CLARA: A Phase 1/2 Multi-center, Randomized, Double-Masked, Prospective, Parallel-Arm Study of AURN001 in Subjects With Corneal Edema Secondary to Corneal Endothelial Dysfunction (ABA-1)
Phase: PHASE1
Conditions: Corneal Edema, Corneal Endothelial Dysfunction
Sponsor: Aurion Biotech

 
CLARA:  A Phase 1/2 Multi-center, Randomized, Double-
Masked, Prospective, Parallel- Arm Study of AURN001 in 
Subjects with Corneal Edema Secondary to Corneal 
Endothelial Dysfunction (ABA-1) 
 
 
Investigational Product 
[AURN001] 
 
Protocol Number: ABA-1 
Version: 6.0 
Version Date: 23-Sep-2024 
 
 
Sponsor 
Aurion Biotech, Inc 
117 E. Louisa Street 
#561 
Seattle, WA 98102 
 
 
CONFIDENTIALITY STATEMEN`T 
This document contains trade secrets, or commercial or financial information, privileged and 
confidential, delivered in confidence and reliance that such information will not be released to the 
public without the express written consent of Aurion Biotech.  This document and its associated 
attachments or appendices are subject to United States Freedom of Information Act Exemption 4.

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 2 of 67 
 
Investigator Statement of Compliance 
 
CLARA:  A Phase 1/2 Multi-center, Randomized, Double-Masked, Prospective, Parallel-Arm 
Study of AURN001 in Subjects with Corneal Edema Secondary to Corneal Endothelial 
Dysfunction (ABA-1) 
 
The study will be carried out in accordance with the United States (US) Code of Federal 
Regulations (CFR) applicable to clinical studies (21 CFR Part 11, Part 50, Part 54, Part 56, and 
Part 312) and other regional regulatory agency requirements. In addition, compliance with the 
International Council for Harmonization E6 Good Clinical Practice Guideline is expected. 
Adherence to the clauses of the Clinical Trial Agreement and proper oversight of all staff members 
completing any activities for the study are required.  
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the Institutional Review Board (IRB) for review and approval.  Approval of both 
the protocol and the consent form must be obtained before any participant is screened.  Any 
amendment to the protocol will require review and approval by the IRB before the changes are 
implemented to the study.  In addition, all changes to the consent form will be IRB-approved; a 
determination will be made regarding whether a new consent needs to be obtained from 
participants who provided consent, using a previously approved consent form. 
 
 
Accepted by: 
 
 
 
Principal Investigator Signature 
Date 
Printed Name 
 
 
 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 5 of 67 
TABLE OF CONTENTS 
1 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS .................................. 8 
2 
SYNOPSIS ................................................................................................................... 10 
3 
PRINCIPAL CONTACTS ........................................................................................... 16 
4 
BACKGROUND INFORMATION ............................................................................ 17 
4.1 
Corneal Edema Secondary to Corneal Endothelial Dysfunction ................................. 17 
4.2 
Investigational Product Rationale ................................................................................ 17 
4.3 
Nonclinical Findings .................................................................................................... 19 
4.4 
Risk-Benefit Analysis .................................................................................................. 19 
4.4.1 
Potential Risks ............................................................................................................. 20 
4.5 
Dose Justification ......................................................................................................... 21 
4.6 
Trial Population ........................................................................................................... 23 
5 
TRIAL OBJECTIVES ................................................................................................. 23 
6 
TRIAL DESIGN .......................................................................................................... 23 
6.1 
Description of Trial ...................................................................................................... 23 
6.2 
Study Endpoints ........................................................................................................... 24 
6.2.1 
Efficacy Endpoints ....................................................................................................... 24 
6.2.1.1 
Primary Efficacy Endpoints ......................................................................................... 25 
6.2.1.2 
Secondary Efficacy Endpoints ..................................................................................... 25 
6.2.1.3 
Exploratory Efficacy Endpoints ................................................................................... 25 
6.2.2 
Safety Evaluations ....................................................................................................... 25 
6.3 
Randomization and Masking ....................................................................................... 26 
6.4 
Trial Treatment ............................................................................................................ 26 
6.5 
Trial Duration .............................................................................................................. 26 
6.6 
Trial Material Accountability ...................................................................................... 26 
7 
SELECTION AND WITHDRAWAL OF SUBJECTS ............................................... 27 
7.1 
Inclusion Criteria ......................................................................................................... 27 
7.2 
Exclusion Criteria ........................................................................................................ 28 
7.3 
Subject Recruitment, Screening, Rescreening and Treatment ..................................... 30 
7.4 
Withdrawal Criteria ..................................................................................................... 31 
7.4.1 
Withdrawal Methods .................................................................................................... 31 
7.4.2 
Collection of Data from Withdrawn Subjects .............................................................. 31 
7.4.3 
Subject Replacement .................................................................................................... 31 
8 
SUBJECT TREATMENT ........................................................................................... 31 
8.1 
Treatment Regimen ...................................................................................................... 31 
8.2 
Prior and Concomitant Therapy ................................................................................... 31 
8.3 
Rescue Therapy ............................................................................................................ 32 
8.4 
Study Assessments by Visit ......................................................................................... 32 
8.4.1 
Visit 1 (77 to 7 Days Prior to Day 1) Screening .......................................................... 32 
8.4.2 
Visit 2 Procedure/Day 1 ............................................................................................... 33 
8.4.3 
Visit 3 Day 2 (+2 Days) ............................................................................................... 33 
8.4.4 
Visit 4 Week 1/Day 8 (+2 days) .................................................................................. 33 
8.4.5 
Visit 5 Week 4/Day 30 (± 7 Days)............................................................................... 34 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 6 of 67 
8.4.6 
Visit 5.1 Month 2/Day 60 (± 7 Days) - Optional ......................................................... 34 
8.4.7 
Visit 6 Month 3/Day 90 (±7 Days) .............................................................................. 34 
8.4.8 
Visit 7 Month 4.5/Day 135 (±14 Days) ....................................................................... 35 
8.4.9 
Visit 8 Month 6/Day 180 (±14 Days) .......................................................................... 35 
8.4.10 
Visit 9 Month 9/Day 270 (±14 Days) .......................................................................... 36 
8.4.11 
Visit 10 Month 12/Day 360 (±14 Days) ...................................................................... 36 
8.4.12 
Unscheduled Visits ...................................................................................................... 37 
9 
ADVERSE EVENTS ................................................................................................... 37 
9.1 
Definition of an Adverse Event ................................................................................... 38 
9.2 
Definition of Serious Adverse Event ........................................................................... 38 
9.3 
Disease-Related Events or Outcomes Not Qualifying as AE/SAE’s .......................... 38 
9.4 
Monitoring and Recording of AEs and SAEs .............................................................. 39 
9.4.1 
Adverse Events ............................................................................................................ 39 
9.4.2 
Serious Adverse Events ............................................................................................... 39 
9.4.3 
All Events .................................................................................................................... 39 
9.5 
Immediate Reporting of Serious Adverse Events and Pregnancies ............................. 39 
9.6 
Death ............................................................................................................................ 40 
9.7 
Evaluating AEs and SAEs ........................................................................................... 40 
9.7.1 
Severity ........................................................................................................................ 40 
9.7.2 
Relationship to Investigational Product or Procedure ................................................. 40 
9.7.3 
Expectedness of Events ............................................................................................... 41 
9.8 
Procedures for Handling Special Situations ................................................................ 41 
9.8.1 
Pregnancy ..................................................................................................................... 41 
9.8.2 
Unmasking for Medical Emergencies .......................................................................... 41 
9.8.3 
Regulatory Reporting ................................................................................................... 42 
10 
STATISTICAL METHODS AND DATA ANALYSIS ............................................. 42 
10.1 
Study Reporting ........................................................................................................... 42 
10.2 
Statistical Methods ....................................................................................................... 42 
10.3 
Unit of Analysis ........................................................................................................... 42 
10.4 
Sample Size Determination ......................................................................................... 42 
10.5 
Analysis Sets ................................................................................................................ 43 
10.6 
Statistical Significance ................................................................................................. 43 
10.7 
Efficacy Analyses ........................................................................................................ 43 
10.8 
Safety Analyses ............................................................................................................ 43 
11 
STUDY MANAGEMENT AND DATA COLLECTION .......................................... 44 
11.1 
Confidentiality ............................................................................................................. 44 
11.2 
Source Documents ....................................................................................................... 44 
11.3 
Case Report Forms ....................................................................................................... 44 
11.4 
Records Retention ........................................................................................................ 45 
12 
STUDY MONITORING, AUDITING, AND INSPECTING ..................................... 45 
12.1 
Study Monitoring Plan ................................................................................................. 45 
13 
ETHICAL CONSIDERATIONS ................................................................................. 46 
14 
REFERENCES ............................................................................................................ 47 
 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 8 of 67 
1 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Term 
Definition 
AE 
Adverse Event/Experience 
AURN001 
Neltependocel and Y-27632 
 
 
BCVA 
Best Corrected Visual Acuity 
C 
Celsius 
CD 
Compact Disc 
CEC 
Corneal Endothelial Cells 
CFB 
Change from Baseline 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CV 
Curriculum Vitae 
 
 
EDC 
Electronic Data Capture 
ETDRS 
Early Treatment of Diabetic Retinopathy Study 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICH 
International Council on Harmonization 
ICF 
Informed Consent Form 
ID 
Subject Identification 
IEC 
Independent Ethics Committee 
IOL 
Intraocular Lens 
IOP 
Intraocular Pressure 
IP 
Investigational Product 
IRB 
Institutional Review Board 
IUD 
Intra-Uterine Device 
 
 
LogMAR 
Logarithm of the Minimum Angle of Resolution 
MR 
Manifest Refraction 
NDA 
New Drug Application 
NEI 
National Eye Institute 
neltependocel 
Allogeneic human corneal endothelial cells 
NSAID 
Nonsteroidal Anti-Inflammatory Drug 
OCT 
Optical Coherence Tomography 
OD 
Oculus Dexter or Right Eye 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 9 of 67 
Term 
Definition 
OS 
Oculus Sinister or Left Eye 
PC-IOL 
Posterior Chamber Intraocular Lens 
PKP 
Penetrating Keratoplasty 
PPS 
Per Protocol Set 
PRO 
Patient Reported Outcomes 
QD 
quaque die (one a day) 
RAPD 
Relative Afferent Pupillary Defect 
SD-OCT 
Spectral Domain Optical Coherence Tomography 
SAE 
Serious Adverse Event/Experience 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TEAE 
Treatment Emergent Adverse Event 
UCVA 
Uncorrected Visual Acuity 
UPT 
Urine Pregnancy Test 
US 
United States 
VA  
Visual Acuity 
 
 
WOCBP 
Women of Childbearing Potential 
Y-27632 
A Rho-kinase inhibitor small molecule drug 
YAG 
Yttrium Aluminum Garnet 
 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 11 of 67 
Safety Evaluations 
• 
Incidence and severity of ocular treatment-emergent adverse events 
(TEAEs) 
• 
Incidence and severity of non-ocular TEAEs 
• 
Loss from baseline in BCVA ≥ 15 letters 
• 
Rescue rate 
• 
Graft rejection 
Study Design and Overview 
This is a multicenter, randomized, double-masked, parallel-arm, dose-ranging, 
Phase 1/2 study of AURN001 in subjects with corneal edema secondary to 
corneal endothelial dysfunction.  
The efficacy and safety of AURN001 will be assessed in a clinical trial setting 
in adult subjects with corneal edema secondary to corneal endothelial 
dysfunction. 
Three doses of AURN001 compared with the 2 components of AURN001 
separately (neltependocel and Y-27632) will be evaluated to assess the 
contribution of these 2 elements to the efficacy and safety of AURN001.  
This trial will enroll approximately 100 subjects in the 5 treatment arms with 
approximately 20 subjects per arm. A randomized treatment sequence will be 
assigned. The sponsor will assess the actual enrollment in each arm on an on-
going basis throughout the study to maintain a randomization ratio of 1:1:1:1:1. 
The sponsor will make adjustments to the randomized treatment sequence and 
the number of subjects to be treated in each cohort as needed. 
The treatment arms are as follows: 
Arm 
No. of 
Subjects 
Neltependocel 
Dose 
Y-27632 Dose 
Endothelial 
Polishing? 
1 
20 
1.0 × 106 
100 µM 
Yes 
2 
20 
5.0 × 105 
100 µM 
Yes 
3 
20 
2.5 × 105 
100 µM 
Yes 
4 
20 
None 
100 µM 
Yes 
5 
20 
1.0 × 106 
None 
Yes 
 
This study will have a screening period, a surgery/treatment day during which 
treatment will be administered, and a 12-month observation period. The 
primary efficacy analysis will be conducted at Month 6. 
The study will have up to 10 visits with one optional visit: the Screening Visit 
(Visit 1, -77 days to -7 days); Surgery/Treatment (Visit 2, Day 1); and Follow-
up (Visits 3 through 10, Day 2, Week 1, Week 4, and Months 2 (optional), 3, 
4.5, 6, 9, and 12, respectively).  Unscheduled visits will be allowed, as deemed 
necessary by the investigator. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 12 of 67 
If the investigator considers it clinically appropriate, after discussion with the 
medical monitor, subjects who do not meet all study criteria at the Screening 
Visit may be rescreened within 6 weeks of the Screening Visit. In this case, 
baseline will be defined by the most recent measure prior to treatment. 
At the Screening Visit (-77 days to -7 days), subjects who sign the informed 
consent form (ICF) will undergo screening procedures to determine their 
eligibility to participate in the study. Surgery will be scheduled in accordance 
with the manufacturing and delivery schedule of fresh investigational product. 
The investigators, subjects, and all study site personnel will remain masked to 
study treatment throughout this process. 
Only one eye of each subject will receive treatment based on the ocular 
eligibility criteria; the treated eye will be designated as the “study eye.”  If both 
eyes qualify for treatment, the study eye will be selected at the investigator’s 
discretion, in consultation with the Medical Monitor, based on the eye where 
visual acuity is most affected by corneal edema. The other eye will be 
designated as the “non-study eye.  
Although only one eye is being treated, it is important to note that both eyes 
will undergo all ocular assessments as outlined in the Schedule of Assessments. 
IP Mode of Administration 
Subjects assigned to active treatment will receive a single injection of 
AURN001 (neltependocel with Y-27632), neltependocel alone, or Y-27632 
alone into the anterior chamber of the study eye. The dose of neltependocel will 
be either 1.0 × 106, 5.0 × 105 or 2.5 × 105; the dose of Y-27632 will be 100 µM. 
The total volume of administration will be approximately 300 µL. 
Surgical Procedure: The injection of study treatment into the study eye will be 
performed under local anesthesia (administration method at the investigator’s 
discretion). After creating a small incision at the corneal limbus, the corneal 
endothelium will be polished to a diameter of approximately 8 mm. Study 
treatment will be injected into the anterior chamber using a 27-gauge needle. 
Immediately after completion of surgery, subjects will lie face down for 
approximately 3 hours (±15 minutes). 
For detailed instructions, please refer to the Procedure Manual, which includes 
Sponsor observation language. 
Inclusion Criteria 
Subjects must meet all of the following criteria to be eligible for study 
participation: 
General Criteria: 
1. Be 18 years of age or older at the time of signing consent. 
2. Able to understand and willing to sign an ICF approved by an Institutional 
Review Board. 
3. Are willing and able to lie face down for approximately 3 hours (±15 min) 
immediately after the surgical procedure on Day 1. 
4. Are reliable and willing to comply with study instructions and return for all 
scheduled examinations post-operatively. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 13 of 67 
5. Women of child-bearing potential must have a negative urine pregnancy 
test at the Screening Visit and be willing to use birth control, as described 
below: 
All subjects of child-bearing potential, male and female, must agree to use 
a reliable method of birth control for the entire duration of the study 
(i.e., 12 months post treatment). Acceptable methods of birth control 
include oral contraceptives; implantable contraceptives; injectable 
contraceptives; a contraceptive patch; barrier methods such as diaphragms 
with contraceptive jelly, cervical caps with contraceptive jelly, condoms 
with contraceptive foam, or intrauterine devices; a partner with vasectomy. 
Birth control is not required if the female is infertile due to surgical 
sterilization (at least 6 weeks after surgical bilateral oophorectomy, 
hysterectomy, or at least 6 weeks after tubal ligation) confirmed by medical 
history or menopause (after at least 12 consecutive months from last 
menstruation). Post-menopausal females are not required to use birth 
control.  
Men are eligible to participate if they agree to the following for the entire 
duration of the study (i.e., 12 months post treatment): 
a. 
Refrain from donating sperm. 
b. For men with partners of childbearing potential or partners who are 
pregnant or breastfeeding: Use a male condom and should also be 
advised of the benefit for a female partner to use a highly effective 
method of contraception as a condom may break or leak when having 
sexual intercourse with a woman of childbearing potential who is not 
currently pregnant. 
Ocular Criteria in the Study Eye: 
6. Have a diagnosis of corneal edema secondary to corneal endothelial 
dysfunction, requiring surgery (full- or partial-thickness endothelial 
keratoplasty). 
7. Be pseudophakic with a posterior chamber intraocular lens (PC-IOL) 
located fully within the capsular bag without evidence of zonular 
instability. 
8. Have at least 42 days (6 weeks) since cataract surgery + PC-IOL, a 
minimum of 14 days (2 weeks) since yttrium-aluminum garnet (YAG) 
capsulotomy prior to screening visit.  
9. BCVA between 65 Early Treatment of Diabetic Retinopathy Study 
(ETDRS) letters (i.e., 0.4 LogMAR or approximate 20/50 Snellen 
equivalent) and 5 ETDRS letters (i.e., 1.6 LogMAR or approximate 
20/800 Snellen equivalent). 
10. Have a CCT in the study eye of less than 1000 microns and greater than 
575 microns. If CCT is less than 575 microns, must have other documented 
clinical findings of corneal edema (i.e., Descemet’s folds, bullous 
keratopathy, microcystic edema, or stromal haze). 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 14 of 67 
Exclusion Criteria 
Subjects will not be eligible for study participation if they meet any of the 
following criteria at screening: 
General Criteria 
1. History of human immunodeficiency virus or hepatitis B. 
2. Have current systemic infection or inflammation that may require antiviral 
therapy that will not be completed prior to the Screening Visit, or that in the 
opinion of the investigator and with concurrence of the Medical Monitor, 
may either put the subject at risk or may influence the results of the study, 
or the subject’s ability to participate in the study. 
3. History of malignancy within 1 year, except for basal or squamous cell 
carcinoma of the skin or carcinoma in situ of the cervix that has been 
successfully treated. 
4. Women who are pregnant or breastfeeding. 
5. Are investigator site personnel directly affiliated with this study and/or their 
immediate families. Immediate family is defined as a spouse, parent, child, 
or sibling, whether biological or legally adopted. 
6. Have a history of any clinically significant disease or disorder, ocular or 
otherwise (e.g., uncontrolled systemic disease such as diabetes mellitus) 
which, in the opinion of the investigator, may put the subject at risk for 
study participation, influence the results of the study, or affect the subject's 
ability to participate in the study. 
Ocular Criteria 
7. Have conditions associated with clinically meaningful corneal 
thinning/ectasia in the study eye (for example, keratoconus). 
8. Have progressive stromal or anterior corneal dystrophies or degenerations 
in the study eye. 
9. Have pre-operative corneal epithelial, sub-epithelial or stromal scarring or 
other opacity that is paracentral/central and visually significant, but not 
suspected to be secondary to corneal endothelial disease with the potential 
to improve from treatment in the study eye. 
10. Have visually significant posterior capsule opacification in the study eye. 
YAG posterior capsulotomy should be performed prior to screening where 
clinically indicated.  
11. Have prior history of corneal transplantation, glaucoma 
(e.g., trabeculectomy, valve), or vitreoretinal surgery, aphakic, anterior 
chamber-IOL, or iris claw IOL, in the study eye. 
12. Have evidence of vitreous prolapse into the anterior segment of the study 
eye or zonular instability in the study eye. 
13. Have uncontrolled glaucoma or intraocular pressure greater than 24 mmHg 
that is not controlled with medication or surgery at the time of the 
Screening Visit. 
14. Have uncontrolled co-morbidities of the ocular surface, and/or anterior 
segment, such as ocular surface disease, exposure keratopathy, visually 
significant or symptomatic pterygium, or clinically significant vascularized 
cornea in the study eye. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 15 of 67 
15. History of or findings consistent with active or prior uveitis in the study 
eye. 
16. Have a history of or current evidence of ocular herpetic diseases (including 
herpes simplex virus, varicella zoster or cytomegalovirus) in the study eye. 
17. Have history or presence of an ocular disease other than corneal endothelial 
dysfunction that could affect vision or safety assessments.   
18. Have relative afferent pupillary defect (RAPD). 
19. Monocular 
Medications 
20. Have used medications known to be toxic to the cornea, retina, lens, or 
optic nerve within 1 month prior to the Screening Visit. These medications 
include, but are not limited to, carbonic anhydrase inhibitors [systemic or 
topical ophthalmic]; amiodarone; indomethacin; 
chloroquine/hydrochloroquine; isotretinoin [AccutaneTM]; belantamab 
mafodotin or other antibody-drug conjugates used for immunotherapy; 
deferoxamine; chlorpromazine; phenothiazines; tamoxifen; and ethambutol. 
21. Have known hypersensitivity or allergy to fluorescein (e.g., bronchospasm, 
rash, etc.) or to any component of the study products or a contraindication 
to dilation of the pupil; mild allergies without angioedema or need for 
treatment may be acceptable if deemed not to be of clinical significance in 
the opinion of the investigator (including but not limited to mild seasonal 
hay fever). 
Rescue Therapy 
RESCUE CRITERIA: 
Subjects whose clinical status declines in the study eye may be evaluated for 
rescue surgery by Standard of Care Keratoplasty [Descemet membrane 
endothelial keratoplasty (DMEK), Descemet stripping endothelial keratoplasty 
(DSEK), or penetrating keratoplasty (PK)]. 
Consultation with the Medical Monitor is required prior to any procedure. 
Evaluation will include the subject’s visual symptoms, problems, or complaints, 
and ocular examination findings as available. Subjects who undergo a rescue 
procedure should be followed for approximately 1 month and may be 
discontinued from the study thereafter. 
All decisions involving rescue surgery should be documented in the eCRF.  In 
addition, all post-rescue follow-up visits should be documented in the eCRF. 
Efficacy and  
Safety Assessments 
The efficacy evaluation will be based on measurements of BCVA (using 
ETDRS), ultrasonic contact pachymetry,
, 
 
The safety evaluation will be based on adverse event (AE) reporting, laboratory 
findings (clinical chemistry and hematology), and ophthalmic examinations, 
including Goldmann tonometry, Slit Lamp biomicroscopy, gonioscopy, dilated 
fundoscopy, and BCVA (as measured by ETDRS).  
All ocular assessments will be conducted on both eyes. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 16 of 67 
Sample Size Considerations 
This sample size is based on clinical feasibility and adequate size to characterize 
safety in the study population, without consideration for statistical power.  
Statistical Methods 
Analysis Sets 
The Full Analysis Set (FAS) will be defined as all eligible subjects who 
received any amount of study drug during intracameral injection. All subjects in 
FAS will be analyzed according to the treatment they actually received. 
Per Protocol Set (PPS) is a subset of FAS who completed the study without 
major protocol deviations. 
The Safety Analysis Set will be the same as FAS.   
Efficacy Analyses 
For the primary endpoint and other binary endpoints, number and percentage of 
subjects, with associated 2-sided exact (Clopper-Pearson) 95% confidence 
intervals (CIs), will be presented by treatment in each category (response, non-
response). The distribution of responders will be compared between treatment 
arms using a two-sided Fisher’s exact test.  
Analyses of change from baseline in BCVA, CCT and 
 will be conducted 
using the Full Analysis Set and a restricted maximum likelihood based mixed-
effect model for repeated measures to evaluate the effect over time.  The 
dependent variable will be the change from baseline.  The model will include 
treatment arm (3 levels), categorical time, treatment arm by time interaction, 
and baseline value as a covariate. 
Safety Analyses 
All safety analyses will be conducted on the Safety Analysis Set. No formal 
statistical tests of treatment difference are planned. 
AEs will be coded using the Medical Dictionary for Regulatory Activities 
TEAEs (i.e., AEs that begin or worsen in severity after initiation of study drug) 
will be summarized by treatment arm and overall in the study eye. Non-ocular 
TEAEs will also be summarized. Additionally, TEAEs and serious AEs will be 
summarized in a similar manner by maximum severity and relationship to study 
drug and the surgical procedure. 
Changes from baseline of quantitative measurements (ophthalmic evaluations, 
laboratory findings) will be summarized by treatment arm and timepoint. 
 
3 
PRINCIPAL CONTACTS 
Please refer to the Contact List provided under separate cover. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 17 of 67 
4 
BACKGROUND INFORMATION 
4.1 
Corneal Edema Secondary to Corneal Endothelial Dysfunction 
Corneal edema secondary to corneal endothelial dysfunction and ultimately cell failure is the 
global leading indication for keratoplasty1. Corneal endothelial dysfunction is a serious, 
debilitating condition with significant, progressive impact on patients’ lives as corneal clarity 
gradually diminishes, and vision is lost. The main etiologies that lead to corneal endothelial 
dysfunction are as follows:  
• Primary endothelial dystrophy (i.e., Fuchs dystrophy, posterior polymorphous corneal 
dystrophy, congenital hereditary endothelial dystrophy, etc.)  
• Postsurgical endothelial dysfunction (i.e., pseudophakic/aphakic corneal edema, bullous 
keratopathy, glaucoma tube shunts, etc.) 
• Graft failure or rejection (penetrating or endothelial keratoplasty [PKP or EK]) 
• Other causes of endothelial dysfunction (i.e., primary/secondary keratoplasty failure, 
endotheliitis, toxic anterior segment syndrome, etc.) 
There is a wide spectrum of severity associated with all of the etiologies that lead to corneal 
endothelial dysfunction, and current available therapies leave significant room for improvement. 
While some topical therapies like hypertonic solutions are available to treat mild stages of 
corneal endothelial dysfunction, they are primarily treating the symptoms rather than the root 
cause of the disease, and therefore, may be limited in their long-term success. Alternatively, for 
moderate and severe stages of corneal endothelial dysfunction, EK or PKP remain the only 
treatment options. Issues of concern with these approaches include limited transplant material, 
surgical complexity, burdensome post-operative recovery, induced astigmatism, interface issues, 
potential need for multiple procedures, and long visual recoveries taking months. 
A potential therapeutic approach which can span the disease spectrum while decreasing the risks 
associated with corneal transplantation is the injection of AURN001 into the anterior chamber of 
the eye. This approach allows for a replacement of the diseased endothelial cells with a healthy 
monolayer of new corneal endothelial cells, which are able to re-establish corneal deturgescence 
and overall clarity.  
4.2 
Investigational Product Rationale 
There are no FDA-approved products for the treatment of corneal edema secondary to corneal 
endothelial dysfunction. The only treatment option to date to restore sight is corneal transplant 
surgery (PKP or EK). The current standard of care in the US is corneal transplantation including 
full thickness corneal transplant (penetrating keratoplasty) and more commonly lamellar corneal 
transplantation including Descemet stripping endothelial keratoplasty (DSAEK, DSEK) and 
Descemet Membrane Endothelial Keratoplasty (DMEK). All require a donor cornea, one donor 
cornea per host.  

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 20 of 67 
potential to reduce the risk of surgically induced complications, including corneal irregularities 
and the risk of post-operative graft detachment and/or dislocation of partial or full thickness 
corneal grafts, while allowing for the potential of one donor cornea to produce cells to treat many 
patients. The patient experience is improved post-operatively as positioning is limited to the first 
few hours following surgery, unlike keratoplasty which limits the patients' mobility for several 
days. In addition, there is a potential lower risk of graft rejection with AURN001 compared with 
EK or PKP.  
In summary, the benefit-risk assessment is such that continued investigation in a clinical study 
setting is warranted. 
4.4.1 
Potential Risks 
Potential risks can be categorized as those risks associated with intraocular surgical procedure 
and those risks associated with the IMP (AURN001). 
Potential Risks Associated with Surgery 
Potential risks associated with this intraocular procedure include loss of vision, ocular pain 
and/or discomfort, ocular hyperemia, dry eye, eyelid edema, increased tearing, subconjunctival 
hemorrhage, corneal or conjunctival abrasion, corneal ulcer, surgical wound leak, shallowing or 
collapse of the anterior chamber, Descemet’s membrane tear, vitreous prolapse, damage to the 
iris or other structures, changes to the pupil, intraocular bleeding, infection, endophthalmitis, 
inflammation (uveitis), worsening of corneal edema, posterior capsular opacification (PCO), 
worsening of cataract, increased IOP, macular edema (including CME and DME), increase in 
vitreous opacities, posterior vitreous detachment, and retinal detachment, among others.  
Potential Risks Associated with the IMP  
Potential risks associated with the IMP (AURN001) include ocular pain and/or discomfort, 
ocular hyperemia, dry eye, failure to improve corneal edema, corneal ulcer, intraocular 
inflammation (uveitis), infection, endophthalmitis, increased IOP, graft rejection or failure, 
changes to the pupil, iris or other structures, posterior capsular opacification (PCO), worsening 
of cataract, increase in vitreous opacities, and macular edema (including CME and DME) among 
others. Although tumor formation has not been observed in any animal or clinical studies to date, 
this is a theoretical risk of receiving any cell therapy.  
Previous Experience 
In prior clinical trials conducted with AURN001 or an earlier formulation in Japan and El 
Salvador, the most common risks (>5% occurrence) with both the surgical procedure and IMP 
were as follows:  
First In-Human Clinical Trial (Japan) 
• Cystoid macular edema (19%) 
• Increased IOP (16%) 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 21 of 67 
Other Clinical Trials (Japan) 
• Ocular pain (33%) 
• Increased IOP (15%) 
• Eyelid edema (7%) 
• Increased tearing (7%) 
Clinical Trials (El Salvador) 
• Posterior capsular opacification (PCO) (29%) 
• Pupillary disorder (9%) 
• Increased IOP (7%) 
• Iris disorder (6%) 
• Descemet’s membrane tear (6%) 
Other less common risks (<5% occurrence) included dry eye, blepharitis, macular edema, and 
anterior chamber inflammation. 
4.5 
Dose Justification 
Human Corneal Endothelial Cells – Neltependocel 
In humans, the cornea has a diameter of about 11.5 mm and a thickness of 0.5 to 0.6 mm in the 
center and 0.6 to 0.8 mm at the periphery. Learnings from the current standard of care show that 
removing the dysfunctional corneal endothelial cells with a graft diameter of approximately 8 
mm can improve patient outcomes. 
Aurion calculated the number of cells that would be needed to restore 
 to 
normal levels 
 Given the current procedure involves polishing 
an area of the corneal endothelium of approximately 8 mm in diameter, to replace those corneal 
endothelial cells, one would need approximately 
 to effectively form the monolayer 
(assuming an equivalent area of polished cornea of approximately 50.27 mm2). In order to 
account for potential attrition and displacement 
 of AURN001, 
approximately 
 are assumed to be the minimally efficacious dose of neltependocel. 
Clinical experience from the 3 trials conducted in Japan and the two trials conducted in 
El Salvador identified 1.0 × 106 neltependocel as the most commonly used dose. This dose was 
found to have a favorable safety profile in conjunction with evidence of biological activity 
indicated by improvement in vision and reduction in corneal edema (as measured by BCVA and 
CCT). Lower doses of 5.0 x 105 and 2.0 x 105 were also found to be effective in improving 
vision and decreasing corneal edema; however, the number of subjects treated at these doses was 
low. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 22 of 67 
Three doses of neltependocel will be evaluated in this study: (1) 1.0 x 106 with 100 µM of 
Y-27632, (2) 5.0 x 105 with 100 µM of Y-27632, and (3) 2.5 x 105 with 100 µM of Y-27632. 
Doses will be delivered by single intracameral injection of a total volume of 300 µL. One of the 
important objectives of this first US clinical trial is to identify the minimally effective dose of 
neltependocel. 
Rho-Kinase Inhibitor – Y-27632 
Y-27632 is a novel, low molecular weight, ROCK inhibitor that is injected in conjunction with 
corneal endothelial cells. Y-27632 enhances the adherence of injected endothelial cells and 
promotes the development of fully functional corneal endothelial cells. Aurion has conducted 
human clinical trials in El Salvador where endothelial cells alone were injected intracamerally 
(n=20) and when compared with the co-injection of endothelial cells with Y-27632, biological 
activity of the endothelial cells alone was meaningfully diminished as measured by visual acuity 
improvement, decrease in corneal edema as measured by CCT, overall assessment of corneal 
clarity, and need for rescue therapy. 
In addition, Aurion has performed ROCK activity measurements using an in-vitro biochemical 
assay and determined that in AURN001’s matrix (
), a 100 µM 
concentration of Y-27632 inhibits about 95% of ROCK activity (data on file). Preclinical and 
clinical studies indicate that this level of ROCK inhibition is sufficient to ensure AURN001 
efficacy. 
  
Furthermore, Aurion’s safety pharmacology studies indicate that Y-27632 was well 
tolerated after intravenous administration of a single dose of up to 100 mg/kg in rabbits 
(Study 010179.001) as well as in a single dose intravenous and intracameral pharmacokinetic 
study in rabbits (Study 020179.002). In the doses employed in the rabbit pharmacokinetic study, 
which are up to 50X the equivalent of the clinical dose, systemic concentrations of Y-27632 fall 
below the lower limit of quantitation (LLOQ) of the pharmacokinetic assay (10 ng/mL) within 
15 minutes after dosing.  
Y-27632 has been evaluated in 130 subjects and over 150 procedures in human clinical trials in 
Japan and El Salvador at doses between 10 µM and 100 µM (single intracameral injection of a 
total volume of 300 µL). Most of the procedures were conducted using 100 µM dosing in 
combination with endothelial cells administered by single intracameral injection of a total 
volume of 300 µL. No systemic pulmonary or cardiovascular toxicity has been observed to date 
with intracameral administration. The most common adverse events seen are transient IOP 
elevations and focal iris changes (approximately 5% of subjects). These iris changes are 
generally considered to be mild and peak around 3 months after injection. As the technique for 
injecting endothelial cells has improved and refined, the incidence of severity of these iris 
changes has diminished. 
The most recent ongoing clinical study, the Escalon study in El Salvador, is a randomized, 
double-masked, parallel group, dose ranging study of Y-27632 in 22 subjects which evaluated 
10 µM, 20 µM and 100 µM of Y-27632 co-administered with 1.0 x 106 neltependocel injected 
intracamerally in a total volume of 300 µL. This study showed that subjects treated with 20 µM 
and 100 µM Y-27632 had better evidence of biological activity at six months as measured by 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 23 of 67 
improvements in visual acuity and decreased in corneal edema compared to subjects treated with 
10 µM Y-27632 and 1.0 x 106 cells. No differences in safety profile were noted between the 
three doses of Y-27632. Based on this study, Y-27632 seems to have a wide safety margin with 
most therapeutic benefit seen between 20 µM and 100 µM. Given these data, this US clinical 
trial will enroll subjects using 100 µM of Y-27632. 
4.6 
Trial Population 
Approximately 100 subjects diagnosed with corneal edema secondary to corneal endothelial 
dysfunction will be screened and assigned to one of five treatment arms. 
5 
TRIAL OBJECTIVES 
The primary objective of this trial is to evaluate the: 
• Efficacy of a single injection of different concentrations of neltependocel in combination 
with Y-27632 (i.e., AURN001), neltependocel alone, and Y-27632 alone in subjects with 
corneal edema secondary to corneal endothelial dysfunction 
The secondary objective of this trial is to evaluate the: 
• Safety and tolerability of a single injection of different concentrations of neltependocel in 
combination with Y-27632 (i.e., AURN001), neltependocel alone, and Y-27632 alone in 
subjects with corneal edema secondary to corneal endothelial dysfunction 
6 
TRIAL DESIGN 
6.1 
Description of Trial 
This is a multicenter, randomized, double-masked, parallel-arm, dose-ranging, Phase 1/2 study of 
AURN001 in subjects with corneal edema secondary to corneal endothelial dysfunction. The 
efficacy and safety of AURN001 will be assessed in a clinical trial setting in North America in 
adult subjects with corneal edema secondary to corneal endothelial dysfunction. Three doses of 
AURN001 compared with the 2 components of AURN001 separately (neltependocel and 
Y-27632) will be evaluated to assess the contribution of these 2 elements to the efficacy and 
safety of AURN001. 
This trial will enroll approximately 100 subjects in the 5 treatment arms with approximately 
20 subjects per arm. A randomized treatment sequence will be assigned. The sponsor will assess 
the actual enrollment in each arm on an on-going basis throughout the study to maintain a 
randomization ratio of 1:1:1:1:1. The sponsor will make adjustments to the randomized treatment 
sequence and the number of subjects to be treated in each cohort as needed. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 24 of 67 
 
The treatment arms are as follows: 
Table 1 
Treatment Assignment Paradigm 
Arm 
No. of Subjects 
Neltependocel Dose  
Y-27632 Dose 
Endothelial Polishing? 
1 
20 
1.0 × 106 
100 µM 
Yes 
2 
20 
5.0 × 105 
100 µM 
Yes 
3 
20 
2.5 × 105 
100 µM 
Yes 
4 
20 
None 
100 µM 
Yes 
5 
20 
1.0 × 106 
None 
Yes 
 
This study will have a screening period, a surgery/treatment day during which treatment will be 
administered, and a 12-month observation period. The primary efficacy analysis will be 
conducted at Month 6.  The study will have up to 10 visits with one optional visit: the Screening 
Visit (Visit 1, -77 days to -7 days); Surgery/Treatment (Visit 2, Day 1); and Follow-up (Visits 3 
through 10, Day 2, Week 1, Week 4, and Months 2 (optional), 3, 4.5, 6, 9, and 12, respectively).  
Unscheduled visits will be allowed, as deemed necessary by the investigator. 
This study will be conducted per the schedule shown in Figure 2. 
Figure 2 Study Schematic 
 
6.2 
Study Endpoints 
6.2.1 
Efficacy Endpoints 
All ocular assessments will be conducted on both eyes. The efficacy evaluations will be based on 
measurements of BCVA (using ETDRS), ultrasonic contact pachymetry, 
 
 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 27 of 67 
Note: IP expires 
 after filling of the vial and a check of the expiry date and time must be 
performed prior to administering the product. 
The IP must not be used outside of this study. 
7 
SELECTION AND WITHDRAWAL OF SUBJECTS 
This trial will include approximately 100 subjects from approximately 10-20 sites. 
7.1 
Inclusion Criteria 
Subjects must meet all of the following criteria to be eligible for study participation: 
General Criteria: 
1. Be 18 years of age or older at the time of signing consent. 
2. Able to understand and willing to sign an ICF approved by an Institutional Review Board. 
3. Are willing and able to lie face down for approximately 3 hours (±15 min) immediately after 
the surgical procedure on Day 1. 
4. Are reliable and willing to comply with study instructions and return for all scheduled 
examinations post-operatively. 
5. Women of child-bearing potential must have a negative urine pregnancy test at the Screening 
Visit and be willing to use birth control, as described below: 
All subjects of child-bearing potential, male and female, must agree to use a reliable method 
of birth control for the entire duration of the study (i.e., 12 months post treatment). 
Acceptable methods of birth control include oral contraceptives; implantable contraceptives; 
injectable contraceptives; a contraceptive patch; barrier methods such as diaphragms with 
contraceptive jelly, cervical caps with contraceptive jelly, condoms with contraceptive foam, 
or intrauterine devices; a partner with vasectomy. Birth control is not required if the female is 
infertile due to surgical sterilization (at least 6 weeks after surgical bilateral oophorectomy, 
hysterectomy, or at least 6 weeks after tubal ligation) confirmed by medical history or 
menopause (after at least 12 consecutive months from last menstruation). Post-menopausal 
females are not required to use birth control. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 28 of 67 
Men are eligible to participate if they agree to the following for the entire duration of the 
study (i.e., 12 months post treatment): 
a. Refrain from donating sperm. 
b. For men with partners of childbearing potential or partners who are pregnant or 
breastfeeding: Use a male condom and should also be advised of the benefit for a female 
partner to use a highly effective method of contraception as a condom may break or leak 
when having sexual intercourse with a woman of childbearing potential who is not 
currently pregnant.  
Ocular Criteria in the Study Eye: 
6. Have a diagnosis of corneal edema secondary to corneal endothelial dysfunction, requiring 
surgery (full- or partial-thickness endothelial keratoplasty). 
7. Be pseudophakic with a posterior chamber intraocular lens (PC-IOL) located fully within the 
capsular bag without evidence of zonular instability. 
8. Have at least 42 days (6 weeks) since cataract surgery + PC-IOL, a minimum of 14 days 
(2 weeks) since yttrium-aluminum garnet (YAG) capsulotomy prior to screening visit. 
9. BCVA between 65 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters 
(i.e., 0.4 LogMAR or approximate 20/50 Snellen equivalent) and 5 ETDRS letters 
(i.e., 1.6 LogMAR or approximate 20/800 Snellen equivalent). 
10. Have a CCT in the study eye of less than 1000 microns and greater than 575 microns, 
confirmed as per standard of care. If CCT is less then 575 microns, must have other 
documented clinical findings of corneal edema (i.e., Descemet’s folds, bullous keratopathy, 
microcystic edema, or stromal haze). 
7.2 
Exclusion Criteria 
Subjects will not be eligible for study participation if they meet any of the following criteria at 
screening: 
General Criteria 
1. History of human immunodeficiency virus or hepatitis B. 
2. Have current systemic infection or inflammation that may require antiviral therapy that will 
not be completed prior to the Screening Visit, or that in the opinion of the investigator and 
with concurrence of the Medical Monitor, may either put the subject at risk or may influence 
the results of the study, or the subject’s ability to participate in the study. 
3. History of malignancy within 1 year, except for basal or squamous cell carcinoma of the skin 
or carcinoma in situ of the cervix that has been successfully treated. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 29 of 67 
4. Women who are pregnant or breastfeeding. 
5. Are investigator site personnel directly affiliated with this study and/or their immediate 
families. Immediate family is defined as a spouse, parent, child, or sibling, whether 
biological or legally adopted. 
6. Have a history of any clinically significant disease or disorder, ocular or otherwise 
(e.g., uncontrolled systemic disease such as diabetes mellitus) which, in the opinion of the 
investigator, may put the subject at risk for study participation, influence the results of the 
study, or affect the subject's ability to participate in the study. 
Ocular Criteria 
7. Have conditions associated with clinically meaningful corneal thinning/ectasia in the study 
eye (for example, keratoconus). 
8. Have progressive stromal or anterior corneal dystrophies or degenerations in the study eye. 
9. Have pre-operative corneal epithelial, sub-epithelial or stromal scarring or other opacity that 
is paracentral/central and visually significant, but not suspected to be secondary to corneal 
endothelial disease with the potential to improve from treatment in the study eye. 
10. Have visually significant posterior capsule opacification in the study eye. YAG posterior 
capsulotomy should be performed prior to screening where clinically indicated.  
11. Have prior history of corneal transplantation, glaucoma (e.g., trabeculectomy, valve), or 
vitreoretinal surgery, aphakic, anterior chamber-IOL, or iris claw IOL, in the study eye. 
12. Have evidence of vitreous prolapse into the anterior segment of the study eye or zonular 
instability in the study eye. 
13. Have uncontrolled glaucoma or intraocular pressure greater than 24 mmHg that is not 
controlled with medication or surgery at the time of the Screening Visit. 
14. Have uncontrolled co-morbidities of the ocular surface, and/or anterior segment, such as 
ocular surface disease, exposure keratopathy, visually significant or symptomatic pterygium, 
or clinically significant vascularized cornea in the study eye. 
15. History of or findings consistent with active or prior uveitis in the study eye. 
16. Have a history of or current evidence of ocular herpetic diseases (including herpes simplex 
virus, varicella zoster or cytomegalovirus) in the study eye. 
17. Have history or presence of an ocular disease other than corneal endothelial dysfunction that 
could affect vision or safety assessments. 
18. Have relative afferent pupillary defect (RAPD). 
19. Monocular 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 30 of 67 
Medications 
20. Have used medications known to be toxic to the cornea, retina, lens, or optic nerve within 
1 month prior to the Screening Visit. These medications include, but are not limited to, 
carbonic anhydrase inhibitors [systemic or topical ophthalmic]; amiodarone; indomethacin; 
chloroquine/hydrochloroquine; isotretinoin [AccutaneTM]; belantamab mafodotin or other 
antibody-drug conjugates used for immunotherapy; deferoxamine; chlorpromazine; 
phenothiazines; tamoxifen; and ethambutol. 
21. Have known hypersensitivity or allergy to fluorescein (e.g., bronchospasm, rash, etc.) or to 
any component of the study products or a contraindication to dilation of the pupil; mild 
allergies without angioedema or need for treatment may be acceptable if deemed not to be of 
clinical significance in the opinion of the investigator (including but not limited to mild 
seasonal hay fever). 
7.3 
Subject Recruitment, Screening, Rescreening and Treatment  
Each subject must sign the Informed Consent Form (ICF) before his or her participation in the 
study. At the Screening Visit (-77 days to -7 days), subjects who sign the informed consent 
form (ICF) will undergo screening procedures to determine their eligibility to participate in the 
study. A fully signed copy of the ICF must be provided to the subject. Each subject who signs 
an Informed Consent Form (ICF) will be assigned a Subject Identification (ID) number 
consisting of a 3-digit Country Number, 3-digit Site Number, and 3-digit Subject Number 
(e.g., 840-001-001).  
If the investigator considers it clinically appropriate, after discussion with the medical monitor, 
subjects who do not meet all entry criteria at the Screening Visit may be rescreened within 
6 weeks of the Screening Visit. Rescreened subjects will receive a new subject ID but the 
previously assigned subject ID will be recorded. In this case, baseline will be defined by the most 
recent measure prior to treatment. 
The investigators, subjects, and all study personnel will remain masked to study treatment 
throughout this process. 
Only one eye of each subject will receive treatment based on the ocular eligibility criteria; the 
treated eye will be designated as the “study eye.”  If both eyes qualify for treatment, the study 
eye will be selected at the investigator’s discretion, in consultation with the Medical Monitor, 
based on the eye where visual acuity is most affected by corneal edema. The other eye will be 
designated as the “non-study eye.”  
Although only one eye will be treated, it is important to note that both eyes will undergo all 
ocular assessments as outlined in the Schedule of Assessments (see Appendix 1). 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 31 of 67 
7.4 
Withdrawal Criteria 
Any subject who wishes to withdraw from participation in the study for any reason is entitled to 
do so without obligation. Any subject may be discontinued from study participation at the 
discretion of the investigator, in consultation with the Medical Monitor, or by the Sponsor for 
any reason. 
7.4.1 
Withdrawal Methods 
The Sponsor may terminate this study at any time. Reasons for termination may include but are 
not limited to, the following: 
• The incidence or severity of adverse events (AE) in this or other studies point to a 
potential health hazard for trial subjects. 
• Insufficient subject enrollment. 
• Any information becoming available during the study that substantially changes the 
expected benefit risk profile of the study treatments. 
7.4.2 
Collection of Data from Withdrawn Subjects 
In the event that study discontinuation of a treated subject is necessary, the investigator should 
make every attempt to have the subject complete Visit 10 (Month 12) assessments as soon as 
possible.  The reason for premature discontinuation should be recorded in the subject chart and 
entered in the eCRF. 
7.4.3 
Subject Replacement 
Subjects who withdraw will not be replaced.  
8 
SUBJECT TREATMENT 
8.1 
Treatment Regimen 
Subjects will be assigned to one of five treatment arms and will receive a single injection of 
product. The total volume of product administered will be approximately 300 µL. 
8.2 
Prior and Concomitant Therapy  
Table 2 
List of Prohibited/Restricted Medications 
Medications 
Minimum Washout Period Prior to Screening  
(Visit 1) 
carbonic anhydrase inhibitors [systemic or topical 
ophthalmic] amiodarone 
30 days 
indomethacin 
30 days 
chloroquine/hydrochloroquine 
30 days 
isotretinoin [AccutaneTM] 
30 days 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 33 of 67 
• SD-OCT (Macula) 
• CCT by Ultrasonic Contact Pachymetry (Appendix 7) 
• Slit Lamp Biomicroscopy 
• Slit Lamp Photography 
• Goldmann Tonometry (IOP) (Appendix 5) 
• Gonioscopy (Appendix 6) 
• Dilated Fundus Examination 
• Prior/Concomitant Medications 
• 
 
• Laboratory blood draw (hematology, chemistry) (samples to be sent to Central Lab) 
• Urine Pregnancy Test (for women of childbearing potential) 
• Cohort assignment 
8.4.2 
Visit 2 Procedure/Day 1 
• Surgery/Study Treatment  
• Adverse Events 
• Prior Concomitant Medications 
8.4.3 
Visit 3 Day 2 (+2 Days) 
• Uncorrected Visual Acuity (UCVA) 
• Slit Lamp Biomicroscopy 
• Goldmann Tonometry (IOP) 
• Adverse Events 
• Prior/Concomitant Medications 
8.4.4 
Visit 4 Week 1/Day 8 (+2 days) 
• Uncorrected Visual Acuity (UCVA) 
• CCT by Ultrasonic Contact Pachymetry 
• Slit Lamp Biomicroscopy 
• Goldmann Tonometry (IOP) 
• Adverse Events 
• Prior/Concomitant Medications 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 34 of 67 
8.4.5 
Visit 5 Week 4/Day 30 (± 7 Days) 
• Uncorrected Visual Acuity (UCVA) 
• BCVA (ETDRS) by Manifest Refraction (through phoropter) 
• CCT by Ultrasonic Contact Pachymetry 
• Slit Lamp Biomicroscopy 
• Slit Lamp Photography 
• Goldmann Tonometry (IOP) 
• Adverse Events 
• Prior/Concomitant Medications 
8.4.6 
Visit 5.1 Month 2/Day 60 (± 7 Days) - Optional 
This is an optional visit that can be conducted at the investigator’s discretion. 
• Uncorrected Visual Acuity (UCVA) 
• BCVA (ETDRS) by Manifest Refraction (through phoropter) 
• CCT by Ultrasonic Contact Pachymetry 
• Slit Lamp Biomicroscopy 
• Slit Lamp Photography 
• Goldmann Tonometry (IOP) 
• Adverse Events 
• Prior/Concomitant Medications 
8.4.7 
Visit 6 Month 3/Day 90 (±7 Days) 
• SD-OCT (Macula) 
• Uncorrected Visual Acuity (UCVA) 
• BCVA (ETDRS) by Manifest Refraction (through phoropter)  
 
 
 
 
 
 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 36 of 67 
• Slit Lamp Photography 
• Goldmann Tonometry (IOP) 
• Gonioscopy 
• Dilated Fundus Examination 
• Adverse Events 
• Prior/Concomitant Medications 
• 
 
• Laboratory blood draw (hematology, chemistry; samples to be sent to Central Lab) 
8.4.10 
Visit 9 Month 9/Day 270 (±14 Days) 
• BCVA (ETDRS) by Manifest Refraction (through phoropter) 
• CCT by Ultrasonic Contact Pachymetry 
• Slit Lamp Biomicroscopy 
• Slit Lamp Photography 
• Goldmann Tonometry (IOP) 
• Adverse Events 
• Prior/Concomitant Medications 
 
 
8.4.11 
Visit 10 Month 12/Day 360 (±14 Days) 
• BCVA (ETDRS) by Manifest Refraction (through phoropter) 
• Uncorrected Visual Acuity (UCVA) 
• 
 
 
 
 
 
 
 
• SD-OCT (Macula) 
• CCT by Ultrasonic Contact Pachymetry 
• Slit Lamp Biomicroscopy 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 37 of 67 
• Slit Lamp Photography 
• Goldmann Tonometry (IOP) 
• Gonioscopy 
• Dilated Fundus Examination 
• Adverse Events 
• Prior/Concomitant Medications 
• 
 
• Laboratory blood draw (hematology, chemistry; samples to be sent to Central Lab) 
8.4.12 
Unscheduled Visits 
An unscheduled visit may be performed during the course of the trial in order to ensure subject 
safety. 
All procedures performed at an unscheduled visit will be recorded in the source documents and 
on the Unscheduled Visit eCRF pages. 
Evaluations that may be conducted at an Unscheduled Visit may include: 
• BCVA assessment (through phoropter) 
• Slit Lamp Biomicroscopy 
• Slit Lamp Photography 
• Assessment of AEs 
• Assessment of concomitant medications and/or treatments 
• Any other assessments needed in the judgment of the investigator 
9 
ADVERSE EVENTS 
The investigator and study staff are responsible for detecting and recording AEs and SAEs, 
during scheduled safety evaluations and whenever such information is brought to their attention. 
This section of the protocol provides definitions and detailed procedures to be followed. 
During each visit, the investigator will question the subject about adverse events using an open 
question taking care not to influence the subject’s answers.  Throughout the course of the study, 
every effort must be made to remain alert to possible AEs. If an AE occurs, the first concern 
should be for the safety of the subject. If necessary, appropriate medical intervention should be 
provided.  At the signing of the ICF, each subject must be given the names and telephone 
numbers of study site staff in the ICF for reporting AEs and medical emergencies. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 38 of 67 
9.1 
Definition of an Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and that does not necessarily have a causal relationship 
with this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. Examples of an AE include: 
• Exacerbation of a pre-existing condition including either an increase in frequency and/or 
intensity of the condition 
• New conditions detected or diagnosed after IP administration even though it may have 
been present prior to the start of the study. 
• Signs, symptoms of a drug interaction 
9.2 
Definition of Serious Adverse Event 
An SAE is any untoward medical occurrence that at any dose: 
• Results in death. 
• Is life-threatening. 
Note: The term “life-threatening” refers to an event in which the subject was at risk of 
death at the time of the event; it does not refer to an event which hypothetically might 
have caused death if it were more severe. 
• Requires in-patient hospitalization or prolongation of existing hospitalization.  
a. Hospitalizations for elective surgeries do not constitute an SAE. 
• Results in persistent or significant disability/incapacity. 
• Is a congenital abnormality/birth defect. 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered SAEs, such as important medical events that might not be immediately life 
threatening or result in death or hospitalization but might jeopardize the subject or might require 
intervention to prevent one of the other outcomes listed above. 
9.3 
Disease-Related Events or Outcomes Not Qualifying as AE/SAE’s 
Any clinical findings associated with lack of efficacy of the IP are not considered AEs.  

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 39 of 67 
9.4 
Monitoring and Recording of AEs and SAEs 
9.4.1 
Adverse Events 
Any AE experienced by the subject from Visit 2 (Day 1) through Visit 10 (Month 12) is to be 
recorded in the eCRF, regardless of the severity of the event or its relationship to study 
treatment.   
Any AEs already documented at a previous assessment and designated as ongoing, should be 
reviewed at subsequent visits as necessary. If these have resolved, this should be documented.   
Changes in intensity or frequency of AEs should be recorded as separate events (i.e., a new 
record started). 
9.4.2 
Serious Adverse Events 
Any SAE experienced by the subject from Visit 2 (Day 1) through Visit 10 (Month 12) is to be 
recorded on an SAE Form, regardless of the severity of the event or its relationship to study 
treatment.  
Any SAE ongoing when the subject completes the study or discontinues from the study will be 
followed by the investigator until the event has resolved, stabilized, or returned to baseline 
status. 
9.4.3 
All Events 
All events must be assessed to determine the following: 
• If the event meets the criteria for an SAE as defined in Section 9.2. 
• The severity of the event as defined in Section 9.7.1. 
• The relationship of the event to study treatment as defined in Section 9.7.2. 
9.5 
Immediate Reporting of Serious Adverse Events and Pregnancies 
In order to adhere to all applicable laws and regulations for reporting an SAE or pregnancy, the 
study site must formally notify the pharmacovigilance team within 24 hours of the study site 
staff becoming aware of the SAE or pregnancy. It is the investigator’s responsibility to ensure 
that the SAE or pregnancy reporting information is emailed as described in Figure 3. It may be 
necessary for the pharmacovigilance team to directly communicate with the investigator if 
additional information is required. 
After the initial SAE report, the investigator is required to proactively follow each subject and 
provide further information to the pharmacovigilance team on the subject’s condition within 
24 hours. New or updated information will be recorded on the SAE reporting form. The updated 
SAE reporting form should be sent to the pharmacovigilance team within 24 hours. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 40 of 67 
All additional follow-up evaluations must be reported to the pharmacovigilance team. Such data 
should be sent by email (Figure 3) within 10 calendar days. All SAEs will be followed until the 
investigator and Sponsor agree that the event is satisfactorily resolved. 
Figure 3 Reporting Information for SAEs and Pregnancies 
To report initial or follow up SAE or Pregnancy information email a copy of the SAE or 
Pregnancy report form to the following: 
Safety 
Email: safety@aurionbiotech.com 
Phone:  +1.857.639.4165 
 
9.6 
Death 
The death must be recorded on the appropriate eCRF. All causes of death must be reported as 
SAEs. The investigator should make every effort to obtain and send death certificates and 
autopsy reports to the pharmacovigilance team. 
9.7 
Evaluating AEs and SAEs 
9.7.1 
Severity 
The following definitions should be considered when evaluating the severity of AEs and SAEs. 
Mild 
Event is noticeable to the subject, but is easily tolerated and does not interfere 
with the subject’s daily activities 
Moderate 
Event is bothersome, possibly requiring additional therapy, and may interfere 
with the subject’s daily activities 
Severe 
Event is intolerable, necessitates additional therapy or alteration of therapy, and 
interferes with the subject’s daily activities. 
 
For AEs that change in intensity, the start and stop date of each intensity should be recorded.   
An AE that is assessed as severe should not be confused with a SAE. An event is defined as 
‘serious’ when it meets one of the pre-defined outcomes as described in Section 9.2 Definition of 
a SAE. 
9.7.2 
Relationship to Investigational Product or Procedure 
The following definitions should be considered when evaluating the relationship of AEs and 
SAEs to the study product or procedure:  

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 41 of 67 
Definitely Related 
Event with plausible time relationship to product/procedure  
Cannot be explained by disease or other drugs 
Event definitive pharmacologically or phenomenologically  
(i.e., an objective and specific medical disorder or a recognized 
pharmacologic phenomenon) 
Probably Related 
Event with reasonable time relationship to product 
administration/procedure  
Unlikely to be attributed to disease or other drugs 
Possibly Related 
Event with reasonable time relationship to product 
administration/procedure 
Could also be explained by disease or other drugs 
Not Related 
Event or laboratory test abnormality, with a time to drug intake that 
makes a relationship improbable (but not impossible) 
Disease or other drugs provide plausible explanation 
 
9.7.3 
Expectedness of Events 
Expectedness of all AEs will be determined according to the Investigator’s Brochure.  
9.8 
Procedures for Handling Special Situations 
9.8.1 
Pregnancy 
Females should not become pregnant during the study period. If this occurs the subject should 
notify the investigator immediately. The investigator must report the pregnancy as outlined in 
Section 9.5. In addition, the investigator or study site staff must report the outcome of the 
pregnancy to the pharmacovigilance team. 
9.8.2 
Unmasking for Medical Emergencies 
The need to unmask is not expected for this trial. If a need for unmasking arises, the treatment 
assignment may be unmasked and made available to the investigator, sponsor, and/or other study 
personnel involved in the conduct of the study, according to Unmasking Procedure (or other 
documents as applicable). In the absence of medical need, the treatment assignment will not be 
available to the above individuals until after the study is completed and the database is locked.  
In the event of a medical need, the investigator will treat each subject, as medically required. 
If the investigator feels it is necessary to unmask a subject’s treatment assignment after an 
emergency situation, the investigator may call the Medical Monitor and notify the Sponsor. 
The treatment assignment will be revealed on a subject-by-subject basis with the approval of the 
Medical Monitor and Sponsor, leaving the masking of the remaining subjects intact. The Sponsor 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 42 of 67 
will make the final determination if the unmasking request will be granted. Once the unmasking 
request is granted the investigator will be provided with the treatment assignment. The 
investigator must also indicate in source documents and in the eCRF that the mask was broken 
and provide the date, time, and reason for breaking the mask. Any AE or SAE associated with 
breaking the mask must be recorded and reported as specified in this protocol. 
9.8.3 
Regulatory Reporting 
Suspected Unexpected Serious Adverse Reactions (SUSARs) are SAEs that are unexpected and 
judged by the investigator or the Sponsor to be associated to the study treatment administered. 
The Sponsor will report SUSARs to the appropriate authorities within the required regulatory 
timeframes. Reports of SUSARs will be made to IRBs, and investigators, as needed. 
10 
STATISTICAL METHODS AND DATA ANALYSIS 
10.1 
Study Reporting 
There will be two reporting events for this study, one reporting when all subjects complete 
Month 6 visit and another reporting when all subjects complete the study. For the first reporting, 
when all subjects complete the Month 6 visit, data will be cleaned and locked at the subject visit 
level. The study will be unmasked for the 6 months efficacy and safety analyses. For the second 
data reporting, when all subjects complete the entire study, data will be cleaned, and the database 
will be locked. 
10.2 
Statistical Methods 
Summaries for continuous variables will include the sample size, mean, standard deviation, 
median, minimum and maximum. Summaries for discrete variables will include frequencies and 
percentages. The baseline visit will be defined as the last non-missing measure prior to initiation 
of investigational treatment.  
10.3 
Unit of Analysis 
The unit of analysis in this study will be the study eye for all efficacy and ocular safety 
summaries. Additionally, non-ocular adverse events (AEs) and medical history will be presented 
at the subject level. 
The non-study eye safety summaries will also be presented as appropriate.  
10.4 
Sample Size Determination 
This study is not powered to show statistical significance but will provide initial estimates and 
trends of the endpoints for use in future trial designs. The sample size will allow for safety 
information to be obtained, while still limiting the number of subjects exposed to the IP. 
Statistical analyses will be descriptive. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 43 of 67 
10.5 
Analysis Sets 
The Full Analysis Set (FAS) will be defined as all eligible subjects who received any amount of 
study drug during intracameral injection. All subjects in FAS will be analyzed according to the 
treatment they actually received. 
Per Protocol Set (PPS) will be defined as all subjects completing the study without major 
protocol deviations.  
The Safety Analysis Set will be the same as FAS. 
10.6 
Statistical Significance 
All statistical testing will be done at the two-sided alpha level of 0.05. As this is a Phase 1/2 
study, no adjustments to alpha will be made for testing of multiple comparisons and multiple 
endpoints. Statistical analyses will be descriptive.  
10.7 
Efficacy Analyses 
For the primary endpoint and other binary endpoints, number and percentage of subjects, with 
associated 2-sided exact (Clopper-Pearson) 95% confidence intervals (CIs), will be presented by 
treatment in each category (response, non-response). The distribution of responders will be 
compared between treatment arms using a two-sided Fisher’s exact test.  
Analyses of change from baseline in BCVA, CCT and 
 will be conducted using the full 
analysis set and a restricted maximum likelihood based mixed-effect model for repeated 
measures to evaluate the effect over time.  The dependent variable will be the change from 
baseline.  The model will include treatment arm, categorical time, treatment arm by time 
interaction, and baseline value as a covariate. 
10.8 
Safety Analyses 
All safety analyses will be conducted on the Safety Analysis Set.  No formal statistical tests of 
treatment difference are planned. 
AEs will be coded using the Medical Dictionary for Regulatory Activities TEAEs (i.e., AEs that 
begin or worsen in severity after initiation of study drug) will be summarized by treatment arm 
and overall, in the study eye. Non-ocular TEAEs will also be summarized.  Additionally, TEAEs 
and serious AEs will be summarized in a similar manner by maximum severity and relationship 
to study drug and the surgical procedure. 
Changes from baseline of quantitative measurements (ophthalmic evaluations, laboratory 
findings) will be summarized by treatment arm and timepoint. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 44 of 67 
11 
STUDY MANAGEMENT AND DATA COLLECTION 
11.1 
Confidentiality 
All trial subject data collected and processed for the purposes of this trial should be maintained 
by the investigator and his/her staff with adequate precautions as to ensure that the 
confidentiality of the data is in accordance with local, state, and federal laws and regulations. 
Monitors, auditors and other authorized representatives of CRO drug safety, the Sponsor, the 
IRB/IEC approving this trial, the FDA, the Department of Health and Human Services, other 
domestic government agencies, and other foreign regulatory agencies will be granted direct 
access to the trial subject’s original medical and trial records for verification of the data and/or 
clinical trial procedures. Access to this information will be permitted to the aforementioned 
individuals to the extent permitted by law. 
A report of the results of this trial may be published or sent to the appropriate health authorities 
in any country in which the IP may ultimately be marketed, but the subject’s identity will not be 
disclosed in these documents. 
11.2 
Source Documents 
Source documents may include a subject’s medical records, hospital charts, clinic charts, the 
investigator’s trial subject files, as well as the results of diagnostic tests such as SD-OCT. The 
investigator’s electronic copy of the eCRFs serves as the investigator’s record of a subject’s trial-
related data. 
11.3 
Case Report Forms 
All subject data will be captured in the subject source documents which will be transcribed to the 
eCRFs. The investigator is responsible for ensuring that trial data is completely and accurately 
recorded on each subject’s eCRF, source documents, and all trial-related materials. All trial data 
should also be attributable, legible, contemporaneous, original, accurate and complete. Recorded 
data should only be corrected in a manner that does not obliterate, destroy, or render illegible the 
previous entry (e.g., by drawing a single line through the incorrect entry and writing the revision 
next to the corrected data). An individual who has corrected a data entry should make clear who 
made the correction and when, by adding to the correction his/her initials as well as the date of 
the correction. 
Data entry of all screened and treated subjects will use software that conforms to 21 CFR Part 11 
requirements and will be performed only by staff that have been trained on the system and have 
access to the system. Minimal data will be entered for screen failure subjects. An audit trail will 
be maintained within the electronic system to capture all changes made within the eCRF 
database. After the end of the trial and database lock, compact discs (CDs) or similar media 
containing copies of all applicable subjects’ eCRFs will be provided to each investigator site to 
be maintained on file by the investigator. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 45 of 67 
11.4 
Records Retention 
All trial related correspondence, subject records, consent forms, record of the distribution and 
use of all IP and copies of case report forms should be maintained on file for at least  2 years in 
the US, and 15 years in Canada, after the last approval of a marketing application in an 
ICH region and until there are no pending or contemplated marketing applications in an 
ICH region; or until at least 2 years in the US, and 15 years in Canada, have elapsed since the 
formal discontinuation of clinical development of the IP. These documents will be retained for a 
longer period if required by the applicable regulatory requirements or by an agreement with the 
Sponsor. It is the responsibility of the Sponsor to inform the investigator/institution as to when 
these documents no longer need to be retained. The investigator must notify the Sponsor prior to 
destroying trial documentation even after the above-mentioned time has passed. 
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping trial records, custody must be transferred to a person who will accept 
the responsibility. The Sponsor must be notified in writing of the name and address of the new 
custodian. 
12 
STUDY MONITORING, AUDITING, AND INSPECTING 
12.1 
Study Monitoring Plan 
Each investigator must adhere to the protocol as detailed in this document and agrees that any 
changes to the protocol must be approved by the Sponsor, prior to seeking approval from the 
IRB/Ethics Committee.  Investigators’ proficiency in observing and scoring ophthalmic 
observations will be established and documented via review of academic training and 
experience, prior to examining subjects.  Each investigator will be responsible for enrolling only 
those subjects who have met protocol eligibility criteria. During study conduct, Sponsor and/or 
its representative will conduct periodic monitoring visits to ensure that the protocol and Good 
Clinical Practice (GCP) are being followed. The monitors may review source documents to 
confirm that the data recorded on the electronic case report forms (eCRFs) are accurate.  Further 
details of the trial monitoring (including medical monitoring) will be outlined in a monitoring 
plan. 
The investigator and institution will allow Sponsor, monitors or its representatives and 
appropriate regulatory authorities direct access to source documents and CRFs to perform this 
verification. Data Managers will also review data and may interact with site personnel for 
clarifications. 
It is important that the investigator(s) and their relevant personnel are available during the 
monitoring visits and possible audits or inspections and that sufficient time is devoted to the 
process. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 46 of 67 
13 
ETHICAL CONSIDERATIONS 
This study will be conducted according to the standards of International Council on 
Harmonization, Good Clinical Practice Guideline, Research Ethics Committee regulations, any 
applicable government regulations, Trust and Research Office policies and procedures.  
This protocol, the ICF, relevant supporting information, and all types of subject recruitment or 
advertisement information must be submitted to the IRB/Ethics Committee for review and must 
be approved before the study is initiated. Any amendments to the protocol must also be approved 
by the IRB/Ethics Committee prior to implementing changes in the study. The investigator is 
responsible for keeping the IRB/Ethics Committee apprised of the progress of the study, any 
SAEs, and any changes made to the protocol according to the requirements of the site’s IRB.  
 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
Page 47 of 67 
14 
REFERENCES 
1.  
2019 Eye Banking Statistical Report. 2019. 
2.  
Feizi S. Corneal endothelial cell dysfunction: etiologies and management. Ther Adv 
Ophthalmol. 2018;10. doi:10.1177/2515841418815802 
3.  
Hassan SS, Wilhelmus KR, Dahl P, et al. Infectious Disease Risk Factors of Corneal 
Graft Donors. Arch Ophthalmol. 2008;126(2):235-239. 
doi:10.1001/archophthalmol.2007.45 
4.  
Ho Wang Yin G, Hoffart L. Post-keratoplasty astigmatism management by relaxing 
incisions: a systematic review. Eye Vis (Lond). 2017;4(1). doi:10.1186/s40662-017-0093-
7 
5.  
Almeida HG, Kara-José N, Hida RY, Kara-Junior N. A 15-Year Review of Corneal 
Transplant in Brazil. Eye Contact Lens. 2018;44(2):S376-S381. 
doi:10.1097/ICL.0000000000000554 
6.  
Hara H, Cooper DKC. Xenotransplantation-The Future of Corneal Transplantation? 
Cornea. 2011;30(4):371-378. doi:10.1097/ICO.0b013e3181f237ef 
7.  
Jeng, Ahmad. In Pursuit of the Elimination of Corneal Blindness: Is Establishing Eye 
Banks and Training Surgeons Enough? Ophthalmology. 2021;128(6):813-815. 
doi:10.1016/j.ophtha.2020.06.042 
8.  
Kim, Hara. Current status of corneal xenotransplantation. International Journal of 
Surgery. 2015;23:255-260. doi:10.1016/j.ijsu.2015.07.685 
9.  
Lamm V, Hara H, Mammen A, Dhaliwal D, Cooper DKC. Corneal blindness and 
xenotransplantation. Xenotransplantation. 2014;21(2):99-114. doi:10.1111/xen.12082 
10.  
Lee A, Ni MY, Luk ACK, et al. Trends and Determinants of Familial Consent for 
Corneal Donation in Chinese. Cornea. 2017;36(3):295-299. 
doi:10.1097/ICO.0000000000001091 
11.  
Wong KH, Kam KW, Chen LJ, Young AL. Corneal blindness and current major 
treatment concern-graft scarcity. Int J Ophthalmol. 2017;10(7):1154-1162. 
doi:10.18240/ijo.2017.07.21 
12.  
York NJ, Tinley C. Corneal donations in South Africa: A 15-year review. S Afr Med J. 
2017;107(8):697-701. doi:10.7196/SAMJ.2017.v107i8.12482 
13.  
Gain P, Jullienne R, He Z, et al. Global Survey of Corneal Transplantation and Eye 
Banking. JAMA Ophthalmology. 2016;134(2):167-173. 
doi:10.1001/jamaophthalmol.2015.4776 
14.  
Yoon, Choi, Kim. Corneal xenotransplantation: Where are we standing? Prog Retin Eye 
Res. 2021;80. doi:10.1016/j.preteyeres.2020.100876 
15.  
Ding V, Chin A, Peh G, Mehta JS, Choo A. Generation of novel monoclonal antibodies 
for the enrichment and characterization of human corneal endothelial cells (hCENC) 
necessary for the treatment of corneal endothelial blindness. MAbs. 2014;6(6):1439-1452. 
doi:10.4161/mabs.36249 
16.  
Numa, Imai, Ueno, et al. Five-Year Follow-up of First 11 Patients Undergoing Injection 
of Cultured Corneal Endothelial Cells for Corneal Endothelial Failure. Ophthalmology. 
2021;128(4):504-514. doi:10.1016/j.ophtha.2020.09.002 
17.  
Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD. Development of the 
25-Item National Eye Institute Visual Function Questionnaire. Arch Ophthalmol. 
2001;119(7):1050-1058. doi:10.1001/archopht.119.7.1050 
 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
 
ABA-1 Study 
23-Sep-2024 
 
Confidential 
 
Page 48 of 67 
Appendix 1 Schedule of Assessments 
Study Period 
Screening 
 Visit 
Observation Period 
Day 1/  
Procedure 
Day 2 
Week 1  
Week 4 
 Month 2 
(optional) 
Month 3  
Month 4.5 
Month 6 
Month 9 
 Month 12 
/  
Study Exit 
Un-
scheduled 
Visit 
Visit Number 
1 
2 
3 
4 
5 
5.1 
6 
7 
8 
9 
10 
 
Study Day (D) or Week (W)/ 
Visit Window  
-77 to  
-7 
D1 
D2  
(+2d) 
D8  
(+2d) 
D30 
(±7d) 
D60 
(±7d) 
D90  
(±7d) 
D135 
(±14d) 
D180 
(±14d) 
D270  
(±14d) 
D360 
(±14d) 
N/A 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical/Surgical History 
X 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Review 
X 
 
 
 
 
 
 
 
 
 
 
 
Cohort Assignment 
X 
 
 
 
 
 
 
 
 
 
 
 
Surgery/Study Treatment 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Ophthalmic Assessments (To be Conducted in Both Eyes)  
UCVA a 
X 
 
X 
X 
X 
X 
X 
 
X 
 
X 
(x) 
BCVA (ETDRS) by MR (through 
phoropter) a 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
(x) 
SD-OCT (Macula) 
X 
 
 
 
 
 
X 
 
X 
 
X 
(x) 
CCT by Ultrasonic Contact Pachymetry 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
(x) 
Slit Lamp Biomicroscopy 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
(x) 
Slit Lamp Photography 
X 
 
 
 
X 
X 
X 
 
X 
X 
X 
(x) 
Goldmann Tonometry (IOP) 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
(x) 
Gonioscopy 
X 
 
 
 
 
 
X 
 
X 
 
X 
(x) 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
 
 
 
ABA-1 Study 
023-Sep-2024 
 
Confidential 
 
Page 49 of 67 
Study Period 
Screening 
 Visit 
Observation Period 
Day 1/  
Procedure 
Day 2 
Week 1  
Week 4 
 Month 2 
(optional) 
Month 3  
Month 4.5 
Month 6 
Month 9 
 Month 12 
/  
Study Exit 
Un-
scheduled 
Visit 
Visit Number 
1 
2 
3 
4 
5 
5.1 
6 
7 
8 
9 
10 
 
Study Day (D) or Week (W)/ 
Visit Window  
-77 to  
-7 
D1 
D2  
(+2d) 
D8  
(+2d) 
D30 
(±7d) 
D60 
(±7d) 
D90  
(±7d) 
D135 
(±14d) 
D180 
(±14d) 
D270  
(±14d) 
D360 
(±14d) 
N/A 
Dilated Fundus Examination 
X 
 
 
 
 
 
X 
 
X 
 
X 
(x) 
Other Assessments 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior/Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory blood draw (hematology, 
chemistry) 
X 
 
 
 
 
 
 
 
X 
 
X 
 
Urine Pregnancyb 
X 
X------------------------------------------------------------------------------------------X 
(x) 
; BCVA = best-corrected visual acuity; ETDRS = Early Treatment of Diabetic Retinopathy Study; MR = manifest refraction; IOP = intraocular 
pressure; N/A = not applicable;; PRO = patient reported outcome; SD-OCT = spectral domain-optical coherence tomography; (x) = optional (at the discretion of the investigator); 
UCVA = uncorrected visual acuity; VA = visual acuity; 
 
 
 
 b. For women of childbearing potential, a urine pregnancy test is to be conducted at the Screening Visit. Thereafter, if the subject misses 2 consecutive menstrual 
cycles, a urine pregnancy test is to be conducted and followed by a serum pregnancy test if the urine test is positive.  
 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
 
 
Page 50 of 67 
Appendix 2 Best Corrected Visual Acuity 
Please refer to the Phoropter Refraction and Best-Corrected Visual Acuity (BCVA) Procedure 
Manual. 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
 
 
Page 51 of 67 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
 
 
Page 52 of 67 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
 
 
Page 53 of 67 
Appendix 5 Intraocular Pressure (IOP) 
Please measure IOP with a properly sterilized Goldmann Applanation Tonometer.  
1. The patient should be seated comfortably at the Slit Lamp. 
2. The instrument should be calibrated by adjusting the height of the tonometer probe before 
initiating measurement. 
3. The patient’s eye is topically anesthetized.  
4. The patient is asked to fixate on a target while the tonometer probe is gently placed on the 
cornea. 
5. Operator reads the IOP value displayed on the tonometer scale. If necessary, the 
measurement can be repeated to obtain an average IOP value. 
Note: Assessment of IOP by means other than Goldmann tonometry (e. g, air puff tonometer or 
tonopen) is acceptable in any event where the assessor is unable to capture an accurate measure 
via Goldmann applanation tonometry (i.e., poor visibility of semicircles or subject mobility 
issues). 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
 
 
Page 55 of 67 
Appendix 7 Ultrasonic/Contact Corneal Pachymetry 
The ultrasonic pachymeter is based on traditional A-scan ultrasonography. 
Before turning on the pachymeter, use a sterile alcohol prep pad to clean and sterilize the 
pachymeter probe. Let the probe tip completely air dry prior to use to avoid a chemical corneal 
abrasion from the residual alcohol. Calibrate the pachymeter, following the manufacturer 
instructions, before measurement.  
Anesthetize both eyes. Instruct the subject to gaze straight ahead. Gently touch the central cornea 
with the probe tip, applying as little pressure as possible and keeping the probe perpendicular 
to the cornea during measurement to avoid errors. When the measurement is obtained, the probe 
should be withdrawn from the cornea and reapplied in the same manner for subsequent 
measurements.  
Take a minimum of three measurements for each eye and record them. All three measurements 
should be consistent and in proximity of one another. Values are recorded in microns.  
Note: If an outlier measurement is obtained, which deviates from the overall average of the other 
consistent values, it is important to repeat the measurement two to three times to confirm the value. 
Repeated measurements must be consistent in order to be considered a valid result. (Potential 
sources of error in measuring corneal thickness include holding the probe at an oblique angle to 
the cornea and measuring away from the central corneal apex, both of which would result in 
elevated readings of central corneal thickness (because corneal thickness increases from the center 
to the periphery). 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
 
 
Page 56 of 67 

AURN001 
Aurion Biotech, Inc. 
Version 6.0 
ABA-1 Study 
23-Sep-2024 
 
 
Confidential 
 
 
 
 
 
Page 57 of 67 
© R 1996 
 

Version 2000 
© R 1996 
 
 

Version 2000 
© R 1996 
 
 
 

- 2 - 
Version 2000 
© R 1996 
 
 

- 3 - 
Version 2000 
© R 1996 
 
 

- 4 - 
Version 2000 
© R 1996 
 
 
 

- 5 - 
Version 2000 
© R 1996 
 
 

- 6 - 
Version 2000 
© R 1996 
 
 

- 7 - 
Version 2000 
© R 1996 
 
 

- 8 - 
Version 2000 
© R 1996 
 
 

Version 2000 
- 9 - 
© R 1996