A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Multiple Doses of LT3001 Drug Product in Subjects With Acute Ischemic Stroke (AIS)
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Sponsor: Lumosa Therapeutics Co., Ltd.

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
This document is confidential. 
 
 
1 
FINAL CLINICAL STUDY PROTOCOL 
 
 
 
Lumosa Therapeutics Co., Ltd. 
 
Protocol Title: BRIGHT - A Phase II, Double-Blind, Randomized, Placebo-Controlled Study to 
Evaluate the Safety and Efficacy of Multiple Doses of LT3001 Drug Product in Subjects with 
Acute Ischemic Stroke (AIS) 
Protocol Number: LT3001-205 
 
 
 
 
Name of Investigational Product: 
LT3001 drug product 
Phase of Development: 
II 
Indication: 
Acute Ischemic Stroke (AIS) 
Sponsor: 
Lumosa Therapeutics 
4th Floor, No. 3-2, Park Street, 
Nangang District, Taipei, 
11503, Taiwan 
Tel: +886-2-26557918 
Fax: +886-2-26557919 
Protocol Version:  
8.1 
Protocol Date: 
23 Apr 2025 
 
-CONFIDENTIAL- 
This document and its contents are the property of and confidential to Lumosa Therapeutics Co., Ltd. Any 
unauthorized copying or use of this document is prohibited. 
 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
 
INVESTIGATOR SIGNATURE PAGE 
Protocol Title: 
BRIGHT - A Phase II, Double-Blind, Randomized, Placebo-Controlled 
Study to Evaluate the Safety and Efficacy of Multiple Doses of LT3001 
Drug Product in Subjects with Acute Ischemic Stroke (AIS) 
Protocol Number: 
LT3001-205 
Confidentiality and Current Good Clinical Practice (GCP)/E6(R2) Compliance Statement 
• I, the undersigned, have reviewed this protocol (and amendments, as applicable), including 
appendices, and I will conduct the study as described in compliance with this protocol (and 
amendments), GCP, and relevant International Council for Harmonisation (ICH) 
guidelines. 
• I am thoroughly familiar with the appropriate use of the investigational product, as 
described in this protocol and any other information provided by Lumosa Therapeutics Co., 
Ltd including, but not limited to, the current investigator’s brochure. 
• Once the protocol has been approved by the independent ethics committee 
(IEC)/institutional review board (IRB), I will not modify this protocol without obtaining 
prior approval of Lumosa Therapeutics Co., Ltd and of the IEC/IRB. I will submit the 
protocol amendments and/or any informed consent form modifications to Lumosa 
Therapeutics Co., Ltd and the IEC/IRB, and approval will be obtained before any 
amendments are implemented. 
• I ensure that all persons or party assisting me with the study are adequately qualified and 
informed about Lumosa Therapeutics Co., Ltd’s investigational product and of their 
delegated study-related duties and functions as described in the protocol. 
• I ensure that source documents and trial records that include all pertinent observations on 
each of the site’s trial subjects will be attributable, legible, contemporaneous, original, 
accurate, and complete.  
• I understand that all information obtained during the conduct of the study with regard to 
the subjects’ state of health will be regarded as confidential. No subjects’ names will be 
disclosed. All subjects will be identified by assigned numbers on all case report forms, 
laboratory samples, or source documents forwarded to the Sponsor. Clinical information 
may be reviewed by the Sponsor or its agents or regulatory agencies. Agreement must be 
obtained from the subject before disclosure of subject information to a third party. 
• Information developed in this clinical study may be disclosed by Lumosa Therapeutics Co., 
Ltd to other clinical investigators, regulatory agencies, or other health authority or 
government agencies as required. 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
 
INVESTIGATOR’S AGREEMENT 
 
I have read the LT3001-205 Protocol Version 8.1 dated 23 Apr 2025 and agree to conduct the 
study as outlined.  I agree to maintain the confidentiality of all information received or developed 
in connection with this protocol. 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 3 of 83 
2. 
Subject or if applicable subject’s legally acceptable representative/ legally 
designated representative consents to participation by signing the informed consent 
form after receiving full information about the study. 
3. 
Subject 
 is aged 18 to 90 years (inclusive) 
 
 is aged 18 to 80 years (inclusive) at the time of Screening (Visit 1). 
4. 
Subject has an NIHSS of 4 to 25. 
5. 
Subject 
 is able 
to receive the 1st IP within 24 hours after stroke symptoms onset. 
 
 
 
 
 
6. 
Subjects who are women of childbearing potential, or men whose sexual partners 
are women of childbearing potential, are able and willing to use at least 1 highly 
effective method of contraception during the study until 3 months after the last 
dosing of IP administration. 
Neuroimaging Inclusion Criteria: 
1. 
Subject has adequate renal function, has no history of severe allergic reactions to 
contrast agents, and is able to undergo a contrast brain perfusion with either MRI 
or computed tomography (CT). 
2. 
 
 
subjects must adhere to the following Mismatch Profile on MRI (perfusion is 
included) or CTP
 
**. 
** The mismatch ratio is determined in real time by site routine practice (e.g., RAPID or 
similar software, or other similar analyses) based on the difference between the ischemic core 
lesion volume and the Tmax >6s lesion volume. If both a multimodal MRI and CTP are 
performed before enrollment, the later of the 2 scans is assessed to determine eligibility. 
 
Exclusion Criteria: 
1. 
During the current AIS episode, the subject has received or is scheduled to receive 
EVT and/or intravenous thrombolytic (e.g., recombinant tissue-type plasminogen 
activator) treatment based on the investigator's assessment of its potential benefit.  
2. 
Subject has a pre-stroke disability (mRS >2). 
3. 
Subject has Alberta Stroke Program Early CT Score of ≤5. 
4. 
Subject has symptoms of suspected subarachnoid hemorrhage, even if CT is 
normal. 
5. 
Subject has imaging evidence of acute intracranial hemorrhage, intracranial tumor 
(except 
meningioma 
without 
parenchymal 
mass 
effect), 
arteriovenous 
malformations, other central nervous system lesions that could increase the risk of 
bleeding, or aneurysm requiring treatment. 
6. 
Subject has significant mass effect with midline shift. 
7. 
Subject has pre‐existing medical, neurological, or psychiatric disease that would 
confound the neurological or functional evaluations, e.g., seizures at onset of the 
current AIS, dementia. 
8. 
Subject has current uncontrolled hypertension despite treatment: systolic blood 
pressure >185 mmHg or diastolic blood pressure >110 mmHg before dosing at 
Screening (Visit 1). 
9. 
Subject has hemorrhagic diathesis, coagulation factor deficiency or recent oral 
anticoagulant therapy with International Normalized Ratio >1.7 or activated partial 
thromboplastin time >1.5 times of upper limit of normal range at Screening 
(Visit 1). 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 4 of 83 
10. 
Subject has received conventional heparin within 48 hours before the 1st IP 
administration, except for low dose subcutaneous conventional heparin or low 
molecular weight heparin at a preventive dose. 
11. 
Subject has received one of the new oral anticoagulants within 48 hours before the 
1st IP administration, e.g., dabigatran, apixaban, rivaroxaban, and edoxaban, except 
for dabigatran-treated subject who has been given a reversal agent, idarucizumab, 
before the 1st IP administration. 
12. 
Subject has platelet count <100,000/mm3 at Screening (Visit 1). 
13. 
Subject has blood glucose concentration <50 mg/dL or >400 mg/dL at Screening 
(Visit 1). 
14. 
Subject has moderate or severe hepatic, renal, and/or active infectious disease at 
Screening (Visit 1) as judged by the investigator. Subject with confirmed COVID-
19 or influenza infection can be enrolled at the investigator's discretion. 
15. 
Subject is lactating, pregnant (pregnancy test required for all female subjects of 
childbearing potential), or planning to become pregnant during the study.  
16. 
Subject has had history of sICH, prior AIS, myocardial infarction, or serious head 
trauma within 90 days before Screening (Visit 1). 
17. 
Subject has had any major surgery within 90 days before Screening (Visit 1), e.g., 
intracranial or intraspinal surgery, coronary artery bypass graft, obstetrical 
delivery, organ biopsy. 
18. 
Subject has had a bleeding event within 21 days before Screening (Visit 1), e.g., 
gastrointestinal hemorrhage. 
19. 
Subject has puncture of noncompressible vessels within 7 days before Screening 
(Visit 1). 
20. 
Subject has a history of severe allergic reactions to LT3001 or excipients. 
21. 
Subject has participated in another investigational study and received IP within 
30 days before Screening (Visit 1) or 5 half-lives (whichever is longer). 
22. 
In the opinion of the Investigator, the subject has serious, advanced, or terminal 
illness that will prevent improvement or follow-up visits. 
23. 
In the opinion of the Investigator, the subject is not appropriate for the study for 
any other reason. 
Planned Sample Size: 
Approximately 200 eligible subjects will be randomized 1:1 to LT3001 drug product or 
placebo.  
 
 
  
 
 
 
 
Investigational Therapy: 
LT3001 drug product
 
Reference Therapy: 
Placebo
 
Treatment Duration: 
All subjects will receive the first dose of IP within 24 hours after stroke symptoms on Day 
0 and will be hospitalized for the care of AIS according to each study site’s current 
standard of care. Each subject will receive 
 LT3001 drug product or placebo 
via a 30-minutute intravenous infusion twice within every approximately 24 hours, total 
6 doses of IP within approximately 72 hours. 
The participation for each subject is approximately 92 days from the Screening (Visit 1) 
to the last visit. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 10 of 83 
3 
TABLE OF CONTENTS 
1 
FINAL CLINICAL STUDY PROTOCOL .............................................................................1 
2 
SYNOPSIS ..............................................................................................................................1 
3 
TABLE OF CONTENTS ......................................................................................................10 
3.1 
List of In-text Tables ........................................................................................................13 
3.2 
List of In-text Figures .......................................................................................................13 
4 
LIST OF ABBREVIATIONS ...............................................................................................14 
5 
INTRODUCTION .................................................................................................................16 
5.1 
General Information on Acute Ischemic Stroke ...............................................................16 
5.2 
Background on LT3001 ....................................................................................................17 
5.2.1 
Nonclinical Studies ..................................................................................................17 
5.2.2 
Clinical Studies ........................................................................................................20 
5.3 
Clinical Risks/Benefits of LT3001 ...................................................................................21 
5.4 
Study Rationale ................................................................................................................24 
6 
STUDY OBJECTIVES AND ENDPOINTS ........................................................................25 
6.1 
Study Objectives ...............................................................................................................25 
6.1.1 
Primary Objective ....................................................................................................25 
6.1.2 
Secondary Objective ................................................................................................25 
6.2 
Study Endpoints................................................................................................................25 
6.2.1 
Primary Endpoint .....................................................................................................25 
6.2.2 
Secondary Endpoints ................................................................................................25 
7 
INVESTIGATIONAL PLAN ...............................................................................................27 
7.1 
Description of Overall Study Design and Plan.................................................................27 
7.2 
Discussion of Study Design..............................................................................................28 
7.3 
End of Study .....................................................................................................................29 
8 
SELECTION OF STUDY POPULATION ...........................................................................30 
8.1 
Inclusion Criteria ..............................................................................................................30 
8.2 
Exclusion Criteria .............................................................................................................32 
8.3 
Study Withdrawal, Removal, and Replacement of Subjects ............................................33 
8.3.1 
Study and Site Closure .............................................................................................34 
9 
TREATMENTS .....................................................................................................................36 
9.1 
Details of Study Treatments .............................................................................................36 
9.2 
Dosage Schedule ..............................................................................................................36 
9.3 
Measures to Minimize Bias: Study Treatment Assignment and Blinding .......................36 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 11 of 83 
9.3.1 
Method of Study Treatment Assignment .................................................................37 
9.3.2 
Blinding ....................................................................................................................37 
9.4 
Treatment Accountability and Compliance ......................................................................38 
9.5 
Prior and Concomitant Therapy .......................................................................................38 
9.5.1 
Prior and Concomitant Medications ........................................................................38 
9.6 
Post-Trial Treatments .......................................................................................................39 
10 
STUDY PROCEDURES .......................................................................................................40 
10.1 Informed Consent .............................................................................................................43 
10.2 Study Procedures ..............................................................................................................44 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
11 
EFFICACY ASSESSMENTS ...............................................................................................48 
11.1 Modified Rankin Scale .....................................................................................................48 
11.2 National Institute of Health and Stroke Scale ..................................................................48 
11.3 Montreal Cognitive Assessment .......................................................................................48 
11.4 Magnetic Resonance Imaging or Computed Tomography Perfusion ..............................49 
12 
SAFETY ASSESSMENTS ...................................................................................................50 
12.1 Bleeding Assessment ........................................................................................................50 
12.2 Medical History/Concomitant Illness ...............................................................................50 
12.3 Vital Signs ........................................................................................................................50 
12.4 Complete/Limited Physical Examination .........................................................................51 
12.5 Electrocardiograms ...........................................................................................................51 
12.6 Laboratory Assessments ...................................................................................................51 
12.7 Adverse Events .................................................................................................................52 
12.7.1 
Adverse Events ........................................................................................................52 
12.7.2 
Serious Adverse Events ...........................................................................................54 
12.7.3 
Serious Adverse Event Reporting ............................................................................54 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 12 of 83 
12.7.4 
Suspected Unexpected Serious Adverse Reactions .................................................55 
12.7.5 
Pregnancy .................................................................................................................56 
12.7.6 
Overdose ..................................................................................................................56 
13 
STATISTICAL ANALYSIS .................................................................................................57 
13.1 Determination of Sample Size ..........................................................................................57 
13.2 Analysis Populations ........................................................................................................58 
13.3 Efficacy Analysis..............................................................................................................59 
13.3.1 
Analysis of Secondary Efficacy Endpoints ..............................................................59 
13.4 Safety Analysis .................................................................................................................65 
13.4.1 
Analysis of Primary Endpoint ..................................................................................65 
13.4.2 
Analysis of Secondary Safety Endpoint ...................................................................65 
13.5 Interim Analysis ...............................................................................................................67 
14 
STUDY MANAGEMENT ....................................................................................................68 
14.1 Approval and Consent ......................................................................................................68 
14.1.1 
Regulatory Guidelines ..............................................................................................68 
14.1.2 
Institutional Review Board/Independent Ethics Committee ....................................68 
14.1.3 
Informed Consent .....................................................................................................68 
14.2 Data Handling ...................................................................................................................68 
14.3 Source Documents ............................................................................................................69 
14.4 Record Retention ..............................................................................................................69 
14.5 Monitoring ........................................................................................................................70 
14.6 Quality Control and Quality Assurance ...........................................................................70 
14.7 Protocol Amendment and Protocol Deviation ..................................................................70 
14.7.1 
Protocol Amendment ...............................................................................................70 
14.7.2 
Protocol Deviations ..................................................................................................71 
14.8 Ethical Considerations ......................................................................................................71 
14.9 Financing and Insurance ...................................................................................................71 
14.10 Publication Policy/Disclosure of Data..............................................................................71 
15 
REFERENCES ......................................................................................................................73 
16 
APPENDICES .......................................................................................................................75 
Appendix 1: 
Contraception Guidelines ...................................................................................76 
Appendix 2: 
Modified Rankin Scale (Sample) .......................................................................78 
Appendix 3. 
National Institute of Health and Stroke Scale (Sample).....................................79 
Appendix 4. 
Country-Specific Requirements for Informed Consent Forms ..........................83 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 13 of 83 
3.1 
List of In-text Tables 
Table 1. Schedule of Assessments ..............................................................................................41 
Table 2. Laboratory Assessments................................................................................................52 
Table 3. Classification of Adverse Events by Intensity ..............................................................53 
Table 4. Classification of Adverse Events by Relationship to Investigational Product ..............53 
 
3.2 
List of In-text Figures 
Figure 1. Study Design .................................................................................................................28 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 14 of 83 
4 
LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
AE 
adverse event 
aICH 
asymptomatic intracranial hemorrhage 
AIS 
acute ischemic stroke 
 
 
aPTT 
activated partial thromboplastin time 
 
 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CS 
clinically significant 
CT 
computed tomography 
CTP 
computed tomography perfusion 
DSMB 
Data Safety Monitoring Board 
eCRF 
electronic case report form 
ECG 
electrocardiogram 
EDC 
electronic data capture 
EVT 
endovascular thrombectomy 
FDA 
Food and Drug Administration 
GCP 
good clinical practice 
GLP 
Good Laboratory Practice 
GMR 
geometric mean ratio 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
INR 
International Normalized Ratio 
IP 
investigational product 
IRB 
institutional review board 
ITT 
Intent-to-Treat 
IV 
intravenous/intravenously 
LAR 
legally acceptable representative 
LDR 
legally designated representative 
 
 
MoCA 
Montreal Cognitive Assessment 
MRI 
magnetic resonance imaging 
mRS 
Modified Rankin Scale 
MTD 
maximum tolerated dose 
NCS 
not clinically significant 
NIHSS 
National Institute of Health Stroke Scale 
 
 
PD 
pharmacodynamic(s) 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 15 of 83 
Abbreviation 
Definition 
PK 
pharmacokinetic(s) 
PP 
Per-Protocol 
PT 
prothrombin time 
rtPA 
recombinant tissue-type plasminogen activator 
 
 
 
 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
sICH 
symptomatic intracranial hemorrhage 
SoC 
standard of care 
SUSAR 
suspected unexpected serious adverse reactions 
WOCBP 
women of childbearing potential 
US 
United States 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 16 of 83 
5 
INTRODUCTION 
5.1 
General Information on Acute Ischemic Stroke 
Stroke is classically characterized as a neurological deficit attributed to an acute focal injury of 
the central nervous system by a vascular cause.1 Ischemic strokes account for about 87% of all 
strokes; 10% are intracerebral hemorrhage strokes, whereas 3% are subarachnoid haemorrhage 
strokes.2 Annually, 15 million people worldwide suffer a stroke; in the United States (US), on 
average, someone experiences stroke every 40 seconds.2,3 Globally, stroke is the second leading 
cause of death in individuals above the age of 60 years and is the leading cause of disability.3,4 
The ultimate result of ischemic cascade initiated by acute stroke is neuronal death along with an 
irreversible loss of neuronal function via direct starvation from lack of glucose, failure of 
adenosine triphosphate production, membrane depolarization, rise in intracellular calcium, and 
free radical production.4,5 Furthermore, free radicals directly damage cells and also initiate other 
reactions that lead to cerebral edema.6 Based on the pathogenesis of ischemic stroke, the 2 main 
aims of the treatment strategies in ischemic stroke are restoration of cerebral blood flow and 
reduction of the harmful effects of ischemia on neurons.4 
Alteplase (Activase®), a recombinant tissue-type plasminogen activator (rtPA), was the first 
medication approved for the treatment of ischemic stroke by the US Food and Drug 
Administration (FDA) in 1996 (BLA 103172/S-1055). Although alteplase has been shown to 
improve the outcome of subjects with acute ischemic stroke (AIS), its use has been limited 
because of the low eligibility rate for this medication. The most common exclusion for alteplase 
is the delay in seeking medical attention; only 22% to 31% of patients with ischemic stroke 
present to an emergency department within the time window approved for rtPA administration, 
which is 3 or 4.5 hours after symptom onset.7 In addition, symptomatic intracerebral hemorrhage 
is the most feared complication after intravenous (IV) alteplase; with nearly 5-fold risk even 
when alteplase was given within 3 hours, as shown in a recent meta-analysis of 1779 subjects.7 
The time window allowed for rtPA treatment varies among countries; for example, the US FDA 
did not approve the change from 3 hours to 4.5 hours after their review of the trial results and 
unpublished data from alteplase manufacturer.7 Administration later than 4.5 hours is associated 
with an increased risk of mortality, and the risk-benefit ratio has not been established (SIGN 
2008).8 
Restoration of the blood supply is essential to minimize the damage caused by the ischemic 
condition, but reperfusion by thrombolytic drugs such as alteplase and angioplasty techniques 
often lead to an increase in the extent of brain injury. This reperfusion injury is thought to be 
caused by the activity of free radicals.9 Although the benefit of alteplase is well established, its 
adverse effects remain the major concerns for the use of the thrombolytic agent. Additionally, 
rtPA also has potential for direct neurotoxicity that is not related to its thrombolytic activity.10 
Due to the abovementioned reasons, the usage rate of alteplase is low, with only approximately 
5% of stroke patients being administered alteplase.11 As such, there is a need to develop 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 17 of 83 
treatments that can offer similar efficacy to alteplase but with a lower increase of bleeding and/or 
longer therapeutic window. 
5.2 
Background on LT3001 
LT3001 
 is a novel small molecule designed to have both 
thrombolytic and free radical scavenging activities, which were characterized in various in vitro 
and in vivo models. In vitro studies have shown that LT3001 exhibits substantial anti-oxidation 
activity. In animal studies, LT3001 can restore blood flow, reduce cerebral infarct volume, and 
improve neurological outcome in rodent and non-human primate stroke models, with an apparent 
wider therapeutic time window and a better safety profile than those reported for rtPA. Effect of 
LT3001 on the bleeding time was evaluated in male Institute of Cancer Research mice using an 
amputation tail model. The tail bleeding time of mice treated with 
 LT3001 was 
comparable to animals that received vehicle control and significantly shorter than those treated 
with rtPA (10 mg/kg). 
LT3001 appears to have both thrombolytic and free radical scavenging effects with minimal risk 
of bleeding and potentially extended treatment time window. Therefore, LT3001 is being 
developed for the treatment of AIS. 
5.2.1 Nonclinical Studies 
The nonclinical program for LT3001 included the following: 
• In vitro pharmacology studies to evaluate antioxidant activity, anti-platelet activity, 
 induced leukocyte migration, interaction with 
Aspirin, and binding to receptors and critical enzymes; 
• In vivo pharmacology studies to evaluate efficacy in mouse, rat, and monkey models of 
stroke; 
• In vivo pharmacology study to evaluate the interaction with Aspirin, Clopidogrel, 
Apixaban, or Dabigatran in a rat model; 
• Good Laboratory Practice (GLP) safety pharmacology studies, involving neurological 
and respiratory in rats, cardiovascular in dogs and mini-pigs, an in vitro human Ether-a-
go-go Related Gene assay, and a non-GLP cardiovascular study in monkeys; 
• In vivo pharmacokinetic (PK)/toxicokinetic evaluations in rats, dogs, and mini-pigs; 
• In vitro absorption, distribution, and metabolism studies using mouse, rat, dog, monkey, 
mini-pig, and human hepatocytes; 
• Acute toxicity studies in rats, dogs, monkeys, and mini-pigs; 
• 14-day repeat-dose GLP toxicity studies in rats and dogs; 
• 6-day repeat-dose GLP toxicity study in mini-pigs; 
• In vitro genotoxicity studies and in vivo genotoxicity evaluation in rats; and 
• In vitro phototoxicity study. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 18 of 83 
A summary of noteworthy findings from these nonclinical studies is listed below: 
• Effect of LT3001 
 on the bleeding time was evaluated in male Institute of 
Cancer Research mice and was comparable to animals that received vehicle control and 
significantly shorter than those treated with rtPA (10 mg/kg). 
• LT3001 showed superior total antioxidant capacity than the known antioxidant control 
substances (Trolox®, L-ascorbic acid, and Edaravone) in CUPric Ion Reducing 
Antioxidant Capacity assay in vitro. 
• LT3001 significantly inhibits 
 polymorphonuclear leukocytes migration and 
 platelet aggregation. 
• LT3001, administered 
 at 3 and 6 hours post stroke, was 
considered efficacious in the preclinical rat embolic stroke model. 
• Repeat administration of LT3001 once- or thrice-daily for 6 consecutive days was 
considered efficacious in a preclinical rat embolic stroke model. In addition, twice-daily 
administration of LT3001 also showed a significant smaller infarct size than vehicle 
control and rtPA-treated stroke rat model.  
• In a dose range finding and blood flow monitoring study, LT3001 
 
 increased the blood flow compared to those of vehicle control in 
embolic stroke rat model. There was a dose-dependent effect, higher dose LT3001 had a 
better therapeutic effect of restoring blood flow. 
• In macaque monkey of embolic stroke model, LT3001 
 
 improved neurological deficit score measured at 24, 48, and 
72 hours after ischemia, which was induced by injection of pooled clots into the internal 
carotid artery, when compared to that improved by rtPA. 
• The interaction of LT3001 and Aspirin was assessed by optical microplate-based assay 
and in male Wistar rats. LT3001 
 showed no effect on Aspirin’s 
anti-platelet aggregation activity in vitro. LT3001 
 has no impact on 
Aspirin induced bleeding time elongation or gastric mucosal injury in vivo. 
• The interaction of LT3001 and Dabigatran, Clopidogrel, or Apixaban was assessed in 
male Sprague-Dawley rats. Dabigatran, Clopidogrel, and Apixaban prolonged the 
prothrombin time (PT), activated partial thromboplastin time (aPTT), and/or thrombin 
time in the rat clotting time assay. LT3001 
 in combination with 
Dabigatran, Clopidogrel, or Apixaban did not elicit synergistic effects in clotting time 
assay in vivo. 
• In secondary pharmacodynamics (PD) studies, LT3001
had no effect on 
any of the receptors or critical enzymes evaluated. 
• In GLP safety pharmacology studies in vivo, LT3001 
 
showed no biologically significant effect in either the central nervous system Irwin test or 
respiratory physiological parameters in rats. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 21 of 83 
. This study 
also determined the effect of multiple doses of LT3001 drug product on blood pressure 
and coagulation function. 
• LT3001-105 was a two-part Phase I study of multiple doses of LT3001 drug product 
 
in healthy adult subjects in the US. Part A was randomized, double-blind, 
placebo-controlled design to evaluate the safety, tolerability, and PK of multiple doses of 
LT3001 drug product. Part B was open-label without placebo-controlled design to assess 
the drug-drug interaction of LT3001 drug product when co-administered with aspirin, 
clopidogrel, apixaban or dabigatran. 
• LT3001-201, a Phase IIa, double-blind, single-dose, randomized, placebo-controlled 
study to evaluate the safety, tolerability, and potential efficacy of LT3001 drug product  
 in subjects with AIS. 
In addition, 3 studies on LT3001 are planned/ongoing (enrollment stage): 
• LT3001-202: Randomized, double-blind, placebo-controlled, parallel-group study to 
determine the safety and efficacy of multiple doses of LT3001 drug product  
 in patients with AIS. 
• LT3001-203: Randomized, double-blinded, placebo-controlled Phase II study to evaluate 
the safety and efficacy of LT3001 drug product 
 
in subjects with AIS undergoing endovascular thrombectomy. 
• LT3001-205: current study described in this protocol. 
5.3 
Clinical Risks/Benefits of LT3001 
In the first-in-human LT3001-101 study for single dose of LT3001 drug product 
 
(Cohort 0) and 
 (Cohort 1) 
 healthy human 
volunteers, the LT3001 drug product was safe and well tolerated in both dosing cohorts. There 
were no severe adverse events (AEs) or serious adverse events (SAEs) reported in either cohort. 
There were no AEs reported in Cohort 0. In Cohort 1, 1 subject presented with an allergy to 
medical tape, 1 subject developed a hematoma that was acquired during IV needle removal, and 
1 subject receiving 
 LT3001 drug product developed a headache. All AEs occurred 
post dosing, were classified as mild in severity, and were resolved. The AE of headache was 
considered by the Investigator to be mild in intensity and possibly related to the investigational 
product (IP); the other AEs were considered unrelated. 
Safety data collected in this study also included vital signs (pulse rate, blood pressure, respiratory 
rate, and body temperature), ECGs, clinical biochemistry, hematology, and coagulation/clotting 
parameters. There were no clinically significant findings in any of the safety parameters 
measured. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 24 of 83 
3. Clinical laboratory tests including hematology and clinical biochemistry. 
4. Coagulation/clotting parameters, including PT, and aPTT. 
5. Monitoring of AEs. 
Overdose 
The dose level of LT3001 drug product will be calculated by the Investigator or a qualified 
designee 
. Because drug accumulation is not anticipated 
, and subjects will only receive LT3001 drug product 
administered by an Investigator or a qualified designee and under close monitoring, it is 
anticipated that the risk of overdose or medication error will be low. 
Any overdose, with or without associated AEs, should be promptly reported by the Investigator 
or designee 
 Pharmacovigilance (see contact details in 
Section 12.7.3). Overdoses and medication errors will be documented as protocol deviations and 
communicated to the Study Monitor. 
No specific therapy for overdose of LT3001 drug product exists. In the event of overdose or 
medication error, appropriate standard of care (SoC) therapy for the subject’s symptoms and 
clinical status will be provided. 
Details regarding known or anticipated benefits and risks, as well as reasonably anticipated AEs 
for LT3001 may be found in the investigator’s brochure. 
5.4 
Study Rationale 
Tissue plasminogen activator (alteplase) is the only approved drug treatment for stroke in the US 
and Taiwan. Per the labeling, it must be administered within 3 hours of stroke symptom onset. 
The approved window of administration in some other countries is 4.5 hours of stroke symptom 
onset. 
LT3001 is a novel chemical entity designed to have both thrombolytic and free radical 
scavenging activities, which were characterized in various in vitro and in vivo models. Its 
advantages over IV rtPA include: shorter infusion time, within 24 hours of stroke onset (as 
opposed to 3 to 4.5 hours), better recanalization rate, prevention of reperfusion injury by 
scavenging free radicals, no effect on bleeding time, no evidence of increase in intracranial 
hemorrhage (as seen with IV rtPA), and ease of use. 
This Phase II, double-blind, randomized, placebo-controlled study is to evaluate the efficacy and 
safety of multiple doses of LT3001 drug product in subjects with AIS. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 25 of 83 
6 
STUDY OBJECTIVES AND ENDPOINTS 
6.1 
Study Objectives 
6.1.1 Primary Objective 
The primary objective is to determine the safety of multiple doses of LT3001 drug product in 
subjects with AIS. 
6.1.2 Secondary Objective 
The secondary objective is to determine the efficacy of multiple doses of LT3001 drug product 
in subjects with AIS. 
6.2 
Study Endpoints 
6.2.1 Primary Endpoint 
The proportion of subjects with AEs, judged to be probably or definitely related to the IP within 
90 days after the 1st IP administration. 
6.2.2 Secondary Endpoints 
Clinical efficacy outcomes: 
1. Functional outcome 
a. The proportion of subjects achieve 
 mRS 0-1 
. The proportion of subjects achieve 
 
 mRS 0-2 
. 
b. The proportion of subjects with independent functional outcome, defined as mRS 
≤2 
 after the 1st IP. 
c. The proportion of subjects with excellent functional outcome, defined as mRS ≤1 
 after the 1st IP. 
d. The shift of proportion of subjects with each grade on mRS 
 
 from Baseline. 
2. Neurological outcome 
a. The NIHSS 
 after the 1st IP 
 
. 
b. The proportion of subjects with neurological outcome improvement, defined as a 
decrease in NIHSS ≥4 points 
 
from Baseline. 
c. The proportion of subjects with neurological outcome improvement, defined as a 
decrease in NIHSS ≥4 points or NIHSS of 0 to 1 point 
 
 from Baseline. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 26 of 83 
d. The proportion of subjects with NIHSS ≤2 
 
after the 1st IP. 
e. The proportion of subjects with NIHSS ≤1 
 
after the 1st IP. 
f. Change in NIHSS 
 from 
Baseline. 
3. The occurrence of recurrent stroke within 90 days after the 1st IP. 
4. The change of cognition assessment by Montreal Cognitive Assessment (MoCA)  
 from Baseline 
. 
Imaging outcomes: 
1. The change of infarct volume 
 from Baseline by 
magnetic resonance imaging (MRI)/computed tomography perfusion (CTP). 
2. The change of hypoperfusion lesion 
 from Baseline 
by perfusion-weight imaging MRI/CTP. 
3. The proportion of subjects with 90% reduction in hypoperfusion lesion 
 
 from Baseline by perfusion-weight imaging MRI/CTP. 
4. The infarct volume 
 after the 1st IP by MRI/CTP 
 
. 
Safety outcomes: 
1. The occurrence of sICH 
 after the 1st IP; clinical deterioration 
defined as an increase in the NIHSS of 4 points or more AND confirmed by magnetic 
resonance (MR)/computed tomography (CT–) imaging - documentation. 
2. The occurrence of aICH 
 after the 1st IP. 
3. The occurrence of mortality due to any reason within 90 days after the 1st IP. 
4. The number and severity of AEs within 90 days after the 1st IP. 
5. The number of subjects with AEs within 90 days after the 1st IP. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 28 of 83 
Figure 1. 
Study Design 
7.2 
Discussion of Study Design 
Because there is no approved drug treatment for AIS for administration beyond 3 hours of stroke 
onset in the US and in Taiwan and 4.5 hours in some countries, a placebo-controlled study will 
be ethically acceptable to evaluate the drug effect objectively. 
Efficacy will be evaluated by assessing the functional outcomes measured by mRS, neurological 
outcome assessed by NIHSS, the occurrence of recurrent stroke, and cognition assessed by the 
MoCA; and imaging outcomes measured by change in infarct volume and hypoperfusion lesion. 
Safety assessments include occurrence of sICH, aICH, and mortality, and AEs. Besides, vital 
signs, physical examinations, 12-lead ECGs recordings, laboratory results (hematology, clinical 
biochemistry, and coagulation) will also be assessed. 
The dose and regimen chosen are based on results from the nonclinical studies, the completed 
clinical studies, and US FDA recommendations. Based on the NOEL of the more sensitive 
species 
 and the safety factor of 10 recommended by the “Guidance for Industry - 
Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in 
Adult Healthy Volunteers, CDER, July 2005,” the proposed human doses for the Phase I 
single-ascending-dose first-in-human study, LT3001-101, was determined 
 
. The 
 has an excellent safety profile, with even the highest dose at 
 producing only 1 mild AE (headache) and no clinically significant findings in any of 
the safety parameters measured (AEs, vital signs, electrocardiograms, clinical chemistry, 
urinalysis, hematology, or coagulation parameters). 
The dose for the phase II single-dose study in patients with acute ischemic stroke, LT3001-201, 
is 
, based on the “no adverse event observed” dose tested in the Phase I single-dose 
study. No subject was reported with sICH during the study or within 7 days of receiving IP. 
Eleven serious TEAEs were reported by 4 subjects (25%) in the LT3001 drug product group and 
by 2 subjects (25%) in the placebo group, all of which were considered as unrelated or unlikely 
related to IP. The single-dose regimen was generally safe and well tolerated in AIS patients. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 31 of 83 
** The mismatch ratio is determined in real time by site routine practice (e.g., RAPID or similar software, 
or other similar analyses) based on the difference between the ischemic core lesion volume and the Tmax 
>6s lesion volume. If both a multimodal MRI and CTP are performed before enrollment, the later of the 2 
scans is assessed to determine eligibility. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 32 of 83 
8.2 
Exclusion Criteria 
Individuals meeting any of the following criteria at Screening (Visit 1) or Baseline are ineligible 
to participate in this study: 
1. During the current AIS episode, the subject has received or is scheduled to receive EVT 
and/or IV thrombolytic (e.g., rtPA) treatment based on the investigator's assessment of its 
potential benefit.   
2. Subject has a pre-stroke disability (mRS >2). 
3. Subject has Alberta Stroke Program Early CT Score of ≤5. 
4. Subject has symptoms of suspected subarachnoid hemorrhage, even if CT is normal. 
5. Subject has imaging evidence of acute intracranial hemorrhage, intracranial tumor 
(except meningioma without parenchymal mass effect), arteriovenous malformations, 
other central nervous system lesions that could increase the risk of bleeding, or aneurysm 
requiring treatment. 
6. Subject has significant mass effect with midline shift. 
7. Subject has pre‐existing medical, neurological, or psychiatric disease that would 
confound the neurological or functional evaluations, e.g., seizures at onset of the current 
AIS, dementia. 
8. Subject has current uncontrolled hypertension despite treatment: systolic blood pressure 
>185 mmHg or diastolic blood pressure >110 mmHg before dosing at Screening 
(Visit 1). 
9. Subject has hemorrhagic diathesis, coagulation factor deficiency or recent oral 
anticoagulant therapy with International Normalized Ratio (INR) >1.7 or aPTT >1.5 
times of upper limit of normal range at Screening (Visit 1). 
10. Subject has received conventional heparin within 48 hours before the 1st IP 
administration, except for low dose subcutaneous conventional heparin or low molecular 
weight heparin at a preventive dose. 
11. Subject has received one of the new oral anticoagulants within 48 hours before the 1st IP 
administration, e.g., dabigatran, apixaban, rivaroxaban, and edoxaban, except for 
dabigatran-treated subject who has been given a reversal agent, idarucizumab, before the 
1st IP administration. 
12. Subject has platelet count <100,000/mm3 at Screening (Visit 1). 
13. Subject has blood glucose concentration <50 mg/dL or >400 mg/dL at Screening 
(Visit 1). 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 33 of 83 
14. Subject has moderate or severe hepatic, renal, and/or active infectious disease at 
Screening (Visit 1) as judged by the investigator. Subject with confirmed COVID-19 or 
influenza infection can be enrolled at the investigator's discretion. 
15. Subject is lactating, pregnant (pregnancy test required for all female subjects of 
childbearing potential), or planning to become pregnant during the study.  
16. Subject has had history of sICH, prior AIS, myocardial infarction, or serious head trauma 
within 90 days before Screening (Visit 1). 
17. Subject has had any major surgery within 90 days before Screening (Visit 1), e.g., 
intracranial or intraspinal surgery, coronary artery bypass graft, obstetrical delivery, 
organ biopsy. 
18. Subject has had a bleeding event within 21 days before Screening (Visit 1), e.g., 
gastrointestinal hemorrhage. 
19. Subject has puncture of noncompressible vessels within 7 days before Screening 
(Visit 1). 
20. Subject has a history of severe allergic reactions to LT3001 or excipients. 
21. Subject has participated in another investigational study and received IP within 30 days 
before Screening (Visit 1) or 5 half-lives (whichever is longer). 
22. In the opinion of the Investigator, the subject has serious, advanced, or terminal illness 
that will prevent improvement or follow-up visits. 
23. In the opinion of the Investigator, the subject is not appropriate for the study for any other 
reason. 
8.3 
Study Withdrawal, Removal, and Replacement of Subjects 
If a subject discontinues study treatment and is withdrawn from the study for any reason, the 
study site must immediately notify the Medical Monitor (see contact details in Section 12.7.3). 
The date and the reason for study discontinuation must be recorded on the electronic case report 
form (eCRF). Subjects who discontinue early from the study will be asked to complete all 
assessments listed at Visit 6 as indicated in the Schedule of Assessments (Table 1). 
In the event that a subject discontinues prematurely from the study because of a AE or serious 
AE, the AE or serious AE will be followed up until it resolves (returns to normal or baseline 
values) or stabilizes, or until it is judged by the Investigator to no longer be clinically significant. 
Once a subject is withdrawn from the study, the subject may not reenter the study. 
A subject may voluntarily withdraw or be withdrawn from the study at any time for reasons 
including, but not limited to, the following: 
• unacceptable toxicity or AE 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 34 of 83 
• subject withdrawal of consent: at any time,’ a subject's participation in the study may be 
terminated at his/her request or on the basis of the Investigator’s clinical judgment. The 
reason for subject withdrawal will be noted on the eCRF. 
• intercurrent illness: a condition, injury, or disease unrelated to the primary diagnosis that 
became apparent during treatment and necessitated the subject’s termination from the 
study 
• general or specific changes in the subject's condition that renders him/her ineligible for 
further treatment according to the inclusion/exclusion criteria 
• subject fails to adhere to the protocol requirements (e.g., drug noncompliance, failure to 
make the return visits in the Follow-Up Period)  
• lost to follow-up: the subject stopped coming for visits, and study personnel were unable 
to contact the subject 3 times 
• pregnancy, as indicated in Section 12.7.5. 
Additionally, the Sponsor may stop the study at any time for safety, regulatory, legal, or other 
reasons aligned with good clinical practice (GCP). This study may be terminated at the discretion 
of the Sponsor or any regulatory agency. An Investigator may elect to discontinue or stop the 
study at his or her study site for any reason, including safety or low enrollment. 
Randomized but not treated subjects will not be replaced. 
8.3.1 Study and Site Closure 
The Sponsor reserves the right to close the study sites or terminate the study at any time for any 
reason at its sole discretion. All study sites will be closed after the study is completed or 
following the decision to close or terminate the study. A study site is considered closed when 
all subjects have completed study procedures 
 all 
protocol-required data have been collected and entered into the electronic data capture (EDC) 
system, all required documents have been collected and reconciled, and the study-site closure 
visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. Reasons for the early 
closure of a study site by Sponsor or the Investigator may include but are not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IEC/IRB 
or health authorities, Sponsor’s procedures, or ICH-GCP guidelines. 
• Difficulties in the recruitment of planned number of subjects in the indicated time with 
insufficient recruitment rate. 
• Discontinuation of further LT3001 development. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 35 of 83 
Sponsor or health authorities may terminate the study for reasonable cause. Conditions that 
may warrant termination of the study include, but are not limited to: 
• Negative risks/benefits assessment. 
• New scientific evidence of any unexpected, serious, or unacceptable risks of LT3001 that 
could impact the subjects’ enrolled or continuing in the study. 
• Sponsor decision to suspend or discontinue testing, evaluation, or development of 
LT3001. 
If the study is prematurely terminated or suspended, the Sponsor shall promptly inform the 
Investigators, IECs/IRBs, regulatory authorities, and any contracted vendors used in the study 
of the reason for termination or suspension, as specified by the applicable regulatory 
requirements. The Investigator shall promptly inform the subjects and ensure appropriate 
therapy and/or follow-up. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 36 of 83 
9 
TREATMENTS 
9.1 
Details of Study Treatments 
Each eligible subjects will be randomized centrally in a ratio of 1:1 to LT3001 drug product or 
placebo. 
LT3001 drug product will be provided 
 
 in glass vials with butyl rubber stoppers and flip-off aluminum crimp seals. Each vial 
will contain LT3001 drug substance 
 
 
 
  
 
 
 
 
 
 
All drug supplies will be provided by the Sponsor. 
9.2 
Dosage Schedule 
Subjects randomized to the study 
 
. 
The 1st IP will be administered within 24 hours after stroke symptoms onset.
 
 
9.3 
Measures to Minimize Bias: Study Treatment Assignment and Blinding 
The study is placebo-controlled to lessen the risk that events due to chance are falsely attributed 
to LT3001 drug product. 
The study is randomized to control for factors known and unknown between the treatment 
groups. 
The study is blinded so that the subjects, site staff administering the IP, and site staff conducting 
study assessments will not know which treatment a subject receives to allow assessment of the 
study objectives without bias. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 37 of 83 
9.3.1 Method of Study Treatment Assignment 
Subjects will be randomly assigned to receive LT3001 drug product or placebo in a ratio of 1:1. 
The randomization will be stratified according to age 
, baseline NIHSS 
, and the time of AIS symptoms onset to the planned 1st IP 
 
. The stratified randomization is to ensure similar risk distributions 
 
.  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
At Screening (Visit 1), 
 EDC system will assign a unique subject 
identification number to the subject known as the Subject Number. This number will be 
associated with the subject throughout the study. Every subject who signs an ICF (or has a LAR/, 
LDR or impartial witness sign the ICF on their behalf) must be entered into 
 EDC system 
regardless of eligibility in order to obtain a Subject Number.
 
 
The unblinded statistician will produce a Master Randomization list for the 
random assignment of subjects to each treatment 
 and a 
Kit Randomization list for the random assignment of kit numbers for labelling to each treatment. 
 
 Randomization Manager will receive the Master randomization list and the 
Kit randomization list 
. 
The subjects will be centrally randomized at a study level.  
9.3.2 Blinding  
According to the randomization schedule as indicated in the Schedule of Assessments (Table 1) 
and in accordance with the Pharmacy Manual, the Investigator or designee will obtain the 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 38 of 83 
Randomization Number and the Kit Number from 
 EDC system for each randomized 
subject.
 
 
 
Study site 
personnel, subjects, Sponsor personnel, or Sponsor designees will be blinded to treatment 
assignment throughout the duration of the study unless unblinding is required. If an Investigator 
becomes unblinded to a given subject’s study treatment, that subject will be discontinued from 
the study unless there are ethical reasons for that subject not to be discontinued; approval from 
the Medical Monitor must be obtained in such instances. 
Subject unblinding will only occur if details of the treatment assigned to the subject are 
necessarily required to determine the care needed to manage an AE or other serious safety 
situation. The Investigator and at least one designee will have the access to the unblinding 
module 
 and will be 
able to perform subject unblinding in an emergency. 
 Investigator must make 
every effort to contact the Medical Monitor before unblinding a subject (contact details are 
provided in Section 12.7.3). In the rare event that contact with the Medical Monitor is not 
possible prior to unblinding, the Investigator reserves the right to unblind in a true emergency, 
where subject safety is at immediate risk. 
 
The unblinding and its cause will also be documented in the eCRF
. 
9.4 
Treatment Accountability and Compliance 
The pharmacist or designee will maintain records of IP delivered to the study site, the inventory 
at the study site, the distribution to and use by each subject, and the return of materials to the 
Sponsor for storage or disposal. These records should include dates, quantities, batch/serial 
numbers, retest dates, in-clinic temperature log, and unique code numbers assigned to the 
product and study subjects. 
Investigators will maintain records that adequately document that the subjects were administered 
the correct study treatment and reconcile the products received from the drug dispensing center. 
IP will not be returned to the Sponsor until accountability has been fully monitored. 
Administration of IP will be supervised by study site personnel to ensure compliance. 
9.5 
Prior and Concomitant Therapy 
9.5.1 Prior and Concomitant Medications 
Restricted prior therapies are provided in Section 8.2. Low dose subcutaneous conventional 
heparin or low molecular weight heparin at a preventive dose are allowed. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 39 of 83 
All medications and other treatments taken by the subject during the course of the study, 
including those treatments initiated before Screening (Visit 1), must be recorded in the eCRF. 
The entry must include the dose, regimen, route, indication, and dates of use. 
After the subject has been administered the IP, medication to treat minor treatment-emergent 
illness(es) will generally be permitted. The SoC of AIS therapies will be permitted when 
appropriate.  
9.6 
Post-Trial Treatments 
Sponsor does not intend to provide any investigational or non-investigational products (specified 
in this protocol), or any other interventions to subjects who have completed the study or who are 
withdrawn earlier. When subjects leave the study, they will be under the care of their regular 
health care provider who will decide the best way to follow up with the AIS condition, including 
taking anti-platelet or anti-coagulant drugs to prevent secondary ischemic stroke, and receiving 
rehabilitation to improve physical functions. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 40 of 83 
10 STUDY PROCEDURES 
Table 1 outlines the timing of procedures and assessments to be performed throughout the study. 
Section 12.6 specifies laboratory assessment samples to be obtained. See Section 11 and 
Section 12 for additional details regarding efficacy assessments and safety assessments, 
respectively. 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 41 of 83 
Table 1. 
Schedule of Assessments 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
This document is confidential. 
Page 42 of 83 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 43 of 83 
10.1 Informed Consent 
Before performing any study-related procedures except the SoC assessments of AIS therapies, 
the Investigator or designee will obtain the signed ICF from the subject or if applicable the 
subject’s LAR/LDR, impartial witness or decision of independent physician who is not from the 
clinical study team. Country-specific considerations are provided in Appendix 4. 
In acute phase of AIS, patients may suffer from dizziness, loss of balance, trouble walking, 
weakness on one side of the body, trouble speaking or understanding speech, or trouble seeing 
with different severity. The AIS patients may be affected by the stroke symptoms and influenced 
in his/her decision. 
The following points should be considered while obtaining the signed ICF: 
• If the subject is unconscious, incapacitated and/or incapable, the Investigator or designee 
must obtain the signed ICF from the subject’s LAR/LDR.  
• If the subject has a known history or ongoing condition of anosognosia, the Investigator 
or designee must obtain the signed ICF from the subject’s LAR/LDR. 
• Where the subject is conscious but is unable to read and/or write or the subject’s 
LAR/LDR is unable to read and/or write, consent may be given and recorded through 
appropriate alternative means in the presence of at least one independent impartial 
witness.  
The impartial witness must not be a member of the clinical study team. In that case, the impartial 
witness shall sign and date the ICF. By signing the ICF, the impartial witness attests that 
• the information in the ICF and any other written information was accurately explained to, 
and apparently understood by, the subject or the subject’s LAR/LDR; 
• adequate time was given for the subject or the subject’s LAR/LDR to consider the 
decision to participate in the study and 
• that informed consent was freely given by the subject or the subject’s LAR/LDR. 
The informed consent shall be documented. The subject or, where the subject is not able to give 
informed consent, the subject’s LAR/LDR shall be provided with a copy of the document (or the 
record) by which informed consent has been given. Subjects and/or subject’s LAR/LDR will not 
be given any incentives or financial inducements, except for the compensation for expenses 
directly related to the participation in this trial.  
In all these situations, the subject must be informed about the study in a way that is adequate in 
view of their capacity to understand it. The subject shall as far as possibly take part in the 
informed consent procedure. The informed consent of the subject and subject’s LAR/LDR must 
be obtained as soon as possible to continue or withdraw from the trial. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 44 of 83 
In any country where national rules prohibiting the conduct of clinical trials on incapacitated 
subjects, ICF should not contain signature line for the incapacitated subject’s LAR/LDR and 
incapacitated subjects must not be enrolled in the study. 
The study will comply with ICH-GCP guidelines, Regulation (EU) No. 536/2014 and applicable 
regulatory requirements of each country. 
10.2 Study Procedures 
Assessments and their timing are to be performed as outlined in the Schedule of Assessments 
(Table 1). The SoC assessments of AIS patients may be used to evaluate the eligibility of 
subjects, including but not limited to laboratory and MRI/CTP assessments. The SoC 
assessments will not need to be repeated at Screening (Visit 1). Section 12.6 specifies laboratory 
assessment samples to be obtained.  
Assessments and procedures scheduled at a visit where IP is administered should be performed 
before administration of treatment unless otherwise indicated in the Schedule of Assessments 
(Table 1). 
Efficacy assessments are described in Section 11. Efficacy will be evaluated by assessing the 
functional outcomes measured by mRS, neurological outcome assessed by NIHSS, occurrence of 
recurrent stroke, and cognition as assessed by the MoCA; and imaging outcomes measured by 
change in infarct volume and hypoperfusion lesion. 
Safety assessments are described in Section 12 and include the occurrence of sICH, aICH, 
mortality, and AEs. Besides, vital signs, physical examinations, 12-lead ECG recordings, clinical 
laboratory results (hematology, clinical biochemistry, and coagulation) will also be assessed. 
The Investigator may, at his/her discretion, arrange for a subject to have an unscheduled 
assessment, especially in the case of AEs that require follow-up or are considered by the 
Investigator to be possibly related to the use of IP. The unscheduled visit page in the eCRF must 
be completed.  
Study discontinuation procedures are described in Section 8.3. 
Assessments will be done at each visit as detailed in the subsections below. Assessments at 
individual visit could occur over multiple days as long as assessments are still within the visit 
window as specified. 
 
 
 
 
 
 
 
 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 45 of 83 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 46 of 83 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 47 of 83 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 48 of 83 
11 EFFICACY ASSESSMENTS 
The Schedule of Assessments (Table 1) outlines the efficacy assessments to be performed 
throughout the study and their timing. Efficacy will be evaluated by assessing the functional 
outcomes measured by mRS, neurological outcome assessed by NIHSS, the occurrence of 
recurrent stroke, and cognition as assessed by the MoCA; and imaging outcomes measured by 
change in infarct volume and hypoperfusion lesion. 
11.1 Modified Rankin Scale 
The mRS measures the degree of disability or dependence in the daily activities of patients who 
have suffered a stroke. The scale runs from 0 (perfect health without symptoms) to 6 (dead). 
 
 The score and corresponding 
description for the mRS is provided in Appendix 2. 
11.2 National Institute of Health and Stroke Scale 
The NIHSS is a systematic assessment tool that provides a quantitative measure of stroke-related 
neurologic deficit. It consists of 11 items, each with a score range of 0 to 2 or 4, with higher 
scores indicating more deficit/impairment in that specific ability. The total score ranges from 0 
(no deficit) to 42 (dead). The score and corresponding description for the NIHSS is provided in 
Appendix 3. 
 
 
 
11.3 Montreal Cognitive Assessment 
The MoCA is a 30-question test for assessment of cognitive impairment and takes approximately 
10 minutes to administer. It screens 8 domains: visuospatial/executive, naming, memory, 
attention, language, abstraction, delayed recall, and orientation. The score ranges between 
0 and 30. A score of 26 to 30 is normal, a score of 18 to <26 is considered as mild cognitive 
impairment, a score of 10 to 17 is considered as moderate cognitive impairment, and a score of 
<10 is considered as severe cognitive impairment. 
 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 49 of 83 
11.4 Magnetic Resonance Imaging or Computed Tomography Perfusion 
Magnetic resonance imaging, including perfusion, is a widely used imaging technique and plays 
an important role in the evaluation of patients with AIS. 
 
 
 
 
 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 50 of 83 
12 SAFETY ASSESSMENTS 
Safety assessments (vital signs, physical examinations, 12-lead ECG recordings, AEs, clinical 
laboratory results [hematology, clinical biochemistry, and coagulation]) are to be performed at 
protocol -specified visits, as specified in the Schedule of Assessments (Table 1). 
12.1 Bleeding Assessment 
Bleeding assessment will be done by the Investigator or designee and categorized as sICH and 
aICH. The occurrence of sICH and aICH 
 after the 1st IP will be 
assessed. 
• Symptomatic ICH: clinical deterioration is defined as an increase in the NIHSS of 
4 points or more AND confirmed by MR/CT imaging-documentation. 
• Asymptomatic ICH is defined per the Heidelberg Bleeding Classification: new 
hemorrhage that has no implications for prognosis or change in management, and there is 
no substantive change in the subject’s neurological status. 
12.2 Medical History/Concomitant Illness 
Medical history, including AIS (the primary disease), will be recorded before the 1st IP 
administration 
. Investigators should document the occurrence, signs, and symptoms of 
the subject’s preexisting conditions, including all prior significant illnesses, up to and including 
1 year before Screening (Visit 1). Additional preexisting conditions present at the time when 
informed consent is given and up to the time of the initiation of the 1st IP administration 
 
are to be regarded as concomitant illnesses. Medical history will include alcohol consumption 
and smoking history, if applicable. 
Illnesses first occurring or detected during the study and/or worsening of a concomitant illness 
during the study are to be documented as AEs on the eCRF in accordance with Section 12.7. All 
changes not present at Baseline or described in the past medical history and identified as 
clinically noteworthy must be recorded as AEs. 
Additionally, demographic data will be collected for all subjects and include date of birth or age 
according to applicable regulations, gender, and race. 
12.3 Vital Signs  
Vital signs (body temperature, pulse rate, respiration rate, and systolic and diastolic blood 
pressure measurements) will be evaluated at the visits indicated in the Schedule of Assessments 
(Table 1). All vital signs will be measured after the subject has been resting in a supine position 
for at least 5 minutes. Blood pressure measurements are to be taken in the same arm for the 
duration of the study.  

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 51 of 83 
Vital sign measurements will be repeated if clinically significant or machine/equipment errors 
occur. Out-of-range blood pressure, respiration rate, or pulse rate measurements will be repeated 
at the Investigator’s or designee’s discretion. Any confirmed, clinically significant vital sign 
measurements must be recorded as AEs. 
Body weight (without shoes) will be recorded at Screening (Visit 1) only. For subjects who 
cannot stand on a scale, bed weight measurement is allowed at the Investigator’s or designee’s 
discretion. 
12.4 Complete/Limited Physical Examination 
A complete physical examination (head, eyes, ears, nose, and throat; heart; lungs; abdomen; 
skin; cervical and axillary lymph nodes; and musculoskeletal systems) including neurological 
examination (mental status, cranial nerve functions, motor and sensory function, cerebellar 
function, speech, gait) will be performed at Screening (Visit 1). The complete physical 
examinations will be performed by a physician. 
 
 
 
 
 
12.5 Electrocardiograms 
A 12-lead, resting ECG will be obtained at the visits indicated in the Schedule of Assessments 
(Table 1). 
At Screening (Visit 1), the Investigator will examine the ECG traces for signs of cardiac disease 
that could exclude the subject from the study. An assessment of normal or abnormal will be 
recorded; if the ECG is considered abnormal, the abnormality will be documented on the eCRF. 
ECGs will be repeated if clinically significant abnormalities are observed or artifacts are present 
at the Investigator’s or designee’s discretion. 
 
 
 
 
12.6 Laboratory Assessments 
Laboratory assessment samples (Table 2) are to be obtained at designated visits as detailed in the 
Schedule of Assessments (Table 1). 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 52 of 83 
Table 2. 
Laboratory Assessments 
Blood and urine samples will be analyzed at each study site and used only for the tests in the 
above-mentioned table for this study. Blood and urine samples will be tested and destroyed 
according to the standard procedures of the study site laboratory. All laboratory reports must be 
reviewed, signed, and dated by the Investigator. A legible copy of all reports must be filed with 
both the subject’s eCRF and medical record (source document) for that visit. Any laboratory test 
result considered by the Investigator or designee to be clinically significant should be considered 
an AE (clinically significant AEs include those that require an intervention). Clinically 
significant abnormal values occurring during the study will be followed up until repeat test 
results return to normal, stabilize, or are no longer clinically significant. 
12.7 Adverse Events 
12.7.1 Adverse Events 
An AE is any symptom, physical sign, syndrome, or disease that either emerges during the study 
if present on or after the 1st IP administration 
, worsens during the study, regardless of 
the suspected cause of the event. All medical and psychiatric conditions present 
 before 
the subject receives the 1st IP administration will be documented in the medical history eCRF. 
Changes in these conditions and new symptoms, physical signs, syndromes, or diseases should 
be noted on the AE eCRF during the rest of the study. Clinically significant laboratory 
abnormalities should also be recorded as AEs. Surgical procedures that were planned before the 
subject enrolled in the study are not considered AEs if the conditions were known before study 
inclusion; the medical condition should be reported in the subject’s medical history. 
Subjects will be instructed to report AEs during the study. All AEs are to be followed up until 
resolution or a stable clinical endpoint is reached. 
Each AE is to be documented on the eCRF with reference to date of onset, duration, frequency, 
severity, relationship to IP, action taken with IP, treatment of event, and outcome. Furthermore, 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 53 of 83 
each AE is to be classified as being serious or nonserious. Changes in AEs and resolution dates 
are to be documented on the eCRF. 
For the purposes of this study, the period of observation for collection of AEs extends from the 
subject receives the 1st IP 
 until the last follow-up visit. Follow-up of the AE, even after 
the date of therapy discontinuation, is required if the AE persists, until the event resolves or 
stabilizes at a level acceptable to the Investigator. 
When changes in the intensity of an AE occur more frequently than once a day, the maximum 
intensity for the event should be noted. If the intensity category changes over a number of days, 
then those changes should be recorded separately (with distinct onset dates). 
Specific guidelines for classifying AEs by intensity and relationship to IP are given in Table 3. 
and Table 4. 
Table 3. 
Classification of Adverse Events by Intensity 
MILD: An event that is easily tolerated by the subject, causing minimal discomfort and not interfering with 
everyday activities. 
MODERATE: An event that is sufficiently discomforting to interfere with normal everyday activities. 
SEVERE: An event that prevents normal everyday activities. 
 
Table 4. 
Classification of Adverse Events by Relationship to Investigational Product 
UNRELATED: This category applies to those AEs that are clearly and incontrovertibly due to extraneous 
causes (disease, environment, etc). 
UNLIKELY: This category applies to those AEs that are judged to be unrelated to the IP but for which no 
extraneous cause may be found. An AE may be considered unlikely to be related to IP if or when it meets 2 of 
the following criteria: (1) it does not follow a reasonable temporal sequence from administration of the IP ; 
(2) it could readily have been produced by the subject’s clinical state, environmental or toxic factors, or other 
modes of therapy administered to the subject; (3) it does not follow a known pattern of response to the IP; or 
(4) it does not reappear or worsen when the IP is readministered. 
POSSIBLY: This category applies to those AEs for which a connection with the IP administration appears 
unlikely but cannot be ruled out with certainty. An AE may be considered possibly related if or when it meets 
2 of the following criteria: (1) it follows a reasonable temporal sequence from administration of the IP; (2) it 
could not readily have been produced by the subject’s clinical state, environmental or toxic factors, or other 
modes of therapy administered to the subject; or (3) it follows a known pattern of response to the IP. 
PROBABLY: This category applies to those AEs that the investigator feels with a high degree of certainty are 
related to the IP. An AE may be considered probably related if or when it meets 3 of the following criteria: (1) 
it follows a reasonable temporal sequence from administration of the IP; (2) it could not be reasonably 
explained by the known characteristics of the subject’s clinical state, environmental or toxic factors, or other 
modes of therapy administered to the subject; (3) it disappears or decreases on cessation or reduction in dose 
(note that there are exceptions when an AE does not disappear upon discontinuation of the IP, yet drug-
relatedness clearly exists; for example, as in bone marrow depression, fixed drug eruptions, or tardive 
dyskinesia); or (4) it follows a known pattern of response to the IP. 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 54 of 83 
DEFINITELY: This category applies to those AEs that the investigator feels are incontrovertibly related to IP. 
An AE may be assigned an attribution of definitely related if or when it meets all of the following criteria: (1) 
it follows a reasonable temporal sequence from administration of the IP; (2) it could not be reasonably 
explained by the known characteristics of the subject’s clinical state, environmental or toxic factors, or other 
modes of therapy administered to the subject; (3) it disappears or decreases on cessation or reduction in dose 
and recurs with reexposure to drug (if rechallenge occurs); and (4) it follows a known pattern of response to 
the IP. 
Abbreviation: AE, adverse event; IP, investigational product. 
 
12.7.2 Serious Adverse Events 
An SAE is any untoward medical occurrence, in the view of either the Investigator or Sponsor, 
that: 
• results in death, 
• is life-threatening, 
• results in inpatient hospitalization or prolongation of existing hospitalization, 
• results in persistent or significant disability/incapacity, and/or 
• is a congenital anomaly/birth defect. 
Other important medical events that may not be immediately life-threatening or result in death or 
hospitalization, based upon appropriate medical judgment, are considered SAEs if they are 
thought to jeopardize the subject and/or require medical or surgical intervention to prevent one of 
the outcomes defining an SAE. SAEs are critically important for the identification of significant 
safety problems; therefore, it is important to take into account both the Investigator’s and the 
Sponsor’s assessment. If either the Sponsor or the Investigator believes that an event is serious, 
the event must be considered serious and evaluated by the Sponsor for expedited reporting. 
12.7.3 Serious Adverse Event Reporting 
An SAE occurring from the subject receives the 1st IP 
, during the study, or within 
3 months of stopping the treatment must be reported to 
 
Pharmacovigilance group and will be communicated to the Sponsor. Any such SAE due to any 
cause, whether or not related to the IP, must be reported within 24 hours of occurrence or when 
the Investigator becomes aware of the event. Notification can be made using the dedicated fax 
line or email 
 
 
 
The Medical Monitor should be contacted in the event of medical emergencies. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 55 of 83 
If the Investigator contacts 
 Pharmacovigilance group by telephone, 
then a written report must follow within 24 hours and is to include a full description of the event 
and sequelae in the format detailed in the SAE reporting form. 
The event must also be recorded on the standard AE eCRF. Preliminary reports of SAEs must be 
followed up by detailed descriptions later on, including clear and anonymized photocopies of 
hospital case reports, consultant reports, autopsy reports, and other documents when requested 
and applicable. SAE reports must be made whether or not the Investigator considers the event to 
be related to the investigational product. 
Appropriate remedial measures should be taken to treat the SAE, and the response should be 
recorded. Clinical, laboratory, and diagnostic measures should be employed as needed in order to 
determine the etiology of the problem. The Investigator must report all additional follow-up 
evaluations to 
 Pharmacovigilance group within 24 hours of 
becoming aware of the additional information or as soon as is practicable. All SAEs will be 
followed up until the Investigator and Sponsor agree the event is satisfactorily resolved. 
Any SAE that is not resolved by the end of the study or upon discontinuation of the subject’s 
participation in the study is to be followed up until it either resolves, stabilizes, returns to 
baseline values (if a baseline value is available), or is shown to not be attributable to the IP or 
procedures. 
12.7.4 Suspected Unexpected Serious Adverse Reactions 
AEs that meet all of the following criteria will be classified as suspected unexpected serious 
adverse reactions (SUSARs) and reported to the appropriate regulatory authorities in accordance 
with applicable regulatory requirements for expedited reporting: 
• serious 
• unexpected (i.e., the event is not consistent with the safety information in the 
investigator’s brochure) 
• there is at least a reasonable possibility that there is a causal relationship between the 
event and the IP 
The Investigator will assess whether an event is causally related to IP. The Sponsor 
 
 will consider the Investigator’s assessment and determine whether the event meets the 
criteria for being reportable as a 7-day or 15-day safety report. SUSARs that are fatal or 
life-threatening must be reported to the regulatory authorities and the independent ethics 
committee (IEC)/institutional review boards (IRBs) (where required) within 7 days after the 
Sponsor 
 has first knowledge of them, with a follow-up report submitted 
within a further 8 calendar days. Other SUSARs must be reported to the relevant regulatory 
authorities and the IEC/IRBs within 15 calendar days after the Sponsor 
 first 
has knowledge of them. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 56 of 83 
The Sponsor 
 is responsible for reporting SUSARs and any other events 
required to be reported in an expedited manner to the regulatory authorities and for informing 
investigators of reportable events, in compliance with applicable regulatory requirements within 
specific timeframes. Investigators will notify the relevant IEC/IRBs of reportable events within 
the applicable timeframes. 
12.7.5 Pregnancy 
All female subjects of childbearing potential must have a negative pregnancy test at Screening 
(Visit 1). Following administration of IP, any known cases of pregnancy in female subjects or in 
male subjects whose sexual partners are WOCBP will be reported until 3 months after the last 
dose of study treatment. The pregnancy will be reported immediately by faxing/emailing a 
completed pregnancy report to the Sponsor (or designee) within 24 hours of knowledge of the 
event. The pregnancy will not be processed as an SAE; however, the Investigator will follow up 
with the subject until completion of the pregnancy and must assess the outcome in the shortest 
possible time but not more than 30 days after completion of the pregnancy. The Investigator 
should notify the Sponsor (or designee) of the pregnancy outcome by submitting a follow-up 
pregnancy report. If the outcome of the pregnancy involved spontaneous or therapeutic abortion 
(any congenital anomaly detected in an aborted fetus is to be documented), stillbirth, neonatal 
death, or congenital anomaly, the Investigator will report the event by faxing/emailing a 
completed pregnancy report form to the Sponsor (or designee) within 24 hours of knowledge of 
the event. 
If the Investigator becomes aware of a pregnancy occurring in the female partner of a male 
subject participating in the study, the pregnancy should be reported to the Sponsor (or designee) 
within 24 hours of knowledge of the event. Information regarding the pregnancy must only be 
submitted after obtaining written consent from the pregnant partner. The Investigator will 
arrange counseling for the pregnant partner by a specialist to discuss the risks of continuing with 
the pregnancy and the possible effects on the fetus. 
Upon discontinuation from the study, only those procedures that would not expose the subject to 
undue risk will be performed. The Investigator should also be notified of pregnancy occurring 
during the study but confirmed after completion of the study. In the event that a subject is 
subsequently found to be pregnant after inclusion in the study, any pregnancy will be followed to 
term, and the status of mother and child will be reported to the Sponsor after delivery. 
12.7.6 Overdose 
See Section 5.3. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 57 of 83 
13 STATISTICAL ANALYSIS 
A SAP will be prepared after the protocol is approved. This document will provide further details 
regarding the definition of analysis variables and analysis methodology to address all study 
objectives. The SAP will serve as a compliment to the protocol and supersedes it in case of 
differences. 
The statistical evaluation will be performed using SAS® software version 9.4 or higher 
(SAS Institute, Cary, NC). All data will be listed, and summary tables will be provided. 
Summary statistics will be presented by treatment group and overall (wherever applicable). For 
continuous variables, data will be summarized with the number of subjects (n), mean, standard 
deviation, median, minimum, and maximum by treatment group. For categorical variables, data 
will be tabulated with the number and proportion of subjects for each category by treatment 
group. 
 
 
 
 
 
 
Further details of statistical analyses including relevant SAS code will be presented in the SAP. 
13.1 Determination of Sample Size 
 
 
 
 
  
 
  

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 59 of 83 
13.3 Efficacy Analysis 
13.3.1 Analysis of Secondary Efficacy Endpoints 
Analyses of all secondary efficacy and imaging endpoints will be performed on the ITT 
population as the main analysis and will be repeated on the PP and Completers populations as 
supportive analysis. 
Efficacy endpoints will be summarized and statistically compared between the treatment groups 
and in the subgroups of the variables used for randomization stratification, also. 
 
 
 
 
 
Proportion of subjects with independent functional outcome and excellent functional 
outcome 
 after the 1st IP administration 
The number and percentage of subjects who achieve a score of 0 to 2 on the mRS 
 
will be presented by treatment group. The number and percentage of subjects achieve 
 mRS 0-1 
, and the number and percentage of 
subjects achieve 
 mRS 0-2 
 
. The difference of the proportions between the treatment groups with the 
corresponding 95% confidence intervals (CIs) will be presented for the defined timepoints. 
 
The same 
analysis will also be presented for subjects who achieve a score of ≤1 on the mRS.
 
 
 
 
 
 
 
 
 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 61 of 83 
 
 
 
 
 The same analysis will also 
be presented for the proportion of subjects with decrease in NIHSS ≥4 points or NIHSS of 0 to 1 
point.  
 
 
 
 
 
 
 
 
Proportion of subjects with NIHSS ≤2 
 after the 1st IP 
The number and percentage of subjects with NIHSS of 0 to 2 points will be presented by 
treatment group at each defined timepoint, and the difference of the proportions between the 
treatment groups with the corresponding 95% CIs will be presented. 
 
 
 
 
 The same analysis will also be presented for subjects with 
NIHSS of 0 to 1 point.
 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 62 of 83 
 
 
 
 
 
 
 
 
 
Change in NIHSS 
 from Baseline 
The total score and change from baseline in NIHSS will be summarized at each defined 
timepoint by treatment group and overall. A figure will be presented with the percentage of 
subjects with a decrease of ≥4 points compared to baseline, a decrease of 1 to 3 points, no change 
(0 points), increase of 1 to 3 points, and increase of ≥4 points for each defined timepoint by 
treatment group – with change presented on the x-scale and timepoint/visit presented on the 
y-scale. 
 
 
 
 
 
  
 
 
 
 
 
 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 63 of 83 
 
Occurrence of recurrent stroke within 90 days after the 1st IP 
The number and percentage of subjects who have a recurrent stroke within 90 days after the 1st IP 
will be presented by treatment group. The difference of the proportions between the treatment 
groups with the corresponding 95% CI will be presented. 
 
 
 
 
 
 
Change of cognition assessment by MoCA  
The MoCA total score and change from baseline will be summarized 
 
 
 
 
 
Change of infarct volume 
 from Baseline by 
MRI/CTP 
The absolute and percentage change from baseline of infarct volume in MRI or CTP examination 
will be presented 
 
 
 
 
 
 
 
 
 
 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 64 of 83 
 
 
The infarct volume 
 after the 1st IP by MRI/CTP adjusted for the baseline 
infarct volume. 
A comparison between the treatment group 
 
 
 
 
. 
Change of hypoperfusion lesion 
 from Baseline 
The absolute and percentage changes from baseline in hypoperfusion lesion in perfusion-weight 
imaging MRI or CTP will be summarized
 
 
 
 
 
 
 
 
 
Proportion of subjects with 90% reduction in hypoperfusion lesion 
 
 from Baseline 
The number and percentage of subjects showing 90% reduction in hypoperfusion lesion
 
 
 
 
 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 65 of 83 
 
 
 
 
 
 
 
 
 
13.4 Safety Analysis 
All safety analyses will be performed using the Safety population. No imputation of missing 
safety data will be applied. 
13.4.1 Analysis of Primary Endpoint 
Proportion of subjects with AEs, judged to be probably or definitely related to the IP 
within 90 days after the 1st IP. 
The number and percentage of subjects with AEs, judged to be probably or definitely related to 
the IP within 90 days after the 1st IP will be presented by treatment group. The difference of the 
proportions between the treatment groups with the corresponding exact 95% Clopper Pearson 
CIs will be presented.
 
 
 
 
 
 
13.4.2 Analysis of Secondary Safety Endpoint 
Occurrence of sICH 
 after the 1st IP 
The number and percentage of subjects with sICH (clinical deterioration defined as an increase 
in the NIHSS score of 4 points or more AND confirmed by MR/CT imaging - documentation) 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 66 of 83 
 
 
 
Occurrence of aICH 
 after the 1st IP 
The number and percentage of subjects with aICH 
 
 
 
 
 
. 
Occurrence of mortality due to any reason within 90 days after the 1st IP 
The number and percentage of subjects who have died because of any reason within 90 days 
after the 1st IP will be presented by treatment group and overall. 
 
 
Other safety analyses 
All reported AEs will be coded using the Medical Dictionary for Regulatory Activities in place 
at the time of analysis. An overall summary of AEs will be presented including categories of 
serious AEs, related AEs, AEs leading to IP discontinuation and AEs with fatal outcome. The 
incidence of AEs will be summarized by System Organ Class and Preferred Term. Summary of 
AEs by maximum severity and AEs leading to permanent discontinuation of IP will be included. 
The summary tables will include the number of subjects and the number of events. Percentages 
will be based on the number of subjects in the Safety population. Events with missing onset dates 
will be included as AEs. If a subject experiences more than 1 occurrence of the same AE, the 
occurrence with the greatest severity and the closest association with the IP will be used in the 
summary tables. All AEs will be listed by subject, along with information regarding onset, 
duration, severity and relationship to IP, action taken with IP, treatment of event, and outcome. 
Local laboratory data will be summarized in shift tables presenting the number and percentage of 
subjects with values below / within / above reference range in each post-baseline visit compared 
to baseline. Abnormal laboratory results will be flagged in the data listings.
 
 
 
Vital signs and 12-lead ECG parameters will be summarized using descriptive statistics, 
including mean values and mean change from baseline values. 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 67 of 83 
 
 
For laboratory tests, vital signs and 12-lead ECG overall evaluation, abnormal values (NCS or 
CS) will be flagged in the data listings. 
Summary tables will be provided for concomitant medications initiated during the study period. 
13.5 Interim Analysis 
No interim analysis is planned. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 68 of 83 
14 STUDY MANAGEMENT 
14.1 Approval and Consent 
14.1.1 Regulatory Guidelines 
This study will be conducted in accordance with the accepted version of the Declaration of 
Helsinki and/or all relevant regulations, as set forth in Parts 50, 56, 312, Subpart D, of Title 21 of 
the US Code of Federal Regulations (CFR); Regulation (EU) No. 536/2014; and in compliance 
with International Council for Harmonisation (ICH) and GCP guidelines, and according to the 
appropriate regulatory requirements in the countries where the study was conducted. 
14.1.2 Institutional Review Board/Independent Ethics Committee 
Conduct of the study must be approved by an appropriately constituted IEC/IRB. Approval is 
required for the study protocol, protocol amendments (if applicable), investigator’s brochure, 
ICFs, recruitment material and subject information sheets, and other subject-facing material. 
14.1.3 Informed Consent 
For each study subject, written informed consent will be obtained before any protocol-related 
activities. As part of this procedure, the Investigator or designee must explain orally and in 
writing the nature of the study, its purpose, procedures, expected duration, alternative therapy 
available, and the benefits and risks involved in study participation. The subject should be 
informed that he/she may withdraw from the study at any time, and the subject will receive all 
information that is required by local regulations and guidelines for the ICH. The Investigator will 
provide the subject or its representative with a copy of the IEC-/IRB-approved ICF before the 
start of the study. 
14.2 Data Handling 
Any data to be recorded directly on the eCRFs (to be considered as source data) will be 
identified at the start of the study. Data reported on the eCRF that are derived from source 
documents should be consistent with the source documents, or the discrepancies must be 
explained. See also Section 14.3. 
Clinical data will be entered by site personnel on eCRFs for transmission to the Sponsor. Data on 
eCRFs transmitted via the web-based data system must correspond to and be supported by source 
documentation maintained at the study site, unless the study site makes direct data entry to the 
databases for which no other original or source documentation is maintained. In such cases, the 
study site should document which eCRFs are subject to direct data entry and should have in 
place procedures to obtain and retain copies of the information submitted by direct data entry. 
All study forms and records transmitted to the Sponsor must only include coded identifiers such 
that directly identifying personal information is not transmitted. Only the Investigator and 
authorized personnel will be able to connect the codes to subject names. The primary method of 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 69 of 83 
data transmittal is via the secure, internet-based EDC system 
. 
Access to the EDC system is available to only authorized users via the study’s internet web site, 
where a user unique assigned username and password are required for access. 
Any changes made to data after collection will be made through the use of the EDC system. 
Electronic CRFs will be considered complete when all missing and/or incorrect data have been 
resolved. 
14.3 Source Documents 
Source documents are considered to be all information in original records and certified copies of 
original records of clinical findings, observations, data, or other activities in a clinical study 
necessary for the reconstruction and evaluation of the study. The Investigator will provide direct 
access to source documents and/or source data in the facilitation of trial-related monitoring, 
audits, review by IECs/IRBs, and regulatory inspections. 
The Investigator/institution should maintain adequate and accurate source documents and trial 
records that include all pertinent observations on each of the site’s trial subjects. Source data 
should be attributable, legible, contemporaneous, original, accurate, and complete. Changes to 
source data should be traceable, not obscure the original entry, and be explained if necessary. 
14.4 Record Retention 
Study records and source documents must be preserved for at least 15 years after the completion 
or discontinuation of/withdrawal from the study, at least 2 years after the drug being studied has 
received its last approval for sale, or at least 2 years after the drug development has stopped, and 
in accordance with the applicable local privacy laws, whichever is the longer time period. 
The Investigator agrees to comply with all applicable federal, state, and local laws and 
regulations relating to the privacy of subject health information, including, but not limited to, the 
Standards for Individually Identifiable Health Information, 45 CFR, Parts 160 and 164 (the 
Health Insurance Portability Accountability Act of 1996 Privacy Regulation), and the EU 
2016/679 General Data Protection Regulation (GDPR). The Investigator shall ensure that study 
subjects authorize the use and disclosure of protected health information in accordance with 
Health Insurance Portability Accountability Act of 1996 Privacy Regulation, the EU GDPR, and 
in a form satisfactory to the Sponsor. 
In case of a suspected personal data breach related to the processing of subject health 
information, Sponsor and the Investigator will jointly decide on the basis of all available 
information and applicable laws if the incident will be considered personal data breach and 
arrange for prompt notification to data subjects, government authorities, and other third parties if 
required by applicable laws, in order to mitigate the possible adverse effects. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 70 of 83 
14.5 Monitoring 
The study will be monitored according to the study monitoring plan to ensure that it is conducted 
and documented properly according to the protocol, GCP, and all applicable regulatory 
requirements. 
Monitoring visits (on-site and remote [telephone] or a combination of both) and contacts will be 
made at appropriate times during the study. The Principal Investigator will assure he/she and 
adequate site personnel are available throughout the study to collaborate with clinical monitors. 
Clinical monitors must have direct access to source documentation in order to check the 
completeness, clarity, and consistency of the data recorded in the eCRFs for each subject. 
The Investigator will make available to the clinical monitor all source documents and medical 
records necessary to review protocol adherence and eCRFs. In addition, the Investigator will 
work closely with the clinical monitor and, as needed, provide them appropriate evidence that the 
study is being conducted in accordance with the protocol, applicable regulations, and GCP 
guidelines. 
14.6 Quality Control and Quality Assurance 
The Sponsor or its designee will perform the quality assurance and quality control activities of 
this study; however, responsibility for the accuracy, completeness, security, and reliability of the 
study data presented to the Sponsor lies with the Investigator generating the data. 
The Sponsor will be responsible for audits as part of the implementation of quality assurance to 
ensure that the study is being conducted in compliance with the protocol, standard operating 
procedures, GCP, and all applicable regulatory requirements. Audits will be independent of and 
separate from the routine monitoring and quality control functions. Quality assurance procedures 
will be performed at study sites to assure that safety and efficacy data are adequate and well 
documented. 
14.7 Protocol Amendment and Protocol Deviation 
14.7.1 Protocol Amendment 
Amendments to the protocol that entail corrections of typographical errors, clarifications of 
confusing wording, changes in study personnel, and minor modifications that have no effect on 
the safety of subjects or the conduct of the study will be classed as administrative amendments 
and will be submitted to the IEC/IRB for information. Submission to regulatory authorities only 
required according to local regulations. The Sponsor will ensure that acknowledgement is 
received and filed. Amendments that are classed as substantial amendments must be submitted to 
the appropriate regulatory authorities and the IECs/IRBs for approval and will not be 
implemented at study sites until such approvals are received other than in the case of an urgent 
safety measure. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 71 of 83 
14.7.2 Protocol Deviations 
Should a protocol deviation occur, the Sponsor must be informed as soon as possible. Protocol 
deviations and/or violations and the reasons they occurred will be included in the clinical study 
report. The Sponsor, or its authorized designee, will report protocol deviations to the IRB/IEC 
and in accordance with applicable regulatory authority. 
 
 
14.8 Ethical Considerations 
This study will be conducted in accordance with this protocol, the accepted version of the 
Declaration of Helsinki and/or all relevant federal regulations, as set forth in Parts 50, 56, 312, 
Subpart D, of Title 21 of the CFR; Regulation (EU) No. 536/2014; and in compliance with GCP 
guidelines. 
IECs/IRBs will review and approve this protocol and the ICF. All subjects are required to give 
written informed consent before participation in the study. 
14.9 Financing and Insurance 
Before the study commences, the Sponsor (or its designee) and the Investigator (or the 
institution, as applicable) will agree on costs necessary to perform the study. This agreement will 
be documented in a financial agreement that will be signed by the Investigator (or the institution 
signatory) and the Sponsor (or its designee). 
The Investigator is required to have adequate current insurance to cover claims for negligence 
and/or malpractice. The Sponsor will provide no-exclusion insurance coverage for the clinical 
study as required by national regulations. 
14.10 Publication Policy/Disclosure of Data 
Both the use of data and the publication policy are detailed within the clinical study agreement. 
Intellectual property rights (and related matters) generated by the Investigator and others 
performing the clinical study will be subject to the terms of a clinical study agreement that will 
be agreed between the institution and the Sponsor or their designee. With respect to such rights, 
the Sponsor or its designee will solely own all rights and interests in any materials, data, and 
intellectual property rights developed by investigators and others performing the clinical study 
described in this protocol, subject to the terms of any such agreement. In order to facilitate such 
ownership, investigators will be required to assign all such inventions either to their institution or 
directly to the Sponsor or its designee, as will be set forth in the clinical study agreement. 
Sponsor will submit a summary of trial results within the periods specified in all EEA MSC or 
globally, in accordance with applicable regulatory authority, except for if the submission of trial 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 72 of 83 
results at a given time would hinder Sponsor’s development of LT3001 drug product, or when it 
is not possible to submit the final trial results within the established timeframes due to a delay in 
data analysis and report writing. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 73 of 83 
15 REFERENCES 
1. Sacco RL, Kasner SE, Broderick JP, et al; on behalf of the American Heart Association 
Stroke Council, Council on Cardiovascular Surgery and Anesthesia, Council on 
Cardiovascular Radiology and Intervention, Council on Cardiovascular and Stroke Nursing, 
Council on Epidemiology and Prevention, Council on Peripheral Vascular Disease, and 
Council on Nutrition, Physical Activity and Metabolism. An updated definition of stroke for 
the 21st century: a statement for healthcare professionals from the American Heart 
Association/American Stroke Association. Stroke. 2013;44(7):2064-2089. doi: 
10.1161/STR.0b013e318296aeca. 
2. Mozaffarian D, Benjamin EJ, Go AS, et al; on behalf of the American Heart Association 
Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke 
statistics—2016 update: a report from the American Heart Association. Circulation. 
2016;133(4):e38-e360. doi: 10.1161/CIR.0000000000000350. 
3. World Health Organization. Available from http://www.emro.who.int/health-topics/stroke-
cerebrovascular-accident/index.html. 
4. Deb P, Sharma S, Hassan KM. Pathophysiologic mechanisms of acute ischemic stroke: An 
overview with emphasis on therapeutic significance beyond thrombolysis. Pathophysiology. 
2010;17(3):197-218. Available from http://www.pathophysiologyjournal.com/article/S0928-
4680(09)00136-9/pdf. 
5. Aldeen A, Pirotte M, Solomon RC. Focus on: Acute ischemic stroke. American College of 
Emergency Physicians News. 2009. Accessed on: 25 June 2021. Available from 
https://www.acepnow.com/article/focus-acute-ischemic-stroke/?singlepage=1. 
6. Wadiwala MF, Sonawalla A, Kamal AK. What is the role of free radical scavengers in acute 
stroke? J Pak Med Assoc. 2012;62(5):512-513.  
7. Demaerschalk BM, Kleindorfer DO, Adeoye OM, et al; on behalf of the American Heart 
Association Stroke Council and Council on Epidemiology and Prevention. Scientific 
rationale for the inclusion and exclusion criteria for intravenous alteplase in acute ischemic 
stroke: a statement for healthcare professionals from the American Heart 
Association/American Stroke Association. Stroke. 2016;47(2):581–641. doi: 
10.1161/STR.0000000000000086.  
8. Scottish Intercollegiate Guidelines Network (SIGN). Management of patient with stroke or 
TIA: assessment, investigation, immediate management and secondary prevention. A 
national clinical guideline. December 2008. Accessed 20 March 2017. Available from: 
https://www.sign.ac.uk/media/1195/pat108.pdf.  
9. Nour M, Scalzo F, Liebeskind DS. Ischemia-reperfusion injury in stroke. Intervent Neurol. 
2012;1(3-4):185-199. doi: 10.1159/000353125. 
10. Kaur J, Zhao Z, Klein GM, Lo EH, Buchan AM. The neurotoxicity of tissue plasminogen 
activator? J Cereb Blood Flow Metab. 2004;24(9):945-963. doi: 
10.1097/01.WCB.0000137868.50767.E8. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 74 of 83 
11. Roth JM. Recombinant tissue plasminogen activator for the treatment of acute ischemic 
stroke. Proc (Bayl Univ Med Cent). 2011;24(3):257–259. doi: 
10.1080/08998280.2011.11928729. 
12.
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 75 of 83 
16 APPENDICES 
Appendix 1 Contraception Guidelines 
Appendix 2 Modified Rankin Scale (Sample) 
Appendix 3 National Institute of Health Stroke Scale (Sample) 
Appendix 4 Country-Specific Requirements for Informed Consent Forms 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 76 of 83 
Appendix 1: Contraception Guidelines 
Women of childbearing potential (WOCBP) and men whose sexual partners are WOCBP must 
use at least 1 highly effective method of contraception during the study and for 3 months after 
the last dose of study treatment.  
A woman is considered to be a WOCBP (fertile) after menarche and until becoming 
postmenopausal, unless she is permanently sterile. Permanent sterilization methods include 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. A postmenopausal state is 
defined as no menses for 12 months without an alternative medical cause. A high 
follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a 
postmenopausal state in women not using hormonal contraception or hormonal replacement 
therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is 
insufficient.  
A man is considered fertile after puberty unless permanently sterile by bilateral orchidectomy. 
Highly effective methods of contraception are those which have a failure rate of <1% 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All subjects will be strongly advised that they (or the female partners of male subjects) should 
not become pregnant while on study treatment or for 3 months after the last dose. A female 
subject will be advised that she must report immediately to the study site for pregnancy testing 
and appropriate management in the event that she may be pregnant. 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 77 of 83 
Reference 
1. [HMA] Heads of Medicines Agencies. Clinical Trial Facilitation Group page. 
Recommendations related to contraception and pregnancy testing in clinical trials. 
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf. 
September 15, 2014. Accessed 22 Aug 2023. 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 78 of 83 
Appendix 2: Modified Rankin Scale (Sample) 
Score 
Description 
0 
No symptoms at all 
1 
No significant disability despite symptoms; able to carry out all usual duties and 
activities 
2 
Slight disability; unable to carry out all previous activities, but able to look after own 
affairs without assistance 
3 
Moderate disability; requiring some help, but able to walk without assistance  
4 
Moderately severe disability; unable to walk without assistance and unable to attend to 
own bodily needs without assistance  
5 
Severe disability; bedridden, incontinent and requiring constant nursing care and 
attention 
6 
Dead 
 
 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 79 of 83 
Appendix 3. National Institute of Health and Stroke Scale (Sample) 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 80 of 83 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 81 of 83 
 

Lumosa Therapeutics 
LT3001-205 
LT3001 
Protocol Version 8.1 dated 23 Apr 2025 
 
This document is confidential. 
Page 82 of 83