 weeks 
Upadacitinib 
4 weeks 
Topical corticosteroids 
1 week 
Topical calcineurin inhibitors 
1 week 
Investigational Products 
4 weeks 
All Other Therapies prescribed for 
therapeutic immunosuppression or 
immunomodulation 
3 weeks or 4 half-lives, whichever is longer 
2) The patient has another dermatologic condition that might confound a diagnosis of AD
or a treatment assessment.
3) The patient has any clinically significant illness that may affect the safety, increase the
risk for seizure or lower the seizure threshold, or potentially confound the study results,
such as cardiovascular, neurologic, pulmonary, hepatic, renal, metabolic, gastrointestinal,
immunologic, endocrine, or psychiatric disease or disorder, or other abnormality. It is the
l Monitor may be warranted.
4) The patient has abnormal laboratory values during the Screening Period: ALT and/or
estimated 
glomerular filtration rate (GFR) < 60 mL/min (based on Cockcroft-Gault calculation), 
3/µL. Individual exceptions may 
be granted with the agreement of the Sponsor and the Investigator. 
5) The patient has a history of anaphylaxis following biologic therapy.
6) The patient has a history of allergy to corticosteroids, diphenhydramine, hydroxyzine,
cetirizine, or fexofenadine.
7) The patient has a history of a clinically significant infection within 4 weeks prior to
Screening.
8) The patient has been diagnosed with a helminthic parasitic infection within 6 months
prior to Screening.
9) The patient has a history of drug abuse (defined as any illicit drug use) or a history of
alcohol abuse within 1 year prior to Screening or is unwilling to agree to abstain from
excessive alcohol consumption and drugs (including cannabinoids) throughout the study.
10) The patient had a major surgical or major dental procedure within 8 weeks prior to
Screening.
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
responsibility of the Investigator to assess the clinical significance of a patient's 
condition; however, consultation with the Sponsor's Medica 
AST> 1.5 times the upper limit of normal (ULN), total bilirubin 
1.5 mg/dL, 
hemoglobin (Hgb) ::S 10 g/dL, platelet count ::S 150 xlQ 

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11) The patient is pregnant or lactating or intends to donate ova before, during, or within 90
days (~ 5 half-lives) since the last dose of study drug.
12) If male, the patient intends to donate sperm during this study or within 90 days (~ 5 half-
lives) since the last dose of study drug.
13) The patient has a history of neurologic abnormalities including abnormal
electroencephalography, brain injury including traumatic injury, perinatal cerebropathy,
postnatal brain damage, blood-brain barrier abnormality, and cavernous angioma.
14) The patient has a history of cerebral arteriosclerosis.
15) The patient has a history of cancer, except for adequately treated basal or squamous cell
skin cancer or in situ cancers; or any other cancer from which the patient has been
disease-free for at least 5 years prior to the first dose of study drug.
16) The patient has a positive test result for HbsAg, anti-HCV, a history of active
tuberculosis, a positive test result for HIV, or a known history of HIV infection at
Screening.
17) The patient has poor peripheral venous access.
18) 
transfusion of any blood product within 90 days prior to the first dose of study drug. 
19) The patient has an abnormal (clinically significant) ECG at Screening and/or on Day1.
Entry of any patient with an abnormal (not clinically significant) ECG must be approved
and documented by signature of the Investigator. In the case of a corrected QT interval
(Fridericia) (QTcF) > 450 ms or > 470 ms (patients with bundle branch block) or PR
interval outside the range of 115 to 220 ms, assessment may be repeated once for
eligibility determination at Screening and/or on Day1.
20) The patient has poorly controlled hypertension and is not considered suitable for
participation in this study in the judgement of the Investigators at Screening and/or on
Day1.
21) The patient has abnormal resting heart rate and is not considered suitable for
participation in this study in the judgement of the Investigator at Screening and/or on
Day1. Assessment is allowed to be repeated once for eligibility determination at
Screening and/or on Day1 if deemed necessary.
22) The patient plans to use any other prohibited medication or undergo any prohibited
procedure during the study. Oral antibiotics are permitted. Bleach baths are not
permitted.
23) The patient has a risk of suicide on the Patient Health Questionnaire-2 (PH-2) or in the
judgment of the Investigator, or the patient has made a suicide attempt or has a history of
deliberate self-harm within 6 months prior to Screening.
24) The patient is compulsorily detained for a medical or psychiatric illness.
25) The patient or their immediate family are personnel at the study site.
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The patient has donated or lost~ 450 mL of blood (including plasmapheresis) or had a 

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26) The patient is unable to comply with restrictions and prohibited activities/treatments as
listed in the study protocol.
8.3 Contraception Requirements 
Women of childbearing potential must use a highly effective method of contraception from 
the time of giving informed consent until at least 90 days after the last dose of study drug. 
Women are considered to be of childbearing potential following menarche until becoming 
postmenopausal (defined as no menses for at least 12 months without an alternative medical 
cause) unless permanently sterile. 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. However, in the absence of 12 
months of amenorrhea, a single FSH measurement is insufficient. Permanent sterilization 
methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. 
Males with partners who are females of reproductive potential must agree to use condoms, 
and their partners will use a highly effective contraceptive method from the time of informed 
consent and for 90 days after the last dose of study drug. 
Highly effective forms of contraception for females are defined as: 
Combined (estrogen- and progestogen-containing) hormonal contraceptives that 
inhibit ovulation, including oral, intravaginal, and transdermal products 
Progestogen-only hormonal contraceptives that inhibit ovulation, including oral, 
injectable, and implantable products 
Intrauterine devices and intrauterine hormone-releasing systems 
Bilateral tubal occlusion (women) 
Male partner vasectomy or other method of surgical sterilization provided that the 
partner is the sole sexual partner of the study patient and the vasectomized partner has 
received medical assessment of the surgical success 
Sexual abstinence in men and women (ie, refraining from heterosexual intercourse 
during the entire period of risk association with the study drugs) when it is the 
preferred and usual lifestyle of the patient; periodic abstinence (such as calendar, 
symptothermal, and postovulation methods), withdrawal (coitus interruptus), and the 
lactational menorrhea method are NOT acceptable methods of contraception. 
The following methods of contraception are NOT considered highly effective: 
Progesterone-only oral hormonal contraception that does not inhibit ovulation 
Barrier methods with or without spermicide, or spermicide alone 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
• 
• 
• 
• 
• 
• 
• 
• 

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9 STUDY DRUG SUPPLIES, DOSING, AND CONCOMITANT MEDICATIONS 
9.1 BSI-045B 
BSI-045B injection is manufactured in compliance and supplied by Wuxi, China. The drug 
substance and drug product are manufactured in compliance with Good Manufacturing 
Practices. All study drugs sent to the study sites will be labeled according to current Good 
Clinical Practice (GCP) and local Therapeutic Goods Administration requirements. 
The strength is 300 mg/2.5 mL/vial/120 mg/mL. Target filling volume is 3.16 mL. 
9.2 Receipt, Dispensing, Storage, and Return of Investigational Product 
BSI-045B injection is provided free of charge by the Sponsor. The clinical research site is 
responsible for the storage, dispensing, and administration of the study drug under 
recommended conditions according to the approved study protocol. The drugs used in this 
study will be received, stored, and dispensed by the site pharmacist, and the receipt, 
administration, distribution, and return of the IP will be documented in accordance with the 
standard operating procedures of the site. The IP is sensitive to light and high temperatures 
and should be stored and transported at 2 C to 8 C, protected from light. At the end of the 
study, the Investigator or designee will return the packaging of all used drugs and the 
remaining unused drugs to the Sponsor. 
9.3 Concomitant Medications 
Concomitant medications for AE treatment are allowed during the study. 
The use of female contraception medications is allowed.  
Oral antibiotics are permitted.  
Use of nonprescription eye lubricant drops is permitted. 
If it is medically necessary to initiate concomitant medications during the study, they will be 
recorded on the Case Report Form (CRF) and the Medical Monitor and/or Sponsor might be 
notified. All medications taken within 30 days of Screening will be recorded on the 
appropriate CRF. 
9.4 Rescue Medications for Exacerbations of Atopic Dermatitis 
 No rescue medication will be permitted during the study.  
9.5 Prohibited Concomitant Medications 
The use of any other investigational agent during the study is prohibited. 
The following interventions are restricted from Screening through completion of the study: 
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0 
0 

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1) Treatment with a live (attenuated) vaccine or any investigational drug
2) Treatment with topical emollients containing additives such as ceramide, hyaluronic
acid, urea, or filaggrin degradation products (patients may continue to use stable
doses of such moisturizers if initiated before the initiation of study drug but should
not change to a different product during the study).
3) Treatment with systemic corticosteroids or nonsteroidal systemic immunosuppressive
drugs (eg, cyclosporine, methotrexate, mycophenolate, azathioprine, calcineurin
inhibitors, etc.) within 2 weeks prior to and during treatment with the study drug.
However, inhaled steroids are allowed.
The following procedures are prohibited during participation in the study: 
1) Major surgical and major dental procedures
2) Phototherapy including facials
3) Tanning in a bed/booth
4) Bleach baths
9.6 Drug Compliance 
During recruitment and the Screening Phase, the purpose of this study will be described in 
detail to fully inform the patient, along with basic information about the study drug, the 
protocol, the study procedures, the dosing regimen (eg, dose, route of administration, etc.), 
clinical observation, frequency and process of biological sample collection, potential risks of 
participating in the trial, compensation and indemnification, etc. Information included in the 
ICF will allow the patient to decide whether to participate in the study and will help to 
increase compliance with the study drug. Before administration of study drug, the patient 
number and dose of the patient will be checked. After administration, administration 
instruments will be checked and the remaining study drug and empty packages will be 
counted. 
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10 ADVERSE EVENT REPORTING 
10.1 Definitions, Acquisition, and Recording of Adverse Events 
An AE is defined as any untoward medical occurrence in a patient administered study drug 
and which does not necessarily have a causal relationship with the treatment. An AE can 
therefore be an unintended sign (including an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a study drug, whether or not related to study 
drug. 
10.2 Definition of Serious Adverse Event 
An event is considered serious if, in the view of either the Investigator or Sponsor, it results 
in any of the following outcomes: 
1) Death
2) A life-threatening AE (places the patient at immediate risk of death)
3) Inpatient hospitalization or prolongation of existing hospitalization
4) A persistent or significant disability/incapacity or
5) A congenital anomaly of birth defect
6) Other important medical event. Infections resulting from contaminated study drugs
will be considered a medically important event and subject to expedited reporting
An SAE may or may not be related to study drug. 
10.3 Assessment of Causal Relationship of Adverse Events and Serious Adverse Events 
The Investigator must separately determine the relationship of the event to the study drug. 
The causal association of an AE or SAE to study drug administration should be determined 
as follows: AEs or SAEs that are considered to have a definite, probable, or possible 
related/suspected
those that are considered to be unlikely or unrelated to treatment with the study drug will be 
/not suspected  
The causal relationship of an AE or SAE will be classified in two categories, suspected and 
not-suspected, according to the detailed criteria defined in Section 10.6. It is the 
responsibility of the Investigator to provide the causality analysis when recording an SAE 
Report; however, the Sponsor, through the pharmacovigilance service provider (Acumen 
Medical Information & Technology Co., Ltd., [AMIT]), may provide additional analysis and 
assessment while submitting the report to FDA following the local regulations. 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
relationship to treatment with the study drug will be recorded as " 
"while 
recorded as "unrelated 
" 

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10.4 Assessment of Severity of Adverse Events and Serious Adverse Events 
The Investigator must determine the severity of each AE based on the grade in Common 
Terminology Criteria for Adverse Events (CTCAE)v5.0 (Table 10). Severity describes the 
intensity of the AE. Events that change severity during the course of follow up should be 
recorded on separate rows on the CRF, using the appropriate verbatim term but with the start 
date of each new event corresponding to the date that the severity increased or decreased. 
Table 10. Assessment of Severity of an Adverse Event 
Grade 
Definition 
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*. 
Grade 3 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL** 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing
money, etc.
**Self-care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications,
and not bedridden.
10.5 Adverse Event and Serious Adverse Event Reporting 
The AE reporting period starts with signing the ICF. Any AE collected before the first 
administration of study drug is considered not suspected or not related to the study drug, 
therefore will not be counted as a related AE in the final Clinical Study Report. Collection of 
AEs continues throughout the study. 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostic reports) related 
to the event. The investigator will then record all relevant AE/SAE information in the CRF. 
The SAE information will be recorded in the SAE Report Form provided by AMIT. It is not 
acceptable for the Investigator to send photocopies of the patien
in lieu of completion of the SAE Report Form/AE/SAE CRF page, unless such medical 
records are requested by AMIT for further understanding the AE/SAE cases. 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. 
For each AE/SAE, the Investigator must document in the medical record that they have 
reviewed the AE/SAE and provided an assessment of causality. There may be situations in 
which an SAE occurs but the Investigator has minimal information to include in the initial 
report to the Sponsor. 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 
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t's medical records to AMIT 

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Sponsor. The Investigator may change their opinion of causality in light of follow-up 
information and send an SAE follow-up report with the updated causality assessment. The 
causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
An AE or SAE is considered unexpected  if it is not listed in the BSI-
Brochure or is not listed at the specificity or severity that has been observed. U
as used in this definition also refers to AEs, SAEs, or suspected adverse reactions that are 
mentioned in the IB as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug, but are not specifically mentioned as occurring with 
the particular drug under investigation. 
Patients in this study who experience an AE or SAE will be followed until the AE or SAE is 
resolved, has stabilized and is not expected to change, or is clearly determined to be due to a 
 stable or chronic condition or intercurrent illness, even if this occurs after the 
Termination Visit. All AEs spontaneously reported by the patient and/or in response to an 
open question from study personnel or revealed by observation, physical examination, or 
other diagnostic procedures will be recorded and reported on the appropriate CRF. 
When a unifying diagnosis has been made that accounts for several possible signs and/or 
symptoms, the unifying diagnosis should be selected as the AE term. For example, the 
combination of general malaise, mild fever, headache, and rhinitis should be described as 
individual symptoms as separate events. 
Safety and tolerability will be determined by symptoms, signs, and laboratory test 
abnormalities. The Investigator will monitor the laboratory test findings. If any laboratory 
test is abnormal during the course of the study, it will be followed at the discretion of the 
Investigator. Abnormalities of laboratory tests, in the opinion of the Investigator, may be 
considered of potential clinical concern and, thus, constitute a laboratory AE or be associated 
with a clinical AE. In such cases, they must be reported on the AE Form. 
10.6 Procedures for Reporting Serious Adverse Events 
All SAEs occurring during the course of the study, as defined by the protocol, regardless of 
the relationship to the study drug, must be reviewed and reported by the Investigator to the 
Sponsor through the contract research organization (CRO), AMIT, Floor 15, Building 14-2, 
Xingzhihui Business Garden, No. 19, Xinghuo Road, Jiangbei New District, Nanjing City, 
Jiangsu Province, China, within 24 h from the point in time when the Investigator becomes 
aware of the SAE. 
The information collected by the Investigator will include at minimum the following: patient 
number, the criteria met for the AE being serious, the event term, date and time of onset, a 
narrative description of the event, and an assessment by the Investigator as to the severity of 
the event and relatedness to the study drug. 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
" 
patient's 
" 
045B Investigator's 
" nexpected" 
"upper respiratory syndrome" if this diagnosis has been made, rather than reporting the 

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The Investigator is obligated to assess the relationship between study intervention and each 
and/or arguments to suggest a causal relationship, rather than that a relationship cannot be 
ruled out. The Investigator will use clinical judgment to determine the relationship. 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, 
as well as the temporal relationship of the event to study intervention administration, will be 
considered and investigated. The Investigator will also consult the BSI-
Brochure, or for marketed products, the product information, in making their assessment. 
If the Investigator does not know whether or not the study intervention caused the event, then 
by the Sponsor in the protocol. In addition, if the Investigator determines that an SAE is 
associated with study procedures, the Investigator must record this causal relationship in the 
source documents and CRF, and report such an assessment in the dedicated section of the 
SAE Report Form and in accordance with the SAE reporting requirements. 
The Investigator will complete the SAE Report Form with their signature and date on each 
page of the report, scan it into a PDF file, and send the file to AMIT and the Sponsor through 
e-mail Biosion-RGPV@rg-pharma.com and submit to the local approving IRB within 24
hours of first awareness of this SAE. In case the Investigator has no access to e-mail, the
signed SAE Report can be sent to AMIT via fax at the number 86-10-8801-9165 and be
additionally shared with the Sponsor by AMIT.
The SAE Report will be further processed by AMIT into the pharmacovigilance database and 
submitted to FDA in case of serious, unexpected, and related AEs (suspected unexpected 
serious adverse reaction [SUSAR]) within 7 days of the day of first awareness for life-
threatening or more severe cases, or 15 days of the day of first awareness for the cases at all 
other severity levels. The reports submitted to FDA will be forwarded to the study operation 
service CRO (ICON Clinical Research Limited [ICON]) through e-mail in the format of 
XML or MedWatch 2500A Form for the purpose of sharing with all the Investigators at the 
earliest availability. The information from all the SAEs will be forwarded to ICON 
periodically. 
The Sponsor will promptly notify the Investigator about important safety or toxicology 
information as it becomes available. It is the responsibility of the Investigator to promptly 
notify the IRB about new and relevant safety information regarding the IP, including serious 
adverse drug reactions involving risk to human patients, in accordance with the applicable 
policies. The SAE reporting period is the same as the AE reporting period (starts with the 
signing of the ICF and continues through the termination visit). 
The Sponsor will notify the FDA or all serious, unexpected, and related AEs within 15 
calendar days after the study team receives knowledge of the event, and all life-threatening 
and/or fatal events within 7 calendar days after the study team receives knowledge of the 
event. 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
AE/SAE. A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
045B Investigator's 
the event will be handled as "related to study intervention" for reporting purposes, as defined 

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10.7 Follow-up of SAEs and AEs 
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 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 healthcare providers. If a subject dies during participation in the study or during a 
recognized follow-up period, the Investigator will provide AMIT 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, AMIT and IRB within 24 hours of receipt of the information. AMIT will further 
process the SAE in the same time frame as for the initial SAE Report. 
10.8 Special Situations 
Regardless of whether associated with an AE or SAE, special situation reports should be 
generated for all instances of medication error, abuse, misuse or overdose, occupational 
exposure, drug interactions, exposure via breastfeeding, unexpected benefit, transmission of 
infectious agents via the study drugs, product complaints, counterfeit of falsified medicine, 
and pregnancy, and forwarded to Sponsor through AMIT via e-mail or fax within one (1) 
working day. 
10.9 Pregnancy Reporting 
If a female study patient becomes pregnant during the study or within 90 days since the last 
dose, BSI-045B should be discontinued and the Sponsor notified within one working day 
using a Pregnancy Monitoring Form. 
If the partner of a male patient becomes pregnant within 90 days since the last dose the 
Sponsor should be notified as soon as possible. Consent by the female partner of a male 
patient must be obtained prior to any data collection. 
Pregnant patients or pregnant partners of male patients should be advised to inform their 
treating physician of their involvement in study BSI-045B-002. 
All pregnancies must be followed up through delivery or other fetal outcome. An abnormal 
pregnancy outcome (eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, 
ectopic pregnancy) is considered an SAE, reportable to the Sponsor within one working day. 
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11 STATISTICAL METHODS 
11.1 Sample Size 
With a minimum sample size of 20 patients, the maximum one-sided 95% confidence 
interval width for the proportion achieving EASI75 equals 21%. 
With a maximum sample size of 24 patients, the maximum one-sided 95% confidence 
interval width for the proportion achieving EASI75 equals 19%. 
11.2 Statistical Approach 
Statistical analyses will be descriptive in nature, with frequencies and percentages generated 
for categorical variables and mean, standard deviation, median, minimum, and maximum 
values generated for continuous variables. Exact one-sided 95% confidence intervals will be 
generated for primary and select secondary efficacy endpoints based on proportions. 
Additional details regarding the statistical analyses will be presented in the Statistical 
Analysis Plan. 
11.3 Study Population 
11.3.1 Patient Disposition 
The number of patients screened, enrolled, and dosed from screening to the completion of the 
study will be listed, and the number and percentage of patients who have completed or 
withdrawn from the study by dose group will be presented. 
Patients who discontinue treatment will be summarized and the primary reason for 
discontinuation. Patient disposition will be summarized. 
11.3.2 Protocol Deviations 
A protocol deviation is defined as any change, divergence, or departure from the study design 
or procedures defined in the protocol. 
An important protocol deviation is defined as a protocol deviation that might significantly 
affect the completeness, accuracy, and/or reliability of the study data or that might 
significantly affect a 
 rights, safety, or well-being. Important protocol deviations 
may result in the removal of patients from the study and the analysis. 
Protocol deviations will be classified as important and non-important by the Sponsor and 
Investigators prior to database lock. 
Protocol deviations will be summarized. 
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patient's 

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11.3.3 Baseline Characteristics 
Baseline characteristics will be summarized descriptively, for demographic information, 
prior medical history, physical examination, vital signs, 12-lead ECG, and clinical laboratory 
tests. Baseline is defined as the most recent non-missing measurement prior to the patient 
receiving their first dose of study drug. 
11.4 Efficacy Assessments 
Statistical analysis of efficacy assessments includes changes in the EASI, IGA, and PP-NRS. 
Methods are described in detail in the SAP. 
11.5 Safety Assessments 
All AEs will be coded using the Medical Dictionary for Regulatory Activities. An AE 
(classified by preferred term) will be considered a TEAE if it was not present before the first 
dose of study drug or if it was present before the first dose of study drug but increased in 
severity during the assessment period for AEs. The incidence of TEAEs will be summarized 
by system organ class and preferred term. Multiple AEs mapped to the same preferred term 
will be counted once per patient. 
Concomitant medications will be coded using The World Health Organization (WHO) Drug 
Dictionary with generic term and Anatomical Therapeutic Chemical (ATC) code and 
summarized by ATC code and WHODrug generic name. Safety laboratory findings, AEs, 
vital signs, and 12-lead ECGs will be summarized using descriptive statistics. Values and 
changes from baseline at scheduled time points will be summarized. Laboratory data will be 
listed and values and changes from baseline will be summarized. 
11.6 Pharmacokinetic Data Analysis 
Pharmacokinetics listings will be provided. Pharmacokinetic parameters will be estimated 
using NONMEM® Version 7.4 (or later versions) software with compartmental modeling 
analysis. Based on data availability, a PK/PD model will be developed to evaluate the 
relationships between serum BSI-045B and clinical efficacy. 
11.6.1 Analysis of Serum Drug Concentration versus Time Data 
The mean (and standard deviation) serum BSI-045B concentration-time profile in a semi-
logarithmic scale for all patients will be plotted based on planned sampling time points. 
Individual concentration-time profiles in a semi-logarithmic scale for each patient will be 
plotted based on actual blood collection times. 
11.7 Immunogenicity Analysis 
The titers of ADA-positive patients will be listed, and the number, incidence, and 95% CI of 
patients with treatment emergent ADA after administration of BSI-045B will be described by 
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blood sampling time points. The time to onset, titer, and duration of the presence of ADAs 
will be described using the mean, SD, median, quartiles, minimum, and maximum. 
11.8 Pharmacodynamic Biomarker Analysis 
The biomarker levels of patients (values and percent changes from baseline) will be 
summarized by descriptive statistics.  
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12 INVESTIGATOR AND ADMINISTRATIVE REQUIREMENTS 
12.1 Institutional Review Board  
The protocol and ICF for this study must be reviewed and approved by an appropriate IRB 
before patients are enrolled in the study. It is the responsibility of the Investigator to assure 
that the study is conducted in accordance with current country and Local Regulations, 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for 
Human Use, GCP, and the Declaration of Helsinki. A letter, documenting the approval that 
specifically identifies the protocol by number and title as well as the Investigator, must be 
received by the Sponsor before initiation of the study. Amendments to the protocol will be 
subject to the same requirements as the original protocol. 
Upon the completion or termination of the study, the Investigator will notify the IRB. 
12.2 Informed Consent 
To obtain valid consent, each patient must be provided with written information describing 
the nature and duration of the study, the risks associated with the study, the burden on the 
patient and details of what will happen to any personal or health information collected. The 
patient must be provided with this information, given an opportunity to ask questions, and be 
given time to be able to consult with support persons or physicians such as a general 
practitioner. The patient must sign a written ICF indicating that they have read and 
understood the information sheet and what they are being asked to do. The ICF must be in a 
language in which the patient is fluent and must be signed before study-specific procedures 
are conducted. The signed and dated ICF will be retained with the study records. 
12.3 Data Reporting and Case Report Forms 
Data for each patient will be entered into the CRF and verified by the Investigator. It is the 
of the data reported on the patient
should indicate the patient
details of study procedures, AEs, and patient
 
The Investigator or designated representative should complete the CRF as soon as possible 
after information is collected, preferably on the same day that a study patient is seen for an 
examination, treatment, or any other study procedure. Any outstanding entries must be 
completed immediately after the final examination. CRF data will be processed in a US 21 
Code of Federal Regulations Part 11-compliant system. 
12.4 Retention of Data 
Regulations require that a copy of records (eg, laboratory data slips, source documents, test 
article disbursement records) that support case records of this study must be retained in the 
files of the responsible Investigator for a minimum of 15 years. 
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Investigator's responsibility to ensure the accuracy, completeness, legibility, and timeliness 
's CRF. Source documentation supporting the CRF data 
's participation in the study and should document the dates and 
's clinical status. 

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12.5 Deviations from the Protocol 
The Investigator will not deviate from the protocol. In medical emergencies, the Investigator 
will use medical judgment and will remove the patient from immediate hazard, and then 
notify the 
 Medical Monitor and the IRB promptly regarding the type of emergency 
and course of action taken. Any action in this regard will be recorded on the appropriate 
CRF. Any other changes or deviations in the protocol will be made as an amendment to the 
protocol and must be approved by the Sponsor and the IRB before the changes or deviations 
are implemented. The Sponsor will not assume any responsibility or liability for any 
deviation or change that is not described as part of an amendment to the protocol, or protocol 
clarification letters. 
12.6 Study Monitoring 
The Investigator will allow representatives of the Sponsor to periodically audit (at mutually 
convenient times before, during, and after the study has been completed) all CRFs and 
relevant portions of office, clinical, and laboratory records for each patient. Appropriate 
source documents, including documents that support patien
concomitant medications) should be made available to the Clinical Monitor. The monitoring 
visits provide the Sponsor with the opportunity to evaluate the progress of the study; verify 
the accuracy and completeness of CRFs; assure that all protocol requirements, applicable 
regulations, and Investigator's obligations are being fulfilled; and resolve any inconsistencies 
in the study records. 
12.7 Disclosure of Data 
Individual patient medical information obtained as a result of this study is considered 
confidential and disclosure to third parties other than those approved by the Sponsor is 
prohibited. Patient confidentiality will be further assured by utilizing patient identification 
code numbers to correspond to treatment data in the computer files. The study personnel, 
employees of the regulatory agencies, including FDA and the Sponsor and its agents will 
need to review patient medical records in order to accurately record information for this 
study. If results of this study are reported in medical journals or at meetings, the patient
identities will remain confidential. 
DocuSign Envelope ID: 42503FC5-ABF5-452E-A429-48DD0C237795 
Sponsor's 
ts' eligibility ( eg, medical history, 
s' 

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13 REFERENCES 
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