A Phase 2, Multicenter, Prospective, Randomized, Double-Masked, Parallel Study of EYP-1901, a Tyrosine Kinase Inhibitor (TKI), Compared to Aflibercept in Subjects With Wet AMD
Phase: PHASE2
Conditions: Wet Age-related Macular Degeneration
Sponsor: EyePoint Pharmaceuticals, Inc.

16.1.1 
Study Protocol 
The latest version of the protocol used during the study is provided in this section.  
Previous versions of the protocol are available on request. 
Protocol EYP-1901-201 Version 6.0 dated 25-January-2024 
17-Dec-2024
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Page 1 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
25 Jan 2024 
CONFIDENTIAL 
Page 1 of 69
EYP-1901 
(VOROLANIB INTRAVITREAL INSERT) 
PROTOCOL EYP-1901-201 / NCT05381948   
A Phase 2, Multicenter, Prospective, Randomized, Double-Masked, 
Parallel Study of EYP-1901, a Tyrosine Kinase Inhibitor (TKI), 
Compared to Aflibercept in Subjects with Wet AMD 
IND Number 
146448 
Sponsor: 
EyePoint Pharmaceuticals, Inc. 
480 Pleasant Street 
Watertown, MA 02472 USA 
Version: 
Version 6.0 
25 Jan 2024 
Version 5.0 
 
21 Dec 2022 
Version 4.0 
 
05 Oct 2022 
Version 3.0  
  29 Apr 2022 
Version 2.1: 
 
20 Apr 2022 
Version 2.0: 
 
12 Apr 2022 
Original Protocol: 28 Jan 2022 
Confidentiality Statement 
This document contains confidential information, which should not be copied, referred to, released, or 
published without written approval from EyePoint Pharmaceuticals, Inc.  Investigators are cautioned that 
the information given in this study protocol might be subject to change and revision.  Any conclusion 
regarding efficacy and safety must be considered provisional. 
17-Dec-2024
This document is confidential.
Page 2 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
Page 3 of 69
 
 
 
INVESTIGATOR’S AGREEMENT 
I have read the attached protocol, concur that it contains all information necessary to conduct the 
study, and agree to follow the study procedures as outlined in this protocol. 
I agree to comply with United States (US) Food and Drug Administration (FDA) regulations 
(21 CFR Parts 50, 54, 56 and 312) and International Conference on Harmonization (ICH) 
guidelines.  I will not initiate the study until I have obtained written approval by the appropriate 
Institutional Review Board/Ethics Committee and have complied with all financial and 
administrative requirements of the governing body of the clinical institution.  I will obtain 
written informed consent from all study participants prior to performing any screening 
procedures. 
This protocol and related information is subject to the Confidentiality Agreement between myself 
and EyePoint Pharmaceuticals, Inc. and as such must be held in confidence and not disclosed to 
any third party for a period of seven (7) years from the date of the Confidentiality Agreement, or 
until said information shall become a matter of public knowledge, or until a formal written 
agreement for that purpose has been entered into by the parties. 
 
 
 
 
 
 
 
Principal Investigator Signature 
 
Date 
Print Name 
 
 
 
 
 
17-Dec-2024
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Page 4 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
Page 5 of 69
 
 
 
SYNOPSIS 
Name of Sponsor/Company: 
EyePoint Pharmaceuticals, Inc. 
Individual Study Table 
Referring to Part 
of the Dossier 
 
Volume: 
 
Page: 
 
 
(for National Authority 
Use only) 
Name of Investigational Product: 
EYP-1901 (Vorolanib intravitreal insert) 
Name of Active Ingredient: 
Vorolanib 
Title of Study:  A Phase 2, Multicenter, Prospective, Randomized, Double-Masked, Parallel Study of 
EYP-1901, a Tyrosine Kinase Inhibitor (TKI), Compared to Aflibercept, in Subjects with Wet AMD 
Protocol Number:  EYP-1901-201 
Phase of Development:  2 
Study Sites:  Approximately 70 sites in the US 
Studied Period:  Up to 56 weeks of follow-up 
Objectives:  To evaluate the efficacy and safety of two doses of the EYP-1901 intravitreal insert in the 
treatment of subjects with neovascular (wet) age-related macular degeneration (wAMD) compared to 
aflibercept. 
Methodology:  A prospective, randomized, double-masked study evaluating ocular efficacy and safety 
of two doses of the EYP-1901 intravitreal insert compared to aflibercept. 
x 
Previously treated subjects with wAMD who meet the study eligibility criteria will be 
randomly assigned to treatment with EYP-1901 2,060 μg, EYP-1901 3,090 μg, or aflibercept 
2 mg (0.05 mL). 
x 
Sham injections will be used for all treatment arms to maintain masking. 
x 
Subjects in the EYP-1901 arms will receive a dose of aflibercept at Day 1 and Week 4; then at 
Week 8 subjects will receive a dose of aflibercept and 30 minutes later the assigned EYP-1901 
dose. Subjects in the aflibercept arm will receive a dose of aflibercept at Day 1 and Week 4; 
then at Week 8 they will receive a dose of aflibercept followed by a sham dose 30 minutes later 
after which they will resume aflibercept dosing at a frequency of every 8 weeks. 
x 
Follow-up examinations will be conducted at Week 12, and every 4 weeks thereafter up to 
Week 56. 
Number of Subjects (planned):  Approximately 50 subjects will be enrolled in each of the 3 treatment 
arms across approximately 70 sites in the US, for a total planned enrollment of 150 subjects. 
Inclusion Criteria: 
1. Male or female subjects, ≥50 years of age. 
2. Documented diagnosis of wAMD in the study eye, with onset of disease that began at any time 
prior to the Screening Visit.  
3. Documented anatomical response (i.e., reduction in fluid on SD-OCT) to previous intravitreal 
anti-vascular endothelial growth factor (anti-VEGF) injections in the study eye prior to the 
Screening Visit. 
4. Previously treated with at least two anti-VEGF intravitreal injections (i.e., bevacizumab, 
ranibizumab, aflibercept, or faricimab) for wAMD per standard of care in the study eye within 
6 months prior to the Screening Visit. 
5. Received previous anti-VEGF therapy 2 to 5 weeks (14 to 35 days) in the study eye prior to the 
Screening Visit, but no more than 42 days prior to randomization to study treatment on Day 1.  
17-Dec-2024
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Page 6 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
Page 6 of 69
 
 
 
6. Best-corrected visual acuity (BCVA) ETDRS letter score of 35 letters (20/200 Snellen 
equivalent) to 85 letters (20/20 Snellen equivalent) in the study eye at Screening Visit and on 
Day 1. 
7. Able to understand, and willingness to sign, the informed consent and to provide access to 
personal health information via Health Insurance Portability and Accountability Act (HIPAA) 
authorization. 
8. Willingness and ability to comply with all scheduled visits, restrictions, and assessments. 
9. For women of childbearing potential, or men with female partners of childbearing potential, 
agreement to the use of an appropriate form of contraception at the Screening Visit and for the 
duration of the study. 
Exclusion Criteria: 
All OCT and FA criteria listed below will be confirmed by the Central Reading Center at the 
Screening Visit. 
1. History of pars plana vitrectomy surgery, submacular surgery, or other surgical intervention for 
AMD in the study eye. 
2. Prior treatment with Visudyne® (verteporfin), external beam radiation therapy, or 
transpupillary thermotherapy in the study eye. 
3. Previous treatment with intravitreal corticosteroid injection or device implantation in the study 
eye. 
4. Previous focal laser photocoagulation used for AMD treatment in the study eye. 
5. Total choroidal neovascularization (CNV) lesion size >12 disc areas (30.5 mm2) as assessed by 
FA in the study eye at Screening Visit. 
6. Central subfield thickness (CST) > 350 μm, in the study eye at Screening Visit or Day 1. 
7. Intraretinal cystic fluid >25 μm in diameter involving the central subfield and/or disruption of 
normal morphology (loss of foveal depression, disruption of external limiting membrane) 
secondary to cystic intraretinal fluid within the central subfield, in the study eye at Screening 
Visit.  Diffuse (non-cystic) intraretinal fluid would not be excluded. 
8. Subretinal hemorrhage in the subfoveal/juxtafoveal location and hemorrhage greater than 
1 disc area (1.8 mm2) if located less than 200 μm from the foveal center in the study eye at 
either Screening Visit or Day 1. 
9. Subfoveal fibrosis, atrophy, or scarring in the center subfield in the study eye at Screening 
Visit. 
10. Fibrosis >50% of the total lesion, in the study eye at Screening Visit. 
11. Retinal pigment epithelium detachment (RPED) thickness >400 μm at any point within 3 mm 
of the foveal center in the study eye at either the Screening Visit or Day 1. 
12. Retinal pigment epithelial tear in the study eye at Screening Visit or Day 1. 
13. Any concurrent intraocular condition in the study eye (e.g., cataract or glaucoma) that, in the 
opinion of the Investigator, would either require surgical intervention during the study to 
prevent or treat visual loss that might result from that condition or affect interpretation of the 
study results. 
14. Historical or active intraocular inflammation (grade trace or above) in the study eye, other than 
expected findings from routine cataract surgery. 
15. History of vitreous hemorrhage in the study eye within 12 weeks prior to the Screening Visit. 
16. History of rhegmatogenous retinal detachment or treatment for retinal detachment or macular 
hole (stage 3 or 4) in the study eye. 
17. Aphakia or pseudophakia with the absence of the posterior capsule in the study eye (YAG 
capsulotomy is permitted). 
17-Dec-2024
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Page 7 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
Page 7 of 69
 
 
 
18. Spherical equivalent of the refractive error in the study eye demonstrating >8 diopters of 
myopia. 
19. For subjects who have undergone prior refractive or cataract surgery in the study eye, 
preoperative refractive error in the study eye exceeding 8 diopters of myopia. 
20. Intraocular surgery (including cataract surgery) in the study eye within 12 weeks prior to the 
Screening Visit. 
21. Uncontrolled ocular hypertension or glaucoma in the study eye (defined as intraocular pressure 
[IOP] >25 mmHg or a cup to disc ratio ≥0.8, despite treatment with 2 or more classes of 
antiglaucoma medication) and any such condition which the Investigator feels may require a 
glaucoma-filtering surgery while in the study. 
22. History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery in the 
study eye. 
23. History of corneal transplant in the study eye. 
24. BCVA using ETDRS charts <30 letters (20/250 Snellen equivalent) in the fellow eye. 
25. Worsening of BCVA ≥10 ETDRS letters in the study eye from Screening Visit to Day 1. 
26. Presence of CNV in either eye due to other causes aside from wAMD, at Screening Visit.  
27. Treatment with Visudyne® in the fellow eye <7 days prior to the Screening Visit. 
28. Prior participation in a clinical trial involving investigational anti-angiogenic drugs 
administered in either eye or systemically within 8 weeks prior to the Screening Visit. 
29. Prior participation in a clinical trial involving investigational ocular gene therapy trial for 
either eye. 
30. History of idiopathic or autoimmune-associated uveitis in either eye. 
31. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye. 
32. Presence of any other systemic or ocular condition which, in the judgment of the investigator, 
could make the subject inappropriate for entry into this study. 
33. Uncontrolled blood pressure (defined as systolic >180 mmHg and/or diastolic >100 mmHg), 
based on the average of three readings taken with the subject in a resting state. 
34. Myocardial infarction within 6 months prior to screening or New York Hospital Association 
(NYHA) Class III or IV heart failure, uncontrolled atrial fibrillation, uncontrolled angina, 
cardiomyopathy, ventricular arrhythmias or other cardiac conditions which, in the judgment of 
the investigator, could make the subject inappropriate for entry into this study. 
35. Serious non-healing wound, ulcer, or bone fracture. 
36. HbA1c greater than 7% at the Screening Visit. 
37. History of other disease, metabolic dysfunction, physical examination finding, or clinical 
laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the 
use of EYP-1901.  
38. Current treatment for any active systemic infection. 
39. Previous use of any systemic anti-VEGF agents or intraocular brolucizumab in the study eye. 
40. Use of oral corticosteroids (prednisone >10 mg/day or equivalent) within 30 days prior to the 
Screening Visit. 
41. History or presence of bleeding disorders, including platelet disorders, hemorrhage, acquired or 
hereditary coagulation disorders (including deep vein thrombosis and pulmonary embolisms), 
acquired or hereditary vascular disorders, stroke, or transient ischemic attack. 
42. Excluding certain skin cancers (specifically, basal cell carcinoma and squamous cell 
carcinoma), any malignancy receiving treatment, or in remission less than 5 years prior to 
study entry. 
43. History of allergy to fluorescein, not amenable to treatment. 
17-Dec-2024
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Page 8 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
Page 8 of 69
 
 
 
44. Inability to obtain fundus photographs, fluorescein angiography (FA), fundus autofluorescence, 
or spectral-domain – optical coherence tomography (SD-OCT) images of sufficient quality to 
be analyzed and graded by the central reading center. 
45. Historical or active diagnosis of any medical or psychological condition that could interfere 
with the ability of the subject to give informed consent, or to comply with study or follow-up 
procedures. 
46. Previous participation in any ocular or non-ocular (systemic) disease studies of investigational 
drugs within 30 days prior to the Screening Visit (excluding vitamins and minerals). 
47. Use of anti-mitotic or anti-metabolite therapy within 30 days or 5 elimination half-lives of the 
Screening Visit, whichever is longer. 
48. Intolerance, contraindication, or hypersensitivity to topical anesthetics, dyes, povidone iodine, 
mydriatic medications, or any of the ingredients of the EYP-1901 insert. 
49. Requirement for continuous use of any protocol-prohibited medications or treatments. 
50. Pregnant or nursing females; females of childbearing potential who are unwilling to use an 
acceptable method of contraception during the study as outlined in this protocol. 
Treatment Assignment:  Subjects will receive intravitreal aflibercept 2 mg (0.05 mL) on Day 1 and at 
Week 4. At Week 8, subjects will receive aflibercept and 30 minutes (+/- 10 minutes) later will receive 
either 2,060 μg or 3,090 μg of the EYP-1901 intravitreal insert (the test article) in the designated study 
eye. 
Control:  Subjects will receive intravitreal aflibercept 2 mg (0.05 mL) dose on Day 1 and at Week 4. 
At Week 8, subjects will receive aflibercept and 30 minutes (+/- 10 minutes) later will receive a sham 
injection, and resume aflibercept dosing at a frequency of every 8 weeks (or when predefined re-
treatment criteria are met) thereafter as the control treatment. 
Duration of Treatment:  Duration of release of the EYP-1901 active ingredient (vorolanib) is 
expected to be at least 9 months. 
Test Article Therapy:  Each EYP-1901 intravitreal, bioerodible insert is 8 mm long and is designed to 
deliver vorolanib into the vitreous humor for at least 9 months.  Multiple inserts will be administered to 
the study eye at Week 8 by injection through the pars plana using a pre-loaded applicator with a 
22-gauge needle as follows: 
x 
2,060 μg dose; 2 inserts, 22-gauge needle 
x 
3,090 μg dose; 3 inserts, 22-gauge needle 
Designation of Study Eye:  For subjects with unilateral wAMD, the affected eye will be designated as 
the study eye; for subjects with bilateral wAMD, the study eye will be the more severely affected eye 
meeting the inclusion/exclusion criteria (i.e., the eye having the worse BCVA or if equal, the eye 
clinically judged to be the more severely affected eye as determined by the Investigator).  If the eyes 
are symmetrically affected, the study eye will be the right eye. 
Study Procedures:  Assessments will include BCVA by Early Treatment Diabetic Retinopathy Study 
(ETDRS), anterior/posterior segment ocular examination, IOP, FA, color fundus photography (CFP), 
SD-OCT,  SD-OCT angiography (SD-OCTA) at pre-specified study sites where equipment is 
available, vital sign measurements, ECG, treatment-emergent ocular and non-ocular adverse events 
(TEAEs), clinical laboratory evaluations (hematology, serum chemistry, coagulation, and urinalysis), 
bioanalytical testing of plasma and aqueous humor vorolanib and its main metabolite levels (see details 
in Table 5–1). During unscheduled visit or if posterior inflammation is present in study eye, CFP and 
OCT of study eye should be collected at a minimum. 
In the event the subject requires vitrectomy during the study, the unmasked investigator or designee 
will collect a vitreous sample and EYP-1901 implants (if applicable) to be sent to the Sponsor as 
described in Appendix 3. 
17-Dec-2024
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Page 9 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
Page 9 of 69
 
 
 
Follow-up Visits:  Following Day 1, follow up examinations will be conducted at Week 4, 8, 12 and 
every 4 weeks thereafter up to Week 56 (see details in Table 5–1). 
Rescue Criteria in the Study Eye: 
Starting from Week 12, aflibercept may be administered in the study eye at the Investigator’s discretion 
if at least one of the following criteria is met: 
x 
BCVA reduction of ≥5 letters from best on study measurement due to wAMD 
  AND 
Increase in CST of ≥75 microns on SD-OCT from lowest on study measurement 
x 
BCVA reduction of ≥10 letters from best on study measurement due to wAMD 
x 
Increase in CST of ≥100 microns on SD-OCT from lowest on study measurement from two 
consecutive visits 
x 
Presence of new or worsening vision-threatening hemorrhage due to wAMD 
If the above rescue criteria are not met, the Investigator may still determine the need for administering 
a rescue medication in the best interest of the subject’s welfare.  In this case the Investigator is required 
to contact the Medical Monitor prior to rescue if feasible. 
Masking:  Except for the investigators administering the study treatments, masking will be maintained 
for both subjects and the investigators conducting the study assessments.  Sham injections will be used 
during the study in all treatment arms to maintain masking of the study treatments.   Only the 
Sponsor/CRO will be unmasked at Week 32 to conduct endpoint analysis. 
Criteria for Evaluation: 
Primary Endpoint:  
x 
Average change in BCVA from Day 1 averaged over Week 28 and Week 32. 
Secondary Endpoints: 
x 
Change from Day 1 in BCVA up to Week 56 
x 
Proportion of subjects with ≥5, ≥10, and ≥15 BCVA letters changes from Day 1 up to Week 56 
x 
Proportion of subjects not receiving a rescue injection of aflibercept in the study eye up to 
Week 56  
x 
Median time to first rescue aflibercept injection in the study eye following the EYP-1901 dose 
at Week 8 
x 
Number of aflibercept injections by Week 56 
x 
Mean change from Day 1 in CST in microns by SD-OCT up to Week 56 
x 
Change from Day 1 in height of subretinal fluid by SD-OCT up to Week 56 
x 
Change from Day 1 in proportion of subjects with no detectable intraretinal fluid/cysts in the 
central subfield up to Week 56 
x 
Change from Day 1 in total lesion area by FA up to Week 56 
x 
Change from Day 1 in total CNV area by FA up to Week 56 
x 
Systemic exposure to EYP-1901 measured through plasma levels up to Week 56 
x 
Ocular exposure to EYP-1901 measured through aqueous levels up to Week 32 
x 
Rates of ocular (study eye and fellow eye) and non-ocular TEAEs up to Week 56 
17-Dec-2024
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
Page 11 of 69
 
 
 
 
Table of Contents 
PROTOCOL APPROVAL PAGE ................................................................................................................. 2 
INVESTIGATOR’S AGREEMENT .............................................................................................................. 3 
PERSONNEL CONTACT INFORMATION ................................................................................................ 4 
SYNOPSIS ...................................................................................................................................................... 5 
TABLE OF CONTENTS ............................................................................................................................. 11 
LIST OF TABLES........................................................................................................................................ 13 
LIST OF ABBREVIATIONS ....................................................................................................................... 14 
1 
INTRODUCTION ............................................................................................................................. 15 
1.1 
BACKGROUND ........................................................................................................................... 15 
1.2 
OVERVIEW OF WAMD ............................................................................................................... 15 
1.3 
STUDY RATIONALE .................................................................................................................... 16 
1.4 
NONCLINICAL EXPERIENCE WITH EYP-1901 .............................................................................. 16 
1.5 
CLINICAL EXPERIENCE WITH EYP-1901 ..................................................................................... 16 
1.6 
CLINICAL EXPERIENCE WITH AFLIBERCEPT ................................................................................ 16 
2 
STUDY OBJECTIVES ...................................................................................................................... 16 
3 
INVESTIGATIONAL PLAN ............................................................................................................ 17 
3.1 
OVERALL STUDY DESIGN .......................................................................................................... 17 
3.1.1 
General Study Methods ............................................................................................. 17 
3.2 
MASKING AND RANDOMIZATION ................................................................................................ 18 
3.3 
DISCUSSION OF STUDY DESIGN, INCLUDING THE CHOICE OF CONTROL GROUPS ........................... 18 
3.4 
DURATION OF STUDY................................................................................................................. 18 
3.5 
RECORDING OF INJECTION PROCEDURE ...................................................................................... 19 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS ..................................................................... 19 
4.1 
INCLUSION CRITERIA ................................................................................................................. 19 
4.2 
EXCLUSION CRITERIA ................................................................................................................ 20 
4.3 
PREGNANCY AND CONTRACEPTION ............................................................................................ 23 
4.4 
STUDY TERMINATION CRITERIA ................................................................................................. 24 
5 
STUDY PROCEDURES .................................................................................................................... 25 
5.1 
MEASUREMENTS AND EVALUATIONS BY VISIT ........................................................................... 26 
5.1.1 
Day -21 to Day -7 (Screening Visit) .......................................................................... 29 
5.1.2 
Day 1 (Randomization and Aflibercept Dosing) ........................................................ 30 
5.1.3 
Week 4 (Aflibercept Dosing) .................................................................................... 31 
5.1.4 
Week 8 (Aflibercept and EYP 1901 Dosing) ............................................................. 31 
5.1.5 
Weeks 12, 28, 36, and 52 (Follow-Up Visits) ............................................................ 32 
5.1.6 
Weeks 16, 24, 32, 40, 48, and Week 56 (Aflibercept or Sham Dosing) ....................... 32 
5.1.7 
Weeks 20 and 44 (Follow-Up Visits)......................................................................... 33 
5.1.8 
Week 56 or Early Termination .................................................................................. 33 
5.2 
APPROPRIATENESS OF MEASUREMENTS ...................................................................................... 34 
6 
STUDY INTERVENTIONS .............................................................................................................. 34 
6.1 
STUDY INTERVENTION IDENTIFICATION AND DESCRIPTION ......................................................... 34 
6.1.1 
EYP-1901 Composition ............................................................................................ 35 
6.1.2 
Aflibercept Composition ........................................................................................... 35 
6.1.3 
EYP-1901/Sham Applicator Packaging ..................................................................... 35 
6.1.4 
Aflibercept Packaging ............................................................................................... 36 
6.2 
STUDY DRUG ADMINISTRATION ................................................................................................. 36 
6.2.1 
EYP-1901 ................................................................................................................. 36 
6.2.2 
Aflibercept ............................................................................................................... 36 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
Page 12 of 69
 
 
 
6.2.3 
EYP-1901 Injection Procedure .................................................................................. 36 
6.2.4 
Aflibercept Injection Procedure ................................................................................. 36 
6.3 
STORAGE AND DISPENSING OF STUDY DRUGS ............................................................................. 36 
6.4 
DRUG ACCOUNTABILITY ............................................................................................................ 37 
6.5 
ANAPHYLAXIS, OVERDOSE, AND DOSE MODIFICATION ............................................................... 37 
6.6 
PRIOR AND CONCOMITANT MEDICATIONS .................................................................................. 38 
6.6.1 
Prior Medications ..................................................................................................... 38 
6.6.2 
Concomitant Medications ......................................................................................... 38 
6.6.3 
Prohibited Concomitant Medications ......................................................................... 38 
6.6.4 
Rescue Treatment ..................................................................................................... 39 
7 
ASSESSMENT OF SAFETY ............................................................................................................ 39 
7.1 
ADVERSE EVENTS ..................................................................................................................... 39 
7.1.1 
Ocular Adverse Events.............................................................................................. 40 
7.1.2 
Serious Adverse Events ............................................................................................ 41 
7.1.3 
Sight-Threatening Ocular Events Defined as SAEs in This Study .............................. 42 
7.1.4 
Clinical Laboratory Adverse Events .......................................................................... 42 
7.1.5 
Adverse Event Severity and Relationship .................................................................. 43 
7.1.6 
Recording of Adverse Events .................................................................................... 44 
7.1.7 
Adverse Event Reporting .......................................................................................... 44 
7.1.7.1 
Reporting of Serious Adverse Events ........................................................ 45 
7.2 
CLINICAL LABORATORY EVALUATIONS ...................................................................................... 47 
7.3 
VITAL SIGNS ............................................................................................................................. 47 
7.4 
ELECTROCARDIOGRAMS ............................................................................................................ 47 
7.5 
CONCOMITANT MEDICATION USE .............................................................................................. 47 
8 
REPORTING OF TECHNICAL PRODUCT COMPLAINTS ........................................................ 48 
9 
PHARMACOKINETICS .................................................................................................................. 48 
10 
ASSESSMENT OF EFFICACY ........................................................................................................ 49 
11 
STATISTICAL METHODS AND DATA ANALYSIS ..................................................................... 49 
11.1 
DETERMINATION OF SAMPLE SIZE .............................................................................................. 49 
11.2 
ANALYSIS POPULATION ............................................................................................................. 49 
11.3 
GENERAL STATISTICAL CONSIDERATIONS .................................................................................. 49 
11.3.1 
Data Summarization ................................................................................................. 49 
11.3.2 
Definition of Baseline ............................................................................................... 50 
11.3.3 
Handling of Missing Data ......................................................................................... 50 
11.3.4 
Multicenter Considerations ....................................................................................... 50 
11.3.5 
Adjustment for Covariates ........................................................................................ 50 
11.3.6 
Interim Analyses ....................................................................................................... 50 
11.3.7 
Multiple Comparisons and Multiplicity ..................................................................... 50 
11.3.8 
Examination of Subgroups ........................................................................................ 50 
11.3.9 
Statistical Software ................................................................................................... 50 
11.4 
ANALYSES ................................................................................................................................ 50 
11.4.1 
Subject Disposition ................................................................................................... 50 
11.4.2 
Demographic and Baseline Characteristics ................................................................ 50 
11.4.3 
Medical History ........................................................................................................ 51 
11.4.4 
Efficacy Analysis ...................................................................................................... 51 
11.4.5 
Pharmacokinetic Analysis ......................................................................................... 51 
11.4.6 
Adverse Events ......................................................................................................... 51 
11.4.7 
Clinical Laboratory Evaluations ................................................................................ 51 
11.4.8 
Vital Signs and Electrocardiograms ........................................................................... 51 
11.4.9 
Prior and Concomitant Medications .......................................................................... 52 
11.4.10 
Use of Prohibited Medications .................................................................................. 52 
12 
ADMINISTRATIVE AND REGULATORY CONSIDERATIONS ................................................. 52 
12.1 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................................................... 52 
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EYP-1901-201 
Version 1.0 Final CSR
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Protocol EYP-1901-201 (Version 6.0) 
 
 
 
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12.2 
INSTITUTIONAL REVIEW BOARDS/INDEPENDENT ETHICS COMMITTEE ......................................... 52 
12.3 
INFORMED CONSENT PROCESS ................................................................................................... 53 
12.4 
SOURCE DOCUMENTATION......................................................................................................... 53 
12.5 
ELECTRONIC CASE REPORT FORMS ............................................................................................ 54 
12.6 
RETENTION OF STUDY RECORDS ................................................................................................ 54 
12.7 
MONITORING THE STUDY AND DATA QUALITY ASSURANCE........................................................ 55 
12.8 
DISCONTINUATION OF THE STUDY .............................................................................................. 55 
12.9 
POLICY FOR PUBLICATIONS ........................................................................................................ 55 
13 
ETHICS ............................................................................................................................................. 56 
13.1 
ETHICS REVIEW ......................................................................................................................... 56 
13.2 
ETHICAL CONDUCT OF THE STUDY ............................................................................................. 56 
13.3 
WRITTEN INFORMED CONSENT .................................................................................................. 56 
14 
REFERENCES .................................................................................................................................. 58 
APPENDIX 1: 
MEASUREMENT OF BCVA BY ETDRS ..................................................................... 60 
APPENDIX 2: 
SLIT LAMP BIOMICROSCOPY, OPHTHALMOSCOPY, AND INTRAOCULAR 
PRESSURE ........................................................................................................................................ 61 
APPENDIX 3: 
PHARMACOKINETIC PROCEDURES AND ANALYSIS ......................................... 64 
APPENDIX 4: 
NCI CTCAE V5.0 ........................................................................................................... 65 
APPENDIX 5: 
SUMMARY OF CHANGES ........................................................................................... 66 
 
List of Tables 
Table 1–1: 
Abbreviations and Specialist Terms ........................................................................... 14 
Table 5–1: 
Schedule of Study Procedures and Assessments, Study EYP-1901-201 ....................... 27 
Table 6–1: 
Characteristics of the Two Intravitreal Doses of EYP-1901......................................... 35 
 
 
 
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EYP-1901-201 
Version 1.0 Final CSR
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Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
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List of Abbreviations 
Table 1–1: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
AE 
Adverse event 
AMD 
Age-related macular degeneration 
ATC 
Anatomical Therapeutic Chemical 
BCVA 
Best corrected visual acuity 
CFP 
Color fundus photography 
CFR 
(US) Code of Federal Regulations 
CI 
Confidence interval 
CNV 
Choroidal neovascularization 
CPR 
Cardiopulmonary resuscitation 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CST 
Central subfield retinal thickness 
CTCAE 
(National Cancer Institute’s) Common Toxicity Criteria for Adverse Events 
DME 
Diabetic macular edema 
EC 
Ethics Committee 
eCRF 
Electronic case report form 
ETDRS 
Early Treatment Diabetic Retinopathy Study 
FA 
Fluorescein angiography 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice (guidelines) 
HIPAA 
Health Insurance Portability and Accountability Act 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IND 
Investigational New Drug application 
IOP 
Intraocular pressure 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
NDA 
New Drug Application 
NYHA 
New York Hospital Association 
OTC 
Over-the-counter 
OU 
Both eyes 
PDGF 
Platelet-derived growth factor 
PK 
Pharmacokinetic 
RPED 
Retinal pigment epithelium detachment 
PRN 
As needed 
PT 
Preferred term 
SADR 
Serious adverse drug reaction 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD-OCT 
Spectral-domain – optical coherence tomography 
SD-OCTA 
Spectral-domain – optical coherence tomography angiography 
SE 
Study eye 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SS-OCTA 
Swept-source – optical coherence tomography angiography 
SUSAR 
Suspected, unexpected serious adverse reaction 
TEAE 
Treatment-emergent adverse event 
TKI 
Tyrosine kinase inhibitor 
US/USA 
United States of America 
VEGF 
Vascular endothelial growth factor 
wAMD 
Wet age-related macular degeneration 
WHO 
World Health Organization 
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EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
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EYP-1901 (Vorolanib Intravitreal Insert) 
 
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Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
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1 INTRODUCTION 
1.1 Background 
Vorolanib is a multi-kinase inhibitor of both vascular endothelial growth factor (VEGF) and 
platelet-derived growth factor (PDGF), which is structurally related to other multi-kinase 
inhibitors and is a potent inhibitor of angiogenesis.  This drug was originally developed as an 
oral pharmaceutical formulation to treat patients with pathologic angiogenesis found in certain 
solid tumors, in von Hippel-Lindau disease, and in exudative age-related macular degeneration 
(AMD).  As a small molecule, vorolanib has more recently been developed as an intravitreal 
formulation utilizing Durasert®, a proprietary sustained delivery technology used in FDA 
approved intraocular products indicated for the treatment of posterior segment uveitis.  Examples 
include Retisert® (Bausch & Lomb, Inc., USA) and Yutiq® (Alimera Sciences, USA), and for the 
treatment of diabetic macular edema (DME), such as Iluvien® (Alimera Sciences, USA).  
EYP-1901 intravitreal insert is a bioerodible, sterile, sustained-release drug delivery system 
formulated in Durasert® and designed to release microgram levels of vorolanib into the ocular 
vitreous chamber for the treatment of wet age-related macular degeneration (wAMD). 
1.2 Overview of wAMD 
AMD is one of the most common causes of visual loss, projected to affect nearly 200 million 
people worldwide (Wong et al. 2014).  Late-stage AMD, characterized by macular atrophy 
(known as geographic atrophy) and choroidal neovascularization (CNV), affects nearly 
11 million people (Wong et al. 2014).  Roughly two-thirds of the cases of late-stage AMD 
involve CNV, manifested by the exudation of fluid and blood, often resulting in vision loss and a 
fibrotic scar if untreated.  Intravitreal injections of VEGF inhibitors diminish the extent of 
exudation arising from CNV.  Ranibizumab (Genentech, USA), bevacizumab (Genentech, USA) 
and aflibercept (Regeneron Pharmaceuticals, USA) inhibit multiple isoforms of VEGF-A and are 
used worldwide to treat CNV secondary to AMD. 
The suggestion that VEGF might be driving the CNV and associated edema seen in AMD led to 
a paradigm shift with the success of the first anti-VEGF therapy, pegaptanib sodium (Ferrara 
2009; Yancopoulos 2010).  Monthly intravitreal injections of 0.5 mg ranibizumab, a humanized 
monoclonal antibody fragment that blocks VEGF, not only prevent vision loss in most patients 
but also lead to significant visual gain in approximately one third of patients (Rosenfeld et al. 
2006; Brown et al. 2006).  The risk of rare but serious adverse events resulting from the 
intravitreal procedure, together with the significant burden of making monthly visits to their 
retinal specialist, have led to extensive efforts to decrease injection and monitoring frequency.  
However, fixed quarterly (Regillo et al. 2008; Schmidt-Erfurth et al. 2011) or “as needed” (PRN) 
dosing regimens (Boyer et al. 2009; Singer et al. 2012), without requiring monthly monitoring 
visits, were not effective at maintaining vision. 
Intravitreal aflibercept, a soluble decoy receptor fusion protein, dosed monthly or every 2 months 
after 3 initial monthly doses produced similar efficacy and safety outcomes as monthly 
ranibizumab (Heier et al. 2012).  This study demonstrated that aflibercept was an effective 
treatment for AMD, with the every-2-month regimen offering the potential to reduce the risk 
from monthly intravitreal injections and the burden of monthly monitoring. 
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EYP-1901-201 
Version 1.0 Final CSR
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Protocol EYP-1901-201 (Version 6.0) 
 
 
 
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1.3 Study Rationale 
Despite the introduction of a number of improved anti-VEGF biologic agents in recent years, 
there remains a need for new therapies that will provide equivalent efficacy and anatomic disease 
control while reducing the need for frequent injections and the burden of mandatory monthly 
monitoring visits.  EyePoint Pharmaceuticals, the Sponsor of this study, has developed 
EYP-1901 intravitreal insert, a sustained and controlled delivery formulation of vorolanib over a 
period of at least 9 months as a therapy to address this unmet medical need. 
1.4 Nonclinical Experience with EYP-1901 
X-82, an oral vorolanib formulation, and EYP-1901(Vorolanib intravitreal insert) were 
investigated in nonclinical efficacy models and in safety and pharmacokinetic nonclinical 
models.  For a summary of the nonclinical experience with these drug formulations please refer 
to the current EYP-1901 Investigator’s Brochure (IB). 
1.5 Clinical Experience with EYP-1901 
This is the second clinical investigational study of EYP-1901 (Vorolanib intravitreal insert); a 
previous phase 1 dose escalation trial in patients with wet AMD was initiated in January 2021 
(first patient dosed).  Interim safety and efficacy analyses conducted upon completion of 
Week 24 provided support for initiation of the present Ph 2 study.  For X-82 (oral vorolanib), two 
previous studies were conducted in wAMD (Jackson et al. 2017; Cohen et al. 2020).  For 
additional details on the clinical experience from previous EYP-1901 and X-82 studies please 
refer to the current EYP-1901 IB. 
1.6 Clinical Experience with Aflibercept 
Two randomized clinical trials were conducted to establish the safety and efficacy in 
2412 patients with wAMD (Heier et al. 2012; Schmidt-Erfurth et al. 2014).  FDA approval was 
granted in 2011 for aflibercept under the brand name EYLEA® for the treatment of wAMD. 
Consult the EYLEA® (aflibercept) label for additional information. 
2 STUDY OBJECTIVES 
The primary objective is to evaluate the efficacy of two doses (2,060 μg and 3,090 μg) of the 
EYP-1901 intravitreal insert on visual acuity compared to aflibercept.  The primary endpoint is 
average change in best corrected visual acuity (BCVA) from Day 1 averaged over Week 28 and 
Week 32. 
The secondary objectives are to evaluate the use of rescue treatments in the study eye, the retinal 
functional and anatomical response to treatment, and the safety following treatment with 
EYP-1901 intravitreal insert compared to aflibercept.  The secondary objectives will be assessed 
with the following secondary endpoints: 
x Change from Day 1 in BCVA up to Week 56 
x Proportion of subjects with ≥5, ≥10, and ≥15 BCVA letters changes from Day 1 up to 
Week 56 
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EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
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EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
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x Proportion of subjects not receiving a rescue injection of aflibercept in the study eye up 
to Week 56 
x Median time to first rescue aflibercept injection in the study eye following the EYP-1901 
dose at Week 8 
x Number of aflibercept injections by Week 56 
x Mean change from Day 1 in CST in microns by SD-OCT up to Week 56 
x Change from Day 1 in height of subretinal fluid by SD-OCT up to Week 56 
x Change from Day 1 in proportion of subjects with no detectable intraretinal fluid/cysts in 
the central subfield up to Week 56 
x Change from Day 1 in total lesion area by FA up to Week 56 
x Change from Day 1 in total CNV area by FA up to Week 56 
x Systemic exposure to EYP-1901 measured through plasma levels up to Week 56 
x Ocular exposure to EYP-1901 measured through aqueous levels up to Week 32 
x Rates of ocular (study eye and fellow eye) and non-ocular TEAEs up to Week 56 
3 INVESTIGATIONAL PLAN 
3.1 Overall Study Design 
The design for this study is a prospective, randomized, double-masked, multicenter trial 
comparing two different doses of the EYP-1901 intravitreal insert to aflibercept in 
previously-treated subjects (≥50 years of age) with wAMD.  Up to 150 subjects will be 
randomized on a 1:1:1 basis to the 3 different treatment arms (2,060 μg EYP-1901, 3,090 μg 
EYP-1901, or 2 mg [0.05 mL] aflibercept) across approximately 70 sites, such that each arm will 
include up to 50 subjects.  All subjects, irrespective of treatment arm, will receive a dose of 
aflibercept on Day 1 and Week 4 in the designated study eye.  At Week 8, all subjects will 
receive a third aflibercept injection and subjects in the EYP-1901 treatment arms will receive the 
assigned dose of the EYP 1901 intravitreal insert 30 minutes (+/- 10 minutes) following 
aflibercept injection, which is expected to deliver vorolanib into the vitreous humor for at least 
9 months, while subjects in the aflibercept treatment arm will receive a sham injection 
30 minutes (+/- 10 minutes) later to maintain masking.  Subjects in the aflibercept arm will be 
re-treated with aflibercept at Week 16 and every 8 weeks thereafter, or when pre-defined 
re-treatment criteria are met (see details in Section 6.6.4 Rescue Treatment), while subjects in the 
EYP-1901 treatment arms will receive a sham injection (or aflibercept when the pre-defined 
re-treatment criteria are met) during these visits.  Subjects will be followed for up to 56 weeks 
from the first dosing at the Baseline Visit (Day 1). The primary objective of this study is to 
evaluate the efficacy and safety of one dose, two different concentrations of the EYP-1901 
intravitreal insert in the treatment of subjects with wAMD compared to aflibercept. 
3.1.1 
General Study Methods 
For subjects with unilateral wAMD, the affected eye will be designated as the study eye; for 
subjects with bilateral wAMD, the study eye will be the more severely affected eye meeting the 
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EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
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EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
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inclusion/exclusion criteria (i.e., the eye having the worse BCVA or if equal, the eye clinically 
judged to be the more severely affected eye as determined by the Investigator).  If the eyes are 
symmetrically affected, the study eye will be the right eye. 
Subjects aged 50 years or greater with an active diagnosis of wAMD at screening, BCVA in the 
study eye using ETDRS charts of 35 letters (20/200 Snellen equivalent) to 85 letters (20/20 
Snellen equivalent), and who satisfy all other protocol eligibility criteria up until dosing on Day 
1, will be enrolled and receive the assigned study treatment.   
Monthly follow-up examinations will be conducted through the 56 weeks following dosing on 
Day 1.  The schedule of study procedures and assessments is presented in Table 5–1.  Study 
procedures will include:  BCVA by ETDRS, anterior/posterior segment ocular examination, IOP, 
FA, color fundus photography (CFP), SD-OCT, SD-OCTA at pre-specified study sites where 
equipment is available, vital signs measurements, ECG, ocular and non-ocular TEAEs, clinical 
laboratory evaluations (hematology, serum chemistry, coagulation, and urinalysis), bioanalytical 
testing of plasma and aqueous humor vorolanib and its main metabolite levels.  During an 
unscheduled visit or if posterior inflammation is present in the study eye, CFP and OCT of the 
study eye should be collected at a minimum. 
In the event the subjects require vitrectomy during the study, the unmasked investigator or 
designee will collect a vitreous sample and EYP-1901 implants (if applicable) to be sent to the 
Sponsor as described in Appendix 3. 
3.2 Masking and Randomization 
Except for the investigators administering the study treatments, masking will be maintained for 
both subjects and the investigators conducting the study assessments.  Sham injections will be 
used during the study to maintain masking of the study treatments.  Only the Sponsor /CRO will 
be unmasked at Week 32 to conduct endpoint analysis. 
The randomization code will be generated with a computer program according to the study 
design, the number of subjects and the number of treatments.  The random allocation of each 
treatment to each subject will be done in such a way that the study is balanced.  Randomization 
will occur on Day 1. 
3.3 Discussion of Study Design, Including the Choice of Control Groups 
The prospective, randomized, double-masked study with an active control group is an acceptable 
design for the evaluation of comparative efficacy and safety of the intravitreal products 
EYP-1901 and aflibercept. 
The two doses (2,060 μg or 3,090 μg) chosen for EYP-1901 were based on the safety profile 
through Week 24 in the completed Phase 1 DAVIO study (see details in Section 1.5). 
The 2 mg (0.05 mL) dose chosen for aflibercept was based on the dosage and administration 
recommendations for wAMD provided in the EYLEA® (aflibercept) label. 
3.4 Duration of Study 
Total study participation will be approximately 59 weeks (including the Screening period).  The 
initial Screening Visit is from Days -21 to -7, during which time subjects may be enrolled, and 
then the study treatments/control will be administered starting on Day 1 if the eligibility criteria 
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EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
Page 19 of 69
 
 
 
are still met.  Subjects who require a longer period between initial screening and Day 1 will be 
re-screened prior to entry into the study.  After dosing of study treatments through Week 8, the 
follow-up period will be up to 48 weeks, specifically visits at Week 12 and every 4 weeks 
thereafter.  Sham injections will be given when necessary to maintain masking.  The primary 
efficacy endpoint will be evaluated at Weeks 28 and 32.  Eligible subjects who are enrolled in 
this study will be seen for the scheduled study visits over approximately 14 months depending on 
the time between Day 1 and the final study visit.  Screen failures will be recorded along with the 
reason(s) for not meeting the eligibility criteria.  Study completion is achieved at the Week 56 
visit (End of Study Visit). 
3.5 Recording of Injection Procedure 
The injection procedure of EYP-1901 or aflibercept may be photographed or video-recorded 
according to the site’s standard procedures.  Images and/or video will be provided to the Sponsor 
who may distribute them to other participating sites or other appropriate parties.  
Subject-identifying information must be redacted from all images and video prior to distribution. 
4 SELECTION AND WITHDRAWAL OF SUBJECTS 
Three treatment groups of up to 50 subjects each will be enrolled to assess the efficacy and safety 
of 2,060 μg or 3,090 μg EYP-1901 intravitreal insert compared to aflibercept 2 mg (0.05 mL) 
injections.   
Subjects will be enrolled in the study only if they meet all the following eligibility criteria during 
the Screening period and with confirmed eligibility at treatment randomization on Day 1, with 
the exception of criteria requiring confirmation by central reading center, which will be assessed 
at screening only. The Investigator will exercise medical and scientific judgement in deciding 
whether a laboratory finding, or other assessment should be reassessed within the Screening 
period. Subjects that do not meet all the requirements as outlined in the eligibility criteria (screen 
failures), may be rescreened at the discretion of the Investigator. 
4.1 Inclusion Criteria 
Subjects will be considered eligible for participation in the study if all of the following inclusion 
criteria are satisfied: 
1. Male or female subjects, ≥50 years of age. 
2. Documented diagnosis of wAMD in the study eye, with onset of disease that began at any 
time prior to the Screening Visit. 
3. Documented anatomical response (i.e., reduction in fluid on SD-OCT) to previous 
intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in the study 
eye prior to the Screening Visit. 
4. Previously treated with at least two anti-VEGF intravitreal injections (i.e., bevacizumab, 
ranibizumab, aflibercept, or faricimab) for wAMD per standard of care in the study eye 
within 6 months prior to the Screening Visit. 
5. Received previous anti-VEGF therapy 2 to 5 weeks (14 to 35 days) in the study eye prior 
to Screening Visit, but no more than 42 days prior to randomization to study treatment on 
Day 1. 
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EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
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EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
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6. BCVA ETDRS letter score of 35 letters (20/200 Snellen equivalent) to 85 letters 
(20/20 Snellen equivalent) in the study eye at the Screening Visit and on Day 1. 
7. Able to understand, and willingness to sign, the informed consent and to provide access 
to personal health information via Health Insurance Portability and Accountability Act 
(HIPAA) authorization. 
8. Willingness and ability to comply with all scheduled visits, restrictions, and assessments. 
9. For women of childbearing potential, or men with female partners of childbearing 
potential, agreement to the use of an appropriate form of contraception at the Screening 
Visit and for the duration of the study. 
4.2 Exclusion Criteria 
All OCT and FA criteria listed below will be confirmed by the Central Reading Center at 
the Screening Visit: 
1. History of pars plana vitrectomy surgery, submacular surgery, or other surgical 
intervention for AMD in the study eye. 
2. Prior treatment with Visudyne® (verteporfin), external beam radiation therapy, or 
transpupillary thermotherapy in the study eye. 
3. Previous treatment with intravitreal corticosteroid injection or device implantation in the 
study eye. 
4. Previous focal laser photocoagulation used for AMD treatment in the study eye. 
5. Total CNV lesion size >12 disc areas (30.5 mm2) as assessed by FA in the study eye at the 
Screening Visit. 
6. Central subfield thickness (CST) > 350 μm in the study eye at the Screening Visit or 
Day 1. 
7. Intraretinal cystic fluid >25 μm in diameter involving the central subfield and/or 
disruption of normal morphology (loss of foveal depression, disruption of external 
limiting membrane) secondary to cystic intraretinal fluid within the central subfield, in 
the study eye at Screening Visit.  Diffuse (non-cystic) intraretinal fluid would not be 
excluded. 
8. Subretinal hemorrhage in the subfoveal/juxtafoveal location and hemorrhage greater than 
1 disc are (1.8 mm2) if located less than 200 μm from the foveal center in the study eye at 
either the Screening Visit or Day 1. 
9. Subfoveal fibrosis, atrophy, or scarring in the center subfield in the study eye at the 
Screening Visit 
10. Fibrosis >50% of the total lesion, in the study eye at the Screening Visit. 
11. Retinal pigment epithelium detachment (RPED) thickness >400 μm at any point within 
3 mm of the foveal center in the study eye at either the Screening Visit or Day 1. 
12. Retinal pigment epithelial tear in the study eye at the Screening Visit or Day 1. 
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EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

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Protocol EYP-1901-201 (Version 6.0) 
 
 
 
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CONFIDENTIAL 
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13. Any concurrent intraocular condition in the study eye (e.g., cataract or glaucoma) that, in 
the opinion of the Investigator, would either require surgical intervention during the study 
to prevent or treat visual loss that might result from that condition or affect interpretation 
of the study results. 
14. Historical or active intraocular inflammation (grade trace or above) in the study eye, 
other than expected findings from routine cataract surgery. 
15. History of vitreous hemorrhage in the study eye within 12 weeks prior to the Screening 
Visit. 
16. History of rhegmatogenous retinal detachment or treatment for retinal detachment or 
macular hole (stage 3 or 4) in the study eye. 
17. Aphakia or pseudophakia with the absence of the posterior capsule in the study eye (YAG 
capsulotomy is permitted). 
18. Spherical equivalent of the refractive error in the study eye demonstrating >8 diopters of 
myopia. 
19. For subjects who have undergone prior refractive or cataract surgery in the study eye, 
preoperative refractive error in the study eye exceeding 8 diopters of myopia. 
20. Intraocular surgery (including cataract surgery) in the study eye within 12 weeks prior to 
the Screening Visit. 
21. Uncontrolled ocular hypertension or glaucoma in the study eye (defined as intraocular 
pressure [IOP] >25 mmHg or a cup to disc ratio ≥0.8, despite treatment with 2 or more 
classes of antiglaucoma medication) and any such condition which the Investigator feels 
may require a glaucoma-filtering surgery while in the study. 
22. History of glaucoma-filtering surgery, tube shunts, or microinvasive glaucoma surgery in 
the study eye. 
23. History of corneal transplant in the study eye. 
24. BCVA using ETDRS charts <30 letters (20/250 Snellen equivalent) in the fellow eye. 
25. Worsening of BCVA ≥ 10 ETDRS letters in the study eye from the Screening Visit to 
Day 1. 
26. Presence of CNV in either eye due to other causes aside from wAMD at the Screening 
Visit. 
27. Treatment with Visudyne® in the fellow eye <7 days prior to the Screening Visit. 
28. Prior participation in a clinical trial involving investigational anti-angiogenic drugs 
administered in either eye or systemically within 8 weeks prior to the Screening Visit. 
29. Prior participation in a clinical trial involving investigational ocular gene therapy trial for 
either eye. 
30. History of idiopathic or autoimmune-associated uveitis in either eye. 
31. Active infectious conjunctivitis, keratitis, scleritis, or endophthalmitis in either eye. 
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EYP-1901-201 
Version 1.0 Final CSR
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EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
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32. Presence of any other systemic or ocular condition which, in the judgment of the 
investigator, could make the subject inappropriate for entry into this study. 
33. Uncontrolled blood pressure (defined as systolic >180 mmHg and/or diastolic 
>100 mmHg), based on the average of three readings taken with the subject in a resting 
state. 
34. Myocardial infarction within 6 months prior to screening or New York Hospital 
Association (NYHA) Class III or IV heart failure, uncontrolled atrial fibrillation, 
uncontrolled angina, cardiomyopathy, ventricular arrhythmias or other cardiac conditions 
which, in the judgment of the investigator, could make the subject inappropriate for entry 
into this study. 
35. Serious non-healing wound, ulcer, or bone fracture. 
36. HbA1c greater than 7% at the Screening Visit. 
37. History of other disease, metabolic dysfunction, physical examination finding, or clinical 
laboratory finding giving reasonable suspicion of a disease or condition that 
contraindicates the use of EYP-1901. 
38. Current treatment for any active systemic infection. 
39. Previous use of any systemic anti-VEGF agents or intraocular brolucizumab in the study 
eye. 
40. Use of oral corticosteroids (prednisone >10 mg/day or equivalent) within 30 days prior to 
the Screening Visit. 
41. History or presence of bleeding disorders, including platelet disorders, hemorrhage, 
acquired or hereditary coagulation disorders (including deep vein thrombosis and 
pulmonary embolisms), acquired or hereditary vascular disorders, stroke, or transient 
ischemic attack. 
42. Excluding certain skin cancers (specifically, basal cell carcinoma and squamous cell 
carcinoma), any malignancy receiving treatment, or in remission less than 5 years prior to 
study entry. 
43. History of allergy to fluorescein, not amenable to treatment. 
44. Inability to obtain fundus photographs, FA, fundus autofluorescence, or SD-OCT images 
of sufficient quality to be analyzed and graded by the central reading center. 
45. Historical or active diagnosis of any medical or psychological condition that could 
interfere with the ability of the subject to give informed consent, or to comply with study 
or follow-up procedures. 
46. Previous participation in any ocular or non-ocular (systemic) disease studies of 
investigational drugs within 30 days prior to the Screening Visit (excluding vitamins and 
minerals). 
47. Use of anti-mitotic or anti-metabolite therapy within 30 days or 5 elimination half-lives 
of the Screening Visit, whichever is longer. 
48. Intolerance, contraindication or hypersensitivity to topical anesthetics, dyes, povidone 
iodine, mydriatic medications, or any of the ingredients of the EYP-1901 insert. 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
Page 23 of 69
 
 
 
49. Requirement for continuous use of any protocol-prohibited medications or treatments. 
50. Pregnant or nursing females; females of childbearing potential who are unwilling or 
unable to use an acceptable method of contraception during the study as outlined in this 
protocol. 
4.3 Pregnancy and Contraception 
Women of childbearing potential are advised to use effective method of birth control before the 
initial dose, during treatment, and for at least 3 months after the last intravitreal injection of 
aflibercept. Examples of acceptable, effective methods of birth control are: oral contraceptive pill 
(e.g., Ortho Tri-Cyclen®); injection (e.g., Depo Provera®); implant (e.g., Norplant®); patch 
(e.g., Ortho Evra Patch®); vaginal ring (e.g., NuvaRing®); intrauterine coil (e.g., Mirena® coil); 
intrauterine device (IUD) with or without hormones; or a barrier method (e.g., latex condom, 
diaphragm, or cap) used with an additional form of contraception (i.e., two methods [e.g., 
sponge, spermicide, hormonal contraceptive pill, or injection]).  A female is considered to be of 
childbearing potential UNLESS she is post-menopausal (no menses for two consecutive years) or 
without a uterus and/or both ovaries. 
Before enrolling a woman of childbearing potential, Investigators must review with the subject 
the following: 
x Pregnancy prevention information 
x Risks to unborn child(ren) 
x Risks if currently nursing 
x Any drug interactions with hormonal contraceptives 
x Contraceptives in current use; and 
x Guidelines for the follow-up of a reported pregnancy 
For subjects who become pregnant during the study positive urine pregnancy results will be 
confirmed by a serum pregnancy test.  Based on the anti-VEGF mechanism of action for both 
EYP-1901 and aflibercept the study treatments may pose a risk to human embryofetal 
development. Subjects should continue participation in the study at the discretion of the 
Investigator and only if the potential benefit justifies the potential risk to the fetus. Subjects 
should be instructed to notify the Investigator if it is determined after completion of the study 
that they became pregnant while participating in the study.  However, it is the Investigator’s 
responsibility to pursue the follow-up.  Whenever possible, a pregnancy should be followed to 
term, any premature terminations of pregnancy should be reported, and the status of the mother 
and the child should be reported to the Medical Monitor after delivery. 
Subjects who are not of childbearing potential meeting one or both of the following criteria will 
not be required to be tested for pregnancy or use contraception: 
x Amenorrheic for >2 years without a hysterectomy and bilateral oophorectomy and a FSH 
value in the postmenopausal range upon pre-trial (screening) evaluation. 
x Post-hysterectomy, bilateral oophorectomy, or tubal ligation.  Tubal ligation must be 
confirmed with medical records of the actual procedure. 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
Page 25 of 69
 
 
 
failure to follow instructions, or inability to complete study assessments).  The violation 
necessitated premature termination from the study. 
Other:  The subject was terminated for a reason other than those listed above, such as termination 
of study by the Sponsor or a regulatory authority.  The Investigator must specify the reason. 
5 STUDY PROCEDURES 
To ensure the health of both eyes, observations of both the study eye and non-study (fellow) eye 
should be made as described in the Schedule of Study Procedures and Assessments (Table 5–1; 
all bilateral procedures and assessments are indicated by cells shaded gray in Table 5–1). 
BCVA by ETDRS:  The equipment and procedures necessary for testing BCVA are presented in 
Appendix 1.  Visual acuity is always tested with the subject’s best correction and should be 
measured prior to pupil dilation and slit lamp biomicroscopy examination or any drops or 
ointments are used.  BCVA by ETDRS will be measured at every study visit (Table 5–1).  Visual 
acuity testing in this study is required at a distance of 4 meters, and for subjects with reduced 
vision at 1 meter.  Each site should have at least one certified refractionist available for the use of 
ETDRS charts.  An ETDRS-certified refractionist should perform all protocol refraction and 
BCVA measurements required by the protocol. 
Slit lamp Biomicroscopy:  Anterior chamber evaluation will be conducted using a slit beam of 
1 mm height and 1 mm width with maximum luminance through the highest powered lens using 
the Investigator’s standard slit lamp equipment and procedure.  This procedure will be the same 
for all subjects observed at the Investigator’s site.  Ocular signs assessments, including vitreous 
haze, the presence of anterior chamber cells, and will be scored according to the scales and 
conventions presented in Appendix 2.  Ocular examinations will be done at the study visits noted 
in (Table 5–1). 
Dilated Ophthalmoscopy:  Will be performed according to the Investigator’s preferred 
procedure.  This procedure will be the same for all subjects observed at the Investigator’s site 
(Appendix 2).  Ocular examinations will be done at the study visits noted in (Table 5–1). 
Intraocular Pressure/Tonometry:  IOP will be measured as described in Appendix 2 at the 
study visits noted in (Table 5–1). 
Fluorescein Angiography and Color Fundus Photography:  A study-certified photographer 
will take mydriatic stereoscopic color photographs and a fluorescein angiogram of both eyes 
according to the standardized procedures described in the Study Manual.  Photography must be 
performed after testing visual acuity if these procedures are performed on the same day.  FA/CFP 
will be done at the study visits noted in (Table 5–1). 
SD-OCT and SD-OCTA Assessments:  Spectral-domain – optical coherence tomography 
assessments of both eyes will be taken by a study-certified OCT technician according to the 
standardized procedures described in the Study Manual.  Because the eye must be dilated for 
OCT, it must be performed after testing visual acuity if these procedures are performed on the 
same day.  SD-OCT and SD-OCTA (at pre-specified study sites where equipment is available) 
testing will be done at the study visits noted in (Table 5–1).  Please note that either SD-OCTA or 
swept-source – optical coherence tomography angiography (SS-OCTA) imaging could be 
collected in this study.  Additionally, historical OCT images in original format for the 9 months 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024  
CONFIDENTIAL 
Page 26 of 69
 
 
 
prior to Screening are to be submitted to the central reading center.  In the event that images are 
not available in the original format of capture, PDFs of the OCTs may be submitted. 
Ocular and Non-ocular TEAEs:  Subjects will be queried regarding ocular and nonocular AEs, 
SAEs, and changes in their general health, concomitant medications or concurrent procedures. 
Both elicited and volunteered reports will be recorded. 
5.1 Measurements and Evaluations by Visit 
The schedule of study procedures and assessments by visit is presented in Table 5–1.  Study 
visits should be conducted within ±5 days for all scheduled visits. 
 
 
 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 28 of 69
 
 
 
Footnotes for Table 5-1: 
a. 
Subjects who terminate the study prior to the Week 56 (End of Study) visit should undergo all procedures noted for the Early Termination Visit. 
b. 
Vital signs will include pulse rate, respiratory rate, body temperature, and systolic and diastolic blood pressure (average of 3 readings will be taken in a resting state). 
c. 
Anterior and posterior segments ocular examination. 
d. 
Check central retinal artery perfusion following study injection. 
e. 
At Week 8: measure IOP at 10 (+/- 5) and 60 (+/- 10) minutes following the second intravitreal injection (i.e., EYP-1901 or sham injection).  If IOP measurements at any 
study time points are ≥30 mmHg, two additional measurements should be performed and IOP recorded as a mean of three measurements. 
f. 
Spectral-domain – optical coherence tomography angiography (SD-OCTA) or swept-source – optical coherence tomography angiography (SS-OCTA) imaging to be 
collected at these time points at pre-specified study sites where SD-OCTA equipment is available. 
g. 
Clinical laboratory testing will include hematology, serum chemistry, coagulation, and urinalysis evaluations (refer to the Study Laboratory Manual). 
h. 
Females of childbearing potential only. Positive urine pregnancy results will be confirmed by a serum pregnancy test. 
i. 
Pharmacokinetic analyses of vorolanib and its main metabolite will be performed on blood plasma and aqueous humor (study eye only) samples.  
j. 
Adverse events, ocular and non-ocular, will be collected from the time the informed consent is signed.  However, for safety analysis, only treatment-emergent adverse 
events (TEAEs) will be summarized. 
 
 
 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
_________________________
_____________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 29 of 69
 
 
 
5.1.1 
Day -21 to Day -7 (Screening Visit) 
The following procedures must be completed during the initial Screening Visit (Table 5–1): 
Informed Consent:  Properly executed informed consent (written and verbal) is to be obtained 
prior to completion of any trial related procedures.  A subject may take as long as needed to 
review the informed consent form (ICF) and consider trial participation; they may take the 
document with them and return at a later date (provided the study is still open for enrollment).  
The subject must review, sign and date the document, and receive a copy. 
Inclusion/Exclusion Criteria:  Inclusion/exclusion criteria (Section 4.1 and Section 4.2, 
respectively) will be reviewed to determine the subject's eligibility to participate in the trial with 
the investigator verifying enrollment eligibility. 
Demography, Medical History, and Medication History:  Demography, complete medical history, 
and recent (previous 30 days) medications (Section 6.6.1) are to be recorded.  When available, 
sites will provide pre-study OCT images collected at the time of original diagnosis of wet AMD, 
1 month following the first intravitreal anti-VEGF injection, and those collected during the 
9 months prior to study screening.  Current contact lens use or ocular trauma in the study eye 
must be documented. 
Ocular procedures to be performed with data collected for both eyes: 
x ETDRS BCVA (Appendix 1) 
x IOP (Appendix 2) 
x Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
x CFP 
x FA 
x SD-OCT assessment (both eyes) 
x SD-OCTA assessment (at pre-specified study sites where equipment is available) 
Non-ocular procedures to be performed: 
x Vital sign measurements (Section 7.3) 
x ECG (Section 7.4) 
x Collect blood and urine samples for clinical laboratory evaluations (Section 7.2) 
x Urine pregnancy test 
x Use of concomitant medications (Section 7.5) 
x Adverse events, which will be collected from the time the ICF is signed (Section 7.1) 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 30 of 69
 
 
 
5.1.2 
Day 1 (Randomization and Aflibercept Dosing) 
The following procedures will be completed during the Day 1 visit (Table 5–1). 
Inclusion/exclusion criteria (Section 4.1 and Section 4.2, respectively) will be reviewed again to 
confirm the subject’s eligibility to keep participating in the trial, with the investigator verifying 
eligibility. 
If meeting the eligibility criteria, study subjects will be randomized to study treatments and all 
subjects will receive the first dose of aflibercept (2 mg) in the designated study eye on Day 1.  
Aflibercept will be administered to the study eye of all subjects, irrespective of treatment arm, by 
injection through the pars plana (Section 6.2.2).  Additionally, historical OCT images in original 
format for the 9 months prior to Screening are to be submitted to the central reading center.  In 
the event that images are not available in the original format of capture, PDFs of the OCTs may 
be submitted. 
For subjects with unilateral wAMD, the study eye will be the affected eye; for subjects with 
bilateral wAMD, the study eye will be the more severely affected eye meeting the 
inclusion/exclusion criteria (i.e., the eye having the worse BCVA or if equal, the eye clinically 
judged to be the more severely affected eye by the investigator).  If the eyes are symmetrically 
affected, the study eye will be the right eye. 
Ocular procedures to be performed with data collected for both eyes (unless otherwise specified): 
x ETDRS BCVA (Appendix 1) 
x IOP (Appendix 2) 
x Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
x CFP 
x SD-OCT assessment (study eye only) 
Non-ocular procedures to be performed: 
x Vital sign measurements (Section 7.3) 
x Use of concomitant medications (Section 7.5) 
x Adverse events (Section 7.1) 
Throughout the study, unscheduled visit assessments may be performed as necessary at the 
discretion of the Investigator and following Sponsor approval.  During an unscheduled visit or if 
posterior inflammation is present in study eye, CFP and OCT of the study eye should be 
collected at a minimum. 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 31 of 69
 
 
 
5.1.3 
Week 4 (Aflibercept Dosing) 
All study subjects will receive the second aflibercept dose (2 mg) in the designated study eye on 
Week 4, as described above in Section 5.1.2. 
The following procedures will be completed during the Week 4 visit (Table 5–1). 
Ocular procedures to be performed with data collected for both eyes (unless otherwise specified): 
x ETDRS BCVA (Appendix 1) 
x IOP (Appendix 2) 
x Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
x SD-OCT assessment (study eye only) 
Non-ocular procedures to be performed: 
x Vital sign measurements (Section 7.3) 
x Use of concomitant medications (Section 7.5) 
x Adverse events (Section 7.1) 
5.1.4 
Week 8 (Aflibercept and EYP 1901 Dosing) 
All study subjects will receive the third aflibercept dose (2 mg) in the designated study eye at 
Week 8, as described above and in Section 6.2.2; subjects assigned to EYP-1901 treatment arms 
will then receive the assigned EYP-1901 dose as bioerodible inserts 30 minutes (+/- 10 minutes) 
after receiving aflibercept and subjects in the aflibercept (control) treatment arm will receive a 
sham injection 30 minutes (+/- 10 minutes) later to maintain masking. 
The following procedures will be completed during the Week 8 visit (Table 5–1). 
Ocular procedures to be performed with data collected for both eyes (unless otherwise specified): 
x ETDRS BCVA (Appendix 1) 
x IOP, including post-injection (Appendix 2) 
x Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2); 
check central retinal artery perfusion following study injection 
x CFP 
x SD-OCT assessment (study eye only) 
Non-ocular procedures to be performed: 
x Vital sign measurements (Section 7.3) 
x Collect blood and urine samples for clinical laboratory evaluations (Section 7.2) 
x Collect blood and aqueous humor (study eye only) samples for PK evaluation of the 
systemic and ocular exposure to EYP-1901 (Section 9) 
x Use of concomitant medications (Section 7.5) 
x Adverse events (Section 7.1) 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 32 of 69
 
 
 
5.1.5 
Weeks 12, 28, 36, and 52 (Follow-Up Visits) 
The following procedures will be completed during the Week 12, Week 28, Week 36, and 
Week 52 visits (Table 5–1). 
Ocular procedures to be performed with data collected for both eyes (unless otherwise specified): 
x ETDRS BCVA (Appendix 1) 
x IOP (Appendix 2) 
x Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
x SD-OCT assessment (study eye only) 
Non-ocular procedures to be performed: 
x Vital sign measurements (Section 7.3) 
x Use of concomitant medications (Section 7.5) 
x Adverse events (Section 7.1) 
5.1.6 
Weeks 16, 24, 32, 40, 48, and Week 56 (Aflibercept or Sham Dosing) 
Study subjects assigned to the control group (aflibercept) will receive the subsequent aflibercept 
dose (2 mg) in the designated study eye (as described above in Section 5.1.2 and in 
Section 6.2.2) at a frequency of every 8 weeks after the Week 8 visit, specifically at the Week 16, 
Week 24, Week 32, Week 40, Week 48, and Week 56 visits, or when predefined re-treatment 
criteria are met (Section 6.6.4).  Subjects in the EYP-1901 treatment arms will receive a sham 
injection at these visits to maintain masking (or aflibercept if the pre-defined re-treatment criteria 
are met). 
The End of Study Week 56 visit procedures are described below in Section 5.1.8. 
The following procedures will be completed during the Weeks 16, 24, 32, 40, and 48 visits 
(Table 5–1). 
Ocular procedures to be performed with data collected for both eyes (unless otherwise specified): 
x ETDRS BCVA (Appendix 1) 
x IOP (Appendix 2) 
x Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
x SD-OCT assessment (study eye only; except at Week 32, this will be performed in both 
eyes) 
Non-ocular procedures to be performed: 
x Vital sign measurements (Section 7.3) 
x Use of concomitant medications (Section 7.5) 
x Adverse events (Section 7.1) 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 33 of 69
 
 
 
In addition to the above, the following procedures will be completed during the Week 32 visit 
only: 
x CFP 
x FA 
x SD-OCTA assessment (at pre-specified study sites where equipment is available) 
x Collect blood and urine samples for clinical laboratory evaluations (Section 7.2) 
x Collect blood and aqueous humor (study eye only) samples for PK evaluation of the 
systemic and ocular exposure to EYP-1901 (Section 9).  
5.1.7 
Weeks 20 and 44 (Follow-Up Visits) 
The following procedures will be completed during the Week 20 and Week 44 visits (Table 5–1). 
Ocular procedures to be performed with data collected for both eyes (unless otherwise specified): 
x ETDRS BCVA (Appendix 1) 
x IOP (Appendix 2) 
x Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
x CFP 
x SD-OCT assessment (study eye only) 
Non-ocular procedures to be performed: 
x Vital sign measurements (Section 7.3) 
x Collect blood and urine samples for clinical laboratory evaluations (Section 7.2) 
x Collect blood and aqueous humor (study eye only) samples for PK evaluation of the 
systemic and ocular exposure to EYP-1901 (Section 9). Aqueous humor will only be 
collected at the Week 20 visit. 
x Use of concomitant medications (Section 7.5) 
x Adverse events (Section 7.1) 
5.1.8 
Week 56 or Early Termination 
As noted above in Section 5.1.6, study subjects assigned to the control group (aflibercept) will 
receive their final aflibercept dose (2 mg) in the designated study eye (as described above in 
Section 5.1.2 and in Section 6.2.2) at the Week 56 visit, or when predefined re-treatment criteria 
are met (Section 6.6.4).  Subjects in the EYP-1901 treatment arms will receive the final sham 
injection at the end of study Week 56 visit to maintain masking (or aflibercept if the pre-defined 
re-treatment criteria are met). 
The following procedures will be completed during the End of Study Week 56 visit (Table 5–1).  
Subjects who terminate the study prior to the Week 56 visit should undergo all procedures noted 
for the Early Termination Visit in Table 5–1. 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 34 of 69
 
 
 
Ocular procedures to be performed with data collected for both eyes: 
x ETDRS BCVA (Appendix 1) 
x IOP (Appendix 2) 
x Ocular examination – dilated ophthalmoscopy and slit lamp biomicroscopy (Appendix 2) 
x CFP 
x FA 
x SD-OCT assessment (both eyes) 
x SD-OCTA assessment (at pre-specified study sites where equipment is available) 
Non-ocular procedures to be performed: 
x Vital sign measurements (Section 7.3) 
x ECG (Section 7.4) 
x Collect blood and urine samples for clinical laboratory evaluations (Section 7.2) 
x Urine pregnancy test 
x Collect blood samples for PK evaluation of the systemic exposure to EYP-1901 
(Section 9).  
x Use of concomitant medications (Section 7.5) 
x Adverse events (Section 7.1) 
5.2 Appropriateness of Measurements 
The efficacy and safety assessments to be utilized in this study (e.g., use of concomitant 
medications, BCVA by ETDRS, slit lamp biomicroscopy, dilated ophthalmoscopy, IOP 
measurements, FA/CFP, SD-OCT, SD-OCTA [where equipment is available], collection of ocular 
and non-ocular AEs, clinical laboratory evaluations, vital signs, ECGs) are standard measures in 
studies evaluating intravitreal investigational products like EYP-1901. 
6 STUDY INTERVENTIONS 
6.1 Study Intervention Identification and Description 
EYP-1901 intravitreal insert is a bioerodible, sterile, sustained-release drug delivery system that 
is designed to release microgram levels of vorolanib into the ocular vitreous chamber for the 
treatment of wAMD.  The intravitreal insert formulation design is based on the Durasert® 
technology that allows EYP-1901 to exhibit the following characteristics: 
x Bioerodible properties 
x Sustained-release kinetics 
x Prolonged duration of release (not less than 9 months)  
x High drug loading 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 35 of 69
 
 
 
x Administration in an office setting through an intravitreal needle injection 
EYLEA® is a marketed anti-VEGF solution containing aflibercept used to treat wAMD. 
6.1.1 
EYP-1901 Composition 
EYP-1901 intravitreal insert contains vorolanib as the active ingredient and polyvinyl alcohol as 
an excipient. 
The drug delivery system is placed into a one-time-use siliconized needle attached to an 
applicator delivery system.  The drug product is sterilized after packaging and prior to 
distribution.  In subject, the needle is inserted through the pars plana and the insert is injected 
into the vitreous. 
Two different doses will be administered by delivering multiple inserts at Week 8 (Table 5–1).  
Table 6–1 summarizes the characteristics of the two intravitreal doses of EYP-1901. 
Table 6–1: 
Characteristics of the Two Intravitreal Doses of EYP-1901 
 
Dose (μg) 
Number of Inserts 
per Single 
Applicator 
Needle 
Gauge 
Insert Length 
(mm) 
2,060 
2 
22 
8 
3,090 
3 
22 
8 
 
6.1.2 
Aflibercept Composition 
EYLEA® contains aflibercept as the active ingredient in a clear to pale yellow aqueous solution 
(40 mg/mL aflibercept in 10 mM sodium phosphate, 40 mM sodium chloride, 0.03% polysorbate 
20, and 5% sucrose, pH 6.2) intended for use as a single 2 mg (0.05 mL) dose.  The pre-filled 
syringe contains more than the recommended dose and the excess volume must be ejected prior 
to administration by depressing the plunger to align the plunger dome edge with a pre-marked 
dosing line found on the syringe. 
EYLEA® comes in a sterilized blister pack and is equipped to attach to a 30-gauge injection 
needle (not provided with syringe).  In subject, the needle is inserted through the pars plana and 
the aflibercept solution is discharged into the vitreous.  
6.1.3 
EYP-1901/Sham Applicator Packaging 
EYP-1901 is packaged at EyePoint Pharmaceuticals.  EYP-1901 loaded applicators (or sham 
applicators) are placed inside a foil chevron pouch and sealed.  The sealed foil pouch is then 
placed inside a Tyvek® chevron pouch. The final pouch is sent for terminal sterilization.  Upon 
completion of sterilization, each pouch is labeled with a “Sterile” label, and then placed into a 
labeled box. 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 36 of 69
 
 
 
6.1.4 
Aflibercept Packaging 
EYLEA® (aflibercept) is supplied as a 2 mg/0.05 mL solution in a single-dose pre-filled syringe 
or as a 2 mg/0.05 mL solution in a single-dose vial.  Use of either format for this trial is 
acceptable. 
6.2 Study Drug Administration 
6.2.1 
EYP-1901 
Each EYP-1901 insert has been designed to deliver vorolanib into the vitreous humor for at least 
9 months.  EYP-1901 will be administered to the study eye by a single injection through the pars 
plana using a pre-loaded applicator with a 22-gauge needle. 
6.2.2 
Aflibercept 
Aflibercept will be administered to the study eye by a single injection per standard of care. 
Aflibercept will be administered initially to all subjects by intravitreal injection at a dose of 2 mg 
(0.05 mL) on Day 1 and at Week 4.  At Week 8, all subjects will receive aflibercept and 
30 minutes later will receive either a sham injection or EYP-1901, and if in the control group 
will resume aflibercept dosing at a frequency of once every 8 weeks (or when predefined re-
treatment criteria are met) thereafter as the control treatment. 
6.2.3 
EYP-1901 Injection Procedure 
For a detailed description of the EYP-1901 injection procedure, please refer to the EYP-1901 
Instructions for Use document. 
6.2.4 
Aflibercept Injection Procedure 
The same aseptic technique described above (Section 6.2.3) for EYP-1901 intravitreal 
injection procedure will be applied for the delivery of aflibercept, along with the standard of care 
for cleansing the eye (use of anesthetic, antibiotics, and Betadine£). 
Aflibercept will be administered as detailed in the EYLEA® (aflibercept) label. 
6.3 Storage and Dispensing of Study Drugs 
EYP-1901 must be stored in a secure place and at controlled room temperature (20°C to 
25°C/68°F to 77°F) and in the original container to protect the product from light.  Temperature 
excursions between 15°C to 30°C/59°F to 86°F are acceptable. 
Aflibercept must be stored in a secure place and refrigerated at a controlled temperature (2°C to 
8°C/36°F to 46°F) and in the original carton to protect from light. 
The Investigator has the overall responsibility of ensuring that EYP-1901 and aflibercept are 
stored in a safe location with limited-access under the specified storage conditions.  Limited 
responsibility may be delegated to a pharmacy representative; however, this delegation must be 
documented. 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 37 of 69
 
 
 
6.4 Drug Accountability 
The Investigator is responsible for ensuring adequate accountability of all used and unused 
EYP-1901 and aflibercept.  While the Investigator may delegate components of drug 
accountability tasks to documented designee(s) (e.g., pharmacist or staff designee), the ultimate 
responsibility for drug control and accountability resides with the Investigator.  This includes 
acknowledgment of receipt of each shipment (quantity and condition), maintenance of subject 
dispensing records and returned (as required) documentation.  Dispensing records will document 
quantities received from the Sponsor (or designee) and quantities dispensed to subjects, 
including treatment kit/package number, date dispensed, subject identification number, subject 
initials, and the initials of the person dispensing drug will be recorded on the drug accountability 
log. 
During study initiation, the study monitor (Clinical Research Associate, CRA) will evaluate and 
obtain a copy of each site’s written standard operating procedure for study drug 
disposal/destruction or return to ensure that it complies with Sponsor requirements if supplies 
will not be returned. 
An inspection for inventory and accounting purposes, and the assurance of proper storage, will 
also be conducted during monitoring visits.  Any significant accounting or storage discrepancy 
will be recorded and reported to the Sponsor and a plan for resolution will be documented.  After 
the monitor has checked and verified drug accountability during interim site visits and at the end 
of the study, any expired, partially-used, and used product should be handled according to the 
Sponsor’s instructions (i.e., returned or destroyed). 
6.5 Anaphylaxis, Overdose, and Dose Modification 
Vorolanib and the inactive ingredients of EYP-1901 are not known to cause hypersensitivity 
reactions.  Aflibercept is rarely associated with hypersensitivity, having been previously reported 
in less than 1% of patients. 
Since EYP-1901 and aflibercept are delivered through a pre-loaded applicator or a syringe, 
respectively, the risk of accidental overdose is minimal.  Refer to the current IB or FDA label for 
information on potential risks associated with EYP-1901 or aflibercept.  Dose modification is not 
applicable since EYP-1901 and aflibercept are for single-delivery only. 
Note:  Hypersensitivity reactions to iodine and/or fluorescein used during ocular assessments are 
also possible. 
Signs and symptoms of hypersensitivity include: 
x Localized or generalized itching 
x Facial flushing, generalized flushing 
x Shortness of breath, wheezing 
x Uneasiness and agitation 
x Local edema followed by facial edema 
x Light-headedness/dizziness 
x Chest tightness 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 38 of 69
 
 
 
x Tachycardia 
x Hypotension 
x Rigors (chills) 
If anaphylaxis occurs, the subject should be managed according to standard cardiopulmonary 
resuscitation (CPR) procedures, as necessary.  The subject may require the following treatment: 
x Epinephrine (adrenaline) to reduce the allergic response 
x Oxygen 
x Intravenous antihistamines and cortisone to reduce airways inflammation and improve 
breathing 
x A beta-agonist (such as albuterol) to relieve breathing symptoms 
6.6 Prior and Concomitant Medications 
6.6.1 
Prior Medications 
Prior medications are defined as all prescription, vaccinations, supplements, herbal therapies, any 
prohibited medications, and over-the-counter (OTC) medications taken within the 30 days 
(whether continuing or not) prior to Day 1 with the exception of previous treatments for wAMD, 
both approved and investigational products.  Previous treatments for wAMD are to be captured 
for the following timepoints:  initial treatment upon diagnosis, 1 month after diagnosis, and for 
12 months prior to Screening. 
All prior medications must be documented on the concomitant medications eCRF. 
6.6.2 
Concomitant Medications 
All prescription and OTC concomitant medications used concurrently (from the Screening Visit 
to Week 56 or Early Termination) must be documented on the concomitant medication eCRF. 
Information to be collected on the concomitant medication eCRF includes the name of the 
medication/therapy, dose, frequency, route, dates of use, and indication for use.  Subjects should 
be instructed not to take any medication including OTC products without first consulting with 
the Investigator.  Any AE(s) that result(s) from taking a concomitant medication following the 
first study dose should be recorded on the AE eCRF. 
6.6.3 
Prohibited Concomitant Medications 
Any medications or therapies that the subject is using during the study period and that would 
preclude eligibility as indicated in the Exclusion Criteria (Section 4.2), are prohibited 
concomitant medications.  In addition, any medication or therapies initiated during the study 
period that, in the Investigator’s judgment, could potentially confound the safety and preliminary 
efficacy of EYP-1901 or aflibercept would also be considered prohibited concomitant 
medications. 
All prohibited concomitant medications used concurrently (from Day 1 to Week 56 or Early 
Termination) must be documented on the concomitant medication eCRF. 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 39 of 69
 
 
 
6.6.4 
Rescue Treatment 
Following the intravitreal injections of either dose of the EYP-1901 insert (2,060 μg or 3,090 μg) 
and aflibercept (2 mg) at Week 8, aflibercept may be administered in the study eye at the 
Investigator’s discretion starting from Week 12 if at least one of the following criteria is met: 
x BCVA reduction of ≥5 letters from best on study measurement due to wAMD 
  AND 
Increase in CST of ≥75 microns on SD-OCT from lowest on study measurement 
x BCVA reduction of ≥10 letters from best on study measurement due to wAMD 
x Increase in CST of ≥100 microns on SD-OCT from lowest on study measurement from 
two consecutive visits 
x Presence of new or worsening vision-threatening hemorrhage due to wAMD 
If the above rescue criteria are not met, the Investigator may still determine the need for 
administering a rescue medication in the best interest of the subject’s welfare.  In this case, the 
Investigator is required to contact the Medical Monitor prior to rescue if feasible.  The use of 
rescue medication during the study will be documented on the concomitant medication eCRF.  
Repeat administration following the first rescue intervention may be required if any of the rescue 
criteria are met again at any subsequent study visit.  Subjects receiving rescue medications will 
continue in the study follow-up (Table 5–1). 
Rescue therapy, other than aflibercept, is prohibited.  Should aflibercept be given as rescue 
therapy at a visit that dosing was not scheduled (i.e., between the 8-week intervals of dosing after 
Week 12), the subject will continue with the subsequent dosing at the next scheduled visit, as the 
interval between both doses will be 4 weeks, which is acceptable as per approved dosing 
regimens.  These subjects will then continue with the dosing regimen of every 8 weeks. 
7 ASSESSMENT OF SAFETY 
Safety assessments will include the incidence and severity of TEAEs reported after screening, 
clinical laboratory evaluations (hematology, serum chemistry, coagulation, and urinalysis), safety 
data collected from ocular examinations and IOP measurements, vital sign measurements, ECGs, 
and the use of concomitant medications. 
Medical safety reviews will be conducted by the Sponsor for all TEAEs and other relevant 
information related to safety on an ongoing basis and throughout the duration of the study 
according to the study Safety Management Plan. 
7.1 Adverse Events 
The following are specific definitions of terms guided by the International Council for 
Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH E2), 
Guidelines for Good Clinical Practice (GCP), and the US Code of Federal Regulations (CFR) 
that apply to the following sections.  The severity of AEs will be graded by CTCAE version 5 or 
higher (Appendix 4). 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 40 of 69
 
 
 
Definition of Adverse Event: 
An AE is defined as any new untoward medical occurrence or worsening of a pre-existing 
medical condition in a patient or clinical investigation subject administered an investigational or 
marketed (medicinal) product and that does not necessarily have a causal relationship with the 
product.  An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding, for example), symptom, or disease temporally associated with the use of a 
medicinal product, whether or not considered related to the product. 
AEs may also include pre- or post-treatment complications that occur as a result of 
protocol-specified procedures (e.g., invasive procedures such as venipuncture, delivery 
procedure, etc.).  Pre-existing conditions that increase in severity or change in nature during (or 
as a consequence of use of a medicinal product) the study will also be considered AEs. 
An AE Will Not Include: 
x Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, transfusion) 
for events that led to the procedure 
x Pre-existing diseases, conditions, or laboratory abnormalities present or detected prior to 
the Screening Visit, unless they worsen during the study 
x Situations where an AE or untoward medical occurrence has not occurred (e.g., 
hospitalization for elective surgery, social and/or convenience admissions) 
Associated with the Use of the Drug (Causality): 
There is a reasonable possibility that the event may have been caused by the study medicinal 
product (and/or the administration procedures). 
Unexpected Adverse Event: 
Any event that is not identified in nature, severity, or frequency in the current version of the IB; 
or in the product labeling for marketed products.  For example, if the IB or product labeling 
referred to elevated hepatic enzymes or hepatitis, then an event of hepatic necrosis would be 
considered unexpected by the virtue of the greater severity.  The Sponsor or designee will 
determine AE expectedness. 
7.1.1 
Ocular Adverse Events 
The following ocular events will be considered AEs for the purposes of this study: 
x Decrease in BCVA of ≥15 letters or ≥3 lines from the previous BCVA measurement 
x Moderate or severe (Grade 2 or 3) ocular findings compared to the last ocular 
examination 
x Worsening of >2 steps in anterior chamber cell count or vitreous haze compared to the 
last ocular examination 
x Increase in IOP of >10 mmHg at two visits at least 1 week apart or an increase in IOP to 
>25 mmHg 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 41 of 69
 
 
 
7.1.2 
Serious Adverse Events 
An SAE is any AE that results in one of the following outcomes: 
x Death. 
x Is life-threatening (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 intense). 
x Requires in-patient hospitalization (formal admission to a hospital for medical reasons for 
any length of time), or prolongs existing hospitalization. 
x Results in a persistent or significant disability/incapacity, or substantial disruption of the 
ability to conduct normal life functions. 
x Congenital anomaly/birth defect (in the child of a subject who was exposed to the study 
treatment). 
x Other important medical event.  Medical and scientific judgment should be exercised in 
determining whether an event is an important medical event.  An important medical event 
may not be immediately life-threatening and/or result in death or hospitalization but 
required medical intervention in order to prevent a SAE outcome.  However, if it is 
determined that the event may jeopardize the subject and/or may require intervention to 
prevent one of the other SAE outcomes, the important medical event should be reported 
as serious.  Examples of such events are intensive treatment in an emergency room or at 
home for allergic bronchospasm; blood dyscrasias or convulsions that do not result in 
hospitalization; or development of drug dependency or drug abuse. 
The following hospitalizations will not be considered SAEs: 
x A visit to the emergency room or other hospital department for <24 hours that does not 
result in in-patient admission (unless considered an “important medical event” or a 
“life -threatening event”). 
x Elective surgery or planned surgery prior to signing the ICF. 
x Admissions as per protocol for a planned medical/surgical procedure. 
x Routine health assessments requiring admission for Baseline/trending of health status 
(e.g., routine colonoscopy). 
x Medical/surgical admission for a purpose other than healthcare purposes and was planned 
prior to entry into the study (appropriate documentation is required in these cases). 
x Admission encountered for another life circumstance that carries no bearing on health 
status and/or requires no medical/surgical intervention (e.g., lack of housing, economic 
inadequacy, care-giver respite, family circumstances, administrative). 
x Progressive disease (wAMD) is expected and will not be considered an SAE. 
Clarification of SAEs: 
x Death is an outcome of an AE, and not an AE in itself. 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 42 of 69
 
 
 
x All deaths, regardless of cause or relationship, must be reported. 
x Complications that occur during hospitalizations are AEs.  If a complication prolongs 
hospitalization, it is an SAE. 
x “In-patient hospitalization” means the subject has been formally admitted to a hospital for 
medical reasons for any length of time.  This may or may not be overnight.  It does not 
include presentation to, and/or care within, an emergency department. 
x The Investigator should attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. 
Note:  Progressive disease should be recorded on the AE eCRF.  However, because it is expected 
in the study population, it will not be considered as an SAE. 
7.1.3 
Sight-Threatening Ocular Events Defined as SAEs in This Study 
In addition to the standard SAE categories described above, this study defines these additional 
ocular events as SAEs: 
x An AE that causes a decrease in visual acuity of ≥30 letters or ≥6 lines from the most 
recent previous measurement of visual acuity, lasting more than 1 hour. 
x An AE that causes a decrease in visual acuity to light perception or worse, lasting more 
than 1 hour. 
x An AE that requires surgical intervention (e.g., conventional surgery, vitreous tap or 
biopsy with intravitreal injection of anti-infectives, or laser or retinal cryopexy with gas) 
to prevent permanent loss of sight. 
x An AE that is associated with severe intraocular inflammation (i.e., 4+ anterior chamber 
cell score or 4+ vitreous haze score). 
x Two consecutive IOP measurements of ≥30 mmHg taken at least 72 hours apart when a 
subject is already being treated with two IOP-lowering medications. 
x An IOP <6 mmHg requiring medical intervention. 
x An AE that in the opinion of the investigator requires medical or surgical intervention to 
prevent permanent loss of sight. 
The Investigator must employ all necessary therapeutic measures to resolve the SAE.  Any 
medications or therapies used to treat the SAE must be recorded in the concomitant medication 
eCRF. 
7.1.4 
Clinical Laboratory Adverse Events 
An abnormal laboratory result should be considered an AE if it: 
x Results in the initiation or change of an intervention (e.g., increased dose of medication), 
based on medical evaluation (e.g., packed red cells for low hemoglobin). 
x Results in any out of range laboratory value that in the Investigator’s judgment fulfills the 
definitions of an AE. 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 43 of 69
 
 
 
x Increases in severity compared to baseline. 
Abnormal laboratory values should not be listed as separate AEs if they are considered to be part 
of the clinical syndrome that is being reported as an AE.  Any laboratory abnormality considered 
to constitute an AE should be reported on the AE eCRF.  It is the responsibility of the 
Investigator to review all laboratory findings in all subjects and determine if they constitute an 
AE.  Medical and scientific judgment should be exercised in deciding whether an isolated 
laboratory abnormality should be classified as an AE. 
All laboratory AEs should be repeated and reassessed by the Investigator to track resolution and 
especially to confirm if they meet the definition of serious.  If serious, they will be reported as 
SAEs. 
The Investigator or a licensed designee must review all laboratory results in a timely manner as 
demonstrated by signature/date. 
7.1.5 
Adverse Event Severity and Relationship 
Adverse event severity is defined as a qualitative assessment of the intensity of an AE as 
determined by the Investigator.  The assessment of severity is made irrespective of the 
relationship or seriousness of the event to EYP-1901, aflibercept, or the injection device. 
In the absence of an assigned severity per the CTCAE version 5.0 or higher (Appendix 4) 
grading criteria, the Investigator will grade AEs according to the following severity criteria:  
Mild/Grade 1: 
the event may be noticeable to subject; does not influence daily 
activities; usually does not require intervention. 
Moderate/Grade 2: 
the event may be of sufficient severity to make subject 
uncomfortable; performance of daily activities may be influenced; 
intervention may be needed. 
Severe/Grade 3: 
the event may cause severe discomfort; usually interferes with daily 
activities; subject may not be able to continue in the study; 
treatment or other intervention usually required. 
Life- or Sight-Threatening/Grade 4: 
the event requires urgent intervention to preserve life and/or 
permanent loss of vision. 
Death/Grade 5: 
 the event resulted in the subject’s death. 
Causality/Relationship to Study Treatment 
The relationship of study treatment (i.e., EYP-1901 or aflibercept), the applicator, or the 
injection procedure, to each AE must be determined by the Investigator according to the 
following: 
Not Related: 
Evidence indicates no plausible direct relationship to the study 
treatment, device, or procedure, or there is a reasonable causal 
relationship between non-study product, concurrent disease, or 
circumstance and the AE; and/or a causal relationship is considered 
biologically implausible. 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 44 of 69
 
 
 
Possibly Related: 
There is reasonable causal relationship between the study treatment, 
device, or procedure and the AE. There may or may not be a 
clinically-plausible temporal sequence between the onset of the AE 
and study treatment, device, or procedure; the AE is not reasonably 
supported by other conditions. 
Probably Related: 
The study treatment, device, or procedure and AE occurrence are 
reasonably related in time; a clinically-plausible temporal sequence 
between the onset of the AE and study treatment, device, or 
procedure is likely; based upon the Investigator’s clinical 
experience, the association of the AE with study treatment, device, 
or procedure is likely; all other potential causes have been ruled 
out. 
If the relationship between the AE/SAE and the sequence study treatment, device, or procedure is 
determined to be “possible” or “probable”, the event will be considered related for the purposes 
of expedited regulatory reporting. 
7.1.6 
Recording of Adverse Events 
Medical conditions or diseases present before a subject starts study treatment are only considered 
AEs if they worsen after the start of the study treatment. 
Adverse events may be spontaneously reported or elicited at each study visit through open-ended 
questioning, examination, or evaluation of a subject.  To prevent reporting bias, subjects should 
not be questioned regarding the specific occurrence of one or more AEs. 
The Investigator will record all AEs in the eCRF.  Where a diagnosis is possible, it is preferable 
to report the diagnosis rather than a series of terms (signs/symptoms) relating to the diagnosis.  If 
a definitive diagnosis is not possible, the individual symptoms and signs should be recorded. 
The following information must be captured for all AEs: 
x Onset and end date 
x Severity 
x Seriousness  
x Relationship to EYP-1901, aflibercept, the injection device, or the procedure 
x Action taken 
x Any treatment required 
x Outcome 
If treatment for the AE was administered, it should be recorded on the appropriate concomitant 
medication/procedure eCRF page.  Each distinct AE should be recorded separately. 
7.1.7 
Adverse Event Reporting 
All subjects enrolled in the study will be evaluated for AEs, which will be collected from the 
time the ICF is signed until study completion (Table 5–1). 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 45 of 69
 
 
 
All AEs will be evaluated from onset until resolution or stabilization, whichever is first.  Adverse 
events that continue after the subject’s discontinuation or completion of the study will be 
followed until their medical outcomes are determined or until no further change in the condition 
is expected.  The event and outcome will be reported in writing by the Investigator to the 
Sponsor.  The Investigator shall supply the Sponsor and Institutional Review Board (IRB)/Ethics 
Committee (EC) with any additional requested information, notably for reported deaths. 
7.1.7.1 
Reporting of Serious Adverse Events 
All SAEs, regardless of cause(s) or relationship to study drugs, must be recorded on the 
appropriate eCRF page and reported to the Sponsor within 24 hours of the Investigator’s first 
awareness using the study’s designated SAE/SADR (Serious Adverse Drug Reaction) Report 
Form. 
Minimal information to be provided on the SAE/SADR Report Form includes: 
x Protocol number 
x Site and Investigator identifiers 
x Subject number 
x Brief description of the event(s) 
x Onset date of the event 
x Outcome of the event as of the date of report, if known 
x Resolution date and time, if the event(s) resolved 
x Any medication administered to treat the event 
x Investigator’s assessment of the causal relationship of the SAE to the study medicinal 
product 
x Additional and follow-up information as requested by Sponsor or its designee 
SAEs must be reported using the study’s designated SAE/SADR Report Form and sent to: 
Email: 
  
Fax: 
 
The Investigator will also compile other relevant documentation with urgent priority (e.g., copies 
of test results, hospital discharge summary, autopsy report, etc.), and send this information to the 
Sponsor (or Sponsor’s designee). 
The FDA and all participating Investigators shall be notified by a written Investigational New 
Drug Application (IND) safety report of any AE associated with the use of the investigational 
product that is both serious and unexpected no later than 15 calendar days from the Sponsor’s 
awareness date of the event.  An SAE is considered to be associated with the use of the 
investigational product if the relationship between the SAE and the investigational product is 
classified by the Investigator as “possibly related” or “probably related” (i.e., suspected, 
unexpected serious adverse reaction [SUSAR]).  Any unexpected fatal or life-threatening SAE 
associated with the use of the investigational product will be reported to the FDA by the Sponsor 
within 7 calendar days. 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________
PPD
PPD

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 46 of 69
 
 
 
The IRB/EC should be notified of SAEs as required in accordance with the local institutional 
policy. 
All Investigators participating in the study will be notified of unexpected SAEs determined to be 
related to study treatment/injection procedure. 
Pregnancy 
Pregnancy that occurs during the study must be immediately reported to the Investigator who 
will immediately notify the Sponsor or designee within 24 hours of first awareness using the 
study’s designated Pregnancy Report Form.  This includes any pregnancy following maternal or 
paternal exposure to the study treatments. 
The pregnancy should be followed to term.  The outcome, including premature termination must 
also be reported to the Sponsor or designee within 24 hours of the Investigator’s awareness using 
the Pregnancy Report Form.  All live births must be followed for a minimum of 4 weeks or to the 
first well-baby visit.  All reports of congenital abnormalities/birth defects and spontaneous 
abortions/miscarriages should be reported as SAEs.  Elective abortion procedures without 
complications should not be considered as AEs. 
If the Investigator becomes aware of a pregnancy occurring in any male subject’s partner during 
the male subject’s treatment with the assigned study medicinal product, the Investigator must 
submit this information to the Sponsor on the Pregnancy Report Form. 
The Pregnancy Report Form should be sent to: 
Email: 
  
Fax: 
 
Special Situations 
Notification must be made to the Sponsor or designee of any special situation which includes the 
following, regardless of any associated AE: 
x A medication error, defined as any unintentional error in the prescribing, dispensing, or 
administration of a medicinal product while in the control of the health care provider or 
subject. 
x Abuse, defined as persistent or sporadic intentional excessive use of a medicinal or other 
product. 
x Misuse, defined as any intentional or inappropriate use of a medicinal product that is not 
in accordance with the protocol instructions or local prescribing information. 
x An overdose, defined as an accidental or intentional administration of a quantity of a 
medicinal product given per administration or cumulatively which is above the maximum 
recommended dose per protocol or in the product labeling.  In cases of a discrepancy in 
drug accountability, overdose will be determined only when it is clear that the subject 
received an excess dose(s). 
Special situations should be reported on the study’s designated SAE/SADR Report Form except 
pregnancies for which there is a dedicated form.  If any special situation results in clinical 
sequela(ae)/AE(s), the event(s) must be recorded on the AE eCRF.  If the AE is serious, the SAE 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________
PPD
PPD

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 47 of 69
 
 
 
eCRF must be completed and a SAE/SADR Report Form must be completed and submitted to 
the Sponsor or designee within 24 hours of first awareness. 
Special situations involving concomitant medication do not need to be reported on the 
SAE/SADR Report Form.  However, special situations involving concomitant medication that 
result in clinical sequelae/AEs should be reported on the AE eCRF.  In addition, any 
inappropriate use of prohibited concomitant medications should not be reported as “misuse” but 
may be more appropriately documented as a protocol deviation. 
Using the SAE/SADR Report Form, reports of special situations should be sent to: 
Email: 
  
Fax: 
 
7.2 Clinical Laboratory Evaluations 
The clinical laboratory tests listed in the Study Laboratory Manual, including hematology, serum 
chemistry, coagulation, and urinalysis parameters, will be performed at the study visits indicated 
in Table 5–1. 
A central laboratory will be used to measure laboratory parameters.  The Investigator will use 
these results for clinical purposes and the laboratory data will be used for safety analyses. 
Normal value ranges and laboratory certification will be collected prior to study initiation. 
Investigators must review and document laboratory test results, as well as address the clinical 
significance and causality (for significant abnormalities).  Clinically significant abnormal 
laboratory results should be repeated as soon as possible.  Section 7.1.4 provides further 
guidance as to when abnormal laboratory results are to be reported as AEs. 
7.3 Vital Signs 
Vital signs will include pulse rate, respiratory rate, body temperature, and systolic and diastolic 
blood pressure (average of 3 readings will be taken in a resting state) at the visits indicated in 
Table 5–1. 
7.4 Electrocardiograms 
Standard 12-lead ECG assessments will be performed at visits indicated in Table 5–1. 
7.5 Concomitant Medication Use 
During the study, rescue treatment with aflibercept for the progression of wAMD may be 
required in the study eye for some subjects as a result of AEs or lack of efficacy of the study 
treatment.  Rescue treatment will be allowed per pre-specified rescue criteria (Section 6.6.4).  If 
the rescue criteria are not met, the medications will be considered prohibited medications.  
Prohibited medications (Section 6.6.3), although discouraged, can be used if necessary (e.g., no 
other alternative) but will be considered protocol deviations.  Information regarding concomitant 
medication use will be collected at the visits specified in Table 5–1. 
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EYP-1901-201 
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PPD
PPD

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
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8 REPORTING OF TECHNICAL PRODUCT COMPLAINTS 
A Product Complaint (PC) is defined as any written, electronic, or verbal expression of 
dissatisfaction regarding the identity, quality, reliability, safety, purity, potency, effectiveness, or 
performance of an investigational or commercial product after it is released for distribution 
(e.g., any failure of the applicator to deliver the intravitreal insert), or dissatisfaction with any 
other characteristic(s) of the drug product (e.g., labeling, packaging, etc.). 
Any/all PCs should be reported to EyePoint within 24 hours using the designated PC Report 
Form.  The complaint report should include the following information: 
x Product identification number 
x Investigator name, study site name, and contact phone number 
x Date the complaint occurred  
x Brief description of the complaint  
x Subject involved? (yes or no); if yes, were any AEs associated with the complaint? (yes 
or no).  If (yes) an AE is associated with the complaint, please refer to Section 7.1 
 
 
 
 
 
The drug container (applicator, foil pouch, and carton) for which the complaint was initiated 
should be retained for return to EyePoint at the address below for analysis. 
Attention: 
Product Returns 
EyePoint Pharmaceuticals, Inc. 
480 Pleasant Street 
Watertown, MA 02472 USA 
Any complaint about an investigational product must be reported regardless of whether the 
defect or deficiency had any effect on a subject or on study personnel. 
9 PHARMACOKINETICS 
Secondary endpoints in this study include the evaluation of the systemic and ocular exposure to 
EYP-1901 as measured through plasma and aqueous humor levels in the study eye, respectively, 
of vorolanib and its main metabolite.  Blood and aqueous humor samples will be collected at the 
visits noted in Table 5–1 for PK analysis of vorolanib and its main metabolite concentrations.  
Collection, handling, storage, and shipment of samples to the designated analytical testing 
laboratory will be conducted according to the procedures described in Appendix 3. 
In the event the subject requires vitrectomy during the study, the unmasked investigator or 
designee will collect a vitreous sample and EYP-1901 implants (if applicable) to be sent to 
sponsor as described in Appendix 3. 
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PPD

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
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11.3.2 Definition of Baseline 
Baseline measurements are those taken at Screening or prior to receiving study drug on Day 1, 
whichever is the latest. 
11.3.3 Handling of Missing Data 
In general, missing data will not be imputed, unless otherwise specified.  Every effort will be 
made to ensure completeness of data collection. 
11.3.4 Multicenter Considerations 
Approximately 70 investigative study sites will participate in the study.  All sites will be located 
in the United States.  Due to the limited sample size, a site effect will not be analyzed, unless 
otherwise specified. 
11.3.5 Adjustment for Covariates 
Not applicable. 
11.3.6 Interim Analyses 
No interim analyses are planned for this study prior to the primary endpoint readout at Week 32. 
11.3.7 Multiple Comparisons and Multiplicity 
Not applicable. 
11.3.8 Examination of Subgroups 
Data will be summarized by treatment arm.  Subgroup analyses could be performed upon 
completion of study follow-up and data collection as described in the SAP. 
11.3.9 Statistical Software 
All statistical summaries and analyses will be produced using SAS, Release 9.3 or higher. 
11.4 Analyses 
11.4.1 Subject Disposition 
A summary table will be prepared indicating the number and percentage of subjects in each 
treatment arm and overall who were included in the ITT population.  Within the ITT population, 
the number and percentage of subjects who did/did not complete the study will be presented.  
Screen failures, including reasons for failing to satisfy eligibility criteria will also be 
summarized.  
Subjects who discontinue any time during the study will be categorized by reason for 
termination, and the percentage within each category will be provided. 
11.4.2 Demographic and Baseline Characteristics 
Demographics and baseline characteristics will be summarized by treatment arm and overall 
using descriptive statistics for the ITT population. 
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11.4.3 Medical History 
Medical history will be coded and listed by treatment arm. 
11.4.4 Efficacy Analysis 
Primary Endpoint:  
The average change in BCVA from Day 1 averaged over Week 28 and Week 32 will be 
descriptively summarized by treatment arm for the efficacy population.  Further details will be 
described in the SAP. 
Secondary Endpoints: 
Descriptive statistics will be provided for the secondary endpoints by treatment arm for the 
efficacy population.  Further details will be described in the SAP. 
11.4.5 Pharmacokinetic Analysis 
Descriptive statistics will be provided for plasma and aqueous humor PK data by treatment arm 
for the ITT population. 
11.4.6 Adverse Events 
Both ocular and non-ocular TEAEs are defined as events that start after the first study drug 
administration, and occur before termination of the study, or were present before first study drug 
administration and worsened after administration.  Descriptive statistics will be provided for all 
TEAEs by treatment arm and overall for the ITT population. 
Adverse events will be coded by System Organ Class (SOC) and preferred term (PT) using the 
current version of the Medical Dictionary for Regulatory Activities (MedDRA).  Ocular and 
non-ocular TEAEs will be summarized separately.  The number and percentage of subjects who 
experience an AE will be presented.  Within each level of summarization (SOC, PT), subjects 
who experience more than one occurrence will only be counted once.  Adverse events will also 
be presented by severity (mild, moderate, severe, life-threatening, fatal), and by relationship to 
study drug (not related, possibly related, probably related).  Listings of deaths, SAEs, and 
withdrawals due to AEs will be presented. 
11.4.7 Clinical Laboratory Evaluations 
Clinical laboratory evaluations (hematology, serum chemistry, coagulation, and urinalysis) will 
be presented using descriptive statistics by treatment arm for the ITT population.  Laboratory 
values will be listed by subject, and values outside of a normal reference range will be flagged.  
Pregnancy test results will be listed separately. 
11.4.8 Vital Signs and Electrocardiograms 
Vital signs (pulse rate, respiratory rate, body temperature, and systolic and diastolic blood 
pressure) and ECG results will be presented using descriptive statistics by treatment for the 
ITT population.  Averages of replicate readings will be used in analysis.  Listings of ECG and 
vital signs data will be provided. 
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11.4.9 Prior and Concomitant Medications 
Medications for both ocular and non-ocular indications will be coded using the World Health 
Organization (WHO) Drug Dictionary.  These medications (prescription, OTC, and nutritional 
supplements) will be summarized by anatomical therapeutic chemical (ATC) classification 
levels, WHO generic name, and treatment arm.  Subjects will only be counted once at each level 
of the generic name or ATC level. 
11.4.10 Use of Prohibited Medications 
Prior to database lock, the Sponsor will conduct a blinded data review of concomitant treatments 
to determine if any fall under prohibited medications (Section 6.6.3).  The proportion of subjects 
receiving these medications will be summarized by treatment arm and time point. 
12 ADMINISTRATIVE AND REGULATORY CONSIDERATIONS 
12.1 Quality Control and Quality Assurance 
The Sponsor’s employees and/or their contracted representatives utilize standard operating 
procedures (SOPs) designed to ensure that research procedures and documentation are 
consistently conducted/prepared to the highest quality standards.  These SOPs also require 
compliance with Health Authority regulations and GCP guidance. 
A Quality Assurance audit may be conducted by the Sponsor or a designee at any time during or 
after completion of this study.  The Investigator will be given adequate notice if he/she is 
selected for an audit.  The audit will include, but is not limited to, a review of all ICFs, a review 
of eCRFs, associated source documents and medical records, a review of regulatory 
documentation, an assessment of study conduct and protocol compliance, and a review of the 
investigational drug accountability.  At the conclusion of an audit, the auditor will conduct a brief 
meeting with the Investigator to review the audit findings. 
12.2 Institutional Review Boards/Independent Ethics Committee 
Prior to the study initiation, the protocol and ICF will be submitted to the IRB/EC for approval. 
The IB may also be submitted as supplemental information.  By signing the “Statement of 
Investigator” form (FDA form 1572), the Investigator is assuring that an IRB/EC that complies 
with the requirements set forth in 21 CFR Part 56 will be responsible for the initial and 
continuing review of the clinical study.  A copy of the IRB/EC approval letter for the protocol, 
and the informed consent, as well as the protocol signature page must be submitted to the 
Sponsor or its designee prior to release of investigational supplies to the study site.  The approval 
letter must refer to the specific protocol and informed consent form.  The study site must 
maintain an accurate and complete record of all reports, documents, and other submissions made 
to the IRB/EC concerning this protocol.  A list of the IRB/EC members, their titles or 
occupations, and their institutional affiliation, or an IRB/EC assurance number must be provided 
to the Sponsor or its designee prior to release of study supplies. 
FDA/relevant health authority regulations require that all advertisements for subject recruitment 
be approved by an IRB/EC prior to implementation.  The complete text and format must be 
submitted to the Sponsor or designee for approval prior to IRB/EC submission. 
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The Investigator is responsible for notifying the IRB/EC of any SAEs.  A copy of the notification 
must be forwarded to the Sponsor or its designee. 
Status reports must be submitted to the IRB/EC at least once a year (or more frequently as 
required by the IRB/EC) and the IRB/EC must be notified of study completion or termination.  
A final report must be provided to the IRB/EC and the Sponsor within 6 months of study 
completion or termination.  This report should include:  any protocol deviations, the number of 
subjects evaluated, the number of subjects who withdrew or were withdrawn and the reasons for 
withdrawal, any significant AEs, and the Investigator’s summation of the study. 
12.3 Informed Consent Process 
It is the responsibility of the investigator to inform each subject, prior to the screening 
evaluation, of the purpose of this clinical trial, including possible risks and benefits and 
document the informed consent process in the subject’s chart.  Prior to entry into the study or 
initiation of any study-related procedures, the subject must read, sign and date the IRB/EC 
approved ICF.  The person executing the consent must also sign and date the final consent form 
page.  One or two signed originals of the ICF will be prepared, in accordance with applicable 
local requirements.  A signed original copy will be retained with the subject records, and either a 
copy of the signed original or the other signed original of the ICF will be given to the subject, in 
accordance with applicable local requirements. 
12.4 Source Documentation 
The Investigator must maintain adequate and accurate source documents upon which eCRFs for 
each subject are based.  These documents are to be separate and distinct from eCRFs, except for 
cases in which the Sponsor has predetermined that direct data entry into specified pages of the 
subject’s eCRF is appropriate.  The Investigator must allow access to the source documents by 
representatives of the Sponsor and regulatory authorities as needed.  These records should 
include detailed notes on: 
x The date the subject entered the study, study protocol number, and name of the Sponsor. 
x The oral and written communication with the subject regarding the study treatment 
(including the risks and benefits of the study).  The date of informed consent must be 
recorded in the source documentation. 
x The subject’s medical history prior to participation in the study and evidence that the 
subject meets study eligibility requirements. 
x The subject’s basic identifying information, such as demographics, that link the subject’s 
source documents with the eCRFs. 
x The dates of all study-related subject visits. 
x The results of all diagnostic tests performed, diagnoses made, therapy provided, and any 
other data on the condition of the subject. 
x The subject’s exposure to study treatment, and documentation of study treatment 
accountability. 
x All AEs. 
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x The subject’s exposure to any concomitant therapy (including start and stop dates, route 
of administration, and dosage). 
x All relevant observations and data on the condition of the subject throughout the study. 
x The date when subject exited the study and a notation as whether the subject completed 
the study or was discontinued, including the reason for discontinuation. 
Upon request, the Investigator will provide the Sponsor with any required background data from 
the study documentation or clinic records.  This is particularly important when source documents 
are illegible or when errors in data transcription are suspected.  In case there are issues or 
governmental queries or requests for audit inspections, it is also necessary to have access to the 
complete study records, provided that subject confidentiality is protected. 
12.5 Electronic Case Report Forms 
All study data must be incorporated in the corresponding eCRFs which are designed for 
computer processing and analysis.  The Investigator will be responsible for recording all data in 
the eCRFs and must ensure the accuracy, completeness, legibility, and timeliness of the data 
reported to the Sponsor in the eCRF and in all required reports. 
Data from clinical laboratory reports, etc., will be incorporated into the eCRFs either by direct 
transcription into appropriate eCRF pages or by inclusion of photocopies of these reports with 
printouts of the appropriate eCRF pages and stored in the site’s Study Binder. 
If corrections are made following official final review and sign-off by the Investigator, the 
Investigator must be made aware of the changes and provide written acknowledgement. 
This study will be conducted in compliance with the regulations contained within 21 CFR 
Part 11, electronic records/electronic signatures regulations. 
12.6 Retention of Study Records 
GCP regulations require that the Investigator retain all documentation related to this clinical trial 
for a period of 2 years after the approval of the NDA in the US (or Product License outside the 
US) for this drug or 2 years after the withdrawal of the IND.  These records include the protocol 
and copies of all documents submitted to the Sponsor or to government authorities, subject 
records (including signed ICFs, subject charts, eCRFs, and other source documents), IRB/EC 
approvals and correspondence, records of drug accountability, and all study communications, 
whether written, telephonic, or electronic.  None of the required documents will be destroyed or 
transferred to the control of another party without the written approval of the Sponsor.  
If the Investigator cannot guarantee the archiving requirement at the site for any or all of the 
documents, special arrangements must be made between the Investigator and the Sponsor to 
store these in a sealed container outside of the study site so that they can be returned sealed to the 
Investigator in case of a regulatory audit.  When source documents are required for the continued 
care of the subject, appropriate copies will be made for storing outside of the study site. 
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12.7 Monitoring the Study and Data Quality Assurance 
Representatives of the Sponsor (or designees) will contact the Investigator and his/her staff prior 
to the start of the trial to review the procedures to be followed in conducting the study and 
recording the findings, and to confirm the facility’s readiness to conduct the trial. 
It will be the monitor’s responsibility to inspect the eCRFs at regular intervals throughout the 
study, to verify the adherence to the protocol and the completeness, consistency, and accuracy of 
the data being entered on them.  The monitor must have access to all study related reports and 
records needed to verify the entries on the eCRF.  The Investigator (or designee) must agree to 
cooperate with the monitor to ensure that any problems detected in the course of these 
monitoring visits are resolved and agree to provide missing information and grant access to all 
study documentation. 
Every attempt must be made to follow the protocol, obtain and record all data requested for each 
subject at the specified times.  However, ethical reasons may warrant the failure to obtain and 
record certain data or to record data at the times specified.  If data is not recorded per protocol, 
the reasons must be clearly documented on the eCRF/records. 
Accurate and reliable data collection will be ensured by the verification of the eCRFs against the 
Investigator’s records by the monitor (source documentation verification).  Collected data will be 
entered into a computer database and subject to electronic and manual quality assurance 
procedures. 
The study data must be verifiable with the source data, which requires access to all original 
recordings, laboratory reports, product accountability records, including access to the subject 
electronic medical record, and source data must be made available for all study data.  Subjects 
must also allow access to their medical records.  They will be informed of this and must consent 
to permission by providing their signature on the ICF prior to enrollment. 
Representatives of the Sponsor (or designees) may audit the study periodically to ensure that all 
records are correct and complete.  The verification of the eCRF data must be by direct inspection 
of source documents. 
12.8 Discontinuation of the Study 
The Sponsor reserves the right to discontinue this study for administrative reasons at any time. 
The trial may also be terminated prematurely if unexpected AEs occur or if the Investigator does 
not adhere to the protocol. 
12.9 Policy for Publications 
The detailed procedures for the review of publications are set out in the clinical trial agreement 
entered into with the Sponsor in connection with this study.  Results from the study shall not be 
made available to any third party by the Investigator or staff outside of the publication policy. 
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13 ETHICS 
13.1 Ethics Review 
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB/EC as appropriate.  The IB may also be provided as 
required.  The Investigator must submit written approval from an IRB/EC to the Sponsor or a 
designee such as a Contract Research Organization (CRO) before the Investigator may initiate 
this study. 
The Principal Investigator is responsible for informing the IRB/EC of any amendment to the 
protocol in accordance with local requirements.  In addition, the IRB/EC must approve all 
advertising used to recruit subjects for the study.  The protocol must be re-approved by the 
IRB/EC upon receipt of amendments and annually, as local regulations require. 
The Principal Investigator is also responsible for providing the IRB with reports of any 
reportable serious adverse drug reactions from any other study conducted with the investigational 
product.  The Sponsor or the CRO will provide this information to the Principal Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the 
IRB/EC according to local regulations and guidelines. 
13.2 Ethical Conduct of the Study 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH/Good Clinical Practice and applicable 
regulatory requirements. 
13.3 Written Informed Consent 
A properly executed, written informed consent document, in compliance with 21 CFR 50, the 
ICH guidelines, and relevant local regulatory requirements, will be obtained from each subject 
before the subject is enrolled into the study and before any study-related procedure is performed.  
Attention will be directed to the basic elements required for incorporation into the informed 
consent under US Federal Regulations for Protection of Human Subjects (21 CFR 50.25[a]) and 
(21 CFR 50.25[b]). 
The informed consent document will be reviewed by the Sponsor or designee for inclusion of all 
required elements prior to submission to the IRB/EC.  The Sponsor must also review any 
revisions to the approved informed consent document prior to submission to the IRB/EC.  The 
final IRB/EC-approved document must be provided to the Sponsor for regulatory purposes.  It is 
the responsibility of the Investigator, or a person designated by the Investigator, to obtain written 
informed consent from each subject (or the subject’s legally authorized representative) 
participating in the study after adequate explanation of the aims, methods, anticipated benefits, 
and potential hazards of the study.  In the case where the subject is unable to read the form, an 
impartial witness will be present during the entire informed consent discussion.  After the subject 
has orally consented to participate in the study, the witness’ signature on the form will attest that 
the information in the consent form was accurately explained and understood. 
A copy of the fully executed informed consent document must be provided to the subject or the 
subject’s legally authorized representative.  If applicable, it will be provided in a certified 
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translation of the local language by the site under the guidance of the Investigator.  Signed 
informed consent documents must remain in each subject’s medical record and be made 
available for verification by the monitor at any time. 
If new safety information results in significant changes in the risk/benefit assessment, the 
consent form will be reviewed and updated as necessary.  All subjects (including those who have 
already been treated with EYP-1901 during the study) will be informed of the new information 
and given a copy of the revised form to provide their consent in order to continue participation in 
the study. 
 
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14 REFERENCES 
Boyer DS, Heier JS, Brown DM, et al. A Phase IIIb study to evaluate the safety of ranibizumab 
in subjects with neovascular age-related macular degeneration. Ophthalmol. 2009;116:1731-
1739. 
Brown DM, Kaiser PK, Michels M, et al. (ANCHOR Study Group). Ranibizumab versus 
verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432-
1444. 
Cohen MN, O’Shaughnessy D, Fisher K, et al. APEX: a phase II randomised clinical trial 
evaluating the safety and preliminary efficacy of oral X-82 to treat exudative age-related macular 
degeneration. Br J Ophthalmol. 2020;0:1-7. 
EYLEA® (aflibercept) label. Regeneron Pharmaceuticals, Inc. Tarrytown, NY. June 2021 
revision. 
Ferrara N. VEGF-A: a critical regulator of blood vessel growth. Eur Cytokine Netw. 
2009;20:158-163. 
Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related 
macular degeneration. Ophthalmol. 2012;119(12):2537-2548. 
Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of Uveitis Nomenclature (SUN) 
Working Group: Standardization of uveitis nomenclature for reporting clinical data. Results of 
the First International Workshop. Am J Ophthalmol. 2005;140:509-516. 
Jackson TL, Boyer D, Brown DM, Chaudhry N, Elman M, et al. Oral tyrosine kinase inhibitor 
for neovascular age-related macular degeneration: a phase 1 dose-escalation study. JAMA 
Ophthalmol. 2017;135(7):761-767. 
Nussenblatt RB, Palestine AG, Chan CC, Roberge F. Standardization of vitreal inflammatory 
activity in intermediate and posterior uveitis. Ophthalmol. 1985;92:467-471. 
Regillo CD, Brown DM, Abraham P, et al, PIER Study Group. Randomized, double-masked, 
sham-controlled trial of ranibizumab for neovascular age-related macular degeneration: PIER 
Study year 1. Am J Ophthalmol. 2008;145:239-248. 
Rosenfeld PJ, Brown DM, Heier JS, et al. (MARINA Study Group). Ranibizumab for 
neovascular age-related macular de-generation. N Engl J Med. 2006;355:1419-1431. 
Schmidt-Erfurth U, Eldem B, Guymer R, et al. EXCITE Study Group. Efficacy and safety of 
monthly versus quarterly ranibizumab treatment in neovascular age-related macular 
degeneration: the EXCITE study. Ophthalmol. 2011;118:831-839. 
Schmidt-Erfurth U, Kaiser PK, Korobelnik JF, et al. Intravitreal aflibercept injection for 
neovascular age-related macular degeneration: ninety-six-week results of the VIEW studies. 
Ophthalmol. 2014;121:193-201. 
Singer MA, Awh CC, Sadda S, et al. HORIZON: an open- label extension trial of ranibizumab 
for choroidal neovascularization secondary to age-related macular degeneration. Ophthalmol. 
2012;119:1175-1183. 
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Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease 
burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob 
Health. 2014;2:e106–116. 
Yancopoulos GD. Clinical application of therapies targeting VEGF. Cell. 2010;143:13-16. 
 
 
 
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APPENDIX 1: MEASUREMENT OF BCVA BY ETDRS 
Please refer to the BCVA Assessment Manual for the study. 
 
 
 
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EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 63 of 69
 
 
 
Intraocular Pressure 
Intraocular pressure will be assessed by applanation tonometry (preferably, Goldmann) and 
should be measured before the slit lamp examination has been completed at all study visits, and 
at the Week 8 visit it should be measured at 10 (+/- 5) and 60 (+/- 10) minutes following the 
second intravitreal injection (i.e., EYP-1901 or sham injection).  If IOP measurements at any 
study time points are ≥30 mmHg, two additional measurements should be performed and IOP 
recorded as a mean of three measurements per eye.  All reasonable efforts should be made to 
have the same examiner obtain all IOP measurement for a given subject.  Measurement should 
be performed before dilated ophthalmoscopy. 
 
 
 
17-Dec-2024
This document is confidential.
Page 64 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 64 of 69
 
 
 
APPENDIX 3: Pharmacokinetic Procedures and Analysis 
Please refer to the Lab Manual for the study. 
 
 
 
17-Dec-2024
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Page 65 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 65 of 69
 
 
 
APPENDIX 4: NCI CTCAE v5.0 
Adapted from: 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_R
eference_5x7.pdf  
 
 
 
 
 
17-Dec-2024
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Page 66 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 66 of 69
 
 
 
APPENDIX 5: Summary of Changes 
The following changes were made to Protocol EYP-1901-201 as Amendment 1 (v2.0): 
SECTION(S) 
CHANGE/RATIONALE 
Synopsis 
Section 2 
Section 3.1 
Section 3.4 
Section 5.1.7 
Table 5–1 Schedule of Assessments 
x 
End of Study visit was changed from Week 60 to Week 56, which 
allows for a 48-week follow-up from EYP-1901 administration. 
Synopsis 
Section 2 
Section 10 
Section 11.4.4 
x 
The primary endpoint was changed from “Change in BCVA from 
Day 1 to Week 32” to “Average change in BCVA from Day 1 
averaged over Week 28 and Week 32”, which allows for a blended 
BCVA to reduce variability. 
Synopsis 
Section 2 
Section 10 
x 
The secondary endpoints were updated to reflect the new end of 
study at Week 56 instead of Week 60. 
Synopsis 
Section 3.2 
x 
The unmasking of study data at Week 32 was clarified. 
Section 3.4 
Section 5.1.1 
Table 5–1 Schedule of Assessments 
x 
Duration of the Screening Period was changed from Days -14 to -7 
to Days -21 to -7, to allow Investigators more time to evaluate 
potential subjects. 
Synopsis 
Section 4.2 
x 
Exclusion criteria #7 (regarding intraretinal fluid at Screening) and 
#36 (regarding HbA1c at Screening) were clarified. 
Section 5 
Section 5.1.2 
x 
Added a new study requirement for historical OCT images in the 
original format for the 9 months prior to Screening to be submitted 
to the central reading center.  In the event that images are not 
available in the original format of capture, PDFs of the OCTs may 
be submitted. 
Section 6.1.4 
x 
Clarified that EYLEA® (aflibercept) is supplied as a 2 mg/0.05 mL 
solution in a single-dose pre-filled syringe or as a 2 mg/0.05 mL 
solution in a single-dose vial, and that either format is acceptable 
for use in this study. 
Section 6.2.3 
x 
Removed reference of study manual for injection procedure. 
Synopsis 
Section 6.6.4 
x 
Rescue treatment criteria were reordered and clarified. 
Section 11.4.8 
x 
Added ECG results to the statistical analysis sections. 
Table 5–1 Schedule of Assessments 
x 
The Schedule of Assessments table was completely revised to 
reflect the change from Week 60 to Week 56 End of Study visit. 
x 
The footnotes for Table 5-1 were also revised accordingly. 
Appendix 5:  Summary of Changes 
x 
Added Appendix 5 due to Amendment 1 changes. 
Throughout 
x 
Changed study week numbers accordingly to reflect the change in 
End of Study Visit week. 
x 
Replaced any reference to the pre-filled syringe of EYLEA® 
(aflibercept) to just EYLEA® (aflibercept). 
x 
Miscellaneous typographical and formatting issues were corrected, 
and some hyperlinks were fixed and/or added. 
 
17-Dec-2024
This document is confidential.
Page 67 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 67 of 69
 
 
 
The following changes were made to Protocol EYP-1901-201 as Amendment 2 (v2.1): 
SECTION(S) 
CHANGE/RATIONALE 
Synopsis 
Section 4.2 
x 
Exclusion criterion #7 (regarding intraretinal cystic fluid at 
Screening) was slightly changed by defining the abbreviations 
(IRF and ELM) and removing them as they are used no where else 
in the protocol. 
Table 1–1 List of Abbreviations 
x 
Removed ELM and IRF from the table. 
Section 5.1.6 
Section 5.1.8 
x 
Updated these sections to reflect changes made in Table 5–1 with 
Amendment 1 regarding aflibercept and sham dosing continuing 
through the new End of Study visit at Week 56. 
Throughout 
x 
Miscellaneous typographical and formatting issues were corrected, 
and some hyperlinks were fixed and/or added. 
 
The following changes were made to Protocol EYP-1901-201 as Amendment 3 (v3.0): 
SECTION(S) 
CHANGE/RATIONALE 
Synopsis 
Section 3.2 
x 
Parties unmasked after last subject completes Week 32 
updated to only the Sponsor/CRO will be unmasked at Week 
32 to conduct endpoint analysis. 
 
The following changes were made to Protocol EYP-1901-201 as Amendment 4 (v4.0): 
SECTION(S) 
CHANGE/RATIONALE 
Synopsis 
Section 4.1 
x 
Modified inclusion criterion #2 to include subjects who onset of 
disease in the past 4 years since the Screening Visit instead of 
9 months in order to expand the subject population. 
Synopsis 
Section 4.1 
x 
Added faricimab to inclusion criterion #4. 
Synopsis 
Section 4.2 
x 
Modified exclusion criterion #6 to adjust the CST in the study eye 
at Screening [Day 1] from >400 μm to >350 μm to allow 
enrollment of subjects with less excess fluid into the study. 
Section 4.2 
x 
Corrected typos in the exclusion criteria #24 to match the correct 
BCVA reading using ETDRS charts listed in the protocol 
synopsis.  
Section 4.3 
x 
As requested by the Central IRB, the pregnancy and contraception 
section was updated to align with the contraception requirements 
for aflibercept. 
Synopsis 
Section 3.1 
Section 5.1.4 
x 
Added the timing window for EYP-1901 and sham administration 
after receiving aflibercept.  
Section 7.1.1 
x 
Ocular AEs was updated to define moderate or severe as Grade 2 
and 3 for consistency with the AE grading descriptions in 
Section 7.1.5 and Appendix 4. 
Table 5–1 Schedule of Assessments 
Appendix 2 
x 
Added the window of time for IOP measurement following study 
treatment administration in Table 5–1 (footnote “e) and in 
Appendix 2.  
Throughout 
x 
Miscellaneous typographical and formatting issues were corrected, 
and some hyperlinks were fixed and/or added. 
 
17-Dec-2024
This document is confidential.
Page 68 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 68 of 69
 
 
 
The following changes were made to Protocol EYP-1901-201 as Amendment 5 (v5.0): 
SECTION(S) 
CHANGE/RATIONALE 
Synopsis 
Section 3.1.1 
Section 4.1 
x 
Changed the BCVA from 20/25 (80 letters) to 20/20 (85 letters) in 
inclusion criterion #6 to include subjects in the study who may 
demonstrate visual stability. 
Synopsis 
Section 3.1 
Section 11.3.4 
x 
Modified the number of study sites from 50 to approximately 70. 
Section 4 
x 
Clarified the details regarding subject eligibility to assist 
Investigators when making decisions to reassess and rescreen 
subjects during the Screening period. 
Synopsis 
Section 4.2 
x 
Added “in the study eye” to exclusion criterion #39. 
Synopsis 
Section 4.1 
x 
Modified inclusion criterion #2 to include subjects who had an 
onset of wAMD disease that began at any time prior the Screening 
Visit instead of 4 years to expand the subject population. 
Synopsis 
Section 4.2 
x 
Changed the RPED thickness from > 300 μm to > 400 μm in 
exclusion criterion #11 to include subjects in the study with larger 
RPEDs. 
Synopsis 
Section 2 
Section 6.6.4 
x 
Modified the rescue criteria to specify that it was specific to the 
study eye. 
Section 7 
x 
Removed the drug safety committee and added details regarding 
the Sponsor conducting ongoing medical safety reviews 
throughout the study. 
Throughout 
x 
Miscellaneous typographical and formatting issues were corrected, 
and some hyperlinks were fixed and/or added. 
 
The following changes were made to Protocol EYP-1901-201 as Amendment 6 (v6.0): 
SECTION(S) 
CHANGE/RATIONALE 
Personal Contact Information 
x 
Changed the Drug Safety Physician from 
 to 
 
Synopsis, Objectives 
Section 2 
x 
Changed the objective regarding the ocular exposure to EYP-1901 
measured through aqueous levels up to Week 32 instead of up to 
Week 56.  The Sponsor has collected the adequate number of 
aqueous humor samples at Week 32. 
Synopsis 
Section 3.1.1 
x 
Clarified that if during an unscheduled visit or if posterior 
inflammation is present in the study eye, CFP and OCT of the 
study eye should be collected at a minimum. 
Table 5–1 
Section 5.1.6 
Section 5.1.7 
Section 5.1.8 
x 
Removed the aqueous humor PK collection from Weeks 44 and 56 
because the Sponsor has collected the adequate number of aqueous 
humor samples. 
Section 1.1 
x 
Changed the Sponsor of Yutiq® from EyePoint Pharmaceuticals, 
Inc to Alimera Sciences. 
Section 3.3 
 
x 
Changed the status of the Phase 1 DAVIO study from “ongoing” 
to “completed”. 
17-Dec-2024
This document is confidential.
Page 69 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________
PPD
PPD

EYP-1901 (Vorolanib Intravitreal Insert) 
 
EyePoint Pharmaceuticals, Inc. 
Protocol EYP-1901-201 (Version 6.0) 
 
 
 
25 Jan 2024 
CONFIDENTIAL 
Page 69 of 69
 
 
 
SECTION(S) 
CHANGE/RATIONALE 
Personal Contact Information 
x 
Changed the Drug Safety Physician from 
 to 
. 
Throughout 
x 
Miscellaneous typographical and formatting issues were corrected, 
and some hyperlinks were fixed and/or added. 
 
17-Dec-2024
This document is confidential.
Page 70 of 70
EyePoint Pharmaceuticals, Inc. 
EYP-1901 (vorolanib intravitreal insert)
EYP-1901-201 
Version 1.0 Final CSR
______________________________________________________________________________________________
PPD
PPD