A Multicenter, Open-Labeled, Phase 2a Study Evaluating the Safety, Tolerability, and Efficacy of Intravitreal AG-73305 in Patients With Diabetic Macular Edema
Phase: PHASE2
Conditions: Diabetic Macular Edema
Sponsor: Allgenesis Biotherapeutics Inc.

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A MULTICENTER, OPEN-LABELED, PHASE 2A STUDY EVALUATING 
THE SAFETY, TOLERABILITY, AND EFFICACY OF INTRAVITREAL 
AG-73305 IN PATIENTS WITH DIABETIC MACULAR EDEMA 
 
 
Protocol Number: 
P2-73305-001 
Sponsor: 
Allgenesis Biotherapeutics Inc. 
9F-3, No.760, Sec. 4, Bade Rd., Songshan Dist., Taipei 
City 105, Taiwan (R.O.C.) 
Tel: +886-2-8787-1232 
Fax: +882-2-8787-1239 
Clinical Research Organization: 
Lexitas Pharma Services 
Address: 313 Foster St., Durham, NC 27701 
IND Number: 
152032 
Clinical Phase: 
2a 
Date: 
05 July 2022 
Protocol Version Number: 
4.0 
Version History: 
2.0 submitted to IND; 22 February 2022 
3.0 Amendment 1; 05 July 2022 
4.0 Amendment 2; 27 December 2022 
 
The study will be conducted according to the protocol and in compliance with Good Clinical 
Practice (GCP), with the Declaration of Helsinki and with other applicable regulatory 
requirements. 
This protocol contains confidential, proprietary information of the Sponsor.  Further 
dissemination, distribution or copying of this protocol or its contents is strictly prohibited. 
 
 

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SPONSOR APPROVAL AND SIGNATURE PAGE 
The following individuals approve this protocol V4.0 dated 27 December 2022 
 
 
 
 
Sunil Patel, MD, PhD 
Chief Medical Officer 
Allgenesis Biotherapeutics Inc. 
 
 
Date 
 
 
 
 
 
 
George Magrath, MD 
Medical Monitor 
Lexitas Pharma Services 
 
Date 
 
 
 

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INVESTIGATOR SIGNATURE PAGE 
I agree to: 
a) Implement and conduct this clinical study diligently and in strict compliance with the 
protocol, Good Clinical Practice (GCP), and all applicable laws and regulations. 
b) Maintain all information supplied by Allgenesis Biotherapeutics Inc. and Lexitas Pharma 
Services in confidence and when this information is submitted to an Institutional Review 
Board (IRB), Human Research Ethics Committee (HREC), Independent Ethics 
Committee (IEC), or other review board, it will be submitted with a designation that the 
material is confidential. 
 
I have read this protocol, P2-73305-001, Version 4.0. dated 27 December 2022, in its entirety 
and agree to all aspects. 
 
 
 
 
Signature of Investigator 
 
 
Date 
Investigator Name (print or type) 
 
 
 
 
 
Name of Facility 
 
 
 
 
 
Location of Facility (city, state) 
 
 
 
 
 
 
Please return to Lexitas Pharma Services 
 
 

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STUDY TITLE 
A Multicenter, Open-Labeled, Phase 2a Study Evaluating the Safety, Tolerability, and Efficacy 
of Intravitreal AG-73305 in Patients with Diabetic Macular Edema 
SHORT NAME 
AG-73305 Single Ascending Dose Cohort Study in DME 
PROTOCOL NUMBER 
P2-73305-001 
 
STUDY PERSONNEL 
Allgenesis Biotherapeutics Inc. 
Chief Medical Officer 
Sunil Patel MD, PhD 
sunil.patel@allgenesis.com 
Lexitas Pharma Services 
Medical Monitor 
George Magrath, MD 
George.magrath@lexitas.com 
Trial Statistician 
Richard Zink, PhD 
Richard.zink@lexitas.com 
 
 
Serious Adverse Events Reporting: 
Drug Safety Navigator (DSN) 
2605 Meridian Pkwy, Suite 115 
Durham, NC 27713 
EMAIL ADDRESS FOR SAE QUESTIONS:  
 pvg@drugsafetynavigator.com 
 
 

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TABLE OF CONTENTS 
1 
Protocol Summary ................................................................................................................... 6 
1.1 
Synopsis ........................................................................................................................... 6 
1.2 
Study Schema ................................................................................................................... 9 
1.3 
Schedule of Activities .................................................................................................... 11 
 
Table 1 
Summary of Open-label Cohorts and Dosing ............................................................... 8 
 
Figure 1 
Single Ascending Dose Design in DME Patients ......................................................... 9 
 
Statement of Compliance 
This study is to be conducted in accordance with Institutional Review Board (IRB) regulations 
(United States [US] 21 Code of Federal Regulations [CFR] Part 56.103) or applicable Human 
Research Ethics Committee (HREC), or Independent Ethics Committee (IEC) regulations.  The 
investigator must obtain approval from a properly constituted HREC/IRB/IEC prior to initiating 
the study and re-approval or review at least annually.  Allgenesis is to be notified immediately if 
the responsible HREC/IRB/IEC has been disqualified or if proceedings leading to 
disqualification have begun.  Copies of all HREC/IRB/IEC correspondence with the investigator 
should be provided to Allgenesis. 
The investigator should not implement any deviation from or changes to the protocol without 
approval by Allgenesis and prior review and documented approval/favorable opinion from the 
HREC/IRB/IEC of a protocol amendment, except where necessary to eliminate immediate 
hazards to study patients, or when the changes involve only logistical or administrative aspects 
of the study (e.g., change in monitors, change of telephone numbers). 
 
 

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1 
PROTOCOL SUMMARY 
1.1 
SYNOPSIS 
Title: A Multicenter, Open-Labeled, Phase 2a Study Evaluating the Safety, Tolerability, and 
Efficacy of Intravitreal AG-73305 in Patients with Diabetic Macular Edema. 
Study Objectives: 
 Evaluate the safety, tolerability, duration of effect, systemic pharmacokinetic (PK) and 
immunogenicity profile of ascending doses of AG-73305 administered by intravitreal (IVT) 
injection in patients with diabetic macular edema (DME). 
 Evaluate pharmacodynamic endpoints (e.g., best-corrected visual acuity [BCVA], spectral 
domain optical coherence tomography [SD-OCT] and OCT-angiography [OCT-A]). 
 Determine the maximum tolerated dose or the highest administered dose for evaluation in 
future studies. 
Study Description: This is a multi-centered, open-labeled, single ascending-dose-cohort study 
with a sentinel patient at each dose level.  Cohort management will be overseen by a Safety 
Review Committee (SRC).  The following hypotheses will be evaluated: 
 AG-73305 has an acceptable safety profile, as measured by the incidence and severity of 
adverse events (AEs). 
 At least 1 dose of AG-73305 demonstrates some clinical beneficial effects as measured by 
SD-OCT, BCVA and OCT-A findings. 
Response Measures: 
Safety assessments:   
• Adverse Events (AEs) 
• ETDRS BCVA 
• Intraocular pressure (IOP) 
• Slit lamp biomicroscopy 
• Dilated fundus exam (DFE) 
• Crystalline lens assessment using AREDS scale 
• Post-injection assessment 
• Laboratory evaluation (hematology, serum chemistry and urinalysis) 
• Electrocardiogram (ECG) 
• Vital signs 
• Physical examination 
• Pregnancy test 
 

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Efficacy assessments: 
• Improvements in ETDRS BCVA 
• SD-OCT (Heidelberg Spectralis, dense scan) as measured by Central Reading Center 
(CRC) 
o Central subfield thickness (CST) 
o Ellipsoid zone (EZ)  
o External limiting membrane (ELM) 
o Intraretinal and subretinal fluid 
o Posterior vitreous detachment 
• OCT-A as measured by CRC 
o Foveal avascular zone (FAZ) 
o Foveal capillary density (CD) (superficial and deep capillary plexuses) 
• Diabetic retinopathy severity score (DRSS) assessed via color fundus photography  
• Time to rescue medication 
Pharmacokinetics:  Plasma concentrations of AG-73305. 
Immunogenicity:  Serum levels of anti-AG-73305 antibodies (using binding and neutralizing 
antibody assays, if available). 
Study Population:  Approximately 25, adult male or female patients with center involving DME 
in the study eye will participate in the study, including a sentinel patient in each of 4 dose 
cohorts (see Figure 1). 
Phase:  2a 
Description of Sites:  Approximately 8 sites in the United States will enroll patients. 
Description of Study Treatment:  AG-73305 is a humanized IgG1 Fc-fusion protein that 
targets vascular endothelial growth factors, placental growth factors and integrins.  AG-73305 is 
a clear solution formulated in a 40 mg/mL concentration for intravitreal injection.  Ascending 
doses of a single injection of AG-73305 will be assigned by cohort to 0.5, 1, 2, and 4 mg or until 
the maximally tolerated (or maximum administered) dose has been reached (see Table 1).   
 
Rescue Medication will be standard-of-care anti-vascular endothelial growth factor (VEGF) 
administered by IVT in the study eye. Rescue medication is allowed at the Week 4 visit or later 
in patients meeting any of the following criteria: 
• Loss of > 10 ETDRS letters from a previous best study visit with worsening of 
intraretinal or subretinal fluid observed by SD-OCT and judged by the Investigator to be 
the cause of the BCVA loss. 
• Loss of > 5 ETDRS letters at 2 consecutive visits (one can be unscheduled) from a 
previous best study visit due to worsening of DME. 

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• An increase in CST > 75 μm from a previous best study visit which remains consistently 
> 75 μm from the previous best study in two consecutive visits, as assessed by SD-OCT. 
The later visit can be an unscheduled visit if determined to be necessary by the 
Investigator.  
• An increase in CST > 50 μm from a previous best study visit, as assessed by SD-OCT 
and a loss of > 5 ETDRS letters, which remains consistently > 50 μm and loss > 5 
ETDRS letters from the previous best study in two consecutive visits. The later visit can 
be an unscheduled visit if determined to be necessary by the Investigator. 
• Progression of or worsening of proliferative diabetic retinopathy. 
Patients will be followed for at least 4 weeks after Rescue medication administration or through 
Week 12, whichever is greater. 
Table 1 
Summary of Open-label Cohorts and Dosing  
Dose (mg) 
Stock Vial 
Concentration 
(mg/mL) 
Dilution 
Requirement 
Volume to be 
Injected (mL) 
0.5 
40 
1:1 with diluent 
0.025 
1 
40 
None 
0.025 
2 
40 
None 
0.050 
4 
40 
None 
0.100 
 
Randomization:  none 
Study Duration:  The anticipated study duration is approximately 52 weeks, including 24 weeks 
for recruitment, up to 4 weeks for screening and 24 weeks of follow-up after administration of a 
single intravitreal injection of AG-73305. In certain cases, screening may be increased to 6 
weeks, for a total of 54 weeks for the study duration. 
Patient Duration:  28 weeks participation for patients from Screening to Exit. For patients 
where screening is increased to 6 weeks, then a total of 30 weeks of participation is expected. 
 

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1.2 
STUDY SCHEMA 
Figure 1 
Single Ascending Dose Design in DME Patients 
 
 
 
 

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1.3 
SCHEDULE OF ACTIVITIES 
 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Activity/Assessment 
Screening 
Baselinea 
 
Next Day 
Follow-upb 
Week 1 
Week 4 
Week 8 
Week 12 
Week 16 
Week 20 
Week 24 or 
Early 
Term 
Visit Day ± Window 
Day -30 
to -2c 
Day 1 
Day 2  
Day 8 ± 2 
Day 28± 5 
Day 56± 5 
Day 84± 5 
Day 112 ± 5 Day 140 ± 5 Day 168 ± 5 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion 
Review 
X 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical and Drug History 
X 
 
 
 
 
 
 
 
 
 
Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concurrent Procedures 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Electrocardiogram (ECG) 
(12-lead) 
X 
 
 
 
X 
 
 
 
 
X 
Vital Signs d 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Physical Examination 
X 
 
 
 
 
 
 
 
 
 
Clinical Lab Tests e 
X 
 
 
 
X 
 
X 
 
 
X 
Pregnancy test f 
 
X 
 
 
 
 
 
 
 
X 
BCVA (ETDRS) g 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
IOP h 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
Color Fundus Photos (7- 
field) i 
 
OU 
 
 
SE 
 
 
 
 
OU 
SD-OCT i 
OU 
OU 
 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OCT-A i, j 
 
OU 
 
 
SE 
 
 
 
 
SE 
Biomicroscopy 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
Ophthalmoscopy k 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
OU 
Prednisolone acetate 1% 
Dispense l 
X 
 
 
 
 
 
 
 
 
 
AG-73305 Dosingm 
 
SE 
 
 
 
 
 
 
 
 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Plasma Drug Monitoring n 
 
X 
X 
X 
X 
 
 
 
 
 
Immunogenicity o 
 
X 
 
X 
X 
X 
 
 
 
X 
 
 

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Abbreviations:  BCVA = best-corrected visual acuity; ECG = electrocardiogram; ETDRS = Early Treatment of Diabetic Retinopathy Study; IOP = intraocular pressure; OU 
= both eyes; SD-OCT = spectral domain optical coherence tomography; OCT-A = OCT angiography; SE = study eye 
a. 
Preferably within Monday-Thursday to ensure next day safety assessment and timely collection of 24-hour post dose plasma drug monitoring sample. Any 
Baseline planned on a Friday needs to be pre-approved by Allgenesis 
b. 
Patients who do not provide PK sample may complete the safety follow-up within 1-3 days post dose 
c. 
An additional 14-day extension to the 30-day screening window is allowed, upon approval from Sponsor and Medical Monitor, on a case-by-case basis 
d. 
Blood pressure, heart rate, body temperature, and respiratory rate 
e. 
Blood chemistries, hematology and urinalysis and drugs of abuse screen (Screening only) 
f. 
Urine pregnancy test, females of childbearing potential only 
g. 
BCVA will use the ETDRS method and chart 
h. 
IOP measurement will be performed prior to and after AG-73305 injection at Baseline/Day1. After injection, IOP will be measured within 15 minutes using a 
tono-pen or tono-pen like device.  If IOP >30mmHg, repeat IOP measurement at 15±5 minutes post injection until pressure is reduced 
i. 
Color fundus photos, OCT-A and SD-OCT images will be submitted to a reading center for grading; not required for eligibility 
j. 
OCT-A is to be performed at baseline and at the visit (OU) when Rescue treatment is given. OCT-A is to be performed prior to the rescue treatment 
k. 
Dilated fundus exam 
l. 
Prednisolone acetate 1% ophthalmic suspension will be provided to patients, who will be instructed to prophylactically treat the study eye QID 2 days prior to the 
Baseline visit.  Patients will be instructed to taper based on the Day 2 follow-up visit 
m. Within 15 minutes following intravitreal injection, a post-injection assessment will be done, including checking for count fingers or hand motion vision 
n. 
At selected sites, blood (~10 mL) will be collected for plasma drug monitoring on Day 1 pre-dose (all Cohorts), 1 hour (Cohort 1 and 2 only), 3 hours (all 
Cohorts), 8 hours (all Cohorts) and 24 hours post dose (Cohort 3 and 4 only), Week 1 (all Cohorts), and Week 4 (all Cohorts) in approximately 2-4 patients.  
o. 
~20 mL of blood will be collected on Day 1 pre-dose and Weeks 1, 4, 8 and 24 from all patients for anti-drug antibody assessments. 
Additional examinations and unscheduled visits can be included as safety concerns arise.