A Phase 2, Proof-of-Concept, Randomized, Double-Masked, Placebo-Controlled Study to Determine the Efficacy and Safety of LASN01 in Patients With Thyroid Eye Disease
Phase: PHASE2
Conditions: Thyroid Eye Disease, Graves Ophthalmopathy, Graves Orbitopathy, Thyroid Associated Ophthalmopathy, Endocrine System Diseases, Orbital Diseases, Proptosis, Eye Diseases
Sponsor: Lassen Therapeutics Inc.

Lassen Therapeutics 
LASN01 
Protocol LASN01-CL-2201
Version 7.0-US
 
15NOV2024 
Confidential  
1 
CLINICAL STUDY PROTOCOL 
Protocol Title:  
A Phase 2, Proof-of-Concept, Randomized, Double-Masked, Placebo-Controlled Study to 
Determine the Efficacy and Safety of LASN01 in Patients with Thyroid Eye Disease 
Protocol Number:  
LASN01-CL-2201 
Version Number:  
7.0, United States Amendment Only 
Compound:  
LASN01 
Study Phase:  
Phase 2 
IND Number: 
167553 
EU CT Number: 
2023-508161-32-00 
Sponsor Name:  
Lassen Therapeutics 1, Inc. (Lassen Therapeutics) 
Legal Registered Address:  
5510 Morehouse Dr., Suite 100, San Diego, CA 92121 
Telephone: +1 858-251-7528 
Sponsor Medical Representative:  
 
Version Date:  
15NOV2024 
Confidentiality Statement: 
This document is a confidential communication from Lassen Therapeutics 1, Inc. Acceptance of this document 
constitutes an agreement by the recipient(s) that no information contained herein will be published or disclosed 
without prior written approval from Lassen Therapeutics 1, Inc., except that this document may be disclosed to 
appropriate Institutional Review Boards and/or Ethics Committees under the condition that they are also required to 
maintain confidentiality. 
 
 

Lassen Therapeutics 
LASN01 
Protocol LASN01-CL-2201
Version 7.0-US
 
15NOV2024 
Confidential  
2 
INVESTIGATOR SIGNATURE PAGE 
I have read and understand protocol LASN01-CL-2201 (dated 15NOV2024). I agree to the 
following: 
1. To conduct the trial in compliance with Good Clinical Practice, with applicable regulatory 
requirement(s), with the protocol agreed to by the Sponsor and given approval/favorable 
opinion by the concerned regulatory authority and/or ethics committee 
2. To comply with procedures for data recording and reporting 
3. To permit monitoring, auditing, and inspection by the Sponsor, its designated representatives, 
and regulatory authorities  
4. To retain the essential documents in the Investigator/institution files until the Sponsor 
informs the Investigator or institution that these documents are no longer needed 
 
INVESTIGATOR SIGNATURE: 
 
 
_____________________________________    ___________________________ 
[Investigator Signature] 
 
 
 
 
Date 
 
 
_____________________________________  
[Investigator Name]  
 
 
 
[Site Name] 
 
 
 
 
 
 

Lassen Therapeutics 
LASN01 
Protocol LASN01-CL-2201
Version 7.0-US
 
15NOV2024 
Confidential  
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TABLE OF CONTENTS 
INVESTIGATOR SIGNATURE PAGE ................................................................................................................... 2 
SPONSOR APPROVAL PAGE ................................................................................................................................. 3 
LIST OF ACRONYMS, ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................. 7 
1. 
PROTOCOL SUMMARY ...................................................................................................................... 10 
1.1. 
Synopsis ..................................................................................................................................................... 10 
1.2. 
Schema ...................................................................................................................................................... 18 
1.3. 
Schedule of Activities ................................................................................................................................ 19 
2. 
INTRODUCTION ................................................................................................................................... 25 
2.1. 
Study Rationale ......................................................................................................................................... 25 
2.1.1. 
Unmet Need in TED .................................................................................................................................. 25 
2.1.2. 
IL-11 Activation of Fibroblasts and Tissue Fibrosis .................................................................................. 25 
2.2. 
Background ................................................................................................................................................ 26 
2.2.1. 
TED ........................................................................................................................................................... 26 
2.2.2. 
LASN01 ..................................................................................................................................................... 27 
2.3. 
Benefit/Risk Assessment ........................................................................................................................... 31 
2.3.1. 
Risk Assessment ........................................................................................................................................ 31 
2.3.2. 
Benefit Assessment .................................................................................................................................... 31 
2.3.3. 
Overall Benefit Risk Conclusion ............................................................................................................... 32 
3. 
OBJECTIVES AND ENDPOINTS ........................................................................................................ 33 
4. 
STUDY DESIGN ..................................................................................................................................... 36 
4.1. 
Overall Design ........................................................................................................................................... 36 
4.2. 
Justification for Dose ................................................................................................................................. 37 
4.3. 
Rationale for Comparator .......................................................................................................................... 37 
4.4. 
Rationale for Post-Teprotumumab Treatment Arm ................................................................................... 38 
4.5. 
End of Study Definition ............................................................................................................................. 38 
5. 
STUDY POPULATION .......................................................................................................................... 39 
5.1. 
Inclusion Criteria ....................................................................................................................................... 39 
5.2. 
Exclusion Criteria ...................................................................................................................................... 40 
5.3. 
Requalification and Rescreening for Entry ................................................................................................ 42 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY................................................... 43 
6.1. 
Study Intervention(s) Administered .......................................................................................................... 43 
6.2. 
Shipping, Storage, Preparation, Handling, and Accountability ................................................................. 43 
6.3. 
Assignment to Study Intervention ............................................................................................................. 44 
6.4. 
For Randomized Treatment Arms: Blinding and Breaking Code .............................................................. 44 
6.5. 
Dose Timing Adjustment after a Missed Dose of Study Drug .................................................................. 45 
6.6. 
Study Intervention Compliance ................................................................................................................. 45 
6.7. 
Treatment of Overdose .............................................................................................................................. 45 
6.8. 
Prior and Concomitant Medications, Substances, and Therapy ................................................................. 46 
6.8.1. 
Previous Medications, Substances, and Therapy ....................................................................................... 46 
6.8.2. 
Concomitant Medications, Substances, and Therapy ................................................................................ 47 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL .............................................................................................. 48 
7.1. 
Stopping Rules ........................................................................................................................................... 48 
7.2. 
Early Discontinuation of Study Intervention ............................................................................................. 48 
7.3. 
Participant Discontinuation/Withdrawal from the Study ........................................................................... 48 
7.4. 
Criteria for Discontinuation of Study ........................................................................................................ 49 
8. 
STUDY ASSESSMENTS AND PROCEDURES .................................................................................. 50 
8.1. 
Efficacy Assessments ................................................................................................................................ 50 

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8.1.1. 
Proptosis .................................................................................................................................................... 50 
8.1.2. 
CAS Assessments ...................................................................................................................................... 50 
8.1.3. 
Lid Aperture .............................................................................................................................................. 52 
8.1.4. 
Lagophthalmos, Eyelid Retraction, and Von Graefe’s Sign ...................................................................... 52 
8.1.5. 
Assessment of Diplopia and Extraocular Movements ............................................................................... 53 
8.1.6. 
Orbital MRI ............................................................................................................................................... 53 
8.1.7. 
Facial Digital Photographs ......................................................................................................................... 53 
8.2. 
Safety Assessments.................................................................................................................................... 53 
8.2.1. 
Best Corrected Visual Acuity, Visual Fields, and Color Defects .............................................................. 54 
8.2.2. 
Slit Lamp Biomicroscopy and Intraocular Pressure................................................................................... 54 
8.2.3. 
Dilated Fundoscopy ................................................................................................................................... 54 
8.2.4. 
Physical Examinations ............................................................................................................................... 54 
8.2.5. 
Body Weight .............................................................................................................................................. 55 
8.2.6. 
Vital Signs ................................................................................................................................................. 55 
8.2.7. 
ECGs .......................................................................................................................................................... 55 
8.2.8. 
Clinical Safety Laboratory Tests ............................................................................................................... 55 
8.2.9. 
Pregnancy Testing ..................................................................................................................................... 56 
8.3. 
AEs, SAEs, and Other Safety Reporting ................................................................................................... 56 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information ...................................................... 56 
8.3.2. 
Method of Detecting AEs and SAEs ......................................................................................................... 56 
8.3.3. 
Follow-Up of AEs and SAEs ..................................................................................................................... 56 
8.3.4. 
Pregnancy .................................................................................................................................................. 56 
8.3.5. 
AESIs ......................................................................................................................................................... 57 
8.4. 
PK Assessments ......................................................................................................................................... 57 
8.5. 
PD and Biomarker Assessments ................................................................................................................ 57 
8.6. 
Immunogenicity Assessments ................................................................................................................... 57 
8.7. 
Retention of Samples ................................................................................................................................. 57 
9. 
STATISTICAL CONSIDERATIONS ................................................................................................... 58 
9.1. 
Analysis Sets ............................................................................................................................................. 58 
9.2. 
Statistical Analyses .................................................................................................................................... 58 
9.2.1. 
General Considerations .............................................................................................................................. 58 
9.2.2. 
Analysis of Study Population and Patient Characteristics ......................................................................... 59 
9.2.3. 
Efficacy Analysis ....................................................................................................................................... 59 
9.2.4. 
Sensitivity Analysis for Primary Endpoint Using MMRM ........................................................................ 59 
9.2.5. 
Safety Analyses ......................................................................................................................................... 62 
9.2.6. 
PK Analyses .............................................................................................................................................. 62 
9.2.7. 
Participant Study Withdrawal and Premature Termination of Study Drug ................................................ 63 
9.2.8. 
Deviation Reporting ................................................................................................................................... 63 
9.3. 
Handling of Dropouts and Missing, Unused, and Spurious Data .............................................................. 63 
9.4. 
Interim Analyses ........................................................................................................................................ 63 
9.5. 
Sample Size Determination ....................................................................................................................... 64 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................................................... 65 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight Considerations .................................................... 65 
10.1.1. 
Regulatory and Ethical Considerations ...................................................................................................... 65 
10.1.2. 
Financial Disclosure .................................................................................................................................. 65 
10.1.3. 
Informed Consent Process ......................................................................................................................... 65 
10.1.4. 
Regulatory Authority and Ethics Committee Approval ............................................................................. 65 
10.1.5. 
Data Protection .......................................................................................................................................... 66 

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10.1.6. 
Data Quality Assurance ............................................................................................................................. 66 
10.1.7. 
Source Documents ..................................................................................................................................... 67 
10.1.8. 
eCRFs ........................................................................................................................................................ 67 
10.1.9. 
Retention of Records ................................................................................................................................. 67 
10.1.10. 
Dissemination of Clinical Study Data ........................................................................................................ 67 
10.1.11. 
Study and Site Start and Closure ............................................................................................................... 68 
10.1.12. 
Publication Policy ...................................................................................................................................... 68 
10.2. 
Appendix 2: Clinical Laboratory Tests ...................................................................................................... 69 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for Recording, Evaluating, 
Follow Up, and Reporting ......................................................................................................................... 70 
10.3.1. 
Definition of AE ........................................................................................................................................ 70 
10.3.2. 
Definition of SAE or Serious Suspected Adverse Reaction ...................................................................... 71 
10.3.3. 
Recording and Follow Up of AE and/or SAE ............................................................................................ 72 
10.3.4. 
Reporting of SAEs ..................................................................................................................................... 74 
10.4. 
Appendix 4: Contraceptive Guidance ........................................................................................................ 76 
11. 
REFERENCES ........................................................................................................................................ 77 
  
LIST OF TABLES 
Table 1.  
Schedule of Assessments and Procedures –Treatment Period ............................................................... 19 
Table 1b.  
Schedule of Assessments and Procedures – Follow-up Period .............................................................. 22 
Table 2. 
Multiple Dose Study Design .................................................................................................................. 36 
Table 3. 
Study Intervention(s) Administered ....................................................................................................... 43 
Table 4. 
CAS 7-point Scale .................................................................................................................................. 51 
Table 5.  
Guidelines for Severity Assessments ..................................................................................................... 73 
Table 6.  
Guidelines for Assessing Relationship of Event to Study Drug ............................................................. 74 
 
LIST OF FIGURES 
Figure 1. 
Overall Study Design ............................................................................................................................. 18 
  
 

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LIST OF ACRONYMS, ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
ADA 
antidrug antibody 
AE 
adverse event 
AESI 
adverse event of special interest 
AUC0-∞ 
area under the time-concentration curve from start of infusion extrapolated to time infinity 
AUC0-15d 
area under the time-concentration curve from start of infusion to 15 days after start of the 
infusion 
AUC0-28d 
area under the time-concentration curve from start of infusion to 28 days after start of the 
infusion 
AUC0-last 
area under the time-concentration curve from start of infusion to last measurable serum 
concentration  
AUC85-99d 
area under the time-concentration curve from Day 85 to Day 99 (ie, 0 to 14 days after fourth 
dose) 
BMI 
body mass index 
CAS 
clinical activity score 
CL 
total body clearance 
Cmax 
maximum serum concentration 
CRO 
clinical research organization 
CSR 
clinical study report 
CT 
computed tomography 
CV% 
coefficient of variation 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EOS 
End of Study 
ERK 
extracellular signal-regulated kinase 1 
EOT 
End of Treatment 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
EUGOGO 
European Group on Graves’ Orbitopathy 
FDA 
Food and Drug Administration 
FSH 
follicle stimulating hormone 
FU 
follow-up 
GCP 
Good Clinical Practices 
GLP 
Good Laboratory Practices 
gp130 
glycoprotein 130 
HA 
hyaluronic acid 
IB 
Investigator’s Brochure 
IC50 
50% inhibitory concentration 
ICF 
Informed Consent Form 
ICH 
International Council on Harmonisation 
IGF-1 
insulin-like growth factor 1 
IGF-1R 
insulin-like growth factor 1 receptor 
IgG4κ 
immunoglobulin G4 kappa  
IL 
interleukin 
IL-11R 
interleukin-11 receptor 

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Abbreviation 
Definition 
IND 
Investigational New Drug 
IP 
investigational product 
IPF 
idiopathic pulmonary fibrosis 
IRT 
interactive response technology 
IV 
Intravenous(ly) 
λz 
elimination rate constant 
MAD 
multiple ascending dose 
MAR 
Missing At Random 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed Mode Repeated Measures 
MRD 
margin reflex distance 
MRI 
magnetic resonance imaging 
mRNA 
messenger ribonucleic acid 
NOAEL 
no-observed-adverse-effect level 
PCR 
polymerase chain reaction 
PD 
pharmacodynamic(s) 
PF-ILD 
progressive fibrosing interstitial lung diseases 
PI 
Principal Investigator 
PK 
pharmacokinetic(s) 
Q2W 
every 2 weeks 
Q4W 
every 4 weeks 
QTcF 
QT interval, corrected for heart rate according to Fridericia's formula 
SAD 
single ascending dose 
SAE 
serious adverse event 
SAER 
serious adverse event report 
SAP 
Statistical Analysis Plan 
SARS-CoV-2 
severe acute respiratory syndrome associated coronavirus 2 
SOC 
standard-of-care 
SOP 
standard operating procedure 
SRC 
Safety Review Committee 
STAT3 
signal transducer and activator of transcription-3 
t1/2 
terminal half-life 
TEAE 
treatment-emergent adverse event 
TED 
thyroid eye disease 
TGFβ 
transforming growth factor beta 
TIMP1 
tissue inhibitor of metalloproteinase 1  
Tmax 
time to maximum serum concentration 
TRAE 
treatment-related adverse event 
TSH 
Thyroid stimulating hormone 
T3 
Triiodothyronine 
T4 
Thyroxine 
UA 
urinalysis 
Vss 
volume of distribution at steady state 

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Abbreviation 
Definition 
Vz 
volume of distribution 
WFI 
Water for Injection 
WOCBP 
women of child-bearing potential  

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Overall Design Synopsis 
This proof-of-concept Phase 2 study comprises the randomized treatment arms and the open-
label post-teprotumumab treatment arm. The randomized portion is designed as a double-
masked, randomized, placebo-controlled study to evaluate the efficacy, safety, tolerability, PK, 
immunogenicity, and PD properties of 2 dose levels of LASN01 administered IV Q4W ×13 
doses in anti-IGF-1R-naïve patients with TED. 
 
 
Following initial analysis of efficacy, the Sponsor may also expand the enrollment in the current 
cohorts and/or initiate additional cohorts with different subpopulations of TED patients (eg, 
chronic disease, recurrence following previous treatment, or in addition to standard of care). 
An amendment to the protocol will be submitted for appropriate regulatory authority review 
and/or approval in such a case.  
Number of Participants 
This study will include up to 36 evaluable patients with TED enrolled in 4 treatment arms. 
Approximately 24 anti-IGF-1R-naïve patients will be randomized (in a 1:1:1 ratio) upon 
enrollment to LASN01 in either a high-dose (600 mg Q4W ×13 doses) or low-dose (300 mg 
Q4W ×13 doses) treatment arm or to placebo
 
 
 Following 48 weeks of dosing (last dose administered on Day 337), 
patients will be followed for an additional 24 weeks, for a total study duration of 72 weeks (EOS 
visit on Day 505 ± 7 days). 
Enrollment Criteria 
Full inclusion and exclusion criteria are provided in Section 5.1 and Section 5.2, respectively.  
To be enrolled in this study, all participants must meet all of the following inclusion criteria and 
none of the exclusion criteria. The Sponsor may request an eligibility review to review key 
inclusion and exclusion criteria. 
Key Inclusion Criteria 
Patients must have met ALL of the following inclusion criteria to be included in the study:  
• Male or female ≥18 years of age at the time of Screening 
• Clinical diagnosis of Graves' disease associated with active TED and a CAS of ≥4 on the 
CAS 7-point scale and proptosis as defined by: 
o Proptosis ≥3 mm above normal for race and gender in the more affected eye (study eye) 
as determined by the PI or designee and  
o Proptosis ≥19 mm in the more affected eye (study eye) 
• Moderate-to-severe active TED (not sight-threatening but has an appreciable impact on daily 
life), as determined by the PI or designee and usually associated with ≥1 of the following: lid 
retraction ≥2 mm, moderate or severe soft tissue involvement, proptosis ≥3 mm above 
normal for race and gender, and/or inconstant or constant diplopia. 

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Study Arms and Duration 
This study will include up to 36 evaluable patients with TED enrolled in 4 treatment arms. 
Approximately 24 patients will be randomized (in a 1:1:1 ratio) upon enrollment to LASN01 in 
either a high-dose (600 mg Q4W ×13 doses) or low-dose (300 mg Q4W ×13 doses) treatment 
arm or to placebo. 
 
  
Study participation (Baseline to the EOS visit) will require approximately 505 days, not 
including the Screening period. The Screening visit will occur up to 30 days before Day 1.  
Treatment assignments will be performed centrally by IRT. 
An interim analysis may be performed when at least 50% of evaluable patients in the randomized 
treatment arms complete at least 8 weeks in the study (details will be provided in the SAP) to 
inform further development. The interim analysis may also include the open-label treatment arm. 
Concomitant Medications, Substances, and Therapy 
Use of the following concomitant medications, substances, and therapies during the study until 
the EOS visit is prohibited. EXCEPTIONS: any medications that are needed as treatment for 
AEs are allowed as determined by the PI or designee. In such cases, the PI or designee and the 
Medical Monitor will determine whether the patient may continue in the study.  
• Corticosteroids (oral or IV); if clinically indicated for conditions other than TED, the PI or 
designee should discuss with the Medical Monitor  
• Rituximab, tocilizumab, teprotumumab, or any monoclonal antibody for immunomodulation 
• Other immunomodulating therapy unless approved by the Medical Monitor 
• Biotin (including multivitamins that include biotin) within 2 days before any laboratory 
collection 
• Selenium 
EXCEPTION: Multivitamins that include selenium are allowed in usual doses 
• Any orbital irradiation/radiotherapy or planned orbital surgery for TED. 
• Vasoconstrictive eye drops and any eye drops (eg prostaglandin analogs) that can cause eye 
redness and swelling that impact the interpretation of study results are not permitted during 
the study; the use of other eye drops may be permitted if approved by the Medical Monitor. 
Artificial tears for dry eyes are permitted. 
Note: Local supportive measures for TED, simple analgesics (eg, acetaminophen, non-steroidal 
anti-inflammatory therapies), and non-steroidal medications/supplements for conditions other 
than TED are permitted during the study. Topical corticosteroids for conditions other than TED 
are allowed. 

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1.3. 
Schedule of Activities 
Table 1.  
Schedule of Assessments and Procedures –Treatment Period 
Study Procedures 
Study Day 
Screen 
(Day-30 
to Day-1) 
1 a 
8 
(±1) 
15 
(±2) 
29 
(±3) 
43 b 
(±2) 
57 
(±4) 
85 
(±4) 
113 
(±4) 
141 
(±4) 
169 
(±4) 
197 
(±4) 
225 
(±4) 
253 
(±4) 
281 
(±4) 
309 
(±4) 
337 
(±4) 
Week 
1 
2 
3 
5 
7 
9 
13 
17 
21 
25 
29 
33 
37 
41 
45 
49 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
evaluation 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Height (Screening only), BMI 
evaluation 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Body Weight 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Medical history  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Complete physical 
examination 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Brief physical examination 
 
X c 
X 
X 
X c 
 
X c 
X c 
X c 
X c 
X c 
X c 
X c 
X c 
X c 
X c 
X c 
Pregnancy test (WOCBP) d 
X 
X a 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Follicle-stimulating hormone 
as applicable e 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine drug screen 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serology (ie, hepatitis B virus 
surface antigen, hepatitis C 
virus antibody, HIV-1, and 
HIV-2) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG 
X 
X f 
X 
 
X f 
 
X f 
X f 
X f 
X f 
X f 
X f 
X f 
X f 
X f 
X f 
X f 
Vital signs g 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CAS h 
X 
X a 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Proptosis measurement v 
X 
X a 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Study Procedures 
Study Day 
Screen 
(Day-30 
to Day-1) 
1 a 
8 
(±1) 
15 
(±2) 
29 
(±3) 
43 b 
(±2) 
57 
(±4) 
85 
(±4) 
113 
(±4) 
141 
(±4) 
169 
(±4) 
197 
(±4) 
225 
(±4) 
253 
(±4) 
281 
(±4) 
309 
(±4) 
337 
(±4) 
Week 
1 
2 
3 
5 
7 
9 
13 
17 
21 
25 
29 
33 
37 
41 
45 
49 
Ophthalmic assessments i 
X 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Visual fields assessment j 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
 
X 
 
 
 
Color vision assessment k 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Dilated fundoscopy 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
Orbital MRI l 
X 
 
 
 
 
 
X 
X 
 
 
 
X 
 
 
X  
 
 
Randomization m 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Facial photography u 
X 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
Dose (LASN01 or placebo) 
administration 
(observed for 4 hours 
following first dose) 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
evaluation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse event evaluations 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology, coagulation 
X 
X n 
X 
X 
X n 
 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
Chemistry  
X 
X n 
X 
X 
X n 
 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
Urinalysis 
X 
X n 
X 
X 
X n 
 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
Hemoglobin A1c 
X 
 
 
 
 
 
 
 
 
X n 
 
X n 
 
X n 
 
 
 
Thyroid tests (TSH, T3, free 
T4) 
X 
X n 
 
 
X n 
 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
Thyroid stimulating 
immunoglobulin 
 
X n 
 
 
X n 
 
 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
PK Assessments 
Blood 
 
X o 
X 
X 
X o 
 
 
 
X o 
 
 
X o 
 
X o- 
 
 
X o 

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Study Procedures 
Study Day 
Screen 
(Day-30 
to Day-1) 
1 a 
8 
(±1) 
15 
(±2) 
29 
(±3) 
43 b 
(±2) 
57 
(±4) 
85 
(±4) 
113 
(±4) 
141 
(±4) 
169 
(±4) 
197 
(±4) 
225 
(±4) 
253 
(±4) 
281 
(±4) 
309 
(±4) 
337 
(±4) 
Week 
1 
2 
3 
5 
7 
9 
13 
17 
21 
25 
29 
33 
37 
41 
45 
49 
Immunogenicity Assessments 
ADA 
 
X p 
 
 
X p 
 
X p 
X p 
X p 
X p 
X p 
X p 
X p 
X p 
X p 
X p 
X p 
PD Assessments 
Blood sample for markers 
relevant to TED 
 
X q 
X 
 
X q 
 
X q 
 X q 
X q 
 
 
X q 
 
X q 
 
 
X q 
Blood sample for analysis of 
IL-11 
 
X r 
X 
X 
X r 
 
X r 
 X r 
X r 
 
 
X r 
 
X r 
 
 
X r 
Blood sample for analysis of 
IL-11R  
 
X r 
X 
X 
X r 
 
X r 
X r  
X r 
 
 
X r 
 
X r 
 
 
X r 
 
 
 

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Table 1b.  
Schedule of Assessments and Procedures – Follow-up Period  
Study Procedures 
Study Day 
344 (±4) 
351 (±4) 
365 (±4) 
379 (±4) 
393 (±4) 
449 (±7) 
505 (±7) 
EOS/ET t 
Week 50 
Week 51 
Week 53 
Week 55 
Week 57 
Week 65 
Week 73 
Height (Screening only), BMI evaluation 
 
 
 
 
 
 
 
Body Weight 
 
 
X 
 
X 
X 
X 
Complete physical examination 
 
 
 
 
 
 
X 
Brief physical examination 
 
 
X 
 
X 
X 
 
Pregnancy test (WOCBP)  
 
 
X 
 
 
 
X d 
12-lead ECG 
 
 
 
 
 
 
X 
Vital signs g 
 
 
X 
 
X 
X 
X 
CAS h 
 
 
X 
 
X 
X 
X 
Proptosis measurement v 
 
 
X 
 
X 
X 
X 
Ophthalmic assessments i 
 
 
X 
 
X 
X 
X 
Visual fields assessment  j 
 
 
X 
 
 
 
X 
Color vision assessment  
 
 
X 
 
X 
X 
X 
Dilated fundoscopy 
 
 
 
 
 
 
X 
Orbital MRI l 
 
 
X 
 
 
 
X 
Facial photography u 
 
 
X 
 
 
 
X 
Concomitant medications evaluation 
X 
X 
X 
X 
X 
X 
X 
Adverse event evaluations 
X 
X 
X 
X s 
X s 
X s 
X s 
Hematology, coagulation  
 
 
X 
 
 
 
X 
Chemistry  
 
 
X 
 
 
 
X 
Urinalysis  
 
 
X 
 
 
 
X 
Hemoglobin A1c 
 
 
X 
 
 
 
X 
Thyroid tests (TSH, T3, free T4)  
 
 
X 
 
X 
X 
X 
Thyroid stimulating immunoglobulin  
 
 
X 
 
X 
X 
X 
PK Assessments 
Blood  
X o 
X 
X 
X 
X 
 
X 
Immunogenicity Assessments 
ADA 
 
 
X 
 
X 
X 
X 

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Study Procedures 
Study Day 
344 (±4) 
351 (±4) 
365 (±4) 
379 (±4) 
393 (±4) 
449 (±7) 
505 (±7) 
EOS/ET t 
Week 50 
Week 51 
Week 53 
Week 55 
Week 57 
Week 65 
Week 73 
PD Assessments 
Blood sample for markers relevant to TED 
 
 
X 
 
 
 
X 
Blood sample for analysis of IL-11 
 
 
X 
 
 
 
X 
Blood sample for analysis of IL-11R  
 
 
X 
 
 
 
X 
 
ADA = antidrug antibody; BMI = body mass index; CAS = clinical activity score; ECG = electrocardiogram; EOS = End of Study; ET = Early Termination; HIV 
= human immunodeficiency virus; IL-11 = interleukin-11; IL-11R = interleukin-11 receptor; MRI = magnetic resonance imaging; PCR = polymerase chain 
reaction; PD = pharmacodynamic; PK = pharmacokinetic; TED = thyroid eye disease; WOCBP = women of childbearing potential  
 
a. 
Day 1 assessments are performed within 3 days before study drug dosing unless otherwise specified. Day 1 ophthalmology assessments (ie, CAS and 
proptosis measurement) and urine pregnancy test should be used to confirm eligibility before first dose is administered. 
b. Safety assessments (concomitant medications and adverse events evaluation) on Day 43 may be completed by telephone call if appropriate 
c. 
Brief physical examination should be performed predose on dosing days 
d. A serum pregnancy test should be performed at Screening and at EOS/ET (Day 505). A urine pregnancy test should be performed at all other specified clinic 
visits. Urine pregnancy test should be performed predose on dosing days 
e. 
For female patients who are postmenopausal to confirm that they are not WOCBP 
f. 
Triplicate 12-lead ECG should be performed predose on dosing days. Perform triplicate ECGs within a 15-minute period, separated by ≥1 minute. ECG 
recordings will be taken after ≥5 minutes in a semi-supine, quiet-rest position (head of bed between 0° and 90°), and before obtaining any blood sample. 
Refer to Section 8.2.7 for details. 
g. Vital signs include seated respiratory rate, blood pressure, pulse rate, and body temperature. Vital signs will be measured predose and post-dose on Day 1 
and predose on all other dosing days. Additional vital signs will be monitored if infusion-associated AEs or other AEs occur at PI discretion (see 
Section 8.2.6 for details). Vital signs on nondosing visits should be taken at approximately the same time (±2 hours) as taken on dosing days, whenever 
possible. Note that the timing of PK samples should take priority over the timing for vital signs. 
h. The same assessor should conduct each CAS evaluation at each visit. Refer to Section 8.1.2 for details on orbital pain, conjunctival redness, eyelid swelling 
and chemosis grading in addition to CAS score. CAS assessment should be completed prior to any eye drops administered for dilation or any other purpose. 
CAS should be assessed predose on dosing days.  
i. 
Lid aperture, visual acuity, diplopia and extraocular movements, lid retraction, lagophthalmos, Von Graefe's sign, slit lamp biomicroscopy, and intraocular 
pressure should be assessed predose on dosing days  
j. 
Visual fields should be assessed predose on dosing days. In the event of elevated IOP or AEs potentially related to decreased optic nerve function, additional 
visual fields may be assessed at PI discretion. 
k. Ishihara color vision assessment should be assessed predose on dosing days  
l. 
Exception: Patients who cannot have an MRI due to the presence of metal or other known reason. In the US only, an orbital CT scan may be performed in 
patients who cannot have an MRI. In such cases all imaging time points must have a CT scan performed.  Images collected within 30 days of consent as part 
of standard of care may be used as the Baseline scan, provided that the acquired image conforms to the study-specific image acquisition parameters and with 
prior approval from the Medical Monitor. 

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m. Randomization will take place by IRT after all eligibility criteria are met and not more than 3 days before dosing  
n. Safety laboratory samples should be obtained predose  
o. PK samples should be obtained predose on the specified dosing days in the schedule of assessments above. On Days 1 and 337, samples should also be 
obtained 30-60 minutes after the end of the infusion. On Day 344, the sample should be collected at a similar time of day when the Day 337 post dose 
sample collection occurred. 
p. ADA samples should be obtained predose on the specified dosing days in the schedule of assessments above. On Day 1, samples should also be obtained at 
end of infusion (≤60 minutes after the end of the infusion).  
q. Blood samples for exploratory biomarkers relevant to TED, fibrosis, and inflammation should be collected predose on the specified dosing days in the 
schedule of assessments above. 
r. 
Serum for analysis of IL-11 and IL-11R should be obtained predose on the specified dosing days in the schedule of assessments above. On Days 1 and 337, 
serum samples should also be obtained 30-60 minutes after the end of the infusion. 
s. 
Treatment-emergent adverse events should be captured until Week 53 (Day 365). From this visit to the EOS/ET (Week 73: Day 505) visit, only treatment-
related AEs should be recorded. 
t. 
Patients who prematurely discontinue study drug should still remain on study for scheduled visits and assessments and every effort should be made to obtain 
protocol-specified assessments.  Patients who withdraw completely from this clinical study should be encouraged to complete the EOS/ET visit. 
u. Facial photographs (including retrospective facial photographs) should be collected only after informed consent is obtained. The five cardinal positions of 
gaze (up, down, right, left and primary gaze) should be captured. 
v. The same instrument and assessor should be used for each visit. If a different assessor than the initial/main assessor is used, then the assessment should be 
repeated by the initial/main assessor as soon as possible. 

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2. 
INTRODUCTION 
LASN01 is a first-in-class, fully human, IgG4κ monoclonal antibody directed against human IL-
11R and is being initially developed for treatment of patients with TED. 
2.1. 
Study Rationale 
2.1.1. 
Unmet Need in TED 
Despite extensive ongoing research, the pathophysiology, prevention, and ideal treatment for 
TED remains elusive (Rashad 2022; Supronik 2022). Teprotumumab (TEPEZZA®) is an insulin-
like growth factor-1 receptor inhibitor approved in the United States in 2020 for the treatment of 
TED (Teprotumumab Prescribing Information 2022). Warnings and precautions include infusion 
reactions, exacerbation of preexisting inflammatory bowel disease, and hyperglycemia. Severe 
cases of TED require aggressive measures to manage the patient’s systemic thyroid disorder. 
Intravenous glucocorticosteroid therapy continues to be generally used as first-line treatment for 
moderate to severe acute TED in the rest of the world, but efficacy is often underwhelming, the 
rate of recurrence is high, and there are significant side effects. The recent EUGOGO guidelines 
propose that mycophenolate be added to IV glucocorticosteroid therapy as a first-line treatment 
in active, moderate-to-severe Graves’ orbitopathy, considering its beneficial effect on long-term 
outcome and less frequent recurrences (Bartalena 2021). Considering the complex pathogenesis 
of TED involving many molecular pathways, a number of agents are proposed as a second-line 
treatment in the event of poor response to IV teprotumumab or glucocorticosteroid therapy or 
disease relapse after treatment. Novel agents with different mechanism of action are needed in 
the treatment of TED. 
2.1.2. 
IL-11 Activation of Fibroblasts and Tissue Fibrosis 
IL-11R is a 422 amino acid type I transmembrane protein that is the sole known receptor for 
IL-11. In common with other members of the IL-6 cytokine family, IL-11 signaling uses a 
common co-receptor, gp130 (also known as IL6ST). IL-11 signaling takes place upon binding of 
IL-11 to IL-11R followed by recruitment of gp130 into a hexameric signaling complex 
containing 2 molecules each of IL-11, IL-11R, and gp130 (Barton 2000). Resultant signaling 
takes place through both the phosphorylation of STAT3 and of ERK (Metcalfe 2020; 
Widjaja 2019). LASN01 inhibits signaling with pM potency through binding specifically to 
IL-11R and inhibiting its ability to form a functional signaling complex with gp130, hence 
preventing IL-11-induced signaling.  
IL-11 signaling has been shown to be an important regulator of fibroblast activation and tissue 
fibrosis. This was demonstrated as early as 1996, when IL-11 overexpression in the airways of 
mice was shown to result in tissue fibrosis and the potentiation of tissue inflammation 
(Tang 1996). Since then, a role has been suggested in a number of human fibroinflammatory 
diseases as described below. 
IL-11 is stimulated by and exhibits crosstalk with other fibroinflammatory mediators such as 
TGFβ, platelet-derived growth factor, connective tissue growth factor, Ang II, and IL-13 
(Ng 2020; Kortekaas 2021; Schafer 2017). In interstitial lung diseases, IL-11 expression has 

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been reported to be increased in tissue from patients with IPF (Ng 2019) and also significantly 
upregulated in invasive IPF fibroblasts compared to healthy controls (Geng 2019). Similarly, 
IL-11 was one of the most highly upregulated genes in tissue from scleroderma-associated 
interstitial lung disease patients (Lindahl 2013). In the heart, RNAseq data on cardiac fibroblasts 
from 84 independent donors revealed that IL-11 was highly upregulated following TGFβ 
treatment, and IL-11R knock-out mice were protected in an angiotensin II-induced cardiac 
fibrosis model (Schafer 2017). Similar correlations between IL-11 expression and tissue fibrosis 
have been noted in nonalcoholic steatohepatitis, kidney disease, ulcerative colitis, and 
Hermansky Pudlak Syndrome (Widjaja 2019; Menendez-Castro 2020; Nishina 2021; 
Strikoudis 2019). These data indicate that IL-11 is a prominent fibroinflammatory mediator and 
suggests that inhibition of IL-11 signaling may provide a novel therapeutic approach to treat 
fibroinflammatory diseases.  
2.2. 
Background 
2.2.1. 
TED 
TED, also known as Graves’ orbitopathy or Graves’ eye disease, is an inflammatory disorder of 
orbital tissue characterized by infiltration of lymphocytic cells, orbital fat expansion, and 
extraocular muscle swelling (Rashad 2022; Supronik 2022). It is associated with the systemic 
disease hyperthyroidism which requires a multimodal approach to treatment in addition to the 
treatment of TED.  Treatment of the systemic disease can also impact TED so patients with 
hyperthyroidism with or without TED should also engage in smoking cessation and other 
measures to treat the hyperthyroidism. 
TED is an autoimmune disorder, with associated thyroid autoimmunity always discernible. The 
presence of one or more shared autoantigens between the thyroid and the orbit may explain why 
retro-orbital tissues are affected. Extraocular muscles and retro-ocular connective tissue are 
infiltrated by lymphocytes, leading to activation of cytokine networks and inflammation and 
interstitial edema of the extraocular muscles. Excess secretion of glycosaminoglycans by orbital 
fibroblasts seems to be an important contributor. The end result is expansion of the volume of 
extraocular muscles, retro-orbital fat, and connective tissue. Similar changes affect the eyelids 
and anterior periorbital tissues. Apart from visible swelling and redness of the eyelids and 
conjunctiva, the other clinical features of thyroid eye disease can also be accounted for by the 
expansion of inflammatory soft tissue within the constraints of the rigid bony orbit. Anterior 
displacement of the globe by the edematous extraocular muscles and orbital fibrofatty tissues 
results in exophthalmos and lower lid retraction. These symptoms in turn may lead to impaired 
lid closure and significant ocular surface disease including corneal ulceration, especially if the 
levator muscle is also infiltrated and its excursion restricted. Edematous extraocular muscles lose 
compliance, restrict eye movements, and can compress the optic nerve at the orbital apex 
(Perros 2009).  
The incidence of clinically relevant TED is 16 per 100,000 in females and 2.9 per 100,000 in 
males. Overall, TED is a sight-threatening, debilitating, disfiguring disease that can profoundly 
affect quality of life.  Other supportive measures that do not bias the assessments in this trial are 

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2.2.2.2.3. 
Genotoxicity 
No genotoxicity studies are required since LASN01 is a monoclonal antibody.  
2.2.2.2.4. 
Reproductive Toxicity 
No reproductive toxicity studies have been conducted to date.  
2.2.2.3. 
Clinical Summary 
A first-in-human 4-part Phase 1/2a (LASN01-CL-1101) randomized, double-blind placebo-
controlled, SAD, and MAD clinical study is ongoing in Australia to determine the safety, 
tolerability, preliminary efficacy, immunogenicity, and PK properties of LASN01 in healthy 
volunteers and in patients with pulmonary fibrosis or TED, as well as preliminary efficacy 
biomarkers in patients with TED.  
In the healthy volunteer portions of the study (ie, SAD and MAD cohorts), interim, topline, 
unblinded safety and PK data for 58 healthy volunteers are available (data cutoff date of 
02JUN2023). In the completed SAD portion of the study (Part A), LASN01 doses of 25, 100, 
300, 600, and 1200 mg IV were evaluated. In the completed MAD portion of the study (Part B), 
LASN01 doses of 600 (B1) and 1200 (B2) mg IV were evaluated. The study is ongoing with 
planned multiple doses of 1200 mg in patients with IPF and PF-ILD (Part C) and TED (Part D).  
Overall, 35 healthy volunteers (60.3%) experienced 61 TEAEs. A total of 13 healthy volunteers 
(22.4%) experienced 18 TEAEs considered potentially related to study drug (LASN01 or 
placebo) by the Investigator. There were no serious or severe TEAEs reported and no subject 
withdrew from the study due to a TEAE. The incidence of TEAEs was not dose related. Most 
TEAEs were not related to study drug and all were mild or moderate in severity. 
The PK of LASN01 follows approximately dose-proportional PK based on both the SAD and 
MAD cohorts. The mean half-life estimates ranged from 165 to 335 hours at doses ≥25 mg/day 
administered as a single IV dose or as 2 administrations 14 days apart, supporting the extended 
dosing intervals under consideration for clinical studies. The PK profile in healthy volunteers is 
consistent with that observed in the cynomolgus monkey. 
Subject samples from all cohorts reduced the ability of hyper IL-11 to stimulate phosphorylated 
STAT3 signal 24 hours after dosing in both the T-cell and monocyte populations to Baseline 
levels. The duration of inhibition of phosphorylated STAT3 signal demonstrated a time-
dependent and dose-dependent relationship.  
Overall, data from Parts A and B of Study LASN01-CL-1101 show favorable safety, predictable 
and linear PK, and target engagement in support of this Phase 2 study in TED. Part C and D have 
completed enrollment and these parts are ongoing. Ongoing safety surveillance of the masked 
patients in Parts C and D does not show any further safety signals and appears to have a similar 
safety profile to Parts A and B. 

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2.3. 
Benefit/Risk Assessment 
2.3.1. 
Risk Assessment 
As this is the second clinical trial of LASN01 in humans, a full risk profile has not yet been 
characterized. In the Phase 1/2a clinical study (LASN01-CL-1101), no safety concerns have 
emerged to date. Patients in Parts C and D in the study have completed enrollment and are 
ongoing without additional safety signals observed with ongoing safety monitoring. Nonclinical 
studies and data from humans with genetic defects in IL-11 production show defects in bone 
development (Nieminen 2011; Keupp 2013). Short-term exposures in adult patients in the 
proposed study are not expected to cause any developmental defects. Inhibition of fibrogenesis 
can potentially affect normal wound healing (Allanki 2021). However, IL-11 is not known to 
affect normal fibrotic processes or normal wound healing. Recombinant IL-11 is an approved 
treatment that stimulates thrombopoiesis. However, IL-11 knockout animals do not display 
platelet defects, and LASN01 and IL-11 have shown no effect on platelet numbers or function in 
nonclinical toxicology studies (Section 2.2.2.2.1).  Liver function tests will be followed closely 
for any clinically significant, adverse changes.  
An additional internal Lassen Therapeutics study investigated the ability of LASN01 to induce 
cytokine release in vitro using either peripheral blood mononuclear cells or whole blood. Results 
show that LASN01 has a low probability of inducing cytokine release in patients. In the 
subsequent healthy volunteer Phase 1 trial, no symptoms of cytokine release were observed in 
any of the patient cohorts, including the high dose of 1200 mg.  
Data is pending on the effects of LASN01 withdrawal on the levels of IL-11 in circulation. 
To ensure the safety of all patients, safety data will be closely followed for all patients. 
No reproductive toxicity studies have been performed with LASN01. Based on published 
literature, reproductive development toxicity has been observed in IL-11 knockout mice. In 
contrast, humans with genetic mutations resulting in impaired IL-11R function appear fertile, 
despite displaying developmental effects such as a craniosynostosis-like phenotype 
(Keupp 2013). These data suggest fertility effects may be species specific.  
This study requires female patients to be nonpregnant, nonlactating, and either postmenopausal, 
surgically sterile, or agree to use highly effective forms of contraception (Appendix 4, 
Section 10.4). Males must be surgically sterile or agree to highly effective methods of 
contraception (Clinical Trials Facilitation and Coordination Group 2020) (Appendix 4, 
Section 10.4). 
2.3.2. 
Benefit Assessment 
This is the first Phase 2 study in patients with TED; the clinical benefit of LASN01 in patients 
with TED has not yet been evaluated. Patients with TED who receive LASN01 may experience 
improvement in signs and symptoms of disease. 

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2.3.3. 
Overall Benefit Risk Conclusion 
Based on the currently available nonclinical and clinical data, LASN01 is anticipated to have a 
favorable benefit to risk profile in patients with TED. The efficacy of LASN01 has been 
established in vitro and in animal models (Section 2.2.2.1.2).  
In the first-in-human, Phase 1, clinical study (LASN01-CL-1101) in healthy volunteers, no 
safety concerns have emerged to date and no serious or severe AEs were reported. Enrollment of 
patients with IPF/PF-ILD (Part C) or TED (Part D) is completed and the study is ongoing to 
evaluate the safety and preliminary efficacy of LASN01 at 1200 mg with a favorable safety 
profile to date.  
Overall, the non-clinical and clinical safety profile of LASN01 remains favorable and supports 
continued development of LASN01 in patients with TED. 
Frequent monitoring of safety data will be performed, with timely review and safety monitoring 
will be adjusted as required if any risks become apparent. An SRC will review safety data on an 
ongoing basis.  
 

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4. 
STUDY DESIGN 
4.1. 
Overall Design 
This proof-of-concept Phase 2 comprises the randomized, double-masked, placebo-controlled 
treatment arms in patients with TED with no prior anti-IGF-1R treatment (ie, anti-IGF-1R-naïve 
patients) 
 
  
The randomized treatment arms will evaluate the efficacy, safety, tolerability, PK, 
immunogenicity, and PD of 2 dose levels of LASN01 administered IV Q4W ×13 doses in anti-
IGF-1R-naïve patients with TED. 
 
 
Following initial analysis of efficacy, the Sponsor may also expand the enrollment in the current 
cohorts and/or initiate additional cohorts with different subpopulations of TED patients (eg, 
chronic disease, recurrence following previous treatment, or in addition to standard of care). An 
amendment to the protocol will be submitted for appropriate regulatory authority review and/or 
approval in such a case. 
This study will include approximately 36 evaluable patients with TED in 4 treatment arms. For 
the randomized treatment arms, approximately 24 patients will be randomized (in a 1:1:1 ratio) 
upon enrollment to LASN01 in either a high-dose (600 mg Q4W ×13 doses) or low-dose 
(300 mg Q4W ×13 doses) treatment arm or to placebo. 
 
  
The Schedule of Assessments and Procedures is presented in Section 1.3  and the study 
schematic is presented in Figure 1. The Screening period will last up to 30 days before Day 1, the 
treatment period will last 48 weeks, and the FU period will last approximately 24 additional 
weeks. The Medical Monitor may extend the Screening period by up to 7 business days if needed 
to accommodate logistical delays. This study is outpatient and does not require admission to a 
clinical research unit. 
Table 2. 
Multiple Dose Study Design 
Randomized 
Treatment Arm 
Dose 
Number 
of Doses 
Number of Patients 
1 
Low-dose LASN01 (300 mg Q4W) 
13 
8 
2 
High-dose LASN01 (600 mg Q4W)  
13 
8 
3 
Placebo (Q4W) 
13 
8 
Total Number of Patients 
24 
 

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4.2. 
Justification for Dose 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
4.3. 
Rationale for Comparator  
In this study, placebo will be used as a comparator to demonstrate the treatment effect of 
LASN01 in patients with TED.  Safety monitoring during the study will include regular 
ophthalmic examinations and the patient’s TED will be monitored closely to ensure safety.  

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4.5. 
End of Study Definition 
A patient is considered to have completed the study if the patient has completed all periods of the 
study including the EOS visit. The study will be defined as ended for all patients as of the date of 
the EOS visit of the last patient. 

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5. 
STUDY POPULATION 
In this study, patients with TED meeting all study eligibility criteria will be included. 
Regulatory, ethical, and study oversight consideration are provided in Appendix 1 (Section 10.1). 
To be enrolled in this study, all participants must meet all of the following inclusion criteria and 
none of the exclusion criteria. The Sponsor may request an eligibility review to review key 
inclusion and exclusion criteria. 
5.1. 
Inclusion Criteria 
Patients must have met ALL of the following inclusion criteria to be included in the study: 
1. Male or female patients ≥18 years of age at the time of Screening 
2. Clinical diagnosis of Graves’ disease associated with active TED and a CAS of ≥4 on the 
CAS 7-point scale and proptosis as defined by: 
o Proptosis ≥3 mm above normal for race and gender in the more affected eye (study 
eye) as determined by the PI or designee and 
o Proptosis ≥19 mm in the more affected eye (study eye) 
3. Moderate-to-severe active TED (not sight-threatening but has an appreciable impact on daily 
life) determined by the PI or designee, usually associated with ≥1 of the following: lid 
retraction ≥2 mm, moderate or severe soft tissue involvement, proptosis ≥3 mm above 
normal for race and gender, and/or inconstant or constant diplopia 
4. For anti-IGF-1R-naïve patients: less than 15 months (at Day 1) from onset of TED symptoms 
in the study eye as determined by the PI or designee. For post-teprotumumab patients who 
did not respond to teprotumumab treatment for any reason, less than 24 months (at Day 1) 
from initial onset of TED symptoms in the study eye, as determined by the PI or designee. 
For post-teprotumumab patients who have reactivation of disease after responding to 
treatment, less than 15 months (at Day 1) from the renewed onset of TED symptoms in the 
study eye, as determined by the PI or designee. 
5. No previous: 
• Medical treatment for TED, with the exception of: 
o Local supportive measures 
o Mycophenolate, and oral or injectable steroids if the maximum cumulative dose is 
≤4.5 g methylprednisolone or equivalent with ≥6 weeks between last administration of 
oral steroids and/or mycophenolate and Screening  
o Previous use of rituximab, tocilizumab, or any monoclonal antibody for 
immunomodulation, more than 9 months before Day 1 
o Previous use of any other immunomodulating therapy more than 3 months before 
Day 1 unless approved by the Medical Monitor 

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23. History of malignancy within 1 year prior to Day 1 as determined by the PI or designee.  
EXCEPTION: patients with basal cell and squamous cell carcinomas of the skin, or in situ 
carcinoma of the cervix uteri that have been completely excised and cured. 
5.3. 
Requalification and Rescreening for Entry 
During the Screening period, procedures may be repeated, if appropriate, and at the discretion of 
the PI or designee. For patients who fulfill entry criteria but are not randomized within the 30-
day Screening visit window, the patient may still be eligible; the Medical Monitor will determine 
which procedures from the original Screening period can be used and which procedures must be 
repeated to confirm eligibility.  
Patients not fulfilling the entry criteria and not randomized may be rescreened once if 
reconsidered for study participation. 

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6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY 
6.1. 
Study Intervention(s) Administered 
LASN01 drug product is supplied as a sterile, colorless to pale brown frozen liquid for thawing 
and dilution with WFI before infusion (Table 3). Each vial of LASN01 drug product is 
comprised of 100 mg of LASN01. Excipients are 20 mM histidine, 200 mM arginine, 125 mM 
sorbitol, and 0.02% (v/v) polysorbate 20. The product is limited to investigational use only.  
Pharmaceutical grade 0.9% sodium chloride will be administered IV as the placebo control.  
Table 3. 
Study Intervention(s) Administered 
Intervention Name 
Low-dose LASN01 
(300 mg) 
High-dose LASN01 
(600 mg) 
Placebo 
Intervention 
Description 
Antibody 
Antibody 
0.9% sodium chloride 
Type  
Biological 
Biological 
0.9% sodium chloride 
Unit Dose 
Strength(s) 
20 mg/mL 
20 mg/mL 
Not applicable 
Total Volume 
Administered 
60 mL 
Bag 1: 30-mL placebo  
Bag 2: 15-mL LASN01 + 
15-mL Water for Injection 
60 mL 
Bag 1: 15-mL LASN01 + 
15 mL Water for Injection  
Bag 2: 15-mL LASN01 + 
15 mL Water for Injection 
60 mL 
Bag 1: 30-mL placebo  
Bag 2: 30-mL placebo 
Storage of 
Prepared 
Investigational 
Product 
Prepared infusion bags should be stored in 1 of 2 conditions: 
1) 2°C to 8°C for no more than 24 hours total  
OR 
2) Room temperature for no more than 6 hours 
Route of 
Administration 
Intravenous infusion 
Intravenous infusion 
Intravenous infusion  
6.2. 
Shipping, Storage, Preparation, Handling, and Accountability 
Each shipment of LASN01 is transferred to the sites on dry ice and will contain a drug 
transmittal and receipt form to assist in maintaining current and accurate inventory records. 
Upon receipt of LASN01, the pharmacy or study personnel will visually inspect the shipment 
and verify the number and condition of vials received. The vials are immediately transferred to 
the storage unit. Vials of LASN01 Solution for Injection are stored at ≤ -60°C and protected 
from light.  
Vialed LASN01 drug product is thawed and diluted with WFI according to Table 3. Once the IP 
dose has been prepared in the infusion bags, the bags should be stored at 2°C to 8°C for no more 
than 24 hours total, or at room temperature for no more than 6 hours. 
LASN01 is infused at a rate of 200mL/hr using an in-line 0.2-micron filter. Pharmaceutical grade 
0.9% sodium chloride will be delivered as a line flush after IP infusion.  

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Similarly, the placebo will follow the details outlined in (Table 3). Placebo will also use an in-
line 0.2-micron filter. The pharmacy or unmasked study personnel are responsible for ensuring 
that a current record of LASN01 inventory and accountability is maintained. An unmasked 
Pharmacy Monitor will be responsible for checking drug accountability at the site. Inventory and 
accountability records must be readily available for inspection by the unmasked Pharmacy 
Monitor and are open to inspection at any time by applicable regulatory authorities.  
Final drug disposition procedures will be detailed in the applicable study manuals.  
Please refer to the Pharmacy Manual for detailed information on study drug storage, preparation, 
handling, and accountability. 
6.3. 
Assignment to Study Intervention 
Patients will be assigned a Screening Number at signing of the ICF.  
For the randomized treatment arms, patients will be randomized to receive LASN01 300 mg, 
LASN01 600 mg, or placebo. Patients are confirmed as eligible for randomization based on 
Screening assessments. Randomization should take place not more than 3 days before dosing.  
Day 1 assessments are performed within 3 days before study drug dosing unless otherwise 
specified. Day 1 ophthalmology assessments (ie, CAS and proptosis measurement) and urine 
pregnancy test should be used to confirm eligibility before first dose is administered.  
 
 
 
 
 
  
The study site’s pharmacist (or pharmacist designee) will obtain the study drug assignment by 
IRT. A patient is considered randomized 
 
 when the pharmacist obtains the study drug assignment. Treatment assignments will be 
performed centrally by IRT. 
6.4. 
For Randomized Treatment Arms: Blinding and Breaking Code 
This study is a randomized, double-masked design. Bias is minimized by patient randomization 
and masking. The PI (or designee), study personnel, and patients should not make any effort to 
determine which study drug therapy is being received. Unmasked pharmacy personnel and 
unmasked study personnel (eg, unmasked Pharmacy Monitor, PK analyst, statistician) will be 
utilized in this study.  
All study personnel, including the Sponsor, PI (or designee), and site personnel involved in study 
conduct, and patients will remain masked to study medication assignment until otherwise 
specified, with the exceptions of a Pharmacy Monitor to monitor drug preparation and drug 
accountability during the study; cases in which unmasking is required due to a safety or 
tolerability issue; by designated unmasked study team members, as needed, to prepare analyses 

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in preparation for SRC meetings; or as requested by the SRC from the unmasked biostatistician 
if needed.  
To maintain study masking, study drug preparation will be performed by an unmasked site 
pharmacist (or qualified unmasked personnel at the study site not involved with study procedures 
or evaluations) in accordance with the procedures outlined in the Pharmacy Manual.  
Only in the case of an emergency, when knowledge of the study drug is essential for the clinical 
management or welfare of a specific patient (eg, an AE to be of such severity as to require 
immediate specific knowledge of the treatment assignment), may the PI (or designee) obtain a 
patient’s treatment assignment. All unmasking events must be reported to the Sponsor and 
Medical Monitor promptly. Prior to any unmasking, the PI (or designee) is strongly advised to 
discuss options with the Medical Monitor or appropriate Sponsor study personnel. As soon as 
possible and without revealing the patient’s study treatment assignment (unless important to the 
safety of patients remaining in the study), the PI (or designee) must notify the Sponsor if the 
mask is broken for any reason and the PI (or designee) was unable to contact the Sponsor before 
unmasking. The PI (or designee) will record the date and reason for revealing the masked 
treatment assignment for that patient and the names and roles of the personnel unmasked in the 
source documentation. 
Unmasked data may be reviewed by designated Sponsor personnel who are not responsible for 
study management or decisions that impact data integrity, in accordance with relevant study 
plans.  
6.5. 
Dose Timing Adjustment after a Missed Dose of Study Drug  
After a missed dose of study drug (ie, dosing not within the specified window allowed), the 
individual patient should be dosed as soon as possible. If study drug dosing is delayed by 
>1 week, it must be approved by the Medical Monitor and subsequent study visits (ie, study 
assessments and study drug dosing) of the patient may be adjusted accordingly in order to 
maintain the planned timing interval between doses. Any additional or alternative changes to the 
timing of individual study visits, assessments, and/or study drug dosing after a missed dose of 
study drug are allowed if approved by the Medical Monitor. 
6.6. 
Study Intervention Compliance 
Treatment compliance will be documented in the eCRF by recording the date, start time, and if 
the dose of study drug was completely infused. 
6.7. 
Treatment of Overdose 
There is no specific antidote for overdose with LASN01. In the event of a suspected overdose, 
contact the Medical Monitor and institute appropriate supportive clinical care, as dictated by the 
patient’s clinical status. 

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6.8.2. 
Concomitant Medications, Substances, and Therapy 
Use of the following concomitant medications, substances, and therapies during the study until 
the EOS visit is prohibited. EXCEPTIONS: any medications that are needed as treatment for 
AEs are allowed as determined by the PI. In such cases, the PI and the Medical Monitor will 
determine whether the patient may continue in the study.  
• Corticosteroids (oral or IV); if clinically indicated for conditions other than TED, the PI 
(or designee) should discuss with the Medical Monitor  
• Rituximab, tocilizumab, teprotumumab, or any monoclonal antibody for immunomodulation 
• Other immunomodulating therapy (unless approved by the Medical Monitor) 
• Biotin (including multivitamins that include biotin) within 2 days before any laboratory 
collection 
• Selenium 
EXCEPTION: Multivitamins that include selenium are allowed in usual doses 
• Orbital irradiation/radiotherapy or planned orbital surgery for TED 
• Vasoconstrictive eye drops and any eye drops (eg prostaglandin analogs) that can cause eye 
redness and swelling that impact the interpretation of study results are not permitted during 
the study; the use of other eye drops may be permitted if approved by the Medical Monitor. 
Artificial tears for dry eyes are permitted. 
Note: Local supportive measures for TED, simple analgesics (eg, acetaminophen, non-steroidal 
anti-inflammatory therapies), and non-steroidal medications/supplements for conditions other 
than TED (eg, topical corticosteroids) are permitted during the study.  
The following prior and concomitant medications are acceptable: 
• Stable doses of thyroid replacement  
• Medications for the treatment of hyperthyroidism  
• Stable doses of oral contraceptive therapy are permissible 
• Killed and inactive vaccines, including mRNA vaccines (eg, pneumonia, influenza, 
SARS-CoV-2) and live attenuated vaccines (eg, varicella) are permitted  
 
 

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7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1. 
Stopping Rules 
Study drug must be discontinued in any individual patient who experiences a study drug-related 
SAE or any other AE that, in the opinion of the PI, warrants discontinuation of study drug. 
Before discontinuation, please discuss with the Medical Monitor. 
7.2. 
Early Discontinuation of Study Intervention 
Patients who prematurely discontinue study drug should still remain on study for scheduled visits 
and assessments and every effort should be made to obtain all protocol-specified assessments to 
avoid losing data that is needed to evaluate safety and efficacy. The assessments for primary, 
secondary, and exploratory endpoints, including the MRI and facial photography, should be 
completed within 30 days of the study drug discontinuation. The reason for premature 
discontinuation of study drug administration should be recorded on the appropriate page(s) of the 
eCRF.  
Study drug must be discontinued in case of progressing disease posing an unacceptable risk to 
the patient that requires immediate treatment. In such cases, the PI should contact the Sponsor 
and the PI and the Sponsor Medical Monitor will discuss and determine whether the patient 
should continue in the study.  
Reasons for withdrawal from study drug may include, but are not limited to: 
• Withdrawal of consent  
• An AE, which, in the opinion of the PI (or designee), warrants the patient’s discontinuation 
of study drug infusion; in the event of study drug withdrawal due to the occurrence of an AE, 
the Medical Monitor must be notified within 24 hours 
• Non-compliance with study drug administration or other protocol procedures 
• Prohibited concomitant medication  
• Physician decision 
• Pregnancy 
• Study termination 
A patient who is withdrawn from study drug, or patients who are randomized, but not dosed, for 
reasons not related to study drug or progression of TED may be replaced at the discretion of the 
Sponsor.  
7.3. 
Participant Discontinuation/Withdrawal from the Study 
Patients who wish to withdraw completely from this clinical study should be encouraged to 
complete the EOS/ET visit. However, patients may withdraw consent to participate in this study 
at any time without penalty or loss of benefits to which the patient is otherwise entitled. Every 
reasonable effort should be made to determine the reason a patient withdraws prematurely, and 

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this information should be recorded on the appropriate page(s) of the eCRF. Patients may be 
withdrawn from the study for any of the following reasons: 
• Withdrawal of consent  
• Protocol non-compliance with protocol procedures 
• Lost-to-follow-up 
• Physician decision 
• Study termination 
7.4. 
Criteria for Discontinuation of Study  
In the event of a negative change to the risk/benefit assessment, study enrollment will be 
suspended and the protocol revised as needed to ensure patient safety. Enrollment will be 
suspended if ANY of the criteria listed below are met. If the study is suspended due to meeting 
any of the criteria below, it may only be restarted after review and agreement by SRC and 
Sponsor. In countries for which restart of enrollment is considered a substantial amendment, 
enrollment will only be restarted once the relevant health authorities approve the revised 
protocol. 
• The occurrence of an SAE or severe AE, assessed as related to the study drug, of similar 
origin in ≥3 patients  
• If unacceptable risks to study patients are identified 
• If, in the Sponsor’s judgment, there are no further benefits to be achieved from the study 
In the event that the clinical development of the study drug is discontinued, the Sponsor shall 
inform the PI/institution and regulatory authorities. 
 
 

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
Before performing any study-related procedures, the PI (or designee) will obtain written 
informed consent from patients.  
Planned timepoints for all safety assessments are provided in the Schedule of Activities 
(Section 1.3). Study procedures should be completed within the windows provided in the 
Schedule of Assessments and Procedures. However, if a patient is unable to attend a visit within 
the specified window, the PI (or designee) should discuss appropriate scheduling with the 
Medical Monitor. 
For this study, the blood sample for LASN01 PK is a key parameter and any time point after start 
of infusion for blood sample needs to be collected within the specified window. All other 
procedures should be completed as close to the prescribed/scheduled time as possible. 
Unscheduled procedures required for urgent evaluation of safety concerns take precedence over 
all routine scheduled procedures. 
No genotyping or DNA “profiling” will be performed on any collected samples.  
8.1. 
Efficacy Assessments 
During determination of eligibility for the study, the more severely affected eye will be defined 
as the study eye by the PI or designee. This will be based on the severity of proptosis in both 
eyes at Day 1. If both eyes are affected equally, the PI or designee will select the study eye and 
may take into account other factors such as the CAS. Both eyes will be assessed for efficacy and 
safety at designated study visits, but the study eye will be used to assess the primary clinical end 
point.  If only one eye is determined to meet the eligibility criteria, that is the study eye by 
default. 
The same assessor should conduct the TED related ophthalmic assessments at each study visit. 
This includes assessment of proptosis, CAS, conjunctival redness, chemosis, lid swelling, lid 
aperture, diplopia and duction testing for extraocular movements. If a different assessor than the 
initial/main assessor performs these assessments at a particular visit due to schedules, etc., then 
these assessments should be repeated by the initial/main assessor as soon as possible.  
The following thyroid eye disease assessments will be further detailed in a study manual 
provided to the sites. 
8.1.1. 
Proptosis 
Assess degree of proptosis and reduction from Baseline in proptosis in the study eye and fellow 
eye using a Hertel Exophthalmometer. The same instrument and assessor should be used for all 
assessments. Instructions will be provided in a study manual.  
8.1.2. 
CAS Assessments 
CAS assessments are presented in Table 4. The same assessor should conduct each CAS 
evaluation at each visit for the full duration of the study. CAS assessment should be completed 
prior to any eyes drops administered for dilation or any other purpose. 

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Table 4. 
CAS 7-point Scale 
Item a 
Description 
7-point 
CAS 
1 
Spontaneous orbital pain. 
 
2 
Gaze evoked orbital pain. 
 
3 
Eyelid swelling that is considered to be due to active (inflammatory phase) TED 
 
4 
Eyelid erythema 
 
5 
Conjunctival redness that is considered to be due to active (inflammatory phase) 
TED (ignore “equivocal” redness) 
 
6 
Chemosis 
 
 
7 
Inflammation of caruncle or plica 
 
Total 7-point CAS 
Add items 1-7 
CAS = clinical activity score; TED = thyroid eye disease  
a 
Each item is scored (1=present; 0=absent), and scores for each item are summed for total score. 
8.1.2.1. 
Spontaneous Orbital Pain and Gaze Evoked Orbital Pain 
Spontaneous orbital pain and gaze evoked orbital pain assessments will use the Numerical 
Rating Scale. The patient is asked to indicate the value of her/his pain on the scale for the right 
eye and the left eye. An 11-point scale is used with “0” representing “no pain” and “10” 
representing the “most severe pain imaginable” in the past 4 weeks. The patient verbally picks 
the number that best describes the pain intensity. Document the patient’s pain score in the source 
documentation. For gaze evoked orbital pain the patient will be asked about orbital pain that 
occurs on eye movement in any direction of gaze. 
The same assessor should conduct the evaluation at each visit for the full duration of the study. 
Instructions will be provided in a study manual. 
8.1.2.2. 
Conjunctival Redness 
Conjunctival redness will be graded from 0 to 3. This is a clinical assessment to evaluate the 
severity of redness. For the overall CAS assessment, Grade 0 and 1 are considered absent (and 
should receive a score of ‘0’ in the CAS scoring) and Grade 2 or 3 are considered present (and 
should receive a score of 1 in the CAS scoring). 
Grade 0 – none 
Grade 1 – mild: equivocal redness 
Grade 2 – moderate: defined redness, <50% redness excluding plica and caruncle 
Grade 3 – severe: >50% redness excluding plica and caruncle 
The same assessor should conduct the evaluation at each visit for the full duration of the study. 
Instructions will be provided in a study manual. 

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8.1.2.3. 
Eyelid Swelling 
Eyelid swelling will be graded from 0 to 3. This is a clinical assessment to evaluate the severity 
of lid swelling. For the overall CAS assessment, Grade 0 and Grade 1 below are considered 
absent (and should receive a score of ‘0’ in the CAS scoring) and Grade 2 and 3 are considered 
present (and should receive a score of “1” in the CAS scoring). 
Grade 0 – none 
Grade 1 – swelling very superficial, changed appearance like thickened skin 
Grade 2 – definite swelling but no lower eyelid festoons, and in the upper eyelid, the skin fold 
becomes angled fold on 45º downgaze 
Grade 3 – lower eyelid festoons or upper lid fold remains rounded on 45º downgaze 
The same assessor should conduct the evaluation at each visit for the full duration of the study. 
Instructions will be provided in a study manual. 
8.1.2.4. 
Chemosis 
Chemosis will be graded from 0 to 3. This is a clinical assessment to evaluate the severity of 
chemosis. For the overall CAS assessment, Grade 0 is considered absent (and should receive a 
score of ‘0’ in the CAS scoring) and Grade 1, 2 or 3 are considered present (and should receive a 
score of 1 in the CAS scoring). 
Grade 0 – None 
Grade 1 – Conjunctiva looks pale and loses transparency 
Grade 2 – Bulging of conjunctiva 
Grade 3 – Chemosis prevents appropriate palpebral closure 
The same assessor should conduct the evaluation at each visit for the full duration of the study. 
Instructions will be provided in a study manual 
8.1.3. 
Lid Aperture  
Distance between the lid margins in mm with the patient looking in the primary position, sitting 
relaxed and with distant fixation. Margin reflex distance 1 (MRD1) and MRD2 parameters will 
be measured. The same assessor should conduct the evaluation at each visit for the full duration 
of the study. Instructions will be provided in a study manual. 
8.1.4. 
Lagophthalmos, Eyelid Retraction, and Von Graefe’s Sign 
Presence or absence of lagophthalmos and Von Graefe’s sign will be recorded.  
Eyelid retraction is a displacement of the upper eyelid superiorly or lower eyelid inferiorly. 
Instructions will be provided in a study manual. 

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8.1.5. 
Assessment of Diplopia and Extraocular Movements 
Bahn-Gorman Scale for Diplopia 
• Grade 0 – Normal 
• Grade I – Intermittent diplopia: present only when patient is fatigued 
• Grade II – Inconstant diplopia: present only on lateral or upward gaze 
• Grade III – Constant diplopia: present on straight and level gaze and correctable with 
prisms 
• Grade IV – Constant diplopia: present on straight and level gaze but not correctable with 
prisms 
Duction Testing for Extraocular Movements 
• Assessment of extraocular movements in all 4 primary directions (up, down, nasal and 
temporal) will be performed. 
The same assessor should conduct the evaluation at each visit for the full duration of the study. 
Instructions will be provided in a study manual. 
8.1.6. 
Orbital MRI 
Axial high-resolution images will be obtained locally and transmitted to a central radiology 
vendor for review. Besides assessment of proptosis, the orbital MRI sequences may provide 
(but not limited to) volumetric analysis of eye compartments such as muscle and fat, and 
assessment of inflammation in the orbit as well as any damage to the optic nerve. Further 
instructions will be provided in a study manual. Patients who cannot have an MRI due to the 
presence of metal or other known reason may participate in the study without having the MRI 
scans. In the US only, an orbital CT scan may be performed if the patient cannot have an MRI 
scan. 
8.1.7. 
Facial Digital Photographs 
External photographs of the eyes that capture at minimum the five cardinal positions of gaze (up, 
down, right, left and primary gaze) may be taken at the study sites and transmitted to a central 
reading vendor for review. The study will only use the 5 cardinal directions of gaze for 
evaluation. The whiteness of the sclera, MRD1, MRD2, and eye movement will be assessed from 
the digital photographs to confirm the clinical assessment including CAS, lid retraction, and eye 
movement measurements. Further instructions will be provided in a study manual. 
8.2. 
Safety Assessments 
An SRC will be formed for periodic reviews of safety and available PK and PD data. For the 
randomized, double-blind treatment arms, the SRC will review masked data.  The SRC will be 
minimally composed of the Medical Monitor, at least 1 study PI, and at least 1 independent 
member with expertise in the treatment of TED. In cases where the SRC determines that an 
unexpected or critical finding requires expert opinion or access to unmasked data, the SRC may 
refer the question to at least 3 independent experts selected by the Sponsor, including the SRC 

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Chair, to assess the situation by reviewing necessary unmasked data and provide 
recommendation back to the SRC. The SRC charter will describe the committee member 
structure and details for the conduct and safety review meetings.  
Safety will be assessed throughout the study by examination of visual acuity, visual fields, and 
color defects; TEAEs; changes in concomitant medications; and changes from Baseline in 
clinical laboratory evaluations, vital signs, 12-lead ECGs, ophthalmic assessments, and physical 
examinations. Safety assessments by visit are listed in Table 1. Safety monitoring 
(Section 10.1.6.1) and reporting (Section 8.3) are summarized. Additional safety assessments 
may occur at the discretion of the PI (or designee). 
Any ongoing study drug-related SAEs or severe TEAEs present at the time of study termination 
will be followed until resolved or until the event stabilizes and the overall clinical outcome has 
been ascertained. All other TEAEs considered related to study drug and SAEs considered not 
related to study drug will be followed for 30 days after the EOS/ET visit or after the last dose of 
study drug, whichever is later. 
In the event of unexplained, treatment-emergent, clinically significant, abnormal laboratory 
values or clinically significant changes in laboratory values from Baseline, the laboratory tests 
should be repeated immediately and followed until the values have returned to within the 
reference range or to Baseline. 
8.2.1. 
Best Corrected Visual Acuity, Visual Fields, and Color Defects  
Change of best corrected visual acuity by ≥3 lines (15 words) at 4m on the ETDRS chart, new or 
increased visual field (by Humphrey field testing) or color defects (Ishihara test) may require 
additional assessments. If a different measure or assessment is used, it must be approved by the 
Medical Monitor and equivalent criteria used for assessment. Instructions will be provided in a 
study manual. 
8.2.2. 
Slit Lamp Biomicroscopy and Intraocular Pressure 
Slit lamp biomicroscopy and intraocular pressure (IOP) should be performed with each 
ophthalmic exam. 
8.2.3. 
Dilated Fundoscopy 
Dilated fundus exam will be assessed by the fundus ophthalmoscopy after dilation of the right 
eye and the left eye.  
8.2.4. 
Physical Examinations 
Complete physical examination includes general appearance, head, ears, eyes, nose, throat, 
dentition, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, 
musculoskeletal, and lymph nodes. 
Brief examinations are limited, symptom-directed, physical examinations as clinically indicated. 

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8.2.5. 
Body Weight 
The study site staff should use a digital precision scale if possible and record the weight in 
kilograms or pounds to the first decimal point (eg, 95.3 kg). The same scale should be used, and 
the patient should wear a standard hospital-type gown or equivalent light clothing and no shoes 
for the body weight measurement. 
8.2.6. 
Vital Signs 
Vital sign measurements in this study will include seated respiratory rate, blood pressure, pulse 
rate, and body temperature. Vital signs should be measured after the patient rests for 
approximately 5 minutes in a sitting position. If infusion-associated events occur during the 
infusion, vital signs will be checked every 5 minutes until stable, then every 15 minutes for two 
more checks. Additionally, vital signs will be monitored every 15 minutes from the start of the 
infusion until 60 minutes after its completion for any subsequent infusions following previous 
immediate or delayed infusion-associated events. 
8.2.7. 
ECGs 
Perform triplicate ECGs within a 15-minute period, separated by ≥1 minute. ECG recordings 
will be taken after ≥5 minutes in a semi-supine, quiet-rest position (head of bed between 0° and 
90°), and before obtaining any blood sample. 
The results of all 12-lead ECGs (heart rate, QTcF, PR interval, RR interval, QRS interval) will 
be recorded to the eCRF.  
If the 12-lead ECG must be performed with the patient in another position (eg, sitting, standing), 
the PI (or designee) should record the alternative position. The PI (or designee) should date and 
sign the ECG tracing and record the clinical significance of any abnormal result on the tracing. 
ECGs will be interpreted by a qualified physician (the PI or designee). 
8.2.8. 
Clinical Safety Laboratory Tests 
Procedures for obtaining, processing, shipping, and handling laboratory specimens will be 
detailed in the Laboratory Manual.  
Clinical laboratory tests include chemistry, hematology, coagulation, UA, urine drug screen, and 
additional tests listed in Appendix 2, Section 10.2. 
The PI (or designee) will evaluate all Screening and safety laboratory reports and will sign and 
date the review. Any out-of-range laboratory results should be assessed for clinical significance. 
The PI (or designee) should follow all clinically significant laboratory abnormalities occurring 
during the study that were not present at Baseline as needed. These abnormalities should be 
evaluated with additional tests, if necessary, until the underlying cause is diagnosed, event 
becomes stable or resolution occurs. The diagnosis and resolution date must be reported to the 
Sponsor via the eCRF. 

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8.2.9. 
Pregnancy Testing 
WOCBP must have a negative serum pregnancy test at Screening, a negative urine pregnancy 
test on Day 1, and be willing to undergo additional pregnancy tests, as required, throughout the 
study. WOCBP will have urine pregnancy tests predose on dosing days and a serum pregnancy 
test at the EOS/ET visit.  
Serum FSH levels will be tested in women at Screening and must be in the menopausal range to 
confirm postmenopausal status. 
8.3. 
AEs, SAEs, and Other Safety Reporting 
The definitions of AEs and SAEs are provided in Appendix 3, Section 10.3. 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE Information 
Detection and recording of AEs and SAEs starts from the signing of the ICF until the Day 
365/Week 53 visit.  From this visit to the EOS visit, only treatment-related AEs/SAEs will be 
recorded. AEs that occur after signing the ICF, but before the first dose of study drug, will be 
recorded to the eCRF as medical history, unless related to a study procedure. Detection and 
recording of TEAEs will start at the time of the first dose of study drug. Any SAE that occurs 
after signing the ICF (before or after the first dose of study drug) will be recorded to the eCRF as 
an SAE.  
8.3.2. 
Method of Detecting AEs and SAEs 
The PI (or designee) is responsible for detection, recording, and reporting of events that meet the 
criteria and definition of an AE (Appendix 3, Section 10.3). 
8.3.3. 
Follow-Up of AEs and SAEs 
Following initial observation of an AE/SAE, the PI (or designee) is required to proactively 
follow progress of the relevant event (Section 10.3.3.4). 
8.3.4. 
Pregnancy 
If a patient’s pregnancy test is positive at Screening or Day 1, she will be referred to her primary 
care provider for follow-up and will not be included in the study.  
Patients must be instructed to inform the PI (or designee) immediately if they (for female 
patients) or their partner (for male patients) become pregnant during the study or for 90 days 
after the last dose of study drug or until the EOS/ET visit, whichever is later. In the event of a 
confirmed pregnancy, the following actions should be taken: 
• Study drug should be discontinued immediately  
• The pregnancy should be reported to the Medical Monitor within 24 hours of notification 
using the applicable Pregnancy Report Form 

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• The PI (or designee) should counsel the patient regarding the possible effects of prior 
LASN01 exposure on the fetus and the need to inform the study site of the outcome of the 
pregnancy 
• The patient must be monitored until the immediate postnatal period or until termination of 
the pregnancy. The outcome should be reported using the Pregnancy Report Form. 
Pregnancy is not an AE, in and of itself. However, any pregnancy complication or elective 
termination of a pregnancy for medical reasons will be recorded as an AE or SAE. A 
spontaneous abortion is always considered an SAE and will be reported as described in the AE 
and SAE sections (Section 10.3.1 and Section 10.3.2). Furthermore, any SAE occurring as an 
adverse pregnancy outcome post-study must be reported to the Medical Monitor. 
8.3.5. 
AESIs 
No AESIs have been identified with LASN01 based on preclinical metabolic and toxicity studies 
and the Phase 1/2a study (LASN01-CL-1101). 
8.4. 
PK Assessments 
Procedures for collection, storage, and shipping of PK samples are described in the Laboratory 
Manual. Blood (serum) samples from all patients who receive ≥1 complete dose of LASN01 will 
be analyzed by a validated enzyme-linked immunosorbent assay method for the concentration of 
LASN01. The serum PK parameters of LASN01 will be determined based upon the LASN01 
concentrations and actual time of PK sample collection relative to the previous dose. 
8.5. 
PD and Biomarker Assessments 
Blood draws will be collected for exploratory assessments of circulating protein biomarkers 
relevant to the IL-11 pathway in TED, fibrosis, and inflammation. Procedures for collection, 
storage, and shipping of PD and biomarker assessments are described in the Laboratory Manual. 
8.6. 
Immunogenicity Assessments 
Immunogenicity will be determined by assessment of ADA levels.  Procedures for collection, 
storage, and shipping of samples for ADA assessments are described in the Laboratory Manual. 
8.7. 
Retention of Samples  
Samples may be retained for a maximum of 15 years after study completion at a storage facility 
before destruction. The retention period enables the use of new technologies, responses to 
regulatory authorities, and investigation of variable responses that may not be apparent until later 
in the development of LASN01 or after LASN01 is commercially available. 
Samples will not be used to conduct unspecified disease or population genetic research. 

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Data will be summarized and listed separately. Continuous data will be summarized using the 
number of patients, mean, standard deviation, median, minimum, and maximum values for 
continuous variables, whilst categorical data will present the numbers and percentages of patients 
within each category. Listings of individual patient data will also be produced.  
 
 
Baseline will be defined as the last available, non-missing observation before the first study drug 
administration. In general, “Unknown”, “Not Done”, “Not Applicable”, and other classifications 
of missing data will not be considered when calculating Baseline observations. However, valid 
categorical observations will be considered for Baseline calculations. In addition, non-missing 
results from unscheduled assessments before the first study drug administration may also be 
considered in the calculation of Baseline observations. 
9.2.2. 
Analysis of Study Population and Patient Characteristics 
Patient disposition, including the number of patients dosed and number of patients completing 
the study, will be summarized. Patient disposition and demographics (including age, race, 
ethnicity, gender, height, weight, and BMI at Screening) and baseline characteristics will be 
summarized for the Safety Population. 
9.2.3. 
Efficacy Analysis 
Efficacy will be assessed using the Efficacy Analysis Population. However, any or all of these 
analyses may also be performed in the Per-Protocol Analysis Population as exploratory analysis. 
 
9.2.3.1. 
Efficacy Analysis for the Randomized Treatment Arms 
The primary clinical endpoint analysis is the percentage of patients in the randomized treatment 
arms who have received LASN01 (pooled analysis of 300 and 600 mg Q4W) showing a response 
in proptosis (≥2 mm decrease from Baseline) in the study eye without deterioration (≥2 mm 
increase) of proptosis in the fellow eye at Week 37 compared with placebo.  
The primary endpoint will be analyzed using a one-tailed Fisher’s exact test at an alpha of 0.10 
and will report the percentage of LASN01 (300 mg and 600 mg Q4W pooled) responders 
compared to placebo responders at the Week 37 timepoint. Results, including p-values, will be 
summarized and presented in contingency table.  95% confidence intervals will be reported. 
9.2.4. 
Sensitivity Analysis for Primary Endpoint Using MMRM 
This analysis will be conducted using an MMRM model.  The model will incorporate fixed 
effects for treatment group, baseline proptosis, and visit (Week 37). An unstructured covariance 
matrix will be used to model the repeated measures. Missing data will be handled under the 
Missing At Random (MAR) assumption. Additionally, alternative covariance structures (e.g., 

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compound symmetry) and covariate adjustments (e.g., age, sex) will be evaluated to test the 
stability of the treatment effect estimates. 
The treatment effect will be estimated by examining the fixed effect of LASN01 versus placebo 
at Week 37. Model comparisons will be conducted to ensure consistency across different 
covariance structures and covariate adjustments. Results will include estimated treatment 
differences with 95% confidence intervals.  Results will be summarized and presented in a table 
for comparison with the primary analysis of the primary endpoint.   
Secondary endpoint analyses related to efficacy in the randomized treatment arms include: 
• Percentage of patients who have received LASN01 (600 mg Q4W) showing a response in 
proptosis (≥2 mm decrease from Baseline) in the study eye without deterioration (≥2 mm 
increase) of proptosis in the fellow eye at Weeks 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 65, 
and 73 following treatment with IV LASN01 compared with placebo 
• Percentage of patients who have received LASN01 (300 mg Q4W) showing a response in 
proptosis (≥2 mm decrease from Baseline) in the study eye without deterioration (≥2 mm 
increase) of proptosis in the fellow eye at Weeks 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 65, 
and 73 following treatment with IV LASN01 compared with placebo 
• Percentage of patients who have received LASN01 (pooled analysis of 300 and 600 mg 
Q4W) showing a response in proptosis (≥2 mm decrease from Baseline) in the study eye 
without deterioration (≥2 mm increase) of proptosis in the fellow eye at Weeks 17, 21, 25, 
29, 33, 41, 45 57, 65, and 73 following treatment with IV LASN01 compared with placebo. 
• Mean change from Baseline in proptosis in patients who have received LASN01 (600 mg 
Q4W) compared with placebo at Weeks 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 65, and 73 
• Mean change from Baseline in proptosis in patients who have received LASN01 (300 mg 
Q4W) compared with placebo at Weeks 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 65, and 73 
• Change in CAS from Baseline on a 7-point scale for pooled LASN01 and each LASN01 dose 
group versus placebo at Weeks 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 65, and 73 
• Change in lid retraction from Baseline (in mm) for pooled LASN01 and each LASN01 dose 
group versus placebo at Weeks 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 65, and 73 
• Change in lid aperture from Baseline (in mm) for pooled LASN01 and each LASN01 dose 
group versus placebo at Weeks 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 65, and 73 
• Percentage of patients with lagophthalmos for pooled LASN01 and each LASN01 dose 
group versus placebo at Weeks 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 65, and 73 
• Percentage of patients with Von Graefe’s sign for pooled LASN01 and each LASN01 dose 
group versus placebo at Weeks 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 65, and 73 
• Change in subjective diplopia by the Bahn-Gorman scale for pooled LASN01 and each 
LASN01 dose group versus placebo at Weeks 17, 21, 25, 29, 33, 37, 41, 45, 49, 53, 57, 65, 
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At a minimum, the following PK parameters will be calculated: 
• Cmax 
• Tmax 
• AUC0-last  
• AUC0-28d 
The following parameters will be calculated as feasible given the observed serum concentration-
time data: 
• AUC0-∞ (first dose only) 
• CL  
• Vz  
• Vss  
• λz 
• t1/2 
Summary statistics (N, mean, standard deviation, coefficient of variation, median, minimum, and 
maximum) will be tabulated by LASN01 dose level for serum concentrations at each nominal 
time and for the PK parameters. Geometric means and geometric coefficient of variations will 
also be presented for all PK parameters with the exception of Tmax. Linear and log-linear plots 
will be created to display mean (by dose level with and without standard deviation) and 
individual concentration-time profiles. Statistical analysis will be performed to assess dose 
proportionality, and additional details will be provided in the SAP. 
9.2.7. 
Participant Study Withdrawal and Premature Termination of Study Drug 
Enrollment and withdrawals from the study and from study drug will be summarized by 
LASN01 treatment arm, dose level and placebo. 
9.2.8. 
Deviation Reporting 
Protocol deviations are defined as any variation from the protocol, including enrollment of a 
patient who did not meet all inclusion and exclusion criteria and failure to perform the 
assessments and procedures within the required time frames. 
9.3. 
Handling of Dropouts and Missing, Unused, and Spurious Data 
Every effort will be made to collect all data at specified times. No substitutions will be made for 
missing data, unless explicitly specified in the SAP. 
9.4. 
Interim Analyses 
Interim analyses may be performed when at least 50% of evaluable patients in the randomized 
treatment arms complete at least 8 weeks in the study (details will be provided in the SAP) to 
inform further development. The interim analysis may also include the open-label treatment arm. 

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9.5. 
Sample Size Determination 
This study will enroll up to 36 evaluable patients with TED in 4 treatment arms. Approximately 
24 patients will be randomized to LASN01 600 mg Q4W, LASN01 300 mg Q4W, or placebo 
treatment arms in a 1:1:1 ratio 
.  
For the three randomized treatment arms: The pooled primary analysis represents an 
aggregate 2:1 randomization of LASN01:placebo with approximately 24 total patients. The 
success rate for placebo was assumed to be 15% (Teprotumumab – FDA Summary Basis of 
Approval 2020). Assuming a pooled success rate for LASN01 of 65% (ie, a pooled absolute 
treatment effect of 50% relative to placebo), the proposed sample size of 8 patients per treatment 
group gives approximately 81% power at the 10% level of statistical significance for a 1-sided 
Fisher’s exact test of superiority of LASN01. If the placebo rate is 10% instead, the proposed 
sample size gives approximately 90% power at the 10% level of statistical significance. All 
calculations were performed using R Core Team (2022) Version 4.2.1. Power was determined 
using simulation methods with a simulation size of 10,000 and simulations were implemented 
using the ‘statmod’ package (Giner 2016). 
 
 
 

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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS 
10.1. Appendix 1: Regulatory, Ethical, and Study Oversight Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
This study will be conducted in compliance with the protocol, ICH Technical Requirements for 
Registration of Pharmaceuticals for Human Use E6: GCP Consolidated Guidelines, the ethical 
principles of the Declaration of Helsinki, the National Health and Medical Research Council 
Statement on Ethical Conduct in Human Research (2007, incorporating all updates as of July 
2018), United States FDA GCP guidelines, and any additional regulatory authority and/or ethics 
committee required procedures. 
10.1.2. 
Financial Disclosure 
The financing and insurance for this study are outlined in the Clinical Trial Agreement. 
10.1.3. 
Informed Consent Process 
This study will be conducted in compliance with ICH E6(R2) GCP: Consolidated Guidelines 
pertaining to informed consent. Patients will give written consent to participate in the study at the 
first visit, prior to initiation of any study-related procedures, after having been informed about 
the nature and purpose of the study, participation and termination conditions, risks, and benefits. 
The ICF must be signed and dated by the patient prior to study participation. A copy of the ICF 
must be provided to the patient. If applicable, it will be provided in certified translation for non-
English-speaking patients. Signed original ICFs must remain in the patient’s study file and be 
available for verification by Sponsor at any time. 
10.1.4. 
Regulatory Authority and Ethics Committee Approval 
This protocol, the ICF, and all relevant supporting data must be submitted to the concerned 
regulatory authority and/or ethics committee for approval. The protocol, ICF, and any 
advertisement used to recruit study patients must be approved by the concerned regulatory 
authority and/or ethics committee. Approval of the protocol and ICF must be obtained by the 
concerned regulatory authority and/or ethics committee before the study may be initiated. 
The PI (or designee) is responsible for informing the concerned ethics committee of the progress 
of the study, any changes made to the protocol, annual updates and/or request for reapproval, and 
when the study has been completed. The PI (or designee) is also responsible for notifying the 
concerned ethics committee of any significant AEs that occur during the study. The PI (or 
designee) may receive written safety reports or other safety-related communications from the 
Sponsor. The PI (or designee) is responsible for ensuring that such reports are reviewed and 
processed in accordance with regulatory requirements and with the policies and procedures 
established by their ethics committee and archived in the site’s study file. 

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10.1.5. 
Data Protection 
Medical information obtained from patients during the course of this study is confidential and 
disclosure to third parties other than those noted (Section 10.1.7) is prohibited. 
10.1.6. 
Data Quality Assurance 
Training sessions, regular monitoring of PIs by Sponsor-designated personnel, instruction 
manuals, data verification, and cross checking will be performed to ensure quality of all study 
data. Investigator meetings will be held to prepare PIs and other study personnel for appropriate 
collection of study data. 
Written SOPs will be followed to ensure that the study is conducted and data are generated, 
documented (recorded), and reported in compliance with the protocol, GCP, and the applicable 
regulatory requirements. Quality control will be applied to each stage of data handling.  
The PI must make every effort to adhere to the protocol as detailed in this document and agree 
that the Sponsor must approve any change to the protocol before seeking approval from the 
concerned regulatory authority and/or ethics committee. The PI will be responsible for enrolling 
only those patients who have met all of the protocol inclusion criteria and none of the exclusion 
criteria.  
10.1.6.1. 
Study Monitoring 
Regular monitoring, as defined in ICH GCP, Section 1.8, “The act of overseeing the progress of 
a clinical trial, and of ensuring that it is conducted, recorded, and reported in accordance with the 
protocol, SOPs, GCP, and the applicable regulatory requirement(s)” will be conducted 
throughout the conduct of the study. Monitoring is an integral role in the quality control of a 
clinical trial and is designed to verify the quality of the study. 
The purpose of monitoring is to verify that: 
• Rights and well-being of the human patients are protected 
• The reported study data are accurate, complete, and verifiable from source documents 
• The conduct of the study is in compliance with the currently approved 
protocol/amendment(s), with GCP, and with the applicable regulatory requirements 
An authorized Sponsor representative will conduct site visits to inspect study data, patients’ 
medical records, and eCRFs in accordance with ICH guidelines, GCP, and the foreign 
regulations and guidelines, as applicable. Both masked and unmasked monitors will be utilized 
for monitoring ongoing dose administration and protocol procedures. 
The PI will allow representatives of the Sponsor and regulatory authorities to inspect facilities 
and records relevant to this study in a timely manner. It will be the responsibility of the PI to 
ensure that the essential documents are available at the PI or institutional site. Any or all of these 
documents may be pertinent to, and should be available for, monitoring by the Sponsor or 
inspection by the regulatory authorities as defined in the monitoring plan. 
The Sponsor will review and validate study data as defined in the monitoring plan.  

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10.1.7. 
Source Documents 
Source documents are defined as documentation related to original observations and activities of 
a clinical investigation. Source documents may include, but are not limited to, study progress 
notes, or study-specific email correspondence, computer printouts, laboratory evaluations, and 
recorded data from automated instruments. All source documents produced in this study will be 
maintained by the PI (or designee) and made available for inspections and monitoring by the 
Sponsor and by regulatory authorities. The original signed ICF for each participating patient 
shall be filed with records kept by the PI (or designee), and a copy shall be given to the patient. 
The PI agrees by his/her participation that the results of this study may be used for submission to 
national or international registration. If required, these authorities will be provided with the name 
of the PI and his or her address, qualifications, and extent of involvement. It is understood that 
the PI (or designee) is required to provide Sponsor with all study data, complete reports, and 
access to all study records. 
Data generated by this study must be available for inspection by any concerned regulatory 
authority and/or ethics committee, and the Sponsor, as appropriate.  
10.1.8. 
eCRFs 
The eCRF will be supplied by Sponsor or designee for the recording of all information and study 
data as specified by this protocol. All eCRFs must be completed by trained study personnel. The 
PI is responsible for ensuring that the eCRF data are entered and completed in a timely manner. 
Once all data queries and issues have been resolved for each patient, the PI will electronically 
sign each patient’s eCRF to attest to the accuracy of the data. 
10.1.9. 
Retention of Records 
Records and documents pertaining to the conduct of this study and the distribution of study 
records including eCRFs, ICFs, laboratory test results, safety reporting forms, source documents, 
medication inventory records, and adequate documentation of relevant correspondences (eg, 
letters, meeting minutes, telephone calls reports) must be kept on file by the PI for a minimum of 
2 years after notification by the Sponsor that a marketing application has been approved for 
LASN01. If no application is filed or approved, these records must be kept for 3 years after the 
investigation has been discontinued and the United States FDA and applicable foreign authorities 
have been notified. The Sponsor will notify the PI of these events. No study records should be 
destroyed without prior authorization from the Sponsor. 
10.1.10. Dissemination of Clinical Study Data 
After the end of study, a CSR will be written and submitted to relevant IRB and regulatory 
authorities in accordance with local requirements. 
At a patient’s request, medical information may be given to his or her personal physician or other 
appropriate medical personnel responsible for his or her welfare. 

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10.1.11. Study and Site Start and Closure 
The Sponsor requires the following data and materials before a study can be considered complete 
or terminated: 
• Laboratory findings, clinical data, and all special test results from Screening visit throughout 
the study until the EOS visit 
• eCRFs (including data queries) properly completed by appropriate study personnel and 
signed and dated by the PI 
• Copies of complete drug accountability records (drug inventory log and an inventory of 
returned or destroyed clinical material) 
• Copies of protocol amendments and concerned regulatory authority and/or ethics committee 
approval and notification, if appropriate 
• A summary of the study prepared by the PI (a summary letter is acceptable from the 
concerned regulatory authority and/or ethics committee) 
10.1.11.1. 
Early Study or Site Termination 
The study or study site may be terminated before study completion at the discretion of the 
Sponsor if any of the following criteria are met: 
• Medical or ethical reasons affecting the continued performance of the study 
• Difficulties in the recruitment of patients 
• Administrative reasons, including, but not limited to, cancelation of IP development 
Throughout the study, the PI is to make a reasonable effort to maintain the enrollment rate that 
was agreed upon with the Sponsor. The PI will also make a reasonable effort to enroll 
appropriate patients. 
10.1.12. Publication Policy 
This clinical study will be registered on https://clinicaltrials.gov/ or other registries by the 
Sponsor as required by local regulations, in keeping with the registration policy of the 
International Committee of Medical Journal Editors (2021). 
Publication of study results may be addressed in the Clinical Trial Agreement. The Sponsor may 
publish the results of this study following completion of data analysis. The data generated in this 
clinical study are the exclusive property of the Sponsor and are confidential.  
 
 

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10.2. Appendix 2: Clinical Laboratory Tests 
Hematology 
Hematocrit  
Hemoglobin 
Platelet count  
Red blood cell count 
Total and differential 
leukocyte count  
Reticulocyte count 
Serum Chemistry 
Alanine aminotransferase 
Albumin 
Alkaline phosphatase 
Aspartate aminotransferase 
Bicarbonate 
Bilirubin (total, indirect, and direct) 
Urea 
Calcium 
Creatine kinase 
Creatinine b 
Chloride 
Gamma glutamyl transferase 
Glucose 
Lactate dehydrogenase 
Potassium 
Sodium 
Total protein 
Hemoglobin A1c 
Thyroid stimulating hormone (TSH) 
Triiodothyronine (T3) 
Thyroxine (free T4) 
Thyroid stimulating immunoglobulin 
(TSI) 
 
Urine Drug Screen 
Amphetamines 
Barbiturates 
Benzodiazepines  
Cannabinoids 
Cocaine 
Methylenedioxymethamphetamine 
Methadone 
Opiates/opioids  
Phencyclidine 
Cotinine test 
 
Urinalysis 
Appearance  
Bilirubin 
Blood a 
Color 
Glucose 
Ketones 
pH 
Protein a 
Leukocyte esterase  
Nitrite 
Specific gravity 
Urobilinogen c 
Additional Tests 
Follicle-stimulating hormone as 
applicable 
Hepatitis B virus surface antigen 
Hepatitis C virus antibody 
Human immunodeficiency virus 
antibody (HIV-1 and HIV-2) 
Severe acute respiratory syndrome  
coronavirus 2 by PCR antibody test c 
Serum or urine pregnancy (for females 
of child-bearing potential only) d 
Coagulation Tests 
Activated partial 
thromboplastin time 
Prothrombin time 
International normalized ratio 
a. 
If urinalysis is positive for protein or blood cells, a microscopic examination (for red blood cells, white blood 
cells, bacteria, casts, and epithelial cells) will be performed. 
b. Creatinine clearance will be calculated using the Cockcroft-Gault formula. 
c. 
To be conducted locally if applicable per the site's standard practice. 
d. To be considered not of child-bearing potential, a female must either be surgically sterile for ≥6 months (ie, 
hysterectomy, bilateral salpingectomy, bilateral oophorectomy), or postmenopausal (no menses ≥12 months 
without an alternative medical cause and follicle-stimulating hormone in menopausal range). 
 

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10.3. Appendix 3: AEs and SAEs: Definitions and Procedures for Recording, Evaluating, 
Follow Up, and Reporting 
10.3.1. 
Definition of AE 
An AE means any untoward medical occurrence associated with the use of a drug in humans, 
whether or not considered study drug related. An AE (also referred to as an adverse experience) 
can be any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom, or 
disease temporally associated with the use of a drug and does not imply any judgment about 
causality. An AE can arise with any use of the study drug (eg, off-label use, use in combination 
with another drug) and with any route of administration, formulation, or dose, including an 
overdose. The following are not AEs: 
• Any non-serious AE that occurs after signing the ICF, but before dosing, unless related to a 
study procedure 
• Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
that are associated with the underlying disease, unless judged by the PI (or designee) to be 
more severe than expected for the patient’s condition 
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the patient’s condition) 
• Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE 
• Situations in which an untoward medical occurrence did not occur (eg, social and/or 
convenience admission to a hospital) 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen 
• Clinical changes consistent with progression of the underlying disease (ie, TED). 
10.3.1.1. 
Definition of Suspected Adverse Reaction 
A suspected adverse reaction is any AE for which there is a reasonable possibility that the drug 
caused the AE. For the purposes of IND safety reporting, ‘‘reasonable possibility’’ means there 
is evidence to suggest a causal relationship between the drug and the AE. Suspected adverse 
reaction implies a lesser degree of certainty about causality than adverse reaction, which means 
any AE caused by a drug. 
10.3.1.2. 
Definition of Life-Threatening AE or Life-Threatening Suspected Adverse 
Reaction 
An AE or suspected adverse reaction is considered ‘‘life threatening’’ if, in the view of either the 
PI (or designee) or Sponsor, its occurrence places the patient or patient at immediate risk of 
death. It does not include an AE or suspected adverse reaction that, had it occurred in a more 
severe form, might have caused death. 

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10.3.1.3. 
Definition of Unexpected AE or Unexpected Suspected Adverse Reaction 
An AE or suspected adverse reaction is considered ‘‘unexpected’’:  
• If it is not listed in the IB or is not listed at the specificity or severity that has been observed, 
or  
• If an IB is not required or available, is not consistent with the risk information described in 
the general investigational plan or elsewhere in the current application, as amended  
For example, under this definition, hepatic necrosis would be unexpected (by virtue of greater 
severity) if the IB referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral 
thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater specificity) 
if the IB listed only cerebral vascular accidents.  
‘‘Unexpected,’’ as used in this definition, also refers to AEs 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. 
10.3.2. 
Definition of SAE or Serious Suspected Adverse Reaction 
An AE or suspected adverse reaction is considered ‘‘serious’’ if, in the view of either the PI 
(or designee) or Sponsor, it results in any of the following outcomes: 
• Death 
• A life-threatening AE (Section 10.1.7) 
• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• A congenital anomaly/birth defect in the offspring of a patient who received study drug 
Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical judgment, they 
may jeopardize the patient or patient and may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include allergic 
bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias, 
or convulsions that do not result in inpatient hospitalization, or the development of drug 
dependency or drug abuse. 
10.3.2.1. 
SAE Definition Clarifications 
• Death is an outcome of an AE, and not an AE in itself 
• All deaths during study drug infusion or occurring up to the EOS/ET visit, regardless of 
cause or relationship, must be reported 
• “Occurring at any dose” does not imply that the patient is actively receiving study drug at the 
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• “Life-threatening” means that the patient was at immediate risk of death from the event as it 
occurred. This does not include an event that might have led to death, had it occurred with 
greater severity. 
• Complications that occur during hospitalizations are AEs. If an AE prolongs hospitalization, 
it is an SAE. 
• “In-patient hospitalization” means the patient has been formally admitted to a hospital for 
medical reasons, for any length of time. This may or may not be overnight. It does not 
include presentation and care within an emergency department (although an emergency 
department visit may define a medically important event, which is also considered an SAE). 
• The PI (or designee) should attempt to establish a diagnosis of the event based on signs, 
symptoms, and other clinical information. In such cases, the diagnosis should be documented 
as the AE or SAE, rather than as the individual signs or symptoms. 
10.3.3. 
Recording and Follow Up of AE and/or SAE 
10.3.3.1. 
AE and SAE Recording 
AEs that occur after signing the ICF, but before the first dose of study drug, will be recorded to 
the eCRF as medical history, unless related to a study procedure.  
Any SAE that occurs after signing the ICF, but before the first dose of study drug, will be 
recorded to the eCRF as an SAE. The PI (or designee) will assess all AEs and SAEs and will 
record the following information on the appropriate eCRF: 
• Date of onset  
• Date of resolution or stabilization 
• Severity 
• Relationship to study drug  
• Action taken with study medication 
Events that, in the opinion of the PI (or designee), may represent intolerance of the IV infusion 
of study drug must be recorded as AEs on the eCRF. In general, these events will be temporally 
related to study drug infusion. 
Laboratory abnormalities should not be recorded as AEs or SAEs unless they are associated with 
clinical signs or symptoms, require medical intervention or lead to interruption of study drug 
infusion or discontinuation. If the laboratory abnormality is part of a clinical condition or 
syndrome, it should be recorded as the syndrome or diagnosis rather than as the individual 
laboratory abnormality. In addition, laboratory abnormalities or other abnormal test assessments 
(eg, ECGs) that are associated with signs or symptoms must be recorded as AEs or SAEs if they 
meet the definition of an AE (or SAE) as described in Section 10.3.1 (or Section 10.3.2). 
Additional details can be found in the applicable study plans. 
 

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10.3.3.2. 
Assessment of Intensity 
All AEs will be graded for severity (Table 5). 
The PI (or designee) will use the terms: Mild, Moderate, or Severe to describe the maximum 
intensity of the AE. For purposes of consistency, these intensity grades are defined in Table 5. 
Table 5.  
Guidelines for Severity Assessments 
CTCAE 
Criteria 
Category 
Description 
1 
Mild 
Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
2 
Moderate 
Minimal, local, or noninvasive intervention indicated; limiting age-appropriate 
instrumental activities of daily living 
3 
Severe 
Medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities 
of daily living  
4 
Life-threatening 
Life-threatening consequences; urgent intervention indicated. 
5 
Death 
Death related to AE 
CTCAE = Common Terminology Criteria for Adverse Events 
Source = CTCAE V5 2017 
10.3.3.3. 
Assessment of Causality 
PI (or designee) should use their knowledge of the patient, the circumstances surrounding the 
event, and an evaluation of any potential alternative causes to determine whether an AE is 
considered to be related to the study drug, indicating "yes" or "no" accordingly.  
The following guidance should be taken into consideration (see also Table 6): 
• Temporal relationship of event onset to the initiation of study drug 
• Course of the event, with special consideration of the effects of dose reduction, 
discontinuation of study drug, or reintroduction of study drug (as applicable) 
• Known association of the event with the study drug or with similar treatments 
• Known association of the event with the disease under study 
• Presence of risk factors in the patient or use of concomitant medications known to increase 
the occurrence of the event 
• Presence of non−treatment-related factors that are known to be associated with the 
occurrence of the event 
These criteria, in addition to good clinical judgment, should be used as a guide for determining 
the causal assessment. If the event is believed to be not related or unlikely related to study drug 
infusion, then an alternative explanation should be provided. 

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Table 6.  
Guidelines for Assessing Relationship of Event to Study Drug 
Is the adverse event suspected to be caused by the study drug on the basis of facts, evidence, science-based 
rationales, and clinical judgment? 
Related 
There is a plausible temporal relationship between the onset of the adverse event and 
administration of study drug, and the adverse event cannot be readily explained by the patient’s 
clinical state, intercurrent illness, or concomitant therapies; and/or the adverse event follows a 
known pattern of response to the study drug; and/or the adverse event abates or resolves upon 
discontinuation of the study drug or dose reduction and, if applicable, reappears upon rechallenge. 
An adverse event will be considered “Related”, unless it fulfills the criteria specified for “Not 
Related”.  
Not Related 
Evidence exists that the adverse event has an etiology other than the study drug (eg, preexisting 
medical condition, underlying disease, intercurrent illness, or concomitant medication); and/or the 
adverse event has no plausible temporal relationship to administration of the study drug (eg, 
cancer diagnosed 2 days after first dose of study drug). 
10.3.3.4. 
Follow-Up of AEs and SAEs 
The PI (or designee) should employ best medical judgment in determining how to manage AEs 
and SAEs. Any questions regarding AE or SAE management should be directed to the Medical 
Monitor. 
Investigator Follow-Up 
Any ongoing study drug-related SAEs or severe TEAEs present at the time of study termination 
for the patient (EOS visit or early termination) will be followed until resolved or until the event 
stabilizes and the overall clinical outcome has been ascertained or is not considered to be of 
clinical significance. All other TEAEs considered related to study drug and SAEs considered not 
related to study drug will be followed for up to 30 days after the later of the EOS/ET visit or the 
last dose of study drug. During the study period, resolution of AEs (with dates) should be 
documented on the AE eCRF and in the patient’s medical record to facilitate source data 
verification. For the subjects who withdraw consent, the SAEs, severe TEAEs, and other TEAEs 
considered related to the study drug will be followed until the date of withdrawal of consent. The 
withdrawal of consent date will be recorded as the end date of the event. 
Sponsor Follow-Up 
For SAEs, AESIs, and pregnancies, the Sponsor or a designee may follow up by telephone, fax, 
electronic mail, and/or a monitoring visit to obtain additional case details and outcome 
information (eg, from hospital discharge summaries, consultant reports, autopsy reports) in order 
to perform an independent medical assessment of the reported case. For the subjects who 
withdraw consent these events will be followed until the date of withdrawal of consent. The 
withdrawal of consent date will be recorded as the end date of the event.  
10.3.4. 
Reporting of SAEs 
The Sponsor has requirements for expedited reporting of SAEs meeting specific criteria to 
regulatory authorities. Therefore, the Sponsor must be notified immediately regarding any SAE 

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that occurs after administration of the study drug and any SAE assessed by the PI (or designee) 
as related to a study procedure that occurs after the participant has signed an ICF.  
All SAEs must be reported to the Medical Monitor within 24 hours of the Investigational Site’s 
knowledge of the event. The study site will transmit a SAER using the designated safety 
mailbox. 
An optional initial report can be made via telephone, but a completed SAER must still be faxed 
or emailed within 24 hours of the site’s knowledge of the event. The Investigational Site will be 
provided with SAER forms wherein the following information is requested. In addition, relevant 
eCRF pages should be appended to communicate relevant study drug and patient outcome 
information. 
• Patient identification number, PI name, and site number 
• SAE information: event term, onset date, severity, and causal relationship 
• The outcomes attributable to the event (eg, death, a life-threatening AE, inpatient 
hospitalization, prolongation of existing hospitalization, a persistent or significant disability 
or incapacity, or other important medical event[s]) 
• A summary of relevant test results, pertinent laboratory evaluations, and any other relevant 
medical history 
• The first and last dates of study drug administration. NOTE: as this is a double-masked 
study, SAERs should not indicate specific study drug assignments 
• Indicate if the study drug was discontinued or the study drug administration schedule 
modified 
• Supplemental information may include the following hospital records: laboratory results, 
radiology reports, progress notes, admission and emergency room notes, holding and 
observation notes, discharge summaries, autopsy reports, and death certificates 
The SAER should be faxed or emailed within 24 hours of the site’s knowledge of the event with 
as much of the above information as available at the time. The following minimum information 
is required for reporting an SAE: patient identification, reporting source, and an event or 
outcome. Supplemental information may be transmitted using a FU report and should not delay 
the initial report. Supplemental information should be marked as a FU report and faxed or 
emailed using the safety mailbox. The Sponsor may contact the Investigational Site to solicit 
additional information or follow up on the event.  
The PI (or designee) must take all therapeutic measures necessary for resolution of the SAE. Any 
medications or procedures necessary for treatment of the SAE must be recorded on the 
appropriate pages of the patient’s eCRF. Withdrawal from the study and therapeutic measures 
taken shall be at the discretion of the PI (or designee). A full explanation for the discontinuation 
from the study should be made in the patient’s medical records and the patient’s eCRF. 
All SAEs must be reported to the Investigational Site’s concerned regulatory authority and/or 
ethics committee by the PI (or designee) in accordance with its regulations.  

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10.4. Appendix 4: Contraceptive Guidance 
The risks of LASN01 administration during pregnancy have not been evaluated.  
Female patients must be nonpregnant nonlactating, and either postmenopausal (ie, no menses for 
≥12 months without an alternative medical cause and FSH level within the postmenopausal 
range), surgically sterile (ie, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) for 
≥6 months, or agree to use a highly effective method of contraception from the start of the study 
and for ≥90 days following the last dose of study drug or until the EOS visit, whichever is later. 
Male patients must use a highly effective method of contraception unless considered 
permanently surgically sterile following a bilateral orchidectomy. 
Highly effective methods of contraception are: 
• Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation: 
o Oral 
o Intravaginal 
o Transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation: 
o Oral 
o Injectable 
o Implantable 
• Intrauterine device (IUD) 
• Intrauterine hormone-releasing system (IUS) 
• Bilateral tubal occlusion 
• Vasectomized partner (having received medical assessment of the surgical success) 
• True sexual abstinence from the start of the study and for ≥90 days following the last dose of 
study drug or until the EOS visit, whichever is later, is acceptable only when refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment, 
as described above.  The reliability of sexual abstinence needs to be evaluated in relation to 
the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic 
abstinence (calendar, symptothermal, postovulation methods), withdrawal (coitus 
interruptus), spermicides only, and lactational amenorrhea methods are not considered “true” 
abstinence and are not acceptable methods of contraception 

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11. 
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